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Henry Ford Health System Publication List – October 2021

This bibliography aims to recognize the scholarly activity and provide ease of access to journal articles, meeting abstracts, book chapters, books and other works published by Henry Ford Health System personnel. Searches were conducted in PubMed, Embase, and Web of Science during the month, and then imported into EndNote for formatting. There are 133 unique citations listed this month, with 7 articles and 2 conference abstracts on COVID-19. Articles are listed first, followed by conference abstracts, books and book chapters, and a bibliography of

publications on COVID-19. Because of various limitations, this does not represent an exhaustive

list of all published works by Henry Ford Health System authors.

Click the “Full Text” link to view the articles to which Sladen Library provides access. If the full-text of the article is not available, you may request it through ILLiad by clicking on “Request Article,” or calling us at (313) 916-2550. If you would like to be added to the monthly email distribution list to automatically receive a PDF of this bibliography, or you have any questions or comments, please contact smoore31@hfhs.org. If your published work has been missed, please use this form to notify us for inclusion on next month’s list. All articles and abstracts listed here are deposited into Scholarly Commons, the HFHS institutional repository.

Articles

Allergy and Immunology

Anesthesiology

Behavioral Health

Services/Psychiatry/Neuropsychology

Cardiology/Cardiovascular Research

Center for Health Policy and Health Services

Research

Dermatology

Diagnostic Radiology

Emergency Medicine

Endocrinology and Metabolism

Gastroenterology

Hematology-Oncology

Hospital Medicine

Internal Medicine

Nephrology

Neurology

Neurosurgery

Obstetrics, Gynecology and Women’s Health

Services

Ophthalmology and Eye Care Services

Orthopedics/Bone and Joint Center

Otolaryngology – Head and Neck Surgery

Pathology and Laboratory Medicine

Pharmacy

Plastic Surgery

Public Health Sciences

Pulmonary and Critical Care Medicine

Radiation Oncology

Surgery

Urology

Conference Abstracts

Administration

Behavioral Health

Services/Psychiatry/Neuropsychology

Cardiology/Cardiovascular Research

Center for Health Policy and Health Services

Research

Diagnostic Radiology

Emergency Medicine

Gastroenterology

Hematology-Oncology

Hospital Medicine

Internal Medicine

Neurology

Obstetrics, Gynecology and Women’s Health

Services

Otolaryngology – Head and Neck Surgery

Pathology and Laboratory Medicine

Public Health Sciences

Pulmonary and Critical Care Medicine

Radiation Oncology

Surgery

Articles

Allergy and Immunology da Silva Antunes R, Sutherland A, Frazier A, Schulten V, Pomés A, Glesner J, Calatroni A, Altman MC, Wood RA, O'Connor GT, Pongracic JA, Khurana Hershey GK, Kercsmar CM, Gruchalla RS, Gill M, Liu AH, Zoratti E, Kattan M, Busse PJ, Bacharier LB, Teach SJ, Wheatley LM, Togias A, Busse WW, Jackson DJ, and Sette A. Heterogeneity of magnitude, allergen immunodominance, and cytokine polarization of cockroach allergen-specific T cell responses in allergic sensitized children. Clin Transl Allergy 2021; 11(8):e12073. PMID: 34691392. Full Text Division of Vaccine Discovery La Jolla Institute for Immunology La Jolla California USA. Basic Research Indoor Biotechnologies, Inc. Charlottesville Virginia USA. Rho Federal Systems Division Chapel Hill North Carolina USA. Benaroya Research Institute Systems Immunology Division Department of Medicine University of Washington Seattle Washington USA. Division of Pediatric Allergy, Immunology and Rheumatology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland USA. Boston University School of Medicine Pulmonary Center Boston Massachusetts USA. Advanced General Pediatrics and Primary Care Ann & Robert H. Lurie Children's Hospital of Chicago Chicago Illinois USA. Division of Asthma Research Cincinnati Children's Hospital Cincinnati Ohio USA. Division of Pulmonary Medicine Cincinnati Children's Hospital Cincinnati Ohio USA. Divisions of Infectious Diseases and Pulmonary Vascular Biology Department of Pediatrics University of Texas Southwestern Medical Center Dallas Texas USA. Department of Pediatrics Children's Hospital Colorado University of Colorado School of Medicine Aurora Colorado USA. Henry Ford Health System and Wayne State University School of Medicine Detroit Michigan USA. College of Physicians and Surgeons Columbia University New York New York USA. Division of Clinical Immunology and Allergy Icahn School of Medicine at Mount Sinai New York New York USA. Department of Pediatrics Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center Nashville Tennessee USA. Center for Translational Research Children's National Hospital Washington DC USA. Division of Allergy, Immunology, and Transplantation National Institute of Allergy and Infectious Diseases National Institutes of Health Rockville Maryland USA. Departments of Pediatrics and Medicine University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA. Department of Medicine University of California San Diego La Jolla California USA. BACKGROUND: Characterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen-specific T cell reactivity in a cohort of CR allergic children with asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild-to-moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining. RESULTS: Highly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL-4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract. CONCLUSIONS: Our results demonstrate that in children with mild-to-moderate asthma, CR-specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.

Allergy and Immunology Fonseca W, Malinczak CA, Fujimura K, Li D, McCauley K, Li J, Best SKK, Zhu D, Rasky AJ, Johnson CC, Bermick J, Zoratti EM, Ownby D, Lynch SV, Lukacs NW, and Ptaschinski C. Maternal gut microbiome regulates immunity to RSV infection in offspring. J Exp Med 2021; 218(11). PMID: 34613328. Request Article Department of Pathology, University of Michigan, Ann Arbor, MI. Department of Medicine-Gastroenterology, University of California, San Francisco, San Francisco, CA. Department of Public Health Sciences, Henry Ford Health System, Detroit, MI. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI. Division of Allergy and Clinical Immunology, Department of Medicine, Henry Ford Health System, Detroit, MI. Department of Pediatrics, Augusta University, Augusta, GA. Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI. Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates. Allergy and Immunology Vesper S, Wymer L, Kroner J, Pongracic JA, Zoratti EM, Little FF, Wood RA, Kercsmar CM, Gruchalla RS, Gill MA, Kattan M, Teach SJ, Patel S, Johnson CC, Bacharier LB, Gern JE, Jackson DJ, Sigelman SM, Togias A, Liu AH, Busse WW, and Khurana Hershey GK. Association of mold levels in urban children's homes with difficult-to-control asthma. J Allergy Clin Immunol 2021; Epub ahead of print. PMID: 34606833. Full Text United States Environmental Protection Agency, Center for Environmental Measurement and Modeling, Cincinnati, Ohio. Electronic address: vesper.stephen@epa.gov. United States Environmental Protection Agency, Center for Environmental Measurement and Modeling, Cincinnati, Ohio. Cincinnati Children's Hospital, Cincinnati, Ohio. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill. Henry Ford Health System, Detroit, Mich. Boston University School of Medicine, Boston, Mass. Johns Hopkins University School of Medicine, Baltimore, Md. University of Texas Southwestern Medical Center, Dallas, Tex. College of Physicians and Surgeons, Columbia University, New York, NY. Children's National Hospital, Washington, DC. St Louis Children's Hospital, St Louis, Mo. University of Wisconsin School of Medicine and Public Health, Madison, Wis. National Institute of Allergy and Infectious Diseases, Rockville, Md. National Jewish Health, Aurora, Colo; Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colo.

BACKGROUND: Mold sensitization and exposure are associated with asthma severity, but the specific species that contribute to difficult-to-control (DTC) asthma are unknown. OBJECTIVE: We sought to determine the association between overall and specific mold levels in the homes of urban children and DTC asthma. METHODS: The Asthma Phenotypes in the Inner-City study recruited participants, aged 6 to 17 years, from 8 US cities and classified each participant as having either DTC asthma or easy-to-control (ETC) asthma on the basis of treatment step level. Dust samples had been collected in each participant's home (n = 485), and any dust remaining (n = 265 samples), after other analyses, was frozen at -20(o)C. The dust samples (n = 265) were analyzed using quantitative PCR to determine the concentrations of the 36 molds in the Environmental Relative Moldiness Index. Logistic regression was performed to discriminate specific mold content of dust from homes of children with DTC versus ETC asthma. RESULTS: Frozen-dust samples were available from 54% of homes of children with DTC (139 of 253) and ETC asthma (126 of 232). Only the average concentration of the mold Mucor was significantly (P < .001) greater in homes of children with DTC asthma. In homes with window air-conditioning units, the Mucor concentration contributed about a 22% increase (1.6 odds ratio; 95% CI, 1.2-2.2) in the ability to discriminate between cases of DTC and ETC asthma. CONCLUSIONS: Mucor levels in the homes of urban youth were a predictor of DTC asthma, and these higher Mucor levels were more likely in homes with a window air-conditioner. Anesthesiology Ahuja S, and Luedi MM. Too little or too much anesthesia: Age paradox of electroencephalogram indices. J Clin Anesth 2021; 73:110358. PMID: 34082269. Full Text Department of Anesthesiology, Pain Management and Perioperative Medicine, Henry Ford Health System, Detroit, MI, United States; Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio, United States. Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: markus.luedi2@insel.ch. Anesthesiology Al Turk Y, Lemor A, Fayed M, and Kim H. Sjögren-related cardiomyopathy presenting with cardiogenic shock. BMJ Case Rep 2021; 14(10). PMID: 34667036. Full Text Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA yaltur1@hfhs.org. Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan, USA. Centro de Investigación de Epidemiología Clínica y Medicina Basada en la Evidencia, Universidad de San Martín de Porres Facultad de Medicina Humana, La Molina, Peru. Anesthesia, Henry Ford Health System, Detroit, Michigan, USA. Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic, infectious and other possible causes, the patient's clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out. Anesthesiology Guerra-Londono CE, Owusu-Agyemang P, Corrales G, Rofaeil MM, Feng L, Fournier K, and Cata JP. ASO Author Reflections: Predicting Hyperthermia and Its Effect in Patients with Peritoneal Surface Malignancies. Ann Surg Oncol 2021; Epub ahead of print. PMID: 34713370. Full Text

Department of Anesthesiology, Pain Management, and Perioperative Medicine, Henry Ford Health System, Detroit, MI, USA. Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA. Baylor College of Medicine, Houston, TX, USA. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. JCata@mdanderson.org. Anesthesiology and Surgical Oncology Research Group, Houston, TX, USA. JCata@mdanderson.org. Anesthesiology Neuman MD, Feng R, Carson JL, Gaskins LJ, Dillane D, Sessler DI, Sieber F, Magaziner J, Marcantonio ER, Mehta S, Menio D, Ayad S, Stone T, Papp S, Schwenk ES, Elkassabany N, Marshall M, Jaffe JD, Luke C, Sharma B, Azim S, Hymes RA, Chin KJ, Sheppard R, Perlman B, Sappenfield J, Hauck E, Hoeft MA, Giska M, Ranganath Y, Tedore T, Choi S, Li J, Kwofie MK, Nader A, Sanders RD, Allen BFS, Vlassakov K, Kates S, Fleisher LA, Dattilo J, Tierney A, Stephens-Shields AJ, and Ellenberg SS. Spinal Anesthesia or General Anesthesia for Hip Surgery in Older Adults. N Engl J Med 2021; Epub ahead of print. PMID: 34623788. Full Text From the Departments of Anesthesiology and Critical Care (M.D.N., L.J.G., N.E., L.A.F.), Biostatistics, Epidemiology, and Informatics (R.F., A.J.S.-S., S.S.E.), and Orthopedic Surgery (S.M.) and the Centers for Perioperative Outcomes Research and Transformation (M.D.N., L.J.G., N.E., L.A.F.) and Clinical Epidemiology and Biostatistics (R.F., J.D., A.T., A.J.S.-S., S.S.E.), University of Pennsylvania Perelman School of Medicine, the Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University (E.S.S.), the Center for Advocacy for the Rights and Interests of the Elderly (D.M.), and the Department of Anesthesiology, Lewis Katz School of Medicine at Temple University (E.H.), Philadelphia; the Division of General Internal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ (J.L.C.); the Department of Anesthesiology and Pain Medicine, University of Alberta Hospital, Edmonton (D.D.), the Department of Orthopaedics, University of British Columbia, Vancouver (T.S.), the Division of Orthopaedics, Ottawa Hospital Civic Campus, Ottawa (S.P.), the Department of Anesthesiology and Pain Medicine, University of Toronto (K.-J.C.), and the Department of Anesthesia, Sunnybrook Health Sciences Centre (S.C.), Toronto, and the Department of Anesthesia, Pain Management, and Perioperative Medicine, Dalhousie University, Halifax NS (M.K.K.) - all in Canada; the Department of Outcomes Research, Cleveland Clinic, Cleveland (D.I.S., S. Ayad); the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions (F.S.), and the Department of Epidemiology and Public Health, University of Maryland School of Medicine (J.M.) - both in Baltimore; the Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School (E.R.M.), and the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School (K.V.), Boston, and the Department of Anesthesiology, Lahey Hospital and Medical Center, Burlington (B.S.) - all in Massachusetts; the Department of Anesthesiology, Perioperative Care, and Pain Medicine, New York University Langone Health (M.M.), and the Department of Anesthesiology, New York-Presbyterian/Weill Cornell Medical Center (T.T.), New York, and the Department of Anesthesiology, Stony Brook University, Stony Brook (S. Azim) - all in New York; the Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC (J.D.J.); the Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh (C.L.); the Department of Orthopedic Surgery, Inova Fairfax Medical Campus, Falls Church (R.A.H.), and the Department of Orthopedic Surgery, Virginia Commonwealth University, Richmond (S.K.) - both in Virginia; the Department of Anesthesiology, Hartford Hospital, Hartford (R.S.), and the Department of Anesthesiology, Yale University School of Medicine, New Haven (J.L.) - both in Connecticut; Division of Hospital Medicine, Oregon Health and Science University, Portland (B.P.); the Department of Anesthesiology, University of Florida College of Medicine, Gainesville (J.S.); the Department of Anesthesiology, University of Vermont Larner School of Medicine, Burlington, VT (M.A.H.); the Department of Anesthesiology, Pain Management, and Perioperative Medicine, Henry Ford Health System, Detroit (M.G.); the Department of Anesthesia, University of Iowa Carver College of Medicine, Iowa City (Y.R.); the Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago (A.N.); Specialty of

Anaesthetics, University of Sydney, Sydney (R.D.S.); and the Division of Multispecialty Anesthesiology, Department of Anesthesiology, Vanderbilt University Medical Center, Nashville (B.F.S.A.). BACKGROUND: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied. METHODS: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 m) independently or with a walker or cane at 60 days after randomization. Secondary outcomes included death within 60 days, delirium, time to discharge, and ambulation at 60 days. RESULTS: A total of 1600 patients were enrolled; 795 were assigned to receive spinal anesthesia and 805 to receive general anesthesia. The mean age was 78 years, and 67.0% of the patients were women. A total of 666 patients (83.8%) assigned to spinal anesthesia and 769 patients (95.5%) assigned to general anesthesia received their assigned anesthesia. Among patients in the modified intention-to-treat population for whom data were available, the composite primary outcome occurred in 132 of 712 patients (18.5%) in the spinal anesthesia group and 132 of 733 (18.0%) in the general anesthesia group (relative risk, 1.03; 95% confidence interval [CI], 0.84 to 1.27; P = 0.83). An inability to walk independently at 60 days was reported in 104 of 684 patients (15.2%) and 101 of 702 patients (14.4%), respectively (relative risk, 1.06; 95% CI, 0.82 to 1.36), and death within 60 days occurred in 30 of 768 (3.9%) and 32 of 784 (4.1%), respectively (relative risk, 0.97; 95% CI, 0.59 to 1.57). Delirium occurred in 130 of 633 patients (20.5%) in the spinal anesthesia group and in 124 of 629 (19.7%) in the general anesthesia group (relative risk, 1.04; 95% CI, 0.84 to 1.30). CONCLUSIONS: Spinal anesthesia for hip-fracture surgery in older adults was not superior to general anesthesia with respect to survival and recovery of ambulation at 60 days. The incidence of postoperative delirium was similar with the two types of anesthesia. (Funded by the Patient-Centered Outcomes Research Institute; REGAIN ClinicalTrials.gov number, NCT02507505.). Behavioral Health Services/Psychiatry/Neuropsychology Felton JW, Triemstra JD, Reynolds EK, Hale N, Magidson JF, and Lejuez CW. The Role of Social Adjustment in a Collegiate Behavioral Activation Program. Behav Modif 2021; Epub ahead of print. PMID: 34595933. Full Text Henry Ford Health Systems, Detroit, MI, USA. Michigan State University, Lansing, USA. Helen DeVos Children's Hospital/Spectrum Health, Grand Rapids, MI, USA. Johns Hopkins University, Baltimore, MD, USA. Calvin University, Grand Rapids, MI, USA. University of Maryland, College Park, USA. University of Connecticut, Storrs, USA. The transition to college is associated with significant changes in social support networks and concomitant increases in depressive symptoms. First-year students who are more socially engaged within their new academic settings may experience greater overall wellbeing. Behavioral activation (BA) is an evidence-based intervention which promotes individuals' engagement with valued activities and has been examined as a possible primary prevention for depressive symptoms among first-year students. Yet, the important role of social adjustment, and its impact on students' activity level, has not yet been considered. The current study is a secondary data analysis of research evaluating a BA-based intervention embedded into a first-year orientation course. The aim of the project was to evaluate the efficacy of BA on improving social adjustment and the effect of social adjustment on subsequent depressive symptoms. A diverse sample of college students (n = 71) attending a state university in the mid-Atlantic region reported on their levels of depression, behavioral activation, and social adjustment. Students then received either BA or standard programming. Results suggest that improved engagement in valued activities at mid-intervention was associated with increases in students' perceptions of their own social adjustment. This, in turn, predicted steeper decreases in rates of depressive symptoms post-intervention. Findings also indicate that greater social adjustment improved the efficacy of a BA-based intervention in reducing

depressive symptoms, but had no impact on depressive symptoms for students receiving the standard orientation programming. Behavioral Health Services/Psychiatry/Neuropsychology Martens K, Pester BD, Hecht LM, Herb Neff KM, Clark-Sienkiewicz SM, Hamann A, Carlin AM, and Miller-Matero LR. Adherence to Post-operative Appointments Is Associated with Weight Loss Following Bariatric Surgery. Obes Surg 2021; Epub ahead of print. PMID: 34651288. Full Text Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, 48202, USA. Cardiology/Cardiovascular Research Abraham J, Blumer V, Burkhoff D, Pahuja M, Sinha SS, Rosner C, Vorovich E, Grafton G, Bagnola A, Hernandez-Montfort JA, and Kapur NK. Heart Failure-Related Cardiogenic Shock: Pathophysiology, Evaluation and Management Considerations: Review of Heart Failure-Related Cardiogenic Shock. J Card Fail 2021; 27(10):1126-1140. PMID: 34625131. Full Text Providence Heart Institute, Center for Cardiovascular Analytics, Research, and Data Science (CARDS), Providence St. Joseph Health, Portland, Oregon. Division of Cardiology, Duke University Medical Center, Durham, North Carolina. Cardiovascular Research Foundation, New York, New York. Medstar Georgetown University Hospital, Washington, D.C. Inova Heart and Vascular Institute, Inova Fairfax Medical Center, Falls Church, Virginia. Northwestern Memorial Hospital, Chicago, Illinois. Henry Ford Hospital, Detroit, Michigan. The Ohio State University Wexner Medical Center, Department of Pharmacy, Columbus, Ohio. Heart and Vascular Institute, Cleveland Clinic Florida, Weston, Florida. The Cardiovascular Center, Tufts Medical Center, Boston, Massachusetts. The Cardiovascular Center, Tufts Medical Center, Boston, Massachusetts. Electronic address: nkapur@tuftsmedicalcenter.org. Despite increasing prevalence in critical care units, cardiogenic shock related to HF (HF-CS) is incompletely understood and distinct from acute myocardial infarction related CS. This review highlights the pathophysiology, evaluation, and contemporary management of HF-CS. Cardiology/Cardiovascular Research Al Turk Y, Lemor A, Fayed M, and Kim H. Sjögren-related cardiomyopathy presenting with cardiogenic shock. BMJ Case Rep 2021; 14(10). PMID: 34667036. Full Text Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA yaltur1@hfhs.org. Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan, USA. Centro de Investigación de Epidemiología Clínica y Medicina Basada en la Evidencia, Universidad de San Martín de Porres Facultad de Medicina Humana, La Molina, Peru. Anesthesia, Henry Ford Health System, Detroit, Michigan, USA. Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic, infectious and other possible causes, the patient's clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure

therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out. Cardiology/Cardiovascular Research Aslam A, Stojanovska J, Khokhar US, Weinberg RL, Ganesh SK, Labounty T, Sutton NR, and Patel S. Spontaneous Coronary Artery Dissection: An Underdiagnosed Clinical Entity-A Primer for Cardiac Imagers. Radiographics 2021; 41(7):1897-1915. PMID: 34652974. Full Text From the Divisions of Cardiothoracic Radiology (A.A., J.S., S.P.), Cardiovascular and Internal Medicine (R.L.W., S.K.G., T.L.), and Interventional Cardiology (N.R.S.), Frankel Cardiovascular Center, and Department of Human Genetics (S.K.G.), Michigan Medicine, 1500 E Medical Center Dr, Ann Arbor, MI 48109; and Division of Interventional Cardiology, Henry Ford Allegiance Health Hospital, Jackson, Mich (U.S.K.). Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction in young and middle-aged women that has gained increasing awareness in recent years. Its diagnosis presents a challenge. Invasive coronary angiography is the primary imaging modality for diagnosing SCAD; however, it carries risk in these patients, who have an increased predisposition to complications. Advances in CT technology enable robust noninvasive evaluation of the coronary arteries at low radiation doses and have been increasingly utilized for the diagnosis or resolution of SCAD, in hemodynamically stable patients or when diagnosis of SCAD is uncertain at invasive angiography, particularly in proximal vessels. However, criteria for the diagnosis of SCAD with use of coronary CT angiography (CCTA) have not been currently established, and sensitivity and specificity for diagnosis have not yet been defined. The appearance of SCAD at CCTA can be subtle and can be missed, especially in distal small-caliber coronary arteries; hence utilization of other noninvasive imaging multimodalities may help solve this diagnostic challenge. Accurate and prompt diagnosis is vital, as management of SCAD differs significantly from that of traditional atherosclerotic acute coronary syndromes, with conservative management preferred for the majority of SCAD patients, and invasive treatment reserved for those with ongoing or recurrent ischemia, heart failure, or hemodynamic compromise. The goal of this review is twofold: (a) to discuss the potential role of CCTA in the diagnosis of SCAD, and (b) to discuss the role of multimodality imaging that may improve diagnostic yield, guide management, and enable subsequent surveillance. An invited commentary by Ordovas is available online. Online supplemental material is available for this article. (©)RSNA, 2021. Cardiology/Cardiovascular Research Bajwa F, O'Connor R, and Ananthasubramaniam K. Epidemiology and clinical manifestations of cardiac amyloidosis. Heart Fail Rev 2021; Epub ahead of print. PMID: 34694575. Full Text Department of Cardiology, University of Rochester Medical Center, Rochester, NY, USA. Henry Ford West Bloomfield Hospital, Heart and Vascular Institute, West Bloomfield, MI, 48322, USA. kananth1@hfhs.org. Cardiac amyloidosis, once considered a rare disease, has garnered significant attention over the last few years due to three key reasons: first, increased recognition of this disease in conjunction with various common cardiac conditions such as heart failure with preserved ejection fraction and aortic stenosis; second, due to the advent of promising new therapies for light chain disease (AL), transthyretin (ATTR) cardiomyopathy, and amyloid neuropathy; finally, the advancements in cardiac imaging including echocardiography, magnetic resonance imaging, and nuclear cardiac scintigraphy aid in non-biopsy diagnosis of ATTR cardiac amyloidosis. The hereditary forms of ATTR have further come into importance with the availability of genetic testing and increased prevalence of certain mutations in African Americans. Recognition of non-cardiac clues to this disease has gained importance and reiterates that high clinical suspicion, detailed patient history, and examination with appropriate use of imaging are vital to confirm the diagnosis.

Cardiology/Cardiovascular Research Cogswell R, Cantor RS, Vorovich E, Kilic A, Stehlik J, Cowger JA, Habib RH, Kirklin JK, Pagani FD, and Atluri P. HVAD(TM) to Heartmate 3(TM) Device Exchange: A Society of Thoracic Surgeons Intermacs Analysis. Ann Thorac Surg 2021; Epub ahead of print. PMID: 34678286. Full Text Department of Medicine. Division of Cardiology, University of Minnesota, Minneapolis, MN. John and James Kirklin Institute for Research in Surgical Outcomes, School of Medicine, University of Alabama at Birmingham, Birmingham, AL. Department of Medicine, Division of Cardiology, Feinberg School of Medicine Northwestern, Chicago, IL. Department of Surgery, Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC. Department of Medicine. Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT. Henry Ford Health System, Detroit, MI. The Society of Thoracic Surgeons Research Center, The Society of Thoracic Surgeons, Chicago, IL. Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL. Department of Cardiac Surgery, University of Michigan, Ann Arbor, MI. Department of Surgery, Division of Cardiothoracic Surgery, University of Pennsylvania Philadelphia, PA. BACKGROUND: On June 3, 2021, Medtronic, Inc. announced discontinuation of the HVAD(TM) left ventricular assist device. The purpose of this analysis is to provide summary data on surgical risks of HVAD to HeartMate 3(TM) exchange and compare survival following HVAD to HeartMate 3 exchange to survival following primary HVAD implantation. METHODS: Three cohorts within The Society of Thoracic Surgeons Intermacs database were identified: 1) primary HVAD implant cohort (1/2017-3/2021, n=3,797); 2) HVAD to HeartMate 3 exchange cohort (n=45, 12/2017-3/2021); and 3) HVAD to HVAD exchange cohort (1/2017-3/2021, n=234). Mortality following HVAD to HeartMate 3 exchange was modeled and compared to the constant hazard phase for risk of mortality while on continued HVAD support. As a secondary analysis, outcomes and survival were compared between patients who underwent HVAD to HeartMate 3 and HVAD to HVAD exchange. RESULTS: HVAD to HeartMate 3 exchange was associated with significantly reduced survival compared to survival while remaining on HVAD support (6 months following exchange 73.8% (68.6-77.8; 70% CI) versus 79.0% (78.3-79; 70% CI) for continued HVAD support). Compared to HVAD to HVAD exchange, survival was higher following replacement with HeartMate 3 (1-year: 85.9% (79.5-90.5%) versus 66.6% (63.0-70.0%), 70% CI, p = 0.009). CONCLUSIONS: Compared to continued support on HVAD, an exchange to HeartMate 3 is associated with a significant increase in mortality. For patients who required pump exchange on HVAD support, exchange to HeartMate 3 demonstrated superior survival. Currently, there is insufficient evidence to support elective exchange from an HVAD to HeartMate 3. Cardiology/Cardiovascular Research El Sabbagh A, Al-Hijji M, Wang DD, Eleid M, Urena M, Himbert D, Chakravarty T, Holzhey D, Pershad A, Fang HK, Nejjari M, Zahr F, Dvir D, Sardar MR, Cheema AN, Alnasser S, Iyer V, Kaddissi G, Webb J, Makkar R, Vahanian A, O'Neill W, Rihal C, and Guerrero M. Predictors of Left Ventricular Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement in Severe Mitral Annular Calcification: An Analysis of the Transcatheter Mitral Valve Replacement in Mitral Annular Calcification Global Registry. Circ Cardiovasc Interv 2021; 14(10). PMID: 34665654. Full Text Department of Cardiovascular Diseases, Mayo Clinic, Jacksonville, FL (A.E.S.). Division of Cardiovascular Diseases, Heart Hospital, Hamad Medical Corporation, Doha, Qatar (M.A.-H). Division of Cardiology, Henry Ford Hospital, Detroit, MI (D.D.W., W.O.). Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (M.E., C.R., M.G.). Department of Cardiology, Bichat Hospital, Paris, France (M.U., D.H.). Division of Cardiology, Cedars Sinai Medical Center, Los Angeles, CA (T.C., R.M.). Division of Cardiac Surgery, Leipzig Heart Center, Germany (D.H.). Division of Cardiology, Chandler Regional and Mercy Gilbert Medical Center, AZ (A.P.). Division of Cardiac Surgery, Banner University Medical Center, Phoenix, AZ (H.K.F.). Division of Cardiology, Centre Cardiologique du Nord, St. Denis, France (M.N.).

Division of Cardiology, Oregon Health & Science University, Portland, OR (F.Z.). Division of Cardiology, University of Washington, Seattle (D.D.). Jesselson Integrated Heart Center, Shaare Zedek Medical Centre, Hebrew University, Jerusalem, Israel (D.D.). Division of Cardiology, Northeast Ohio Medical University, Rootstown, OH (M.R.S.). Division of Cardiology, St. Michael's Hospital, Toronto, Canada (A.N.C., S.A.). Division of Cardiology, Buffalo General Medical Center, Buffalo, NY (V.I.). Division of Cardiology, Cooper University Hospital, Camden, NJ (G.K.). Division of Cardiology, St. Paul's Hospital, Vancouver, Canada (J.W.). Division of Cardiology, University of Paris, Paris, France (A.V.). Cardiology/Cardiovascular Research Eng MH, Qintar M, Apostolou D, and O'Neill WW. Alternative Access for Transcatheter Aortic Valve Replacement: A Comprehensive Review. Interv Cardiol Clin 2021; 10(4):505-517. PMID: 34593113. Full Text Division of Cardiology, Banner- University Medical Center Phoenix, 1111 East McDowell Road, Phoenix, AZ 85006, USA. Electronic address: Marvin.eng@bannerhealth.com. Division of Cardiology, Sparrow Hospital, 1215 East Michigan Avenue, Lansing, MI 48912, USA. Division of Cardiothoracic Surgery, Department of Surgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Division of Cardiology, Center for Structural Heart Disease, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Transfemoral is the most widely used access to perform transcatheter aortic valve replacement (TAVR). However, alternative access is needed in up to 21% of patients with TAVR because of a myriad of factors. The authors provide a comprehensive review on alternative access for TAVR, discussing the relevant data and providing the pros and cons of each access route. Cardiology/Cardiovascular Research Ignatius A, Eng MH, and Frisoli TM. Neurologic Complications in Transcatheter Aortic Valve Replacement. Interv Cardiol Clin 2021; 10(4):519-529. PMID: 34593114. Full Text Center for Structural Heart Disease, Henry Ford Hospital, 2799 W Grand Boulevard, Detroit, MI 48202, USA. Interventional Structural Cardiology, Center for Structural Heart Disease, Heart and Vascular Institute, Henry Ford Hospital, 2799 W Grand Boulevard, Detroit, MI 48202, USA; Henry Ford Allegiance Hospital, 205 N East Avenue, Jackson, MI 49201, USA. Electronic address: tfrisol1@hfhs.org. Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment for severe symptomatic aortic stenosis. Although many TAVR complication rates including mortality and aortic regurgitation have decreased, stroke rates have remained stable for years. TAVR-related strokes are devastating to patients and their families, and very costly for health care systems. The predictors of stroke in TAVR are not yet well defined, although older age, female gender, carotid and peripheral arterial disease, bicuspid aortic valve anatomy, and atrial fibrillation are emerging as risk factors across studies. Cardiology/Cardiovascular Research Kalra S, Ranard LS, Memon S, Rao P, Garan AR, Masoumi A, O'Neill W, Kapur NK, Karmpaliotis D, Fried JA, and Burkhoff D. Risk Prediction in Cardiogenic Shock: Current State of Knowledge, Challenges and Opportunities. J Card Fail 2021; 27(10):1099-1110. PMID: 34625129. Full Text The Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Electronic address: sanjog.kalra@uhn.ca. Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, New York. Einstein Medical Center Philadelphia, Philadelphia, Pennsylvania. Beth Israel Deaconess Medical Center, Boston, Masschusetts.

Henry Ford Health System, Detroit, Michigan. Tufts University Medical Center, Boston, Massachusetts. Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York. Cardiovascular Research Foundation, New York, New York. Cardiogenic shock (CS) is a condition associated with high mortality rates in which prognostication is uncertain for a variety of reasons, including its myriad causes, its rapidly evolving clinical course and the plethora of established and emerging therapies for the condition. A number of validated risk scores are available for CS prognostication; however, many of these are tedious to use, are designed for application in a variety of populations and fail to incorporate contemporary hemodynamic parameters and contemporary mechanical circulatory support interventions that can affect outcomes. It is important to separate patients with CS who may recover with conservative pharmacological therapies from those in who may require advanced therapies to survive; it is equally important to identify quickly those who will succumb despite any therapy. An ideal risk-prediction model would balance incorporation of key hemodynamic parameters while still allowing dynamic use in multiple scenarios, from aiding with early decision making to device weaning. Herein, we discuss currently available CS risk scores, perform a detailed analysis of the variables in each of these scores that are most predictive of CS outcomes and explore a framework for the development of novel risk scores that consider emerging therapies and paradigms for this challenging clinical entity. Cardiology/Cardiovascular Research Lemor A, Basir MB, Truesdell AG, Tamis-Holland JE, Alqarqaz M, Grines CL, Villablanca PA, Alaswad K, Pinto DS, and O'Neill W. Trends in the Outcomes of High-risk Percutaneous Ventricular Assist Device-assisted Percutaneous Coronary Intervention, 2008-2018. Am J Cardiol 2021; 156:65-71. PMID: 34344515. Full Text Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan; Universidad de San Martín de Porres, Facultad de Medicina Humana, Centro de Investigación de Epidemiología Clínica y Medicina Basada en la Evidencia Lima, Peru. Electronic address: alejandrolemor@outlook.com. Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, Michigan. Virginia Heart / Inova Heart and Vascular Institute, Falls Church, Virginia. Division of Cardiovascular Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Heart, New York, New York. Division of Cardiovascular Medicine, Northside Hospital Cardiovascular Institute, Atlanta, Georgia. Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Percutaneous ventricular assist devices (pVAD) are frequently utilized in high-risk percutaneous coronary intervention (HR-PCI) to provide hemodynamic support in patients with complex cardiovascular disease and/or multiple comorbidities who are poor candidates for surgical revascularization. Using the National Inpatient Sample we identified pVAD-assisted PCI (excluding intra-aortic balloon pump) in patients without cardiogenic shock from January 2008 to December 2018. We evaluated the trends in patient and procedural characteristics, and complication rates across the 11-year study period. A total of 26,661 pVAD-PCI was performed. From 2008 to 2018 there has was a 27-fold increase in the number of pVAD-PCIs performed annually. There has also been an increase in the proportion of procedures performed in small to medium sized hospitals. The use of atherectomy, image-guided PCI, FFR/iFR, drug-eluting stents, and multi-vessel intervention has significantly increased. Patients undergoing pVAD-PCI had a higher burden of comorbidities, without a significant difference in mortality over time. There were decreased rates of acute stroke and blood transfusions over time, while vascular complications and acute kidney injury (AKI) requiring dialysis remained mostly unchanged. In conclusion, the use of pVAD for HR-PCI has increased significantly, along with adjunctive PCI techniques such as atherectomy, intravascular imaging, and physiologic lesion assessment. With increasing use of this device, there appeared to be lower rates of peri-procedural stroke, and blood transfusions. Despite a higher burden of comorbidities, adjusted mortality remained stable over time.

Cardiology/Cardiovascular Research Megaly M, Khalil M, Basir MB, McEntegart MB, Spratt JC, Yamane M, Tsuchikane E, Xu B, Alaswad K, and Brilakis ES. Outcomes of successful vs. failed contemporary chronic total occlusion percutaneous coronary intervention. Cardiovasc Interv Ther 2021; Epub ahead of print. PMID: 34716883. Request Article Division of Cardiology, Banner University Medical Center, Phoenix, AZ, USA. Department of Medicine, Lincoln Medical Center, New York, NY, USA. Division of Cardiology, Henry Ford Hospital, Detroit, MI, USA. Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK. Department of Cardiology, St. George's University Hospitals NHS Foundation Trust, London, UK. Department of Cardiology, Sayama Hospital, Saitama, Japan. Department of Cardiology, Toyohashi Heart Center, Aichi, Japan. Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, 920 E 28th Street #300, Minneapolis, MN, 55407, USA. esbrilakis@gmail.com. BACKGROUND: There are limited contemporary data on the impact of success vs. failure on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and a meta-analysis of contemporary studies that compared the outcomes in patients who underwent successful vs. failed contemporary (2010 onwards) CTO PCI. We performed a sensitivity analysis limited to studies that started enrollment after the publication of the hybrid algorithm in 2012. RESULTS: We included five studies with a total of 6,084 patients (successful CTO PCI n = 4,861, failed CTO PCI n = 1,223). During a median follow-up time of 12 months (range 6-60 months), successful CTO PCI was associated with a lower risk of major adverse cardiovascular events [OR: 0.61, 95% CI (0.41, 0.92), p = 0.02, I(2) = 63%] and all-cause death [OR: 0.57, 95% CI (0.33, 0.99), p = 0.05, I(2) = 60%]. Both groups had similar risk of myocardial infarction (MI) [OR 0.69, 95% CI (0.43, 1.10), p = 0.38, I(2) = 80%], target vessel revascularization (TVR) [OR: 0.56, 95% CI (0.25, 1.27), p = 0.17, I(2) = 80%], and stroke [OR: 0.52, 95% CI (0.14, 1.91), p = 0.33, I(2) = 0%]. CONCLUSION: In contemporary practice, successful CTO PCI was associated with a lower incidence of MACE driven by lower all-cause mortality compared with failed CTO PCI at a median follow-up of 1 year. Cardiology/Cardiovascular Research Sabbah HN. Elamipretide for Barth syndrome cardiomyopathy: gradual rebuilding of a failed power grid. Heart Fail Rev 2021; Epub ahead of print. PMID: 34623544. Full Text Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI, 48202, USA. hsabbah1@hfhs.org. Barth syndrome is a rare and potentially fatal X-linked disease characterized by cardiomyopathy, skeletal muscle weakness, growth delays, and cyclic neutropenia. Patients with Barth syndrome are prone to high risk of mortality in infancy and the development of cardiomyopathy with severe weakening of the immune system. Elamipretide is a water-soluble, aromatic-cationic, mitochondria-targeting tetrapeptide that readily penetrates and transiently localizes to the inner mitochondrial membrane. Therapy with elamipretide facilitates cell health by improving energy production and inhibiting excessive formation of reactive oxygen species, thus alleviating oxidative stress. Elamipretide crosses the outer membrane of the mitochondrion and becomes associated with cardiolipin, a constituent phospholipid of the inner membrane. Elamipretide improves mitochondrial bioenergetics and morphology rapidly in induced pluripotent stem cells from patients with Barth syndrome and other genetically related diseases characterized by pediatric cardiomyopathy. Data with elamipretide across multiple models of disease are especially promising, with results from several studies supporting the use of elamipretide as potential therapy for patients with Barth syndrome, particularly where there is a confirmed diagnosis of cardiomyopathy. This review highlights the challenges and opportunities presented in treating Barth syndrome cardiomyopathy patients with elamipretide and addresses evidence supporting the durability of effect of elamipretide as a therapeutic agent for Barth syndrome, especially its likely durable effects on

progression of cardiomyopathy following the cessation of drug treatment and the capability of elamipretide to structurally reverse remodel the failing left ventricle at the global, cellular, and molecular level in a gradual manner through specific targeting of the mitochondrial inner membrane. Cardiology/Cardiovascular Research Sennott J, and Ananthasubramaniam K. Multimodality imaging approach to cardiac amyloidosis: part 2. Heart Fail Rev 2021; Epub ahead of print. PMID: 34694574. Full Text Heart and Vascular Institute, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, 48322, USA. Heart and Vascular Institute, Henry Ford West Bloomfield Hospital, West Bloomfield, MI, 48322, USA. kananth1@hfhs.org. With recent advances in cardiac imaging, genetics, and treatment options, cardiac amyloidosis (CA) is now recognized as an important and under diagnosed condition contributing to cardiovascular morbidity and mortality. Although still considered a rare disease, CA is now recognized as an important contributor to heart failure with preserved ejection fraction (HFPEF) and low gradient aortic stenosis, two important conditions commonly faced in clinical practice. This review uses clinical scenarios to highlight the complementary role of traditional imaging tools such as electrocardiogram (ECG) and echocardiography (echo) in conjunction with advanced cardiac imaging with cardiac magnetic resonance (CMR) and nuclear cardiac scintigraphy using bone avid tracers in the comprehensive workup of CA. We also highlight the importance of workup of light chain disease as part of integration of imaging findings and discuss the key aspects of various imaging modalities. Finally, an algorithm integrating clinical suspicion, laboratory testing, and imaging in the workup of CA is presented. Cardiology/Cardiovascular Research Wang DD, Caranasos TG, O'Neill BP, Stack RS, O'Neill WW, and Chitwood WR. Comparison of a new bioprosthetic mitral valve to other commercially available devices under controlled conditions in a porcine model. J Card Surg 2021; 36(12):4654-4662. PMID: 34610175. Full Text Cardiovascular Masters Consortium, Durham, North Carolina, USA. Division of Cardiology, Center for Structural Heart Disease, Henry Ford Hospital, Detroit, Michigan, USA. Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Department of Medicine, Duke University, Durham, North Carolina, USA. Department of Cardiovascular Sciences, East Carolina University, Greenville, North Carolina, USA. BACKGROUND/AIM: To evaluate three mitral bioprostheses (of comparable measured internal diameters) under controlled, stable, hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography and autopsy comparisons pre- and postvalve implantation. METHODS: Fifteen similar-sized Yorkshire pigs underwent preprocedural computerized tomography anatomic screening. Of these, 12 had consistent anatomic features and underwent implantation of a mitral bioprosthesis via thoracotomy on cardiopulmonary bypass (CPB). Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris bioprostheses. After CPB, epicardial echocardiographic studies were performed to assess hemodynamic function and define any paravalvular leaks, followed by postoperative gated contrast computerized tomography. After euthanasia, animals underwent necropsy for anatomic evaluation. RESULTS: All 12 animals had successful valve implantation with no study deaths. Postoperative echocardiographic trans-valve gradients varied among bioprosthesis manufacturers. The 25-mm Mitris (5.1 ± 2.7)/(2.6 ± 1.3 torr) had the lowest peak/mean gradient and the 27-mm Epic bioprosthesis had the highest (9.2 ± 3.7)/(4.6 ± 1.9 torr). Surgical valve opening area (SOA) varied with the 25-mm Mitris having the largest SOA (2.4 ± 0.15 cm(2) ) followed by the 27-mm Mosaic (2.04 ± 0.23 cm(2) ) and the 27-mm Epic (1.8 ± 0.27 cm(2) ) valve. Bench device orthogonal internal diameter measurements did not match manufacturer device size labeling: 25-mm Mitris (23 × 23 mm), 27-mm Mosaic (23 × 22 mm), 27-mm Epic (21 × 21 mm). CONCLUSIONS: Current advertisement/packaging of commercial surgical mitral valves is not uniform. This study demonstrates marked variations in hemodynamics, valve opening area and anatomic dimensions

between similar sized mitral bioprostheses. These data suggest a critical need for standardization and close scientific evaluation of surgical mitral bioprostheses to ensure optimal clinical outcomes. Center for Health Policy and Health Services Research Martens K, Pester BD, Hecht LM, Herb Neff KM, Clark-Sienkiewicz SM, Hamann A, Carlin AM, and Miller-Matero LR. Adherence to Post-operative Appointments Is Associated with Weight Loss Following Bariatric Surgery. Obes Surg 2021; Epub ahead of print. PMID: 34651288. Full Text Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, 48202, USA. Center for Health Policy and Health Services Research Richesson RL, Marsolo KS, Douthit BJ, Staman K, Ho PM, Dailey D, Boyd AD, McTigue KM, Ezenwa MO, Schlaeger JM, Patil CL, Faurot KR, Tuzzio L, Larson EB, O'Brien EC, Zigler CK, Lakin JR, Pressman AR, Braciszewski JM, Grudzen C, and Fiol GD. Enhancing the use of EHR systems for pragmatic embedded research: lessons from the NIH Health Care Systems Research Collaboratory. J Am Med Inform Assoc 2021; Epub ahead of print. PMID: 34597383. Full Text Department of Learning Health Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA. Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina, USA. Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. US Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA. Duke Clinical Research Institute, Durham, North Carolina, USA. Department of Medicine, University of Colorado Medicine, Denver, Colorado, USA. Center for Health Sciences, St. Ambrose University, Davenport, Iowa and Department of Physical Therapy and Rehabilitation Science, University of Iowa, Iowa City, Iowa, USA. Department of Biomedical and Health Information Sciences University of Illinois Chicago, Chicago, Illinois, USA. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Department of Biobehavioral Nursing Science, University of Florida, College of Nursing, Gainesville, Florida, USA. Department of Human Development Nursing Science, University of Illinois Chicago, College of Nursing, Chicago, Illinois, USA. Department of Physical Medicine and Rehabilitation, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. Kaiser Permanente Washington Health Research Institute, Seattle, Washington, USA. Palliative Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. Center for Health Systems Research, Sutter Health Center for Health Systems Research, Walnut Creek, California, USA. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA. Department of Emergency Medicine, New York University School of Medicine, New York, New York, USA. Department of Biomedical Informatics, University of Utah, Salt Lake City, Utah, USA. OBJECTIVE: We identified challenges and solutions to using electronic health record (EHR) systems for the design and conduct of pragmatic research. MATERIALS AND METHODS: Since 2012, the Health Care Systems Research Collaboratory has served as the resource coordinating center for 21 pragmatic clinical trial demonstration projects. The EHR Core working group invited these demonstration projects to

complete a written semistructured survey and used an inductive approach to review responses and identify EHR-related challenges and suggested EHR enhancements. RESULTS: We received survey responses from 20 projects and identified 21 challenges that fell into 6 broad themes: (1) inadequate collection of patient-reported outcome data, (2) lack of structured data collection, (3) data standardization, (4) resources to support customization of EHRs, (5) difficulties aggregating data across sites, and (6) accessing EHR data. DISCUSSION: Based on these findings, we formulated 6 prerequisites for PCTs that would enable the conduct of pragmatic research: (1) integrate the collection of patient-centered data into EHR systems, (2) facilitate structured research data collection by leveraging standard EHR functions, usable interfaces, and standard workflows, (3) support the creation of high-quality research data by using standards, (4) ensure adequate IT staff to support embedded research, (5) create aggregate, multidata type resources for multisite trials, and (6) create re-usable and automated queries. CONCLUSION: We are hopeful our collection of specific EHR challenges and research needs will drive health system leaders, policymakers, and EHR designers to support these suggestions to improve our national capacity for generating real-world evidence. Center for Health Policy and Health Services Research Thurm A, Halladay A, Mandell D, Maye M, Ethridge S, and Farmer C. Making Research Possible: Barriers and Solutions For Those With ASD and ID. J Autism Dev Disord 2021; Epub ahead of print. PMID: 34716842. Full Text National Institute of Mental Health, Bethesda, MD, USA. athurm@mail.nih.gov. Autism Science Foundation, New York, NY, USA. Rutgers University, Piscataway, NJ, USA. University of Pennsylvania, Philadelphia, PA, USA. Henry Ford Health System, Detroit, MI, USA. National Institute of Mental Health, Bethesda, MD, USA. Participation in research can provide direct and indirect benefit to individuals with autism spectrum disorder (ASD), their caregivers, families, and society at large. Unfortunately, individuals with high support needs, including those with intellectual disability, cognitive disability or minimal verbal ability, are often systematically excluded from research on ASD. This limits the ability to generalize discoveries to all people with ASD, and results in a disparity in who benefits from research. This piece outlines the importance and extent of the problem, which is part of a broader lack of inclusivity in ASD research. It also provides examples of studies that have directly addressed issues that arise when conducting inclusive research and makes recommendations for researchers to reduce disparities in research participation. Dermatology Jiang AJ, Soon SL, Rullan P, Brody HJ, Monheit GD, and Lee KC. Chemical Peels as Field Therapy for Actinic Keratoses: A Systematic Review. Dermatol Surg 2021; 47(10):1343-1346. PMID: 34238790. Full Text Department of Dermatology, Henry Ford Health System, Detroit, Michigan. Department of Dermatology, The Skin Clinic MD, San Diego, California. Department of Dermatology, Dermatology Institute, Chula Vista, California. Department of Dermatology, University of California San Diego, San Diego, California. Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia. Department of Dermatology, Total Skin and Beauty Dermatology Center, Birmingham, AL. Department of Dermatology, Main Line Center for Laser Surgery, Ardmore, Pennsylvania. BACKGROUND: Actinic keratoses (AKs) are a common premalignant cutaneous neoplasm and can progress to squamous cell carcinoma. A variety of treatment options are available for field therapy of diffuse AKs. OBJECTIVE: This review systematically analyzes the use of chemical peels for treatment of AKs. MATERIALS AND METHODS: A systematic review of PubMed was performed searching from 1946 to March 2020 to identify the literature on chemical peels for AKs. RESULTS: Of the 151 articles identified, 5 met inclusion criteria for review. Four of the reviewed articles demonstrated the efficacy of

chemical peels in reducing AK count and minimal adverse effects. In some studies, chemical peels exhibited potential to prevent additional AK formation and development of keratinocyte carcinomas. CONCLUSION: Chemical peels are an efficacious and affordable treatment option for field treatment of AKs. With improved patient tolerance and adherence, chemical peels are an attractive option for field therapy of AKs for both dermatologists and patients. Dermatology Lim HW, Mohammad TF, and Wang SQ. Food and Drug Administration's proposed sunscreen final administrative order: How does it affect sunscreens in the United States? J Am Acad Dermatol 2021; Epub ahead of print. PMID: 34606770. Full Text Photomedicine and Photobiology Unit, Department of Dermatology, Henry Ford Health System, Detroit, Michigan. Electronic address: hlim1@hfhs.org. Photomedicine and Photobiology Unit, Department of Dermatology, Henry Ford Health System, Detroit, Michigan. Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York. Dermatology Lopez S, Lourido JO, Lim HW, Ferguson NN, Pandya AG, and Vasquez R. The call to action to increase racial and ethnic diversity in dermatology: A retrospective, cross-sectional study to monitor progress. J Am Acad Dermatol 2021; Epub ahead of print. PMID: 34678231. Full Text University of Texas Southwestern Medical Center, Dallas, TX, 75390. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, 75390. Department of Dermatology, Henry Ford Health System, Detroit, MI 48202. Department of Dermatology, University of Iowa, Iowa City, IA, 52242. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, 75390; Department of Dermatology, Palo Alto Foundation Medical Group, Sunnyvale, CA. Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX, 75390. Electronic address: Rebecca.Vasquez@UTSouthwestern.edu. Dermatology Me R, Gao N, Zhang Y, Lee PSY, Wang J, Liu T, Standiford TJ, Mi QS, and Yu FX. IL-36α Enhances Host Defense against Pseudomonas aeruginosa Keratitis in C57BL/6 Mouse Corneas. J Immunol 2021; Epub ahead of print. PMID: 34686582. Full Text Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI. Center for Cutaneous Biology and Immunology, Department of Dermatology and Immunology Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, MI; and. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI. Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI; fyu@wayne.edu. The IL-36 cytokines are known to play various roles in mediating the immune response to infection in a tissue- and pathogen-dependent manner. The present study seeks to investigate the role of IL-36R signaling in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa infection. IL-36α(-/-), IL-36γ(-/-), and IL-36R(-/-) mice had significantly more severe keratitis than wild-type mice. At six hours postinfection, IL-36α pretreatment augmented P. aeruginosa-induced expression of IL-1Ra, IL-36γ, LCN2, and S100A8/A9. At one day postinfection, exogenous IL-36α suppressed, whereas IL-36α deficiency promoted, the expression of IL-1β. At three days postinfection, exogenous IL-36α suppressed Th1 but promoted Th2 immune response. IL-36α stimulated the infiltration of IL-22-expressing immune cells, and IL-22 neutralization resulted in more severe keratitis. IL-36α alone stimulated dendritic cell infiltration in B6 mouse corneas. Taken together, our study suggests that IL-36R signaling plays a protective role in the pathogenesis of P. aeruginosa keratitis by promoting the innate immune defense, Th2, and/or Th22/IL-22

immune responses. Exogenous IL-36α might be a potential therapy for improving the outcome of P. aeruginosa keratitis. Dermatology Phillips GS, Huang A, Augsburger BD, Kaplan L, Peoples K, Bruckner AL, Khuu P, Tang JY, Lara-Corrales I, Pope E, Wiss K, Levin LE, Morel KD, Hook KP, Paller AS, Eichenfield LF, McCuaig CC, Powell J, Castelo-Soccio L, Levy ML, Price HN, Schachner LA, Browning JC, Jahnke M, Shwayder T, Bayliss S, Lucky AW, and Glick SA. A retrospective analysis of diagnostic testing in a large North American cohort of patients with epidermolysis bullosa. J Am Acad Dermatol 2021; Epub ahead of print. PMID: 34634382. Full Text Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, NY. Cincinnati Children's Hospital Medical Center, Cincinnati, OH. Children's Hospital Colorado, Aurora, CO. Department of Dermatology, University of Colorado School of Medicine, Aurora, CO. Department of Dermatology, Stanford University School of Medicine, Stanford, CA. Section of Dermatology, Division of Paediatric Medicine, Hospital for Sick Children, Toronto, Ontario, Canada. Departments of Dermatology and Pediatrics, University of Massachusetts Medical School, Worcester, MA. Department of Dermatology, Columbia Irving Medical Center, New York, NY. Department of Dermatology, Columbia Irving Medical Center, New York, NY; Department of Pediatrics, Columbia Irving Medical Center, New York, NY. Department of Dermatology, University of Minnesota Medical School, Minneapolis, MN. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL. Departments of Dermatology and Pediatrics, University of California San Diego, San Diego, CA. CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada. Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, PA. Pediatric/Adolescent Dermatology, Dell Children's Medical Center and Departments of Pediatrics and Medicine (Dermatology), Dell Medical School, University of Texas, Austin, TX. Department of Dermatology, Phoenix Children's Hospital, Phoenix, AZ. Department of Dermatology, University of Miami Miller School of Medicine, Miami, FL. Department of Pediatric Dermatology, Children's Hospital San Antonio, San Antonio, TX. Department of Dermatology, Henry Ford Hospital, Detroit, MI. Division of Dermatology, Department of Medicine, Washington University in St. Louis, MO. Department of Dermatology, State University of New York Downstate Health Sciences University, Brooklyn, NY. Electronic address: sharon.glick@downstate.edu. BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort of patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004 to July 8, 2019 was included. Tests concluding the same EB type (EB simplex [EBS], junctional EB [JEB], dominant dystrophic EB [DDEB], recessive dystrophic EB [RDEB]) were considered concordant, different EB types discordant, and non-specific/non-definitive results equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (p<.001). The likelihood of undergoing genetic analysis was greater for JEB and RDEB, and the same for DDEB as compared to EBS. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSION: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

Dermatology Pinter A, Green LJ, Selmer J, Praestegaard M, Gold LS, and Augustin M. A pooled analysis of randomized, controlled, phase 3 trials investigating the efficacy and safety of a novel, fixed dose calcipotriene and betamethasone dipropionate cream for the topical treatment of plaque psoriasis. J Eur Acad Dermatol Venereol 2021; Epub ahead of print. PMID: 34628687. Full Text University Hospital Frankfurt am Main, Dept. of Dermatology, Frankfurt am Main, Germany. George Washington University School of Medicine, Washington, DC, USA. MC2 Therapeutics, Hørsholm, Denmark. Dermatology Clinical Research, Henry Ford Health System, Detroit, Michigan, USA. University Medical Center Hamburg-Eppendorf, Hamburg, Germany. BACKGROUND: Plaque psoriasis is a common, chronic, and relapsing inflammatory skin disease clinically characterized by erythema and scaling desquamation. As over 90% of psoriasis patients benefit from topical therapies, local treatments continue to play an eminent role in management strategies. One such topical treatment is the fixed dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP). METHODS: The data from two Phase 3, multicenter, randomized, investigator-blind, active, and vehicle-controlled trials enrolling patients with psoriasis were pooled and analysed. Investigational products included a CAL/BDP cream based on PAD™ Technology (PAD-cream) designed for high skin penetration and increased patient preference, an active control (marketed CAL/BDP topical suspension/gel, in the following abbreviated as CAL/BDP TS), and cream vehicle, which were applied once daily for 8 weeks. Superiority claims regarding efficacy, safety, and quality of life (QoL) were compared between CAL/BDP PAD-cream and CAL/BDP TS. RESULTS: Efficacy and safety of the novel CAL/BDP PAD-cream formulation for the topical treatment of psoriasis demonstrated superiority for all efficacy endpoints after 8 weeks of treatment. PGA treatment success for CAL/BDP PAD-cream (43.2%) was greater than CAL/BDP TS (31.9%) (p<0.0001), the mean percent reduction in mPASI for CAL/BDP PAD-cream was 64.6% compared to 56.4% for CAL/BDP TS (p<0.0001), and DLQI 0/1 was obtained by 43.8% in the CAL/BDP PAD-cream group versus 34.2% in the CAL/BDP TS group (p=0.0005). There was no adverse drug reaction reported with a frequency of >1%, associated with the CAL/BDP PAD-cream. CONCLUSIONS: The novel fixed dose combination CAL/BDP PAD-cream offers greater efficacy, superior patient QoL and equivalent favorable safety for the topical treatment of psoriasis, in comparison to the currently available topical suspension/gel. This manuscript relates to two Phase 3 studies, with the clinicaltrials.gov identifiers: NCT03308799 and NCT03802344. Dermatology Rehman R, Saad M, Huq F, Oska S, Mehregan D, and Daveluy S. A cross-sectional analysis of popular hidradenitis suppurativa content on TikTok. JAAD Int 2021; 5:98-100. PMID: 34693364. Full Text Oakland University William Beaumont School of Medicine, Rochester, Michigan. Department of Dermatology, Wayne State University, Dearborn, Michigan. Department of Dermatology, Henry Ford Health System, Detroit, Michigan. Dermatology Salameh F, Shumaker PR, Goodman GJ, Spring LK, Seago M, Alam M, Al-Niaimi F, Cassuto D, Chan HH, Dierickx C, Donelan M, Gauglitz GG, Haedersdal M, Krakowski AC, Manuskiatti W, Norbury WB, Ogawa R, Ozog DM, Paasch U, Victor Ross E, Clementoni MT, Waibel J, Bayat A, Goo BL, and Artzi O. Energy-based devices for the treatment of acne scars: 2021 international consensus recommendations. Lasers Surg Med 2021; Epub ahead of print. PMID: 34719045. Full Text Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. VA San Diego Healthcare System and University of California, San Diego, California, USA. Department of General Practice, Monash University, Clayton, Victoria, Australia. Micrographic Surgery and Surgical Oncology, SkinCare Physicians, Chestnut Hill, Massachusetts, USA. Micrographic Surgery and Surgical Oncology, Scripps Clinic, La Jolla, California, USA. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Aalborg University, Aalborg, Denmark. Private Practice, Milan, Italy. Private Practice and Department of Medicine (Dermatology), University of Hong Kong, People's Republic of China. Skinperium Clinic, Luxembourg, Luxembourg. Department of Surgery, Massachusetts General Hospital, Shriners Hospitals for Children-Boston, Harvard Medical School, Boston, Massachusetts, USA. Department of Dermatology and Allergy, Ludwig Maximillian University, Munich, Germany. Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Department of Dermatology, St. Luke's University Health Network, Easton, Pennsylvania, USA. Department of Dermatology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. Department of Surgery, University of Texas Medical Branch, Shriners Hospital for Children-Galveston, Galveston, Texas, USA. Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan. Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA. Department of Dermatology, Venereology, and Allergy, University of Leipzig, Leipzig, Germany. Scripps Clinic, San Diego, California, USA. Laserplast, Milan, Italy. Miami Dermatology and Laser Institute, Miami, Florida, USA. Plastic & Reconstructive Surgery Research, Centre for Dermatology Research, NIHR Manchester Biomedical Research Centre, University of Manchester, England, UK. MRC-SA Wound Healing Unit, Hair & Skin Research Laboratory, Division of Dermatology, University of Cape Town, Cape Town, South Africa. Naeum Dermatology and Aesthetic Clinic/Skin Rehabilitation Center, Seoul, Korea. BACKGROUND AND OBJECTIVES: Acne scars are one of the most distressing and long-term consequences of acne vulgaris, with damaging effect on a person's physical, mental, and social well-being. Numerous treatment options are available including surgical and nonsurgical techniques, depending on the clinical presentation. Although considerable advances in the development of new treatment technologies and applications have been made in the last decade, international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the potential utility of energy-based devices (EBDs) for acne scarring, offer recommendations for safe and efficacious treatment, and provide consensus-based EBD treatment options based on varying presentations demonstrated in a series of real-life clinical photographs. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 24 dermatologists and plastic surgeons from 12 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the treatment of acne scars. A two-step modified Delphi method took place between March 2020 and February 2021 consisting of two rounds of emailed questionnaires. The panel members approved the final manuscript via email correspondence. RESULTS: The manuscript includes a comprehensive discussion and panel recommendations regarding the following topics: 1. the role of EBD in mitigating and treating acne scars in a patient with active acne, 2. the use of various EBDs for the treatment of different acne scar types with special focus on commonly used laser platform such as vascular lasers, ablative fractional lasers (AFLs) and non-AFLs (NAFLs), 3. treatment combinations, and 4. acne scar treatments in skin of color. The last part comprised of 10 photos of real-life clinical cases with the panel recommendation treatment plan to achieve best aesthetic outcome. CONCLUSION: Panel members were unanimous in their view that EBDs have a role in the management of acne scars, with AFLs, NAFLs, vascular lasers, and RF devices preferentially selected by most of the panel experts. EBDs are considered a first-line treatment for a variety of acne scar types and patients without access to these treatments may not be receiving the best available care for optimal cosmetic results. Future high-quality research and updated international treatment guidelines and reimbursement schemes should reflect this status.

Dermatology Stein Gold L, Baldwin H, Kircik LH, Weiss JS, Pariser DM, Callender V, Lain E, Gold M, Beer K, Draelos Z, Sadick N, Pillai R, Bhatt V, and Tanghetti EA. Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug. Am J Clin Dermatol 2021; Epub ahead of print. PMID: 34674160. Full Text Henry Ford Hospital, 6530 Farmington Rd, Ste 101, West Bloomfield, Detroit, MI, 48322, USA. LSTEIN1@hfhs.org. The Acne Treatment and Research Center, Brooklyn, NY, USA. Robert Wood Johnson University Hospital, New Brunswick, NJ, USA. Indiana University School of Medicine, Indianapolis, IN, USA. Physicians Skin Care, PLLC, Louisville, KY, USA. Icahn School of Medicine at Mount Sinai, New York, NY, USA. Georgia Dermatology Partners, Snellville, GA, USA. Gwinnett Clinical Research Center, Inc., Snellville, GA, USA. Eastern Virginia Medical School, Norfolk, VA, USA. Virginia Clinical Research, Inc., Norfolk, VA, USA. Callender Dermatology and Cosmetic Center, Glenn Dale, MD, USA. Howard University College of Medicine, Washington, DC, USA. Austin Institute for Clinical Research, Austin, TX, USA. Tennessee Clinical Research Center, Nashville, TN, USA. University of Miami Miller School of Medicine, Miami, FL, USA. Dermatology Consulting Services, PLLC, High Point, NC, USA. Weill Cornell Medical College, New York, NY, USA. Sadick Dermatology, New York, NY, USA. Bausch Health US, LLC, Petaluma, CA, USA. Center for Dermatology and Laser Surgery, Sacramento, CA, USA. BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017). Dermatology Strock D, Maghfour J, and Dellavalle RP. From the Cochrane Library: Interventions for hand eczema. J Am Acad Dermatol 2021; Epub ahead of print. PMID: 34606772. Full Text

School of Medicine, Eastern Virginia Medical School, Norfolk, Virginia. Department of Dermatology, Henry Ford Health System, Detroit, Michigan. Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado. Electronic address: robert.dellavalle@ucdenver.edu. Dermatology Tisack A, Fotouhi A, Fidai C, Friedman BJ, Ozog D, and Veenstra J. Response to "A clinical and biological review of keratoacanthoma": reply from authors. Br J Dermatol 2021; Epub ahead of print. PMID: 34698380. Full Text Wayne State University School of Medicine, Detroit, MI, USA. Department of Dermatology, Henry Ford Health System, MI, USA. We appreciate the interest of the authors in our review of keratoacanthoma (KA).(1) They raise several points that were discussed in our manuscript. First, they suggest that the histopathological differentiation from KA and well-differentiated squamous cell carcinoma (SCC) is not as problematic as reviewed; however, they qualify that an "adequate specimen is required" and "partial biopsies are not reliable." This is a key point we discussed, as a portion of biopsies may be too small to identify important architectural features or may be unrepresentative of the tumor, which limits the ability of the pathologist to distinguish between KA and SCC(2-4) , and typically leads to an overcall of SCC to avoid a missed malignancy. Indeed, most experienced dermatopathologists can accurately discriminate between KA and SCC when an ample biopsy representative of the tumor is obtained. Second, they question the practicality of using the stereotypical triphasic evolution pattern of KA to aid in diagnosis and state that "patient history is likely to be unreliable." Dermatology Torres AE, Ozog DM, and Hruza GJ. Coronavirus Disease 2019 and Dermatology Practice Changes. Dermatol Clin 2021; 39(4):587-597. PMID: 34556248. Full Text Department of Dermatology, Makati Medical Center, Makati City, Philippines; Department of Dermatology, Henry Ford Health System, 3031 W Grand Blvd, Detroit, MI 48202, USA. Electronic address: angelieloise@gmail.com. Department of Dermatology, Henry Ford Health System, 3031 W Grand Blvd, Detroit, MI 48202, USA. Department of Dermatology, Saint Louis University, 1 N Grand Blvd, St. Louis, MO 63103, USA. The impact of the COVID-19 pandemic on dermatology practice cannot be overstated. At its peak, the pandemic resulted in the temporary closure of ambulatory sites as resources were reallocated towards pandemic response efforts. Many outpatient clinics have since reopened and are beginning to experience a semblance of pre-pandemic routine, albeit with restrictions in place. We provide an overview of how COVID-19 has affected dermatology practice globally beginning with the rise of teledermatology. A summary of expert recommendations that shape the "new normal" in various domains of dermatology practice, namely, dermatology consultation, procedural dermatology, and phototherapy, is also provided. Dermatology Vellaichamy G, Kohli I, Zubair R, Yin C, Braunberger T, Nahhas AF, Nicholson C, Mohammad TF, Isedeh P, Lyons AB, Nartker N, Al-Jamal M, Matsui M, Karaman-Jurukovska N, Zhou L, Lim HW, Mi QS, and Hamzavi IH. An in vivo model of Postinflammatory Hyperpigmentation and Erythema: Clinical, Colorimetric, and Molecular Characteristics. Br J Dermatol 2021; Epub ahead of print. PMID: 34625951. Full Text Henry Ford Health System, Department of Dermatology, Detroit, Michigan, USA. Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health System, Detroit, Michigan, USA. Broward Health Medical Center, Fort Lauderdale, FL, USA.

Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health System, Detroit, Michigan, USA. Beaumont Hospital, Department of Dermatology, Farmington Hills, Michigan, USA. Wayne State University, Department of Dermatology, Dearborn, Michigan, USA. Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Department of Dermatology and Division of Environmental Sciences, School of Public Health, Columbia University, USA. The Estee Lauder Co's, Inc, Melville, New York, USA. BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is a common, acquired pigmentary disorder of the skin associated with significant quality of life impairment, especially in skin of color individuals. Current treatment for PIH is limited, largely due to a poor understanding of disease pathogenesis and the lack of a representative disease model. OBJECTIVES: This study is intended to further develop, update, and validate our previously designed in vivo model of acne-induced PIH/post-inflammatory erythema (PIE) using different concentrations of trichloroacetic acid (TCA), a medium-depth chemical peel. METHODS: 29 patients with skin types I-VI and clinician-confirmed presence of two or more truncal acne pustules and PIH/PIE were included. On the basis of IGA, CPP, colorimetry, and skindex, we (2) experimentally determine an optimum TCA-concentration and assess our model's ability to exhibit a dose-response relationship between degree of inciting insult and severity of resulting pigmentation. We also (3) perform differential microRNA profiling and pathway analysis to explore the potential of microRNAs as molecular adjuncts to our model. RESULTS: Application of 30% TCA produced lesions indistinguishable from acne-induced PIH and PIE lesions on the basis of colorimetry data without causing epidermal necrosis. Application of progressively increasing TCA doses from 20%-30% resulted in concentration-dependent increases in CPP, IGA, and colorimetry scores at all time points during the study. miRNA-31 and miRNA-23b may play a role in PIH pathogenesis, though further validation is required. CONCLUSIONS: Our TCA-based in vivo model, using TCA concentrations between 20-30% with an optimum of 30%, enables the quantitative assessment of the pigmentary response to varying degrees of cutaneous inflammation in a fashion that mirrors natural acne-induced PIH and PIE. Dermatology Vesper S, Wymer L, Kroner J, Pongracic JA, Zoratti EM, Little FF, Wood RA, Kercsmar CM, Gruchalla RS, Gill MA, Kattan M, Teach SJ, Patel S, Johnson CC, Bacharier LB, Gern JE, Jackson DJ, Sigelman SM, Togias A, Liu AH, Busse WW, and Khurana Hershey GK. Association of mold levels in urban children's homes with difficult-to-control asthma. J Allergy Clin Immunol 2021; Epub ahead of print. PMID: 34606833. Full Text United States Environmental Protection Agency, Center for Environmental Measurement and Modeling, Cincinnati, Ohio. Electronic address: vesper.stephen@epa.gov. United States Environmental Protection Agency, Center for Environmental Measurement and Modeling, Cincinnati, Ohio. Cincinnati Children's Hospital, Cincinnati, Ohio. Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Ill. Henry Ford Health System, Detroit, Mich. Boston University School of Medicine, Boston, Mass. Johns Hopkins University School of Medicine, Baltimore, Md. University of Texas Southwestern Medical Center, Dallas, Tex. College of Physicians and Surgeons, Columbia University, New York, NY. Children's National Hospital, Washington, DC. St Louis Children's Hospital, St Louis, Mo. University of Wisconsin School of Medicine and Public Health, Madison, Wis. National Institute of Allergy and Infectious Diseases, Rockville, Md. National Jewish Health, Aurora, Colo; Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colo. BACKGROUND: Mold sensitization and exposure are associated with asthma severity, but the specific species that contribute to difficult-to-control (DTC) asthma are unknown. OBJECTIVE: We sought to

determine the association between overall and specific mold levels in the homes of urban children and DTC asthma. METHODS: The Asthma Phenotypes in the Inner-City study recruited participants, aged 6 to 17 years, from 8 US cities and classified each participant as having either DTC asthma or easy-to-control (ETC) asthma on the basis of treatment step level. Dust samples had been collected in each participant's home (n = 485), and any dust remaining (n = 265 samples), after other analyses, was frozen at -20(o)C. The dust samples (n = 265) were analyzed using quantitative PCR to determine the concentrations of the 36 molds in the Environmental Relative Moldiness Index. Logistic regression was performed to discriminate specific mold content of dust from homes of children with DTC versus ETC asthma. RESULTS: Frozen-dust samples were available from 54% of homes of children with DTC (139 of 253) and ETC asthma (126 of 232). Only the average concentration of the mold Mucor was significantly (P < .001) greater in homes of children with DTC asthma. In homes with window air-conditioning units, the Mucor concentration contributed about a 22% increase (1.6 odds ratio; 95% CI, 1.2-2.2) in the ability to discriminate between cases of DTC and ETC asthma. CONCLUSIONS: Mucor levels in the homes of urban youth were a predictor of DTC asthma, and these higher Mucor levels were more likely in homes with a window air-conditioner. Diagnostic Radiology Bresnahan BW, Jarvik JG, Meier EN, James KT, Gold LS, Rundell SD, Turner JA, Suri P, Luetmer PH, Friedly JL, Sherman KJ, Heagerty PJ, Kallmes DF, Avins AL, Griffith BD, and Kessler LG. Expected Organizational Costs for Inserting Prevalence Information Into Lumbar Spine Imaging Reports. J Am Coll Radiol 2021; 18(10):1415-1422. PMID: 34216559. Full Text Department of Radiology, University of Washington, Seattle, Washington; Department of Health Services, University of Washington, Seattle, Washington; Comparative Effectiveness, Cost, and Outcomes Research Center, University of Washington, Seattle, Washington. Electronic address: bres@uw.edu. Department of Radiology, University of Washington, Seattle, Washington; Department of Neurological Surgery, University of Washington, Seattle, Washington; Department of Health Services, University of Washington, Seattle, Washington; Comparative Effectiveness, Cost, and Outcomes Research Center, University of Washington, Seattle, Washington. Department of Biostatistics, University of Washington, Seattle, Washington. Department of Radiology, University of Washington, Seattle, Washington; Comparative Effectiveness, Cost, and Outcomes Research Center, University of Washington, Seattle, Washington. Comparative Effectiveness, Cost, and Outcomes Research Center, University of Washington, Seattle, Washington; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington. Comparative Effectiveness, Cost, and Outcomes Research Center, University of Washington, Seattle, Washington; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington. Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, Washington; Department of Rehabilitation Medicine, University of Washington, Seattle, Washington. Department of Radiology, Mayo Clinic, Rochester, Minnesota. Kaiser Permanente Washington, Seattle, Washington. Division of Research, Kaiser Permanente Northern California, Oakland, California. Diagnostic Radiology, Henry Ford Hospital, Henry Ford Health System, Detroit, Michigan. Department of Health Services, University of Washington, Seattle, Washington. BACKGROUND: Modifying physician behavior to more closely align with guideline-based care can be challenging. Few effective strategies resulting in appropriate spine-related health care have been reported. The Lumbar Imaging With Reporting of Epidemiology (LIRE) intervention did not result in reductions in spine care but did in opioid prescriptions written. OBJECTIVES: To estimate organizational resource needs and costs associated with implementing a pragmatic, decision support-type intervention that inserted age- and modality-matched prevalence information for common lumbar spine imaging findings, using site-based resource use data from the LIRE trial. RESEARCH DESIGN: Time and cost estimation associated with implementing the LIRE intervention in a health organization. SUBJECTS: Providers and patients assessed in the LIRE trial. MEASURES: Expected personnel costs required to implement the LIRE intervention. RESULTS: Annual salaries were converted to daily average per person costs, ranging from $400 to $2,200 per day (base case) for personnel (range: $300-$2,600). Estimated

total average cost for implementing LIRE was $5,009 (range: $2,651-$12,020), including conducting pilot testing with providers. Costs associated with a small amount of time for a radiologist (6-12 hours) and imaging-ordering providers (1-8 hours each) account for approximately 75% of the estimated total cost. CONCLUSIONS: The process of implementing an intervention for lumbar spine imaging reports containing age- and modality-appropriate epidemiological benchmarks for common imaging findings required radiologists, imaging-ordering providers, information technology specialists, and limited testing and monitoring. The LIRE intervention seems to be a relatively low-cost, evidence-based, complementary tool that can be easily integrated into the reporting of spine imaging. Diagnostic Radiology Chikarmane SA, Harrison BT, Giess CS, Pinkney DM, and Gombos EC. Lobular neoplasia detected at MRI-guided biopsy: imaging findings and outcomes. Clin Imaging 2021; 78:171-178. PMID: 33838434. Full Text Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States of America; Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States of America. Electronic address: schikarmane@partners.org. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States of America. Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States of America; Department of Imaging, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, United States of America. Department of Radiology, Henry Ford Hospital, 2799 W Grand Blvd, Diagnostic Radiology - A-3, Detroit, MI 48202, United States of America. OBJECTIVE: To review MRI findings of pure lobular neoplasia (LN) on MRI guided biopsy, evaluate surgical and clinical outcomes, and assess imaging findings predictive of upgrade to malignancy. METHODS: HIPAA compliant, IRB-approved retrospective review of our MRI-guided breast biopsy database from October 2008-January 2015. Biopsies yielding atypical lobular hyperplasia or lobular carcinoma in situ were included in the analysis; all biopsy slides were reviewed by a dedicated breast pathologist. Imaging indications, MRI findings, and histopathology were reviewed. Statistical analysis was performed using the two-tailed Fisher exact-test and the t-test, and 95% CIs were determined. A p < 0.05 was considered statistically significant. RESULTS: Database search yielded 943 biopsies in 785 patients of which 65/943 (6.9%) reported LN as the highest risk pathologic lesion. Of 65 cases, 32 were found to have LN as the dominant finding on pathology and constituted the study population. All 32 findings were mammographically and sonographically occult. Three of 32 (9.3%) cases of lobular neoplasia were upgraded to malignancy, all LCIS (one pleomorphic and two classical). The most common MRI finding was focal, heterogenous non-mass enhancement with low T2 signal. No clinical features or imaging findings were predictive of upgrade to malignancy. CONCLUSION: Incidence of pure lobular neoplasia on MRI guided biopsy is low, with comparatively low incidence of upgrade to malignancy. No imaging or clinical features are predictive of upgrade on surgical excision, therefore, prudent radiologic-pathologic correlation is necessary. Diagnostic Radiology Patel PY, Dalal I, and Griffith B. [(18)F]FDG-PET Evaluation of Spinal Pathology in Patients in Oncology: Pearls and Pitfalls for the Neuroradiologist. AJNR Am J Neuroradiol 2021; Epub ahead of print. PMID: 34711547. Full Text From the Department of Radiology, Henry Ford Health System, Detroit, Michigan. From the Department of Radiology, Henry Ford Health System, Detroit, Michigan brentg@rad.hfh.edu. [(18)F]FDG-PET is a widely used technique for specific evaluation of disease and treatment response in oncology. However, the principles behind [(18)F]FDG-PET imaging allow a wide-ranging array of benign and malignant pathologies to be identified on both initial and routine surveillance imaging. This is important for clinicians and radiologists, alike, in that effective and accurate evaluation of malignancy and

metastatic disease, specifically involving the spine and central nervous system, is crucial. In this article, we review the normal and posttherapy appearance of the spine on [(18)F]FDG-PET, the various types and patterns of metastatic disease that involve the spine and spinal cord, and, finally, important spinal pathologies that may mimic malignancy on [(18)F]FDG-PET. Emergency Medicine Abboud A, Kui N, Gaggin HK, Ibrahim NE, Chen-Tournoux AA, Christenson RH, Hollander JE, Levy PD, Nagurney JT, Nowak RM, Pang PS, Peacock WF, Walters EL, and Januzzi JL. Multiple Cardiac Biomarker Testing Among Patients with Acute Dyspnea from the ICON-RELOADED Study. J Card Fail 2021; Epub ahead of print. PMID: 34634446. Full Text Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Baim Institute for Clinical Research, Boston, MA, USA. INOVA Heart and Vascular Institute, Falls Church, VA, USA. Azrieli Heart Centre, Jewish General Hospital, Montreal, PQ, Canada. University of Maryland School of Medicine, Baltimore, MD, USA. Thomas Jefferson University, Philadelphia, PA, USA. Wayne State University, Detroit, MI, USA. Henry Ford Health System, Detroit, MI, USA. Indiana University School of Medicine & Indianapolis EMS, Indianapolis, IN, USA. Baylor College of Medicine, Houston, TX, USA. Loma Linda University Medical Center, Loma Linda, CA, USA. Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Baim Institute for Clinical Research, Boston, MA, USA. Electronic address: jjanuzzi@partners.org. BACKGROUND: Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and insulin-like growth factor binding protein-7 (IGFBP7) predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown. METHODS AND RESULTS: Concentrations of NT-proBNP, hs-cTnT, and IGFBP7 were analyzed in 1,448 patients presenting with acute dyspnea from the prospective, multicenter ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all three biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in two biomarkers (18.8%, 44 out of 234), one biomarker (3.8%, 10 out of 260), or no elevated biomarkers (0.4%, 2 out of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite endpoint of mortality and HF rehospitalization. In adjusted models, patients with one, two, and three elevated biomarkers had 3.74 (95% CI, 1.26-11.1; P=0.017), 12.3 (95% CI, 4.60-32.9; P <0.001), and 12.6 (95% CI, 4.54-35.0; P <0.001) fold increased risk of 180-day mortality or HF rehospitalization. CONCLUSIONS: A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization. Emergency Medicine Stevens JS, Harnett NG, Lebois LAM, van Rooij SJH, Ely TD, Roeckner A, Vincent N, Beaudoin FL, An X, Zeng D, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Rauch SL, Lewandowski C, Storrow AB, Hendry PL, Sheikh S, Musey PI, Jr., Haran JP, Jones CW, Punches BE, Lyons MS, Kurz MC, McGrath ME, Pascual JL, Datner EM, Chang AM, Pearson C, Peak DA, Domeier RM, O'Neil BJ, Rathlev NK, Sanchez LD, Pietrzak RH, Joormann J, Barch DM, Pizzagalli DA, Sheridan JF, Luna B, Harte SE, Elliott JM, Murty VP, Jovanovic T, Bruce SE, House SL, Kessler RC, Koenen KC, McLean SA, and Ressler KJ. Brain-Based Biotypes of Psychiatric Vulnerability in the Acute Aftermath of Trauma. Am J Psychiatry 2021; Epub ahead of print. PMID: 34645277. Full Text

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta (Stevens, van Rooij, Ely, Roeckner, Vincent); Division of Depression and Anxiety, McLean Hospital, Belmont, Mass. (Harnett, Lebois, Ressler); Department of Psychiatry, Harvard Medical School, Boston (Harnett, Lebois, Pizzagalli, Ressler); Departments of Emergency Medicine and Health Services, Policy, and Practice, Alpert Medical School of Brown University, Rhode Island Hospital, and the Miriam Hospital, Providence, R.I. (Beaudoin); Department of Anesthesiology, Institute of Trauma Recovery, University of North Carolina, Chapel Hill (An, Linnstaedt, McLean); Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill (Zeng); Departments of Psychiatry and Neurology, University of California, San Francisco (Neylan); Department of Biomedical Informatics, Emory University School of Medicine, Atlanta (Clifford); Institute for Technology in Psychiatry (Germine) and Department of Psychiatry (Rauch), McLean Hospital, Belmont, Mass.; Department of Emergency Medicine, Henry Ford Health System, Detroit (Lewandowski); Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tenn. (Storrow); Department of Emergency Medicine, University of Florida College of Medicine, Jacksonville (Hendry, Sheikh); Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis (Musey); Department of Emergency Medicine, University of Massachusetts Medical School, Worcester (Haran); Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, N.J. (Jones); Department of Emergency Medicine, College of Medicine and College of Nursing, University of Cincinnati, Cincinnati (Punches); Department of Emergency Medicine and Center for Addiction Research, University of Cincinnati College of Medicine, Cincinnati (Lyons); Departments of Emergency Medicine and Surgery, Division of Acute Care Surgery, University of Alabama School of Medicine, Birmingham (Kurz); Center for Injury Science, University of Alabama, Birmingham (Kurz); Department of Emergency Medicine, Boston Medical Center, Boston (McGrath); Departments of Surgery (Pascual) and Neurosurgery (Pascual), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Emergency Medicine, Einstein Health Care Network, Philadelphia (Datner); Department of Emergency Medicine, Jefferson University Hospitals, Philadelphia (Chang); Department of Emergency Medicine, Wayne State University, Detroit (Pearson); Department of Emergency Medicine, Massachusetts General Hospital, Boston (Peak); Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ann Arbor, Mich. (Domeier); Department of Emergency Medicine, Wayne State University School of Medicine, Detroit (O'Neil); Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield (Rathley); Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston (Sanchez); Department of Emergency Medicine, Harvard Medical School, Boston (Sanchez); Department of Psychiatry, Yale School of Medicine, and U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, New Haven, Conn. (Pietrzak); Department of Psychology, Yale University, New Haven, Conn. (Joorman); Department of Psychological and Brain Sciences, Washington University, St. Louis (Barch); Department of Biosciences and Neuroscience and Institute for Behavioral Medicine Research, Ohio State University Wexner Medical Center, Columbus (Sheridan); Department of Psychiatry, University of Pittsburgh, Pittsburgh (Luna); Departments of Anesthesiology and Internal Medicine-Rheumatology, University of Michigan Medical School, Ann Arbor (Harte); the Kolling Institute of Medical Research, Northern Clinical School, University of Sydney, and Faculty of Medicine and Health, University of Sydney, Sydney, Australia (Elliott); Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago (Elliott); Department of Psychology, Temple University, Philadelphia (Murty); Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Detroit (Jovanovich); Department of Psychological Sciences, University of Missouri, St. Louis (Bruce); Department of Emergency Medicine, Washington University School of Medicine, St. Louis (House); Department of Health Care Policy, Harvard Medical School, Boston (Kessler); Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston (Koenen); Department of Emergency Medicine, University of North Carolina, Chapel Hill (McLean). OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N=69; internal replication cohort:

N=77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology. Emergency Medicine Tsalik EL, Henao R, Montgomery JL, Nawrocki JW, Aydin M, Lydon EC, Ko ER, Petzold E, Nicholson BP, Cairns CB, Glickman SW, Quackenbush E, Kingsmore SF, Jaehne AK, Rivers EP, Langley RJ, Fowler VG, McClain MT, Crisp RJ, Ginsburg GS, Burke TW, Hemmert AC, and Woods CW. Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test. Crit Care Med 2021; 49(10):1651-1663. PMID: 33938716. Full Text Durham Veterans Affairs Health Care System, Durham, NC. Center for Applied Genomics and Precision Medicine, Duke University School of Medicine, Durham, NC. Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC. Department of Biostatistics and Informatics, Duke University, Durham, NC. Duke Clinical Research Institute, Durham, NC. BioFire Diagnostics, LLC, Salt Lake City, UT. Duke Regional Hospital, Durham, NC. Institute for Medical Research, Durham, NC. University of North Carolina Medical Center, Chapel Hill, NC. Drexel University, Philadelphia, PA. Rady Children's Institute for Genomic Medicine, San Diego, CA. Henry Ford Hospital System, Detroit, MI. University of South Alabama Health University Hospital, Mobile, AL. OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING: Four U.S. emergency departments. PATIENTS: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS: Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ~45 minutes. MEASUREMENTS AND MAIN RESULTS: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ~45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.

Endocrinology and Metabolism Genere N, Kaur RJ, Athimulam S, Thomas MA, Nippoldt T, Van Norman M, Singh R, Grebe S, and Bancos I. Interpretation of Abnormal Dexamethasone Suppression Test is Enhanced With Use of Synchronous Free Cortisol Assessment. J Clin Endocrinol Metab 2021; Epub ahead of print. PMID: 34648626. Full Text Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine;Saint Louis, MO, United States. Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, United States. Department of Medicine, Division of Endocrinology, Diabetes, Bone and Mineral Disorders, Henry Ford Health System, Detroit, MI, United States. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. CONTEXT: Interpretation of dexamethasone suppression test (DST) may be influenced by dexamethasone absorption and metabolism and by the altered cortisol binding. OBJECTIVE: We aimed to determine the normal ranges of free cortisol during DST in participants without adrenal disorders, and to identify the population of patients where post-DST free cortisol measurements add value to the diagnostic work up. DESIGN AND SETTING: Cross-sectional study conducted in a tertiary medical center. PARTICIPANTS: Adult volunteers without adrenal disorders (n=168; 47 women on oral contraceptive therapy (OCP), 66 women not on OCP, 55 men) and patients undergoing evaluation for hypercortisolism (n=196; 16 women on OCP). MEASUREMENTS: Post-DST dexamethasone and free cortisol (mass spectrometry) and total cortisol (immunoassay). MAIN OUTCOME MEASURES: Reference range for post-DST free cortisol, diagnostic accuracy of post-DST total cortisol. RESULTS: Adequate dexamethasone concentrations (≥0.1 mcg/dL) were seen in 97.6% volunteers and 96.3% patients. Only 25.5% of women volunteers on OCP had abnormal post-DST total cortisol (>1.8 mcg/dL). In volunteers, the upper post-DST free cortisol range was 48 ng/dL in men and women not on OCP, and 79 ng/dL in women on OCP. When compared to post-DST free cortisol, diagnostic accuracy of post-DST total cortisol was 87.3% (95%CI 81.7-91.7); all false positive results occurred in patients with post-DST cortisol between 1.8 and 5 mcg/dL. OCP use was the only factor associated with false positive results (21.1% vs 4.9%, p=0.02). CONCLUSIONS: Post-DST free cortisol measurements are valuable in patients with optimal dexamethasone concentrations and post-DST total cortisol between 1.8 and 5 mcg/dL. Gastroenterology Amjad W, Qureshi W, Malik A, Singh R, and Jafri SM. The outcomes of Clostridioides difficile infection in inpatient liver transplant population. Transpl Infect Dis 2021; Epub ahead of print. PMID: 34695277. Full Text Clinical Investigation, Harvard Medical School, Boston, MA. Internal Medicine, Albany Medical Center, Albany, NY. Cardiovascular Medicine, University of Massachusetts, Worchester, MA. Internal Medicine, Loyola Medical University, Chicago, IL. Internal Medicine, Indiana University, Fort Wayne, IN. Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Gastroenterology and Transplant Hepatology, Henry Ford Health System, Detroit, MI. BACKGROUND: Chronic immunosuppression is a known cause of Clostridioides difficile which presents with colon infection. It is associated with increased mortality and morbidity. Our aim is to determine the inpatient outcomes of liver transplant patients with Clostridioides difficile infection (CDI) and trends in the last few years. METHODS: We utilized the National readmission data (2010-2017) to study the outcomes of C. difficile infection in liver transplant patients. Association of C. difficile with readmission was computed in a multivariable model adjusted for age, sex, gastrointestinal bleeding, hypertension, diabetes, hyperlipidemia, congestive heart failure, cerebrovascular disease, obesity, cancer, insurance, chronic kidney disease, chronic obstructive pulmonary disease, dementia, peripheral vascular disease, smoker, hospital location and teaching status. RESULTS: During 2010 - 2017, there were 310,222 liver transplant patients were hospitalized. Out of these, 9826 had C. difficile infection. CDI infection in liver

transplant patients was associated with higher 30-day readmission (14.3% vs 11.21%, HR: 1.14 95% CI:1.01-1.28, p = 0.02) and in-hospital mortality (OR: 1.36, 95% CI:1.14-1.61, p<0.001). The most common causes of readmission in the CDI group were recurrent C. difficile infection (41.1 %), liver transplant complications (16.5%), and sepsis (11.6%). The median cost for liver transplant patients with C. difficile was significantly higher, $53064 (IQR $24970 - $134830) compared to patients that did not have C. difficile 35703 ($ 18793 - $73871) (p <0.001). The median length of stay was also longer for patients with CDI 6 (4 - 14) days vs. 4 (2 - 7) days (p <0.001). CONCLUSION: Clostridioides difficile infection in post-liver transplant patients was associated with higher mortality, readmission, healthcare cost, and longer length of stay. The most common cause of readmission was recurrent C. difficile infection which raises the question of the efficacy of standard first-line therapy. This article is protected by copyright. All rights reserved. Gastroenterology Shinn B, Boortalary T, Raijman I, Nieto J, Khara HS, Kumar SV, Confer B, Diehl DL, El Halabi M, Ichkhanian Y, Runge T, Kumbhari V, Khashab M, Tyberg A, Shahid H, Sarkar A, Gaidhane M, Bareket R, Kahaleh M, Piraka C, Zuchelli T, Law R, Sondhi A, Kedia P, Robbins J, Calogero C, Bakhit M, Chiang A, Schlachterman A, Kowalski T, and Loren D. Maximizing success in single-session EUS-directed transgastric ERCP: a retrospective cohort study to identify predictive factors of stent migration. Gastrointest Endosc 2021; 94(4):727-732. PMID: 33957105. Full Text Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA. Houston Methodist Hospital, Houston, Texas, USA. Borland Groover Clinic, Jacksonville, Florida, USA. Geisinger Health System, Danville, Pennsylvania, USA. Johns Hopkins University Hospital, Baltimore, Maryland, USA. Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA. Henry Ford Health System, Detroit, Michigan, USA. University of Michigan Medical Center, Ann Arbor, Michigan, USA. Methodist Dallas Medical Center, Dallas, Texas, USA. BACKGROUND AND AIMS: EUS-directed transgastric ERCP (the EDGE procedure) is a simplified method of performing ERCP in Roux-en-Y gastric bypass patients. The EDGE procedure involves placement of a lumen-apposing metal stent (LAMS) into the excluded stomach to serve as a conduit for passage of the duodenoscope for pancreatobiliary intervention. Originally a multistep process, urgent indications for ERCP have led to the development of single-session EDGE (SS-EDGE) with LAMS placement and ERCP performed in the same session. The goal of this study was to identify predictive factors of intraprocedural LAMS migration in SS-EDGE. METHODS: We conducted a multicenter retrospective review that included 9 tertiary medical centers across the United States. Data were collected and analyzed from 128 SS-EDGE procedures. The primary outcome was intraprocedural LAMS migration. Secondary outcomes were other procedural adverse events such as bleeding and perforation. RESULTS: Eleven LAMS migrations were observed in 128 procedures (8.6%). Univariate analysis of clinically relevant variables was performed, as was a binary logistic regression analysis of stent diameter and stent dilation. This revealed that use of a smaller (15 mm) diameter LAMS was an independent predictor of intraprocedural stent migration (odds ratio, 5.36; 95% confidence interval, 1.29-22.24; P = .021). Adverse events included 3 patients who required surgery and 2 who experienced intraprocedural bleeding. CONCLUSIONS: Use of a larger-diameter LAMS is a predictive factor for a nonmigrated stent and improved procedural success in SS-EDGE. Although larger patient cohorts are needed to adequately assess these findings, performance of LAMS dilation and fixation may also decrease risk of intraprocedural LAMS migration and improve procedural success. Gastroenterology Turgeon MK, Shah SA, Delman AM, Tran BV, Agopian VG, Wedd JP, Magliocca JF, Kim A, Cameron A, Olyaei A, Orloff SL, Anderson MP, Kubal CA, Cannon RM, Locke JE, Simpson MA, Akoad ME, Wongjirad CP, Emamaullee J, Moro A, Aucejo F, Feizpour CA, Vagefi PA, Nguyen MH, Esquivel CO, Dhanireddy K, Subramanian V, Chavarriaga A, Kazimi MM, Anderson MS, Sonnenday CJ, Kim SC, Foley DP, Abdouljoud M, Salgia RJ, Moris D, Sudan DL, Ganesh SR, Humar A, Doyle M, Chapman WC, and

Maithel SK. Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation. Ann Surg 2021; 274(4):613-620. PMID: 34506316. Full Text Emory University, Atlanta, Georgia. University of Cincinnati College of Medicine, Cincinnati, Ohio. David Geffen School of Medicine at UCLA, Los Angeles, California. Johns Hopkins, Baltimore, Maryland. Oregon Health and Science University, Portland, Oregon. Indiana University Health, Indianapolis, Indiana. University of Alabama at Birmingham, Birmingham, Alabama. Lahey Hospital and Medical Center, Boston, Massachusetts. Keck Hospital of University of Southern California, Los Angeles, California. Cleveland Clinic, Cleveland, Ohio. UT Southwestern Medical Center, Dallas, Texas. Stanford University Medical Center, Palo Alto, California. Tampa General Hospital, Tampa, Florida. Piedmont Healthcare, Atlanta, Georgia. University of Michigan, Ann Arbor, Michigan. University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Henry Ford Health System, Detroit, Michigan. Duke University School of Medicine, North Carolina. University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Washington University School of Medicine at St. Louis, St. Louis, Missouri. OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results. Hematology-Oncology Al Masalmeh N, Kukreja G, Zaiem F, Raza SN, Kim H, Nagasaka M, and Sukari A. p16 positive oropharyngeal small cell cancer: A case report. Oral Oncol 2021; 121:105391. PMID: 34187735. Full Text Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, United States. Department of Oncology, Henry Ford Health System, Macomb, MI, United States. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, United States. Department of Otolaryngology, Wayne State University School of Medicine, Detroit, MI, United States. Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, United States; St. Marianna University School of Medicine, Kawasaki, Japan. Department of Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, United States. Electronic address: sukaria@karmanos.org.

Extra-pulmonary small cell carcinomas (EPSCC) are rare malignancies. Like small cell lung cancer (SCLC), they are aggressive malignancies with dismal prognosis. We here report a case of a middle-aged man who presented with odynophagia and cervical lymphadenopathy. Diagnostic workup confirmed the diagnosis of locally-advanced p16-positive oropharyngeal cancer (OPC) with a surprising histology of small cell cancer, suggesting a human papilloma virus (HPV)-related oropharyngeal cancer with small cell differentiation. HPV oropharynx infection is a well-known risk factor for squamous cell carcinoma of the oropharynx, but it is unknown if it may increase the risk of other OPC histology. Hematology-Oncology Crawford HC. Anticipating resistance to KRAS inhibition: a novel role for USP21 in macropinocytosis regulation. Genes Dev 2021; 35(19-20):1325-1326. PMID: 34599002. Full Text Henry Ford Pancreatic Cancer Center, Henry Ford Health System, Detroit, Michigan 48202, USA hcrawfo1@hfhs.org. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Virtually all PDAC harbors an oncogenic mutation in the KRAS gene, making it the prime target for therapy. Most previous attempts to inhibit KRAS directly have been disappointing, but recent success in targeting some KRAS mutants presages a new era in PDAC therapy. Models of PDAC have predicted that identifying KRAS inhibitor resistance mechanisms will be critical. In this issue of Genes & Development, Hou and colleagues (pp. 1327-1332) identify one such mechanism in which the deubiquitinase USP21 up-regulates the nutrient-scavenging process of macropinocytosis, rescuing PDAC cells from Kras extinction. Hematology-Oncology Siu LL, Wang D, Hilton J, Geva R, Rasco D, Perets R, Abraham AK, Wilson DC, Markensohn JF, Lunceford J, Suttner L, Siddiqi S, Altura RA, and Maurice-Dror C. First-in-Class Anti-Immunoglobulin-Like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1-Resistance Mechanism in Patients With Advanced Solid Tumors. Clin Cancer Res 2021; Epub ahead of print. PMID: 34598945. Full Text Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University of Toronto lillian.siu@uhn.ca. Henry Ford Cancer Institute/Henry Ford Health System, Clinical Trial Office. Medicine, University of Ottawa. Division of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv University. Phase 1, South Texas Accelerated Research Therapeutics. Oncology, Rambam Health Care Campus and Technion--Israel Institute of Technology. Quantitative Pharmacology and Pharmacometrics (QP2), Merck and Co., Inc. Profiling and Expression, Merck Research Laboratories. Oncology Early Development, Merck & Co., Inc. Biostatistics and Research Decision Sciences, Merck & Co., Inc. Merck and Co., Inc. Oncology Division, Rambam Health Care Campus. PURPOSE: In this first-in-human study (NCT03564691) in advanced solid tumors, we investigated a novel first-in-class human IgG4 monoclonal antibody targeting the immunoglobulin-like transcript 4 (ILT4) receptor, MK-4830, as monotherapy and in combination with pembrolizumab. EXPERIMENTAL DESIGN: Patients with histologically/cytologically-confirmed advanced solid tumors, measurable disease by RECISTv1.1, and evaluable baseline tumor sample received escalating doses of intravenous MK-4830 every 3 weeks as monotherapy (parts A, B) and in combination with pembrolizumab (part C). Safety and tolerability were the primary objectives. Pharmacokinetics, objective response rate per RECISTv1.1, and molecular biomarkers were also evaluated. RESULTS: Of 84 patients, 50 received monotherapy and 34 received combination therapy. No dose-limiting toxicities were observed; maximum-tolerated dose was not reached. MK-4830 showed dose-related target engagement. Eleven of 34 patients in the dose-escalation phase who received combination therapy achieved objective responses; 5 previously had progressive disease on anti-PD-1/PD-L1 therapies. Exploratory evaluation of the association between response and pretreatment gene expression related to interferon-gamma signaling in tumors suggested

higher sensitivity to T-cell inflammation with combination therapy than historically expected with pembrolizumab monotherapy, with greater response at more moderate levels of inflammation. CONCLUSIONS: This first-in-class MK-4830 antibody dosed as monotherapy and in combination with pembrolizumab was well tolerated with no unexpected toxicities, and demonstrated dose-related evidence of target engagement and antitumor activity. Inflammation intrinsic to the ILT4 mechanism may be facilitated by alleviating the myeloid suppressive components of the tumor microenvironment, supporting the target of ILT4 as a potential novel immunotherapy in combination with an anti-PD-1/PD-L1 agent. Hospital Medicine Bossone E, Cademartiri F, AlSergani H, Chianese S, Mehta R, Capone V, Ruotolo C, Tarrar IH, Frangiosa A, Vriz O, Maffei V, Annunziata R, Galzerano D, Ranieri B, Sepe C, Salzano A, Cocchia R, Majolo M, Russo G, Longo G, Muto M, Fedelini P, Esposito C, Perrella A, Guggino G, Raiola E, Catalano M, De Palma M, Romano L, Romano G, Coppola C, Mauro C, and Mehta RH. Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era. J Cardiovasc Dev Dis 2021; 8(10). PMID: 34677195. Full Text Cardiology Division, A. Cardarelli Hospital, 80131 Naples, Italy. Cardiovascular Imaging Center, IRCCS SDN, 80143 Naples, Italy. Cardiac Centre, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia. ProMedica Monroe Regional Hospital, Monroe, MI 48162, USA. Vascular Surgery Unit, A. Cardarelli Hospital, 80131 Naples, Italy. Henry Ford Allegiance Hospital, 205 North East Avenue, Jackson, MI 49201, USA. Post Operative Intensive Care Division, A. Cardarelli Hospital, 80131 Naples, Italy. Health Management Office, A. Cardarelli Hospital, 80131 Naples, Italy. Healthcare Direction, A. Cardarelli Hospital, 80131 Naples, Italy. Diagnostic and Interventional Neuroradiology, AORN Antonio Cardarelli, 80131 Naples, Italy. Urology Department, Antonio Cardarelli Hospital, 80131 Naples, Italy. Liver Intensive Care Unit, AORN A. Cardarelli, 80131 Naples, Italy. Infectious Disease of Healthcare Direction, AORN Antonio Cardarelli, 80131 Naples, Italy. Thoracic Surgery Unit, Antonio Cardarelli Hospital, 80131 Naples, Italy. Nuclear Medicine Department "Cardarelli" Hospital Naples, 80131 Naples, Italy. UOC Chirurgia Generale 2, AORN Cardarelli, 80131 Naples, Italy. Department of General and Emergency Radiology, "Antonio Cardarelli" Hospital, Antonio Cardarelli St. 9, 80131 Naples, Italy. Orthopedic Unit, Antonio Cardarelli Hospital, 80131 Naples, Italy. Duke Clinical Research Institute, Durham, North Carolina, 300 W Morgan St, Durham, NC 27701, USA. Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process.

Hospital Medicine Mann CZ, Abshire C, Yost M, Kaatz S, Swaminathan L, Flanders SA, Prescott HC, and Gagnon-Bartsch JA. Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19: A multicenter retrospective cohort study. Medicine (Baltimore) 2021; 100(40). PMID: 34622851. Full Text Department of Statistics, University of Michigan, Ann Arbor, MI. Michigan Value Collaborative, Ann Arbor, MI. Division of Hospital Medicine, Henry Ford Hospital, Detroit, MI. Internal Medicine, Division of Hospital Medicine, St. Joseph Mercy Hospital, Ann Arbor, MI. Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, MI. Michigan Hospital Medicine Safety Consortium, Ann Arbor, MI. Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI. VA Center for Clinical Management Research, Ann Arbor, MI. As severe acute respiratory syndrome coronavirus 2 continues to spread, easy-to-use risk models that predict hospital mortality can assist in clinical decision making and triage. We aimed to develop a risk score model for in-hospital mortality in patients hospitalized with 2019 novel coronavirus (COVID-19) that was robust across hospitals and used clinical factors that are readily available and measured standardly across hospitals.In this retrospective observational study, we developed a risk score model using data collected by trained abstractors for patients in 20 diverse hospitals across the state of Michigan (Mi-COVID19) who were discharged between March 5, 2020 and August 14, 2020. Patients who tested positive for severe acute respiratory syndrome coronavirus 2 during hospitalization or were discharged with an ICD-10 code for COVID-19 (U07.1) were included. We employed an iterative forward selection approach to consider the inclusion of 145 potential risk factors available at hospital presentation. Model performance was externally validated with patients from 19 hospitals in the Mi-COVID19 registry not used in model development. We shared the model in an easy-to-use online application that allows the user to predict in-hospital mortality risk for a patient if they have any subset of the variables in the final model.Two thousand one hundred and ninety-three patients in the Mi-COVID19 registry met our inclusion criteria. The derivation and validation sets ultimately included 1690 and 398 patients, respectively, with mortality rates of 19.6% and 18.6%, respectively. The average age of participants in the study after exclusions was 64 years old, and the participants were 48% female, 49% Black, and 87% non-Hispanic. Our final model includes the patient's age, first recorded respiratory rate, first recorded pulse oximetry, highest creatinine level on day of presentation, and hospital's COVID-19 mortality rate. No other factors showed sufficient incremental model improvement to warrant inclusion. The area under the receiver operating characteristics curve for the derivation and validation sets were .796 (95% confidence interval, .767-.826) and .829 (95% confidence interval, .782-.876) respectively.We conclude that the risk of in-hospital mortality in COVID-19 patients can be reliably estimated using a few factors, which are standardly measured and available to physicians very early in a hospital encounter. Internal Medicine Al Turk Y, Lemor A, Fayed M, and Kim H. Sjögren-related cardiomyopathy presenting with cardiogenic shock. BMJ Case Rep 2021; 14(10). PMID: 34667036. Full Text Internal Medicine, Henry Ford Health System, Detroit, Michigan, USA yaltur1@hfhs.org. Cardiovascular Medicine, Henry Ford Health System, Detroit, Michigan, USA. Centro de Investigación de Epidemiología Clínica y Medicina Basada en la Evidencia, Universidad de San Martín de Porres Facultad de Medicina Humana, La Molina, Peru. Anesthesia, Henry Ford Health System, Detroit, Michigan, USA. Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic,

infectious and other possible causes, the patient's clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out. Internal Medicine Carney BJ, Wang TF, Ren S, George G, Al Homssi A, Gaddh M, Connolly GC, Shah V, Bogue T, Bartosic A, Neuberg D, Baumann Kreuziger L, and Zwicker JI. Anticoagulation in cancer-associated thromboembolism with thrombocytopenia: a prospective, multi-center cohort study. Blood Adv 2021; Epub ahead of print. PMID: 34662892. Full Text Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States. University of Ottawa, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, Ohio, Canada. Dana-Farber Cancer Institute, Boston, Massachusetts, United States. University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States. Medical College of Wisconsin, Wauwatosa, Wisconsin, United States. Emory University School of Medicine, Atlanta, Georgia, United States. Rochester Regional Health, Rochester, New York, United States. Henry Ford Hospital, detroit, Michigan, United States. The Ohio State University Wexner Medical Center, Columbus, Ohio, United States. Versiti, Milwaukee, Wisconsin, United States. Venous thromboembolism (VTE) with concurrent thrombocytopenia is frequently encountered in patients with cancer. Therapeutic anticoagulation in the setting of thrombocytopenia is associated with a high risk of hemorrhage. Retrospective analyses suggest the utility of modified-dose anticoagulation in this population. To assess the incidence of hemorrhage or thrombosis according to anticoagulation strategy, we performed a prospective, multi-center, observational study. Patients with active malignancy, acute VTE, and concurrent thrombocytopenia (platelet count < 100,000/µL) were enrolled. The cumulative incidences of hemorrhage or recurrent VTE were determined considering death as a competing risk. Primary outcomes were centrally adjudicated and comparisons made according to initial treatment with full-dose or modified-dose anticoagulation. A total of 121 patients were enrolled at six hospitals. Seventy-five patients were initially treated with full-dose anticoagulation (62%), 33 (27%) with modified-dose anticoagulation, while 13 (11%) received no anticoagulation. Most patients who received modified-dose anticoagulation had a hematologic malignancy (31 of 33, 94%) and an acute DVT (28 of 33, 85%). In patients who initially received full-dose anticoagulation, the cumulative incidence of major hemorrhage at 60 days was 12.8% (95% CI, 4.9-20.8%) and 6.6% (95% CI, 2.4-15.7%) in those who received modified-dose anticoagulation (Fine-Gray HR 2.18, 95% CI 1.21-3.93). The cumulative incidence of recurrent VTE at 60 days in patients who initially received full-dose anticoagulation was 5.6% (95% CI, 0.2-11%) and 0% in patients who received modified-dose anticoagulation. In conclusion, modified-dose anticoagulation appears to be a safe alternative to therapeutic anticoagulation in patients with cancer who develop DVT in the setting of thrombocytopenia. Internal Medicine Pilling A, Kim SH, and Hwang C. Androgen receptor negatively regulates mitotic checkpoint signaling to induce docetaxel resistance in castration-resistant prostate cancer. Prostate 2021; Epub ahead of print. PMID: 34672379. Full Text Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, Michigan, USA. Department of Urology, Henry Ford Health System, Detroit, Michigan, USA. BACKGROUND: Despite multiple treatment advances for castration-resistant prostate cancer (CRPC), there are currently no curative therapies and patients ultimately to succumb to the disease. Docetaxel

(DTX) is the standard first-line chemotherapy for patients with metastatic CRPC; however, drug resistance is inevitable and often develops rapidly, leading to disease progression in nearly all patients. In contrast, when DTX is deployed with androgen deprivation therapy in castration-sensitive disease, more durable responses and improved outcomes are observed, suggesting that aberrant androgen receptor (AR) signaling accelerates DTX resistance in CRPC. In this study, we demonstrate that AR dysregulates the mitotic checkpoint, a critical pathway involved in the anticancer action of DTX. METHODS: Androgen-dependent and independent cell lines were used to evaluate the role of AR in DTX resistance. Impact of drug treatment on cell viability, survival, and cell-cycle distribution were determined by plate-based viability assay, clonogenic assay, and cell-cycle analysis by flow cytometry, respectively. Mitotic checkpoint kinase signal transduction and apoptosis activation was evaluated by Western blotting. Pathway gene expression analysis was evaluated by RT-PCR. A Bliss independence model was used to calculate synergy scores for drug combination studies. RESULTS: Activation of AR in hormone-sensitive cells induces a rescue phenotype by increasing cell viability and survival and attenuating G2/M arrest in response to DTX. Analysis of mitotic checkpoint signaling shows that AR negatively regulates spindle checkpoint signaling, resulting in premature mitotic progression and evasion of apoptosis. This phenotype is characteristic of mitotic slippage and is also observed in CRPC cell lines where we demonstrate involvement of AR splice variant AR-v7 in dysregulation of checkpoint signaling. Our findings suggest that DTX resistance is mediated through mechanisms that drive premature mitotic exit. Using pharmacologic inhibitors of anaphase-promoting complex/cyclosome and polo-like kinase 1, we show that blocking mitotic exit induces mitotic arrest, apoptosis, and synergistically inhibits cell survival in combination with DTX. CONCLUSION: Our results suggest that targeting the mechanisms of dysregulated mitotic checkpoint signaling in AR-reactivated tumors has significant clinical potential to extend treatment benefit with DTX and improve outcomes in patients with lethal prostate cancer. Nephrology Astor BC, Hirschman K, Kennedy J, Frinak S, and Besarab A. Development and validation of a risk score to prioritize patients for evaluation of access stenosis. Semin Dial 2021; Epub ahead of print. PMID: 34642963. Full Text Department of Medicine, Division of Nephrology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, USA. Vasc-Alert, LLC, Lafayette, Indiana, USA. Department of Internal Medicine, Henry Ford Hospital, Henry Ford Health System, Detroit, Michigan, USA. Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, California, USA. BACKGROUND: Access flow dysfunction, often associated with stenosis, is a common problem in hemodialysis access and may result in progression to thrombosis. Timely identification of accesses in need of evaluation is critical to preserving a functioning access. We hypothesized that a risk score using measurements obtained from the Vasc-Alert surveillance device could be used to predict subsequent interventions. METHODS: Measurement of five factors over the preceding 28 days from 1.46 million hemodialysis treatments (6163 patients) were used to develop a score associated with interventions over the subsequent 60 days. The score was validated in a separate dataset of 298,620 treatments (2641 patients). RESULTS: Interventions in arteriovenous fistulae (AVF; n = 4125) were much more common in those with the highest score (36.2%) than in those with the lowest score (11.0). The score also was strongly associated with interventions in patients with an arteriovenous graft (AVG; n = 2,038; 43.2% vs. 21.1%). There was excellent agreement in the Validation datasets for AVF (OR = 2.67 comparing the highest to lowest score) and good agreement for AVG (OR = 1.92). CONCLUSIONS: This simple risk score based on surveillance data may be useful for prioritizing patients for physical examination and potentially early referral for intervention.

Nephrology Budde K, Prashar R, Haller H, Rial M, Kamar N, Agarwal A, de Fijter J, Rostaing L, Berger S, Djamali A, Leca N, Allamassey L, Gao S, Polinsky M, and Vincenti F. Conversion from Calcineurin Inhibitor to Belatacept-based Maintenance Immunosuppression in Renal Transplant Recipients: a Randomized Phase 3b Trial. J Am Soc Nephrol 2021; Epub ahead of print. PMID: 34706967. Full Text K Budde, Charité Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Nephrologie und internistische Intensivmedizin, Berlin, Germany klemens.budde@charite.de. R Prashar, Division of Nephrology, Henry Ford Hospital, Detroit, United States. H Haller, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. M Rial, Department of Nephrology, Dialysis and Organ Transplantation, Instituto de Nefrologia, Buenos Aires, Argentina. N Kamar, Department of Nephrology and Organ Transplantation, Université de Toulouse 2, Toulouse, France. A Agarwal, Department of Surgery, UVA Health, Charlottesville, United States. J de Fijter, Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands. L Rostaing, Division of Nephrology, Université Grenoble Alpes, Saint-Martin-d'Heres, France. S Berger, Division of Nephrology, University Medical Centre Groningen, Groningen, Netherlands. A Djamali, Division of Nephrology, University of Wisconsin-Madison, Madison, United States. N Leca, Department of Medicine, University of Washington Medical Center, Seattle, United States. L Allamassey, Bristol Myers Squibb Co, Princeton, United States. S Gao, Bristol Myers Squibb Co, Princeton, United States. M Polinsky, Bristol Myers Squibb Co, Princeton, United States. F Vincenti, Department of Surgery, Kidney Transplant Service, University of California San Francisco, San Francisco, United States. Background Calcineurin inhibitors (CNIs) are standard-of-care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T-cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial (NCT01820572) evaluated the efficacy/safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients. Methods Stable adult kidney transplant recipients, 6-60 months post-transplantation under CNI-based immunosuppression, were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary endpoint was the percentage of patients surviving with a functioning graft at 24 months. Results Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rate of survival with graft function was 98% and 97% in the belatacept and CNI groups, respectively, (adjusted difference: 0.8 [95.1% CI, -2.1 to 3.7]). In the belatacept conversion vs. CNI continuation groups, respectively, 8% vs. 4% of patients experienced biopsy-proven acute rejection (BPAR) and 1% vs. 7% developed de novo donor-specific antibodies (dnDSA). The 24-month estimated glomerular filtration rate was higher with belatacept (55.5 vs. 48.5 mL/min1.73 m2 with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had posttransplant lymphoproliferative disorder. Conclusions Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate, but a lower incidence of dnDSA. Neurology Jum'ah A, Aboul Nour H, Alkhoujah M, Zoghoul S, Eltous L, and Miller D. Neurosyphilis in disguise. Neuroradiology 2021; Epub ahead of print. PMID: 34665270. Full Text Department of Neurology, Henry Ford Hospital, 1350 W. Bethune St, Detroit, MI, 48202, USA. ajumah1@hfhs.org. Department of Neurology, Henry Ford Hospital, 1350 W. Bethune St, Detroit, MI, 48202, USA. Department of Radiology, Hamad Medical Corporation, Doha, Qatar. Jordan University of Science and Technology, Irbid, Jordan.

PURPOSE: Neurosyphilis can mimic different diseases, not only in its clinical presentation but also on imaging. Treponema pallidum is also known as the "great imitator." Having an ultimate diagnosis of neurosyphilis is quite critical as this can affect management drastically. Herein, we discuss the case of a 69-year-old female who was treated for neurosyphilis, while having an atypical imaging finding of anterior temporal lobe enhancement that simulated an infection with herpes simplex virus (HSV); we also review the available literature on different imaging findings in both the early and late stages of the disease. METHODS: We performed a literature search using the new PubMed in June 2021. The terms "neurosyphilis", "MRI", and "neuroimaging" were used either alone or in combination with "early neurosyphilis" or "late neurosyphilis". Data on neurosyphilis and imaging findings was mainly derived from review articles, cohort studies, case series, and individual reports. CONCLUSION: Neurosyphilis can present with an extensive variation and different patterns on the MRI, and clinicians must be aware of the wide variety in radiological presentations. Anterior temporal lobe involvement is a rare presentation and requires evaluating for neurosyphilis to prevent a missed diagnosis and treatment. Neurology Kontopodis N, Charalambous S, Vourakis G, Galanakis N, Mitsias P, Tsetis D, and Ioannou CV. Images in Vascular Medicine: Bright light amaurosis - When external carotid artery stenosis matters. Vasc Med 2021; Epub ahead of print. PMID: 34693850. Full Text Department of Cardiothoracic and Vascular Surgery, Vascular Surgery Unit, University Hospital of Heraklion, Crete, Greece. Department of Medical Imaging, Interventional Radiology Unit, University Hospital of Heraklion, Crete, Greece. Department of Neurology, University Hospital of Heraklion, Crete, Greece. School of Medicine, University of Crete, Heraklion, Greece. Department of Neurology, Henry Ford Hospital, Detroit, MI, USA. Neurology Zhang J, Buller BA, Zhang ZG, Zhang Y, Lu M, Rosene DL, Medalla M, Moore TL, and Chopp M. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system. Exp Neurol 2021; 347:113895. PMID: 34653510. Full Text Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America. Electronic address: jingz@neuro.hfh.edu. Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America. Public Health Sciences, Henry Ford Health System, Detroit, Michigan, United States of America. Department of Anatomy and Neurobiology, Boston University, Boston, Massachusetts, United States of America; Center for Systems Neuroscience, Boston University, Boston, Massachusetts, United States of America. Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America; Department of Physics, Oakland University, Rochester, Michigan, United States of America. Injury of oligodendrocytes (OLs) induces demyelination, and patients with neurodegenerative diseases exhibit demyelination concomitantly with neurological deficit and cognitive impairment. Oligodendrocyte progenitor cells (OPCs) are present in the adult central nervous system (CNS), and they can proliferate, differentiate, and remyelinate axons after damage. However, remyelination therapies are not in clinical use. Multiple sclerosis (MS) is a major demyelinating disease in the CNS. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic promise in animal models and in clinical trials of MS. Exosomes are nanoparticles generated by nearly all cells and they mediate cell-cell communication by transferring cargo biomaterials. Here, we hypothesize that exosomes harvested from MSCs have a similar therapeutic effect on enhancement of remyelination as that of MSCs. In the present study we employed exosomes derived from rhesus monkey MSCs (MSC-Exo). Two mouse models of demyelination were employed: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS; and 2) cuprizone (CPZ) diet model, a toxic demyelination model. MSC-Exo or PBS were intravenously injected twice a week for 4 weeks, starting on day 10 post immunization in EAE mice, or once a week for 2 weeks starting on the

day of CPZ diet withdrawal. Neurological and cognitive function were tested, OPC differentiation and remyelination, neuroinflammation and the potential underlying mechanisms were investigated using immunofluorescent staining, transmission electron microscopy and Western blot. Data generated from the EAE model revealed that MSC-Exo cross the blood brain barrier (BBB) and target neural cells. Compared with the controls (p < 0.05), treatment with MSC-Exo: 1) significantly improved neurological outcome; 2) significantly increased the numbers of newly generated OLs (BrdU(+)/APC(+)) and mature OLs (APC(+)), and the level of myelin basic protein (MBP); 3) decreased amyloid-β precursor protein (APP)(+) density; 4) decreased neuroinflammation by increasing the M2 phenotype and decreasing the M1 phenotype of microglia, as well as their related cytokines; 5) inhibited the TLR2/IRAK1/NFκB pathway. Furthermore, we confirmed that the MSC-Exo treatment significantly improved cognitive function, promoted remyelination, increased polarization of M2 phenotype and blocked TLR2 signaling in the CPZ model. Collectively, MSC-Exo treatment promotes remyelination by both directly acting on OPCs and indirectly by acting on microglia in the demyelinating CNS. This study provides the cellular and molecular basis for this cell-free exosome therapy on remyelination and modulation of neuroinflammation in the CNS, with great potential for treatment of demyelinating and neurodegenerative disorders. Neurosurgery Macki M, Haddad Y, Suryadevara R, Dabaja AL, Chedid M, and Chang V. Prophylactic Low-Molecular-Weight Heparin Versus Unfractionated Heparin in Spine Surgery (PLUSS): A Pilot Matched Cohort Study. Neurosurgery 2021; Epub ahead of print. PMID: 34634115. Full Text Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan, USA. Department of Internal Medicine, Garden City Hospital, Garden City, Michigan, USA. BACKGROUND: Despite a proven superior efficacy of prophylactic low-molecular-weight heparin (LMWH) over unfractionated heparin (UFH) in the majority of surgical specialties, chemoprophylactic techniques after spine surgery have not been established because of the fear of epidural hematomas with LMWH. OBJECTIVE: To determine the efficacy of LMWH vs UFH in the prevention of venous thromboembolism (VTE) events, balanced against the risk of epidural hematoma. METHODS: This is the first matched cohort design that directly compares prophylactic LMWH to UFH after spine surgery for degenerative/deformity pathologies at a tertiary academic center. Prospectively collected patients receiving prophylactic LMWH and a historical cohort of patients receiving prophylactic UFH (prior to 2017) were matched in 1:1 ratio based on age ±5 yr, American Society of Anesthesiologists classification, location in the spinal column, and type of surgery. RESULTS: Of 562 patients, VTE events equaled 1.4% (n = 8): 1.4% (n = 4) with LMWH was exactly equal to 1.4% (n = 4) with UFH. Epidural hematomas reached 0.8% (n = 5): 1.4% (n = 4) with UFH vs 0.3% (n = 1) with the LMWH (P = .178). Utilizing adjusted odds ratio (ORadj), the type of chemoprophylaxis after spine surgery failed to predict VTE events. Similarly, the chemoprophylactic technique failed to predict epidural hematoma in the multivariable regression analysis, although UFH trended toward a higher complication rate (ORadj = 3.15 [0.48-20.35], P = .227). CONCLUSION: Chemoprophylactic patterns failed to predict VTE. Although no differences in epidural hematoma rates were detected, our analysis does highlight a trend toward a safer profile with LMWH vs UFH. LMWH may be a safe alternative to UFH in spine surgery. Neurosurgery Pawloski JA, Fadel HA, Huang YW, and Lee IY. Genomic Biomarkers of Meningioma: A Focused Review. Int J Mol Sci 2021; 22(19). PMID: 34638590. Full Text Department of Neurosurgery, Henry Ford Hospital, Detroit, MI 48202, USA. Department of Neurological Surgery, Henry Ford Hospital, 2799 West Grand Blvd, Detroit, MI 48202, USA. Meningiomas represent a phenotypically and genetically diverse group of tumors which often behave in ways that are not simply explained by their pathologic grade. The genetic landscape of meningiomas has become a target of investigation as tumor genomics have been found to impact tumor location, recurrence risk, and malignant potential. Additionally, targeted therapies are being developed that in the future may provide patients with personalized chemotherapy based on the genetic aberrations within their

tumor. This review focuses on the most common genetic mutations found in meningiomas of all grades, with an emphasis on the impact on tumor location and clinically relevant tumor characteristics. NF-2 and the non-NF-2 family of genetic mutations are summarized in the context of low-grade and high-grade tumors, followed by a comprehensive discussion regarding the genetic and embryologic basis for meningioma location and phenotypic heterogeneity. Finally, targeted therapies based on tumor genomics currently in use and under investigation are reviewed and future avenues for research are suggested. The field of meningioma genomics has broad implications on the way meningiomas will be treated in the future, and is gradually shifting the way clinicians approach this diverse group of tumors. Neurosurgery Schupper AJ, Baron RB, Cheung W, Rodriguez J, Kalkanis SN, Chohan MO, Andersen BJ, Chamoun R, Nahed BV, Zacharia BE, Kennedy J, Moulding HD, Zucker L, Chicoine MR, Olson JJ, Jensen RL, Sherman JH, Zhang X, Price G, Fowkes M, Germano IM, Carter BS, Hadjipanayis CG, and Yong RL. 5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study. J Neurosurg 2021; Epub ahead of print.:1-10. PMID: 34624862. Full Text 1Department of Neurological Surgery, Mount Sinai Health System, New York, New York. 2Department of Neurological Surgery, Henry Ford Medical Center, Detroit, Michigan. 3Department of Neurological Surgery, University of New Mexico Hospital, Albuquerque, New Mexico. 4Department of Neurological Surgery, St. Alphonsus Regional Medical Center, Boise, Idaho. 5Department of Neurological Surgery, University of Kansas Medical Center, Kansas City, Kansas. 6Department of Neurological Surgery, Massachusetts General Hospital, Boston, Massachusetts. 7Department of Neurological Surgery, Milton S. Hershey Medical Center, Hershey, Pennsylvania. 8Centra Care Neurosurgery, St. Cloud, Minnesota. 9Department of Neurological Surgery, St. Luke's University Health Network, Bethlehem, Pennsylvania. 10Department of Neurological Surgery, Delray Medical Center, Delray Beach, Florida. 11Department of Neurological Surgery, Barnes-Jewish Hospital, St. Louis, Missouri. 12Department of Neurological Surgery, Emory University Hospital, Atlanta, Georgia. 13Department of Neurological Surgery, Huntsman Cancer Institute, Salt Lake City, Utah; and. 14Department of Neurological Surgery, George Washington University Hospital, Washington, DC. OBJECTIVE: Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors' knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA-induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS: This single-arm, multicenter, prospective study included adults aged 18-80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3-5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS: Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS: PPIX fluorescence, as judged by the surgeon, has a high sensitivity and

PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity. Neurosurgery Siddiqui MS, Jimenez-Shahed J, Mari Z, Walter BL, De Jesus S, Panov F, Schwalb JM, York MK, Sarva H, Bertoni JM, Patel N, Zhang L, McInerney J, and Rosenow JM. North American survey on impact of the COVID-19 pandemic shutdown on DBS care. Parkinsonism Relat Disord 2021; 92:41-45. PMID: 34688029. Full Text Department of Neurology, Wake Forest School of Medicine, 1 Medical Center, Boulevard, Winston-Salem, NC, 27157, USA. Electronic address: mssiddiq@wakehealth.edu. Icahn School of Medicine at Mount Sinai, 1000 10th Ave., Suite 10c, New York, NY, 10019, USA. Electronic address: Joohi.jimenez-shahed@mountsinai.org. Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W Bonneville Ave, Las Vegas, NV, 89117, USA. Electronic address: mariz@ccf.org. Cleveland Clinic, 9500 Euclid Ave/S2, Cleveland, OH, 44195, USA. Electronic address: walterb7@ccf.org. Pennsylvania State University - Milton S. Hershey Medical Center, 30 Hope Drive, Suite 2800 P.O. Box 859, Mail Code EC037, Hershey, PA, 17033, USA. Electronic address: sdejesus@pennstatehealth.psu.edu. Mount Sinai Medical Center, 1000 10th Ave, Suite 10C, Brooklyn, NY, 11217, USA. Electronic address: fedor.panov@mountsinai.org. Henry Ford Medical Group, 6777 West Maple Road, West Bloomfield, MI, 48322, USA. Electronic address: jschwal1@hfhs.org. Baylor College of Medicine, 7200 Cambridge St, 9th Floor, Houston, TX, 77030, USA. Electronic address: myork@bcm.edu. Weill Cornell Medicine, 428 E 72nd Street, STE 400, NY, NY, 10021, USA. Electronic address: has9059@med.cornell.edu. University of Nebraska Medical Center, 988440 Nebraska Medical Center, Omaha, NE, 68198, USA. Electronic address: jbertoni@unmc.edu. Rush University Medical Center, 1725 West Harrison St. Suite 755, Chicago, IL, 60612, USA. Electronic address: neepa_patel@rush.edu. UCDavis, 4860 Y Street, ACC Building, Suite 3700, Sacramento, CA, 95817, USA. Electronic address: mdzhang@ucdavis.edu. Penn State Health, Milton S. Hershey Medical Center, Department of Neurosurgery, 30 Hope Drive, EC110, Hershey, PA, 17033, USA. Electronic address: jmcinerney@pennstatehealth.psu.edu. Northwestern University Feinberg School of Medicine Department of Neurosurgery, 676 N St. Clair St, Suite 2210, Chicago, IL, USA. Electronic address: JRosenow@nm.org. BACKGROUND: The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada. OBJECTIVE: This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America. METHODS: A survey was distributed through RedCap® to the members of the PSG Functional Neurosurgical Working Group. Only one member from each site was asked to respond to the survey. Responses were collected from May 15 to June 6, 2020. RESULTS: Twenty-three sites participated; 19 (83%) sites were from the USA and 4 (17%) from Canada. Twenty-one sites were academic medical centers. COVID-19 associated DBS restrictions were in place from 4 to 16 weeks. One-third of sites halted preoperative evaluations, while two-thirds of the sites offered limited preoperative evaluations. Institutional policy was the main contributor for the reported practice changes, with 87% of the sites additionally reporting patient-driven surgical delays secondary to pandemic concerns. Pre-post DBS associated management changes affected preoperative assessments 96%; electrode placement 87%; new implantable pulse generator (IPG) placement 83%; IPG replacement 65%; immediate postoperative DBS programming 74%; and routine DBS programming 91%. CONCLUSION: The COVID-19 pandemic related shutdown resulted in DBS practice changes in almost all North American sites who responded to this large survey. Information learned could inform development of future contingency plans to reduce patient delays in care under similar circumstances.

Obstetrics, Gynecology and Women’s Health Services Su WK, Coleman CM, Bossick AS, Lee-Griffith M, and Wegienka G. Racial Differences in Planned Hysterectomy Procedure Route. J Womens Health (Larchmt) 2021; Epub ahead of print. PMID: 34637634. Request Article Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA. Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan, USA. inVIVO Planetary Health, Worldwide Universities Network, West New York, New Jersey, USA. Background: Hysterectomies can be performed with a minimally invasive surgical (MIS) approach or a laparotomic (abdominal) approach. The objective of this study was to assess any racial differences in the likelihood of having a planned MIS hysterectomy. Materials and Methods: A prospective cohort study of women undergoing hysterectomy at Henry Ford Health System was conducted where laparotomic and MIS approaches are available to all patients. All procedures were performed between October, 2015, and August, 2017. For this study, women were asked to report demographic and insurance information and complete validated questionnaires from 2 weeks before hysterectomy and up to six additional times in the year after hysterectomy. Clinical and operative characteristics were collected from electronic health records. Logistic regression and multinomial logistic regression models were applied to assess the association between race and the surgical approach. Results: Analyses included 235 White women and 196 Black women. Black women were less likely to have any MIS planned for their hysterectomy (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.3-0.71, p < 0.05), a laparoscopic hysterectomy (relative risk ratio [RRR] = 0.46, 95% CI 0.29-0.73, p < 0.05), or a vaginal hysterectomy (RRR = 0.45, 95% CI 0.25-0.81, p = 0.01) compared with White women. After adjusting for confounders, uterine weight and indication for surgery was fibroids, these racial differences did not remain statistically significant (MIS vs. abdominal [adjusted odds ratio {aOR} = 0.93, 95% CI 0.55-1.57, p = 0.79], laparoscopic vs. abdominal [adjusted relative risk ratio {aRRR} = 0.89, 95% CI 0.52-1.51, p = 0.54], and vaginal vs. abdominal [aRRR = 1.22, 95% CI 0.61-2.45, p = 0.58]). The associations were not confounded by the baseline survey data from standardized questionnaires on depression, financial distress, and satisfaction with their decision. Conclusions: Black women were not less likely than White women to have planned an MIS hysterectomy after controlling for important confounding variables. These results emphasize the importance of considering all important confounders when examining racial differences. Ophthalmology and Eye Care Services Kasetty VM, Tran AQ, Rosenbaum PS, Dalvin LA, and Tooley AA. Uveal melanoma presenting as panophthalmitis in the absence of an intraocular mass. Can J Ophthalmol 2021; Epub ahead of print. PMID: 34715038. Full Text Henry Ford Health System, Detroit, Mich. Weill Cornell Medical Center, New York, NY. Montefiore Medical Center, New York, NY; Bronxcare Hospital, Bronx, NY. Mayo Clinic, Rochester, Minn. Mayo Clinic, Rochester, Minn. Electronic address: tooley.andrea@mayo.edu. Ophthalmology and Eye Care Services Richey BF, Obrock RS, Gee ZM, Lu DY, Jacobsen G, and Richards SC. Smoking, Rural Residence and Diabetes as Risk Factors for Presumed Ocular Histoplasmosis Syndrome. Retina 2021; Epub ahead of print. PMID: 34690340. Full Text Weber State University, Ogden, Utah The Retinal Institute, Fort Wayne, Indiana Des Moines University, Des Moines, Iowa Henry Ford Hospital Department of Ophthalmology, Detroit, Michigan Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan. PURPOSE: To investigate the relationship of smoking, urbanicity and diabetes to presumed ocular histoplasmosis syndrome (POHS) and associated choroidal neovascularization (CNV). METHODS:

Medical records of 751 adult patients with POHS were reviewed, including 603 patients without CNV and 148 patients with CNV. Age- and gender-matched controls were randomly selected from the same practice for comparison. Statistical comparisons of smoking history, urbanicity, and diabetic history were performed using Chi-Square and conditional logistic regression analyses. RESULTS: Increased rates of current or former smoking, rural residence, and diabetes were found in patients with POHS compared with controls. POHS patients with CNV had increased rates of current or former smoking and rural residence as compared with controls. CONCLUSIONS: A history of current or past smoking is associated with an increased risk of developing both POHS alone and POHS with CNV. We did not find a significant additional risk of smoking on the development of CNV in patients with POHS. Patients living in rural locations are more likely than those in urban locations to develop both POHS and POHS with CNV. Diabetics may be more likely to develop POHS than non-diabetics. Orthopedics/Bone and Joint Center Abbas MJ, Khalil LS, Haikal A, Dash ME, Dongmo G, and Okoroha KR. Eliciting Emotion and Action Increases Social Media Engagement: An Analysis of Influential Orthopaedic Surgeons. Arthrosc Sports Med Rehabil 2021; 3(5):e1301-e1308. PMID: 34712967. Full Text Henry Ford Hospital, Department of Orthopaedic Surgery, Detroit, Michigan, U.S.A. Wayne State University School of Medicine, Detroit, Michigan, U.S.A. Mayo Clinic, Department of Orthopedic Surgery, Minneapolis, Minnesota, U.S.A. PURPOSE: The purpose of this study is to analyze the Instagram practices of current orthopaedic surgeons and the components associated with highest reach and interactions. METHODS: The top 25 orthopaedic surgeon Instagram profiles using the hashtag #ortho were ranked by the number of followers. Account information regarding followers, posts, engagement percentage, average likes, average comments, average video view, average video likes, average video comments, and estimated cost per post was recorded using social media marketing tools. An analysis of each Instagram profiles' top 10 posts, based on number of likes, was conducted. A coding framework was developed to categorized posting strategies utilized. RESULTS: Twenty-five Instagram accounts and 250 Instagram posts were included in the analysis. Accounts with increased engagement rating had a significantly greater number of likes and video views. When examining post characteristics that influenced the number of likes a post generated, posts that elicited negative emotions received 52.6% and 70.7% more likes than positive emotions (P = .04) and neutral emotions (P < .01), respectively. Upon assessment of posting characteristics that influenced the number of comments a post generated, promotional posts were shown to have 43.7% fewer comments than nonpromotional posts (P = .02). When evaluating factors that influenced total number of interactions a post generated, it was found that posts that asked questions generated 26.4% more interactions (P < .01) than those that do not. CONCLUSIONS: The present investigation found that the most effective strategies to generate more interactions on Instagram are those that elicit emotional responses and provoke viewer engagement by asking questions and directing actions. Additionally, it was found that promotional content was not well received by viewers. CLINICAL RELEVANCE: Orthopaedic surgeons have an opportunity to connect with colleagues, patients, and interested viewers through social media platforms in order to enhance their practice, disseminate educational content, and contribute to the social media presence of orthopaedic surgery. Orthopedics/Bone and Joint Center Abbas MJ, Khalil LS, Rahman T, Abbas L, Akioyamen NO, Farley BJ, Bazzi T, and Okoroha KR. Anterior Cruciate Ligament Reconstruction Does Not Impact Career Earnings After Return to Play in National Basketball Association Athletes. Arthrosc Sports Med Rehabil 2021; 3(5):e1491-e1497. PMID: 34712986. Full Text Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit, Michigan, U.S.A. University of Illinois at Chicago College of Medicine, Chicago, Illinois, U.S.A. Wayne State University School of Medicine, Detroit, Michigan, U.S.A. Central Michigan University College of Medicine, Mount Pleasant, Michigan, U.S.A. Department of Orthopedic Surgery, Mayo Clinic, Minneapolis, Minnesota, U.S.A.

PURPOSE: To quantify the financial impact of an anterior cruciate ligament (ACL) injury on the remaining career earnings of National Basketball Association (NBA) players. METHODS: We performed a retrospective review of all NBA players who had an ACL rupture between 2000 and 2019. Players were matched to healthy controls by age, position, body mass index, and player efficiency rating at the time of injury (index year). Player information collected included demographic information, position, team role, draft pick, date of injury, contract length, and earnings during the 3 years before and 7 years after the index year, as well as new contract length and earnings after injury. RESULTS: A total of 12 players (22%) did not return to play (RTP). No statistically significant difference in annual earnings was present at any time point between cohorts. When we examined the mean difference in earnings between the first 3 post-index seasons and the 3 pre-index seasons, both the ACL and control cohorts showed increased salaries as players' careers progressed, without a significant difference in earnings. When comparing cohorts, we found no significant difference in the length and earnings of contracts during the index year. Furthermore, there was no significant difference in the length or earnings of the first new contract signed after the index year between cohorts. Additionally, NBA players who were able to RTP after ACL reconstruction were more likely to experience increased earnings if they had greater experience and performance prior to their injury (P < .01). CONCLUSIONS: Our study found that NBA players did not experience diminished earnings after RTP from an ACL reconstruction when compared with matched controls. Furthermore, no differences were seen in lengths of new contracts or in contract earnings between cohorts. Players with greater experience and performance prior to injury were more likely to have increased earnings after ACL reconstruction. LEVEL OF EVIDENCE: Level III, retrospective case-control study. Orthopedics/Bone and Joint Center Castle JP, Kessler A, Abbas MJ, Wager S, Khalil LS, Okoroha KR, and Mehran N. High Return to Play Rate and Reduced Career Longevity Following Surgical Management of Athletic Pubalgia in National Basketball Association Players. Arthrosc Sports Med Rehabil 2021; 3(5):e1359-e1365. PMID: 34712974. Full Text Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit, Michigan, U.S.A. University of California Los Angeles, Los Angeles, California, U.S.A. Wayne State University School of Medicine, Detroit, Michigan, U.S.A. Department of Orthopedic Surgery, Mayo Clinic, Minneapolis, Minnesota, U.S.A. Department of Orthopaedic Surgery, Kaiser Permanente, Los Angeles, California, U.S.A. PURPOSE: To assess the effects of surgical treatment of athletic pubalgia (AP) on game use and performance metrics in National Basketball Association (NBA) players. METHODS: A retrospective review of all NBA players who underwent surgical management for AP from 1996 to 2018 was performed. A matched control group was created for comparison. The index period was defined as the entire NBA season in which surgery occurred, including the corresponding offseason. Player demographics, use (games played, games started, and minutes per game) and performance (player efficiency rating) metrics were collected for all players. Statistical analysis was performed to compare data before and after return to play. RESULTS: Thirty players with a history of surgical management for AP were included in the final analysis. Following surgery for AP, NBA players were found to have a return to play (RTP) rate of 90.91% (30/33). The average RTP following surgery was 4.73 ± 2.62 months. Compared with control athletes, athletes in the AP group played significantly fewer seasons postinjury (4.17 ± 2.70 vs 5.49 ± 3.04 seasons, respectively; P = .02). During the first year following RTP, NBA players experienced significant reductions in game use and performance, both when compared with the year prior and matched control athletes (P < .05). At 3-year follow-up, players continued to demonstrate significant reductions in game use (minutes per game, P < .05) but not performance. CONCLUSIONS: Following surgical treatment of AP, NBA players demonstrated a high RTP rate, but shortened career. A short-term reduction in game use and performance metrics was found the year of return following surgery. However, 3-year follow-up performance metrics normalized when compared with healthy controls. STUDY DESIGN: Level III; retrospective case-control study.

Orthopedics/Bone and Joint Center Chen AZ, Bovonratwet P, Greaves KM, Trofa DP, Levine WN, and Lynch TS. Academic Influence as Reflected by H-index is Not Associated with Total Industry Payments but Rather with NIH Funding Among Academic Orthopedic Sports Medicine Surgeons. Arthroscopy 2021; Epub ahead of print. PMID: 34715279. Full Text Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA; Weill Cornell Medical College, New York, NY, 10065, USA. Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY 10021, USA. Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA; Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, 08854, USA. Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA. Department of Orthopedic Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: tlynch3@hfhs.org. PURPOSE: The aims of the current study were 1) to compare the total number and dollar amount of industry funding and National Institutes of Health (NIH) funding to academic orthopedic sports medicine surgeons and 2) to examine the impact of academic influence on industry funding and NIH funding to academic orthopedic sports medicine surgeons. METHODS: Academic orthopedic sports medicine surgeons were identified using faculty webpages. Academic influence was approximated by a physician's h-index and number of publications and obtained from the Scopus database. Total industry payments were acquired through the Open Payments Database and NIH funding was determined from the NIH website. Statistical analysis was performed using Mann-Whitney U testing and Spearman correlations with significance set at p < 0.05. RESULTS: Physicians who received industry research payments and NIH funding had a significantly higher mean h-index and mean total publications than physicians that did not receive industry research payments and NIH funding. There were no significant differences in h-index (p= 0.374) or number of publications (p=0.126) between surgeons receiving industry non-research funding and those who did not. H-index and number of publications were both weakly correlated with the amount of industry research and non-research funding. CONCLUSION: While academic influence is associated with industry research funding and NIH funding, there is no association between measures of academic influence and total industry and industry non-research payments. Combined with the weak associations between academic influence and the amount of industry payments, academic influence does not appear to be a major determinant of industry funding to academic orthopedic sports medicine surgeons. CLINICAL RELEVANCE: While surgeons should be cognizant of potential conflicts with industry, the relationship between academic sports medicine surgeons and industry may be less subject to bias than previously believed. Orthopedics/Bone and Joint Center Gaudiani MA, Samuel LT, Diana JN, DeBattista JL, Coon TM, Moore RE, and Kamath AF. Robotic-arm assisted bicompartmental knee arthroplasty: Durable results up to 7-year follow-up. Int J Med Robot 2021; Epub ahead of print. PMID: 34665485. Full Text Department of Orthopaedic Surgery, Henry Ford Health System, Detroit, Michigan, USA. Department of Orthopaedic Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Coon Joint Replacement Institute, St. Helena, California, USA. BACKGROUND: The purpose of our study was to investigate the mid-term clinical and functional outcomes of robotic-arm assisted Bicompartmental knee arthroplasty (BiKA). METHODS: This study reviewed a single-centre prospectively maintained cohort of 50 patients (53 knees) who underwent BiKA (patellofemoral and medial compartment) at 5- and 7-year postoperative follow-up. RESULTS: Mean follow-up was 7.1 ± 0.1 years (range, 7.0-7.3). Kaplan-Meier survivorship rates at 5 and 7 years were 96% and 93%, respectively. At 7-year follow-up, patient satisfaction was 76% satisfied, 13% neutral, and 11% not satisfied. Mean KSS-FS was 80.5 ± 15.8 (range, 30-100) with 82% of patients reporting walking more than 10 blocks, 89% reporting walking without support, and 100% able to go up and down stairs with 61% requiring use of a rail. Three patients (four knees) underwent revision surgery. CONCLUSIONS:

Our study reported excellent survivorship and functional outcomes, and good-excellent satisfaction at mid-term follow-up for robotic-arm assisted BiKA. Orthopedics/Bone and Joint Center Jildeh TR, Castle JP, Abbas MJ, Dash ME, Akioyamen NO, and Okoroha KR. Age Significantly Affects Response Rate to Outcomes Questionnaires Using Mobile Messaging Software. Arthrosc Sports Med Rehabil 2021; 3(5):e1349-e1358. PMID: 34712973. Full Text Department of Orthopaedic Surgery, Henry Ford Hospital, Detroit, Michigan, U.S.A. Wayne State University School of Medicine, Detroit, Michigan, U.S.A. Department of Orthopedic Surgery, Mayo Clinic, Minneapolis, Minnesota, U.S.A. PURPOSE: To investigate the demographic factors that influence time to respond (TTR), time to completion (TTC), and response rate when using a text messaging-based system and to determine the feasibility and applicability of mobile messaging-based services for collection of patient-reported outcomes among orthopaedic sports medicine patients. METHODS: On the day of surgery, patient mobile phone number was collected and the automated mobile messaging service (MOSIO, Seattle, WA) messaged patients for 10 ``days postoperatively. Patient visual analog scale (VAS) scores were collected 3 times daily, side effects were asked each evening, and Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) Short Form was collected on postoperative day 3 and 7. RESULTS: A total of 177 patients were enrolled in the study. The overall response rate to the survey questions was 75.0%. For all patients, the average TTR of questions was 35.09 ± 12.57 minutes. The TTC was 2.75 ± 3.56 minutes for PROMIS-PI, 3.51 ± 1.26 minutes for VAS, and 3.80 ± 6.87 for side-effect questions. When patients were stratified into age groups, the youngest group, 16 to 32 years, had the greatest response rate of 85.2% and patients in the 49 to 59 years group had the lowest response rate of 68.4% and 69.1%, respectively (P < .001). There was no significant difference in the TTR or TTC for VAS, PROMIS-PI, or side-effect questions when patients were stratified by age or sex groups (P > .05). CONCLUSIONS: Collectively, all age groups successfully achieved a mean response rate of 75%; however, significantly lower response rates were observed for patients >49 years old. Differences in age and sex did not impact the overall TTR or TTC for VAS, PROMIS-PI, or side-effect questions. Mobile-based applications present as an emerging opportunity to track postoperative outcome scores and reduce clinic survey load. LEVEL OF EVIDENCE: Case series, level of evidence IV. Orthopedics/Bone and Joint Center Klag EA, Okoroha KR, Kuhlmann NA, Sheena G, Chen C, and Muh SJ. Does the use of periarticular anesthetic cocktail provide adequate pain control following shoulder arthroplasty? Shoulder Elbow 2021; 13(5):502-508. PMID: 34659483. Full Text Henry Ford Health System, Detroit, USA. BACKGROUND: Interscalene nerve block and liposomal bupivacaine have been found to provide adequate pain control following shoulder arthroplasty. We hypothesized that local infiltration of a periarticular cocktail would provide equivalent pain control compared to interscalene nerve block and liposomal bupivacaine. METHODS: Eighty-seven patients undergoing primary shoulder arthroplasty were treated with local infiltration of a periarticular cocktail (200 mg of 0.5% ropivacaine, 1 mg epinephrine, and 30 mg ketorolac), local infiltration of liposomal bupivacaine, or preoperative interscalene nerve block. The outcomes of the study were postoperative visual analog scale scores, opioid consumption, length of stay, and complications. RESULTS: A total of 30 patients receiving local infiltration of a periarticular cocktail, 26 receiving liposomal bupivacaine, and 31 receiving interscalene nerve block were included in the study. Patients who received local infiltration of a periarticular cocktail had a significantly lower mean visual analog scale when compared to interscalene nerve block and liposomal bupivacaine on postoperative day 0 (2.5 versus 4.0 versus 4.8, P = 0.001 and P < 0.001). Pain scores between postoperative day 0-3 were lower in patients who received local infiltration of a periarticular cocktail, but not significantly. Patients who received local infiltration of a periarticular cocktail required significantly less opioids than the interscalene nerve block group on postoperative day 0 (P < 0.001). DISCUSSION: A decrease in early postoperative pain and opioid consumption was found with local infiltration of a periarticular cocktail when

compared with interscalene nerve block and liposomal bupivacaine after shoulder arthroplasty.Level of evidence: Level II. Orthopedics/Bone and Joint Center Lizzio VA, James CL, Pietroski AD, Kuhlmann NA, Franovic S, Warren JR, and Muh SJ. Characterizing Preoperative Expectations for Patients Undergoing Reverse Total Shoulder Arthroplasty. J Shoulder Elbow Surg 2021; Epub ahead of print. PMID: 34619351. Full Text Department of Orthopedic Surgery, Henry Ford Health System, Detroit, MI, USA. Wayne State University, Detroit, MI, USA. Department of Orthopedic Surgery, Henry Ford Health System, Detroit, MI, USA. Electronic address: smuh1@hfhs.org. BACKGROUND: There remains a paucity of information analyzing which factors most influence preoperative expectations for patients undergoing reverse total shoulder arthroplasty (RTSA). The purpose of our study was to characterize preoperative patient expectations for those scheduled to undergo RTSA and to determine the impact of demographic factors, shoulder function, and shoulder pain on these preoperative expectations. METHODS: Patients were prospectively recruited into the study if they were scheduled to undergo an elective unilateral primary RTSA for a diagnosis of glenohumeral arthritis. Preoperative patient expectations were evaluated using the Hospital for Special Surgery's Shoulder Surgery Expectation Survey (HSS-ES). Patients also completed the American Shoulder and Elbow Surgeons Shoulder Score, Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function - Upper Extremity (UE) v2.0 computer adaptive test, PROMIS Pain Interference (PI) v1.1 computer adaptive test, PROMIS Depression (DE) v1.0 computer adaptive test, visual analogue scores, and an itemized satisfaction questionnaire, which paralleled the HSS-ES. Demographic and preoperative shoulder range of motion (ROM) were also recorded. RESULTS: A total of 107 patients scheduled to undergo RTSA were included into the study. Relief of daytime pain (n = 91, 85%), improvement in self-care (n = 86, 80%), and improvement in shoulder ROM (n = 85, 79%) were most commonly cited as a "very important" expectation. In the item-specific analysis, lower PROMIS UE scores were correlated with greater expectations for ability to reach sideways (p = 0.015) and ability to perform daily activities (p = 0.018). Patients with lower shoulder ROM had greater expectations for improved shoulder ROM (internal rotation, arm at 90 degrees, p = 0.004) and improved ability to perform daily activities (forward elevation, p = 0.038; abduction, p = 0.009). In the cumulative analysis, a greater number of "very important" expectations was associated with African American race (p = 0.013), higher PROMIS PI (r = 0.351, p = 0.004), and lower overall preoperative satisfaction (r = 0.334, p < 0.001). CONCLUSION: Patients scheduled to undergo RTSA have the greatest expectations for relief of daytime pain, improvement in self-care, and improvement in shoulder ROM. Patients with limited preoperative ROM have greater expectations for improvement in self-care and ability to perform daily activities in addition to expectations for improvement in shoulder ROM. Greater overall expectations for surgery were not associated with preoperative physical function, but were instead associated with lower preoperative satisfaction and higher PROMIS PI scores. Orthopedics/Bone and Joint Center Moutzouros V, Jildeh TR, Tramer JS, Meta F, Kuhlmann N, Cross A, and Okoroha KR. Can We Eliminate Opioids After Anterior Cruciate Ligament Reconstruction? A Prospective, Randomized Controlled Trial. Am J Sports Med 2021; Epub ahead of print. PMID: 34668795. Full Text Henry Ford Health System, Detroit, Michigan, USA. Mayo Clinic Orthopedics and Sports Medicine, Rochester, Minneapolis, USA. BACKGROUND: Multimodal pain protocols have been effective for postsurgical pain control; however, no published protocol has been effective in eliminating opioid consumption. PURPOSE: To compare a multimodal nonopioid pain protocol versus traditional opioid medication for postoperative pain control in patients undergoing anterior cruciate ligament reconstruction (ACLR). STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 90 patients undergoing primary ACLR were assessed for participation. We performed a prospective, randomized controlled trial in accordance with

the CONSORT (Consolidated Standards of Reporting Trials) 2010 statement. The study arms were a multimodal nonopioid analgesic protocol (acetaminophen, ketorolac, diazepam, gabapentin, and meloxicam) and a standard opioid regimen (hydrocodone-acetaminophen), and the primary outcome was postoperative visual analog scale (VAS) pain scores for 10 days. Secondary outcomes included patient-reported outcomes, complications, and satisfaction. The observers were blinded, and the patients were not blinded to the intervention. RESULTS: A total of 9 patients did not meet inclusion criteria, and 19 patients declined participation. Thus, 62 patients were analyzed, with 28 patients randomized to the opioid group and 34 to the multimodal nonopioid group. Patients receiving the multimodal nonopioid pain regimen demonstrated significantly lower VAS scores compared with patients who received opioid pain medication (P < .05). Patients were administered the Patient-Reported Outcomes Measurement and Information System Pain Interference Short Form, and no significant difference was found in patients' preoperative scores (opioid group, 58.6 ± 7.9; multimodal nonopioid group, 57.5 ± 7.4; P = .385) and 1-week postoperative scores (opioid group, 66.3 ± 8.2; multimodal nonopioid group, 61.4 ± 8.8; P = .147). When we adjusted for possible confounders (age, sex, body mass index, graft type), no significant differences in pain control were found between the 2 groups. The most common adverse effects for both groups were drowsiness and constipation, with no difference between the groups. All patients in the multimodal nonopioid group reported satisfactory pain management. CONCLUSIONS: A multimodal nonopioid pain protocol provided at least equivalent pain control compared with traditional opioid analgesics in patients undergoing ACLR. Minimal side effects, which did not differ between groups, were noted, and all patients reported satisfaction with their pain management. Orthopedics/Bone and Joint Center Saini G, Lawrence RL, Staker JL, Braman JP, and Ludewig PM. Supraspinatus-to-Glenoid Contact Occurs During Standardized Overhead Reaching Motion. Orthop J Sports Med 2021; 9(10). PMID: 34646898. Full Text Division of Rehabilitation Science, Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, Minnesota, USA. Department of Orthopaedic Surgery, Henry Ford Health System, Detroit, Michigan, USA. Division of Physical Therapy, Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, Minnesota, USA. Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota, USA. BACKGROUND: Rotator cuff tears may result from repeated mechanical deformation of the cuff tendons, and internal impingement of the supraspinatus tendon against the glenoid is one such proposed mechanism of deformation. PURPOSE: To (1) describe the changing proximity of the supraspinatus tendon to the glenoid during a simulated overhead reaching task and (2) determine the relationship between scapular morphology and this proximity. Additionally, the patterns of supraspinatus-to-glenoid proximity were compared with previously described patterns of supraspinatus-to-coracoacromial arch proximity. STUDY DESIGN: Descriptive laboratory study. METHODS: Shoulder models were created from magnetic resonance images of 20 participants. Standardized kinematics were imposed on the models to simulate functional reaching, and the minimum distances between the supraspinatus tendon and the glenoid and the supraspinatus footprint and the glenoid were calculated every 5° between 0° and 150° of humerothoracic elevation. The angle at which contact between the supraspinatus and the glenoid occurred was documented. Additionally, the relationship between glenoid morphology (version and inclination) and the contact angle was evaluated. Descriptive statistics were calculated for the minimum distances, and glenoid morphology was assessed using Pearson correlation coefficients and simple linear regressions. RESULTS: The minimum distances between the tendon and the glenoid and between the footprint and the glenoid decreased as elevation increased. Contact between the tendon and the glenoid occurred in all participant models at a mean elevation of 123° ± 10°. Contact between the footprint and the glenoid occurred in 13 of 20 models at a mean of 139° ± 10°. Less glenoid retroversion was associated with lower tendon-to-glenoid contact angles (r = -0.76; R (2) = 0.58; P < .01). CONCLUSION: This study found that the supraspinatus tendon progressively approximated the glenoid during simulated overhead reaching. Additionally, all participant models eventually made contact with the glenoid by 150° of humerothoracic elevation, although anatomic factors influenced the precise angle at which contact occurred. CLINICAL RELEVANCE: Contact between the supraspinatus and the glenoid may occur

frequently within the range of elevation required for overhead activities. Therefore, internal impingement may be a prevalent mechanism for rotator cuff deformation that could contribute to cuff pathology. Orthopedics/Bone and Joint Center Sims BM, Patel AD, Garnica BG, Faraj MT, Tang A, Parsons T, Hoegler JJ, and Day CS. Effect of elective surgery cancellations during the COVID-19 pandemic on patients' activity, anxiety and pain. Br J Surg 2021; Epub ahead of print. PMID: 34611698. Full Text Wayne State University School of Medicine, Detroit, Michigan, USA. Oakland University William Beaumont School of Medicine, Rochester, Michigan, USA. Department of Orthopedic Surgery, Henry Ford Health System, Detroit, Michigan, USA. Patient's perspectives and changes in symptoms after cancellation of their elective procedures due to the COVID-19 pandemic were analysed. Most patients experienced no change in symptoms, but women and black patients experienced adverse impacts at higher rates than other groups. Orthopedics/Bone and Joint Center Tramer JS, Evans H, Ziedas AC, Swantek AJ, Jordan SE, and Makhni EC. Quadriceps Tendon Repair Using Double-Row Suture Anchor Fixation. Arthroscopy Techniques 2021; 10(10):e2337-e2342. PMID: Not assigned. Full Text E.C. Makhni, Department of Orthopaedic Surgery, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI, United States Quadriceps tendon ruptures compromise the knee extensor mechanism and cause an inability to ambulate and significant functional limitations. Therefore, the vast majority of quadriceps tendon ruptures are indicated for operative intervention to restore patient mobility and function. Although these injuries were traditionally repaired using a transosseous repair technique, recent literature has shown that suture anchor repair may offer biomechanical advantages. Additionally, research in other areas of orthopaedics has found that a double-row suture anchor construct can offer additional biomechanical strength to tendinous repair. This technical note describes a safe and effective quadriceps tendon repair using a double-row suture anchor construct. Orthopedics/Bone and Joint Center Ziedas A, Abed V, Bench C, Rahman T, and Makhni MC. PROMIS Physical Function Instruments Compare Favorably to Legacy Patient Reported Outcome Measures in Spine Patients: A Systematic Review of the Literature. Spine J 2021; Epub ahead of print. PMID: 34699997. Full Text Henry Ford Health System. Electronic address: aziedas2@hfhs.org. Henry Ford Health System. Electronic address: vabed1@hfhs.org. Henry Ford Health System. Electronic address: carter.bench@med.wayne.edu. Henry Ford Health System. Electronic address: trahman1@hfhs.org. Henry Ford Health System. Electronic address: mmakhni@bwh.harvard.edu. BACKGROUND CONTEXT: Preliminary evidence has suggested favorable correlation between National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) assessments and traditional ("legacy") patient reported outcome measures (PROMs) in spine surgery. There has been a significant increase in PROMIS research with regards to spinal conditions. PURPOSE: The purpose of this systematic review is to provide an assessment of PROMIS Physical Function (PF) measures in this patient population. STUDY DESIGN/SETTING: Systematic review METHODS: A systematic search of the PubMed/MEDLINE and Embase databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify published articles that referenced the various PROMIS PF measures. Two authors independently reviewed selected studies. The search returned 1,060 studies, 124 of which were selected for independent review by two authors. Of these, 37 were selected for inclusion. Mixed linear models were performed to assess for differences between legacy PROMs and PROMIS measures. RESULTS: The

combined sample size of all included studies yielded 10,296 total patients. Overall, PROMIS Physical Function (PF) measures demonstrated strong correlations with legacy PROMs when evaluating spine patients (weighted Pearson correlation, 0.589, standard error [SE] = 0.023; weighted Spearman correlation, 0.702, SE = 0.028). PROMIS questionnaires had significantly fewer questions than did legacy PROMs (4.2 ± 0.30 vs 9.53 ± 0.82, P = 0.015). In spine studies, the PROMIS PF forms were completed in significantly less time than legacy PROMs (48.1 ± 2.9 vs 174.7 ± 12.6 seconds, P < 0.001). The differences for the reliability measures and the floor and ceiling effects were not significant. CONCLUSIONS: PROMIS PF forms compare favorably with legacy PROMs with regard to correlations, ease of use, and quality criteria in the field of spine surgery. PROMIS PF scores correlate strongly with commonly used legacy PROMs, particularly in spine patients. PROMIS PF forms can be administered efficiently and to a broad patient population while remaining highly reliable. Otolaryngology – Head and Neck Surgery Alamoudi U, and Ghanem T. Solution to vessels mismatch in microsurgery: Vertical arteriotomy technique. Laryngoscope Investigative Otolaryngology. Epub ahead of print. PMID: Not assigned. Full

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[Alamoudi, Uthman] Univ Hail, Dept Otolaryngol Head & Neck Surg, Hail, Saudi Arabia. [Alamoudi, Uthman; Ghanem, Tamer] Henry Ford Hlth Syst, Dept Otolaryngol Head & Neck Surg, 2799 W Grand Blvd, Detroit, MI 48375 USA. Alamoudi, U (corresponding author), Henry Ford Hlth Syst, Dept Otolaryngol Head & Neck Surg, 2799 W Grand Blvd, Detroit, MI 48375 USA. uaua3sa@hotmail.com Background Microvascular anastomosis is the key for successful free flap transplantation. Ideally, the anastomosis should maintain the flow with minimal turbulence, disruption of endothelium, and minimizing the furrow to prevent thrombosis and failure of the flap. One of the main pitfalls of micro-anastomosis is vessels size mismatch. Method and Result There are many ways to overcome this issue, which includes forced mechanical dilation of the smaller vessel, oblique cuts, fish mouth cuts, interposition grafts, end-to-side anastomosis, coupling device, and others. Here, we report a simple technique with single customizable longitudinal arteriotomy of the smaller vessel to achieve an adequate size match to the larger vessel. It has been used for more than 10 years at our institution that allow us to achieve an end-to-end patent anastomosis. Conclusion Vertical arteriotomy is a simple technique that in our experience achieved end-to-end anastomosis high patency rate. Otolaryngology – Head and Neck Surgery Law RH, Larrabee KA, Van Harn M, and Singer MC. Parathyroid Gland Autofluorescence Characteristics in Patients With Primary Hyperparathyroidism. Laryngoscope 2021; Epub ahead of print. PMID: 34612528. Full Text Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, Michigan, U.S.A. Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, U.S.A. OBJECTIVE: Near-infrared imaging for intraoperative parathyroid gland (PG) detection has recently commanded significant attention. The PTeye (Medtronic, Minneapolis, MN) is a probe-based system for near-infrared autofluorescent evaluation of PGs. This study was designed to evaluate the capabilities of the PTeye in the setting of surgery for primary hyperparathyroidism. STUDY DESIGN: Prospective, Cohort study. METHODS: This single-institution, prospective cohort study included all patients undergoing parathyroidectomy for primary hyperparathyroidism with presumed single gland disease from June 2020 to December 2020. Absolute intensity and intensity ratios, with the thyroid as the control tissue, were obtained for the adenoma, ipsilateral normal PG, and adjacent tissue. The ability of the PTeye to function when not in direct contact with tissue was measured. RESULTS: Twenty-two patients were included. The median intensity ratio for the in situ adenomas was 4.38 (interquartile range [IQR]: 2.03-5.87), ipsilateral normal PGs 6.17 (IQR: 3.83-7.67), strap muscle 0.47 (IQR: 0.30-0.60), and fat 0.20 (IQR: 0.17-0.47). All normal PGs and 21/22 adenomas demonstrated autofluorescence above the detection threshold. The PTeye functioned at a maximum distance of separation of 10 mm through saline

medium and 6 mm through clear solid medium. CONCLUSION: This study confirms the PTeye's ability to recognize PGs with a high degree of precision. The device was found to function properly even with the probe not in direct contact with the tissue. Although adenomatous PGs appear to demonstrate altered autofluorescent properties from normal PGs, additional research is required to determine if these differences are clinically useful. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021. Otolaryngology – Head and Neck Surgery Rubin SJ, Sayre KS, Kovatch KJ, Ali SA, and Hanks JE. Segmental mandibular reconstruction in patients with poor lower extremity perfusion, vessel-depleted necks and/or profound medical frailty. Curr Opin Otolaryngol Head Neck Surg 2021; 29(5):407-418. PMID: 34387289. Full Text Department of Otolaryngology-Head and Neck Surgery, Boston University School of Medicine. Department of Oral and Maxillofacial Surgery, Boston University School of Dentistry. Department of Otolaryngology-Head and Neck Surgery, Geisinger Medical Center. Department of Otolaryngology-Head and Neck Surgery, Henry Ford Health System. Department of Otolaryngology-Head and Neck Surgery, VA Boston Medical Center, MA, USA. PURPOSE OF REVIEW: Options for segmental mandibular reconstruction in patients poorly suited to undergo fibula free flap (FFF). RECENT FINDINGS: Although FFF is the current 'gold standard' for segmental mandibular reconstruction, other reconstructive options must be considered when FFF is contraindicated or disfavoured and/or patient frailty precludes a lengthy anaesthetic. In addition to various nonvascularized and soft tissue only reconstructions, excellent osseous free flap alternatives for functional segmental mandibular reconstruction may be employed. The subscapular system free flaps (SSSFF) may be ideal in frail and/or elderly patients, as SSSFF allows for early mobility and does not alter gait. In extensive and/or symphyseal defects, functional mandibular reconstruction in lieu of a free flap is extremely limited. Pedicled segmental mandibular reconstructions remain reasonable options, but limited contemporary literature highlights unpredictable bone graft perfusion and poor long-term functional outcomes. SUMMARY: There are several excellent free flap alternatives to FFF in segmental mandibular reconstruction, assuming adequate cervical recipient vessels are present. On the basis of the current literature, the optimal mandibular reconstruction for the medically frail, elderly and/or patients with extreme vessel-depleted necks is limited and debatable. In qualifying (i.e. limited, lateral) defects, soft tissue only reconstructions should be strongly considered when osseous free flaps are unavailable. Pathology and Laboratory Medicine Alkhateeb KJ, Crane JE, Sak M, Jorgensen CJ, O'Donnell JP, Zumbar CT, Wozniak JA, Salazar CR, Parwani AV, and Lehman NL. Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms. Diagn Pathol 2021; 16(1):98. PMID: 34706741. Full Text Department of Pathology and Laboratory Medicine, The University of Louisville, Louisville, KY, 40202, USA. Department of Pathology and Laboratory Medicine, Henry Ford Hospital Detroit, Detroit, MI, 48202, USA. Department of Biochemistry and Molecular Genetics, The University of Louisville, Louisville, KY, 40202, USA. Department of Pathology, Ohio State University, Columbus, OH, 43210, USA. Department of Pathology and Laboratory Medicine, The University of Louisville, Louisville, KY, 40202, USA. Nllehman1@gmail.com. Department of Biochemistry and Molecular Genetics, The University of Louisville, Louisville, KY, 40202, USA. Nllehman1@gmail.com. Department of Pathology, Wayne State University, Detroit, MI, 48201, USA. Nllehman1@gmail.com. The Brown Cancer Center, The University of Louisville, Louisville, KY, 40202, USA. Nllehman1@gmail.com. BACKGROUND: Aurora-A kinase is important for cellular proliferation and is implicated in the tumorigenesis of several malignancies, including of the ovary. Information regarding the expression patterns of Aurora-A in normal Müllerian epithelium as well as benign, borderline and malignant epithelial

ovarian neoplasms is limited. METHODS: We investigated Aurora-A expression by immunohistochemistry in 15 benign, 19 borderline and 17 malignant ovarian serous tumors, and 16 benign, 8 borderline, and 2 malignant ovarian mucinous tumors. Twelve fimbriae from seven patients served as normal Müllerian epithelium controls. We also examined Aurora-A protein expression by western blot in normal fimbriae and tumor specimens. RESULTS: All normal fimbriae (n = 12) showed nuclear but not cytoplasmic Aurora-A immunoreactivity by immunohistochemistry. Benign ovarian tumors also showed strong nuclear Aurora-A immunoreactivity. Forty-eight percent (13/27) of borderline tumors demonstrated nuclear Aurora-A immunoreactivity, while the remainder (52%, 14/27) lacked Aurora-A staining. Nuclear Aurora-A immunoreactivity was absent in all malignant serous tumors, however, 47% (8/17) demonstrated perinuclear cytoplasmic staining. These results were statistically significant when tumor class (benign/borderline/malignant) was compared to immunoreactivity localization or intensity (Fisher Exact Test, p < 0.01). Western blot analysis confirmed the greater nuclear Aurora-A expression in control Müllerian epithelium compared to borderline and malignant tumors. CONCLUSION: Aurora-A kinase is differentially expressed across normal Müllerian epithelium, benign and borderline serous and mucinous ovarian epithelial neoplasms and malignant serous ovarian tumors., with nuclear expression of unphosphorylated Aurora-A being present in normal and benign neoplastic epithelium, and lost in malignant serous neoplasms. Further studies of the possible biological and clinical implications of the loss of nuclear Aurora-A expression in ovarian tumors, and its role in ovarian carcinogenesis are warranted. Pathology and Laboratory Medicine Aryal SC, Zia S, Rodgers S, Shen Y, Perry K, and Yuan L. BRD3-NUTM1-expressing NUT carcinoma of lung on endobronchial ultrasound-guided transbronchial needle aspiration cytology, a diagnostic pitfall. Diagn Cytopathol 2021; Epub ahead of print. PMID: 34672128. Full Text Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA. BACKGROUND: Nuclear protein in testis (NUT) carcinoma (NC) is an aggressive type of poorly differentiated carcinoma with a variable degree of squamous differentiation. NC is defined by the presence of BRD-NUT fusion oncogenes, the most common fusion form being the BRD4-NUTM1 gene. Variant rearrangements involving the BRD3 and NSD3 genes. Variant rearrangements involving the BRD3 and NSD3 genes occur in approximately one-third of the cases. AIMS: This is the first case regarding the study of cytological features of NC of the lung with BRD3-NUTM1 fusion. MATERIALS AND METHODS: A 36-year-old female with chest heaviness and shortness of breath was found to have a right-sided pleural effusion; she was non-smoker and denied any significant past medical illness. CT-chest revealed an 8.5 cm heterogeneous mass in the right and mid-upper lung. She underwent endobronchial ultrasound-guided (EBUS) transbronchial fine-needle aspiration (FNA) of the lung mass. Thoracocentesis was performed, and pleural fluid was sent to the laboratory for cytological evaluation Results: The cytopathological findings showed atypical squamoid cells with variably prominent single or multiple nucleoli. Monotonous-looking cells with high nuclear to cytoplasmic ratio and hyperchromasia were also present. The atypical squamoid cells showed abundant clear to eosinophilic cytoplasm with rare individual cell keratinization and focal keratin pearl formation. The atypical cells were positive for CK7, p40, p63, mCEA and equivocal for NUT-specific antibody. The cytopathological findings were consistent with squamous cell carcinoma with focal keratinization. The Fusion Panel-Solid Tumor (50 genes) revealed BRD3-NUTM1 fusion gene. Diagnosis was amended to pulmonary NC. DISCUSSION: NC is a diagnostic challenge for pathologists as it can morphologically mimic undifferentiated carcinoma, squamous cell carcinoma, or neuroendocrine carcinoma. The challenge is not how to diagnose NC but rather determining when to include it in the differential diagnosis and perform the diagnostic molecular tests (FISH or NGS) or IHC study for NUT-specific antibody. CONCLUSION: When a specimen demonstrates a dual cell population of squamoid cells and primitive-looking tumor cells in the wrong clinical context (i.e., young patient with no smoking history), further molecular profiling is warranted to include the differential of a primary NC of the lung. The cytological features of NC itself have rarely been documented and moreover, that of a primary NC of the lung with BRD3-NUTM1 fusion has never been reported. We herein report cytological findings of a primary NC of the lung with BRD3-NUTM1 fusion gene.

Pathology and Laboratory Medicine Rohan TE, Ginsberg M, Wang Y, Couch FJ, Feigelson HS, Greenlee RT, Honda S, Stark A, Chitale D, Wang T, Xue X, Oktay MH, Sparano JA, and Loudig O. Molecular markers of risk of subsequent invasive breast cancer in women with ductal carcinoma in situ: protocol for a population-based cohort study. BMJ Open 2021; 11(10). PMID: 34702732. Full Text Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA thomas.rohan@einsteinmed.org. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Providence, Rhode Island, USA. Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA. Institute for Health Research, Kaiser Permanente, Aurora, Colorado, USA. Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Institute, Marshfield, Wisconsin, USA. Center for Integrated Healthcare, Kaiser Permanente, Hawaii Permanente Medical Group, Honolulu, Hawaii, USA. Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA. Breast Oncology Program and Department of Pathology, Henry Ford Health System, Detroit, Michigan, USA. Department of Pathology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA. Department of Oncology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA. INTRODUCTION: Ductal carcinoma in situ (DCIS) of the breast is a non-obligate precursor of invasive breast cancer (IBC). Many DCIS patients are either undertreated or overtreated. The overarching goal of the study described here is to facilitate detection of patients with DCIS at risk of IBC development. Here, we propose to use risk factor data and formalin-fixed paraffin-embedded (FFPE) DCIS tissue from a large, ethnically diverse, population-based cohort of 8175 women with a first diagnosis of DCIS and followed for subsequent IBC to: identify/validate miRNA expression changes in DCIS tissue associated with risk of subsequent IBC; evaluate ipsilateral IBC risk in association with two previously identified marker sets (triple immunopositivity for p16, COX-2, Ki67; Oncotype DX Breast DCIS score); examine the association of risk factor data with IBC risk. METHODS AND ANALYSIS: We are conducting a series of case-control studies nested within the cohort. Cases are women with DCIS who developed subsequent IBC; controls (2/case) are matched to cases on calendar year of and age at DCIS diagnosis. We project 485 cases/970 controls in the aim focused on risk factors. We estimate obtaining FFPE tissue for 320 cases/640 controls for the aim focused on miRNAs; of these, 173 cases/346 controls will be included in the aim focused on p16, COX-2 and Ki67 immunopositivity, and of the latter, 156 case-control pairs will be included in the aim focused on the Oncotype DX Breast DCIS score®. Multivariate conditional logistic regression will be used for statistical analyses. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Boards of Albert Einstein College of Medicine (IRB 2014-3611), Kaiser Permanente Colorado, Kaiser Permanente Hawaii, Henry Ford Health System, Mayo Clinic, Marshfield Clinic Research Institute and Hackensack Meridian Health, and from Lifespan Research Protection Office. The study results will be presented at meetings and published in peer-reviewed journals.

Pharmacy Beavers CJ, DiDomenico RJ, Dunn SP, Cox J, To L, Weeks P, Trujillo TC, and Jennings DL. Optimizing Anticoagulation for Patients Receiving Impella Support. Pharmacotherapy 2021; Epub ahead of print. PMID: 34597429. Full Text University of Kentucky College of Pharmacy, Lexington, Kentucky. University of Illinois Chicago College of Pharmacy, Department of Pharmacy Practice, Chicago, Illinois. University of Virginia Heart and Vascular Center, Department of Pharmacy, Charlottesville, Virginia. Prisma Health Richland Hospital, Department of Pharmacy, Columbia, South Carolina. Henry Ford Health System, Department of Pharmacy, Detroit, Michigan. Memorial Hermann Health system, Department of Pharmacy, Houston, Texas. University of Colorado, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Hospital, Denver, Colorado. Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Department of Pharmacy Practice, New York, New York. Department of Pharmacy, New York-Presbyterian Hospital Columbia University Medical Center, New York, New York. Anticoagulation of patients treated with the Impella percutaneous mechanical circulatory support (MCS) devices is complex and lacks consistency across centers, potentially increasing the risk of complications. In order to optimize safety and efficacy, an expert committee synthesized all available evidence evaluating anticoagulation for patients receiving Impella support in order to provide consensus recommendations for the management of anticoagulation with these devices. The evidence synthesis led to the creation of 42 recommendations to improve anticoagulation management related to the use of the Impella devices. Recommendations address purge solution management, intravenous anticoagulation, monitoring, evaluation and management of heparin-induced thrombocytopenia (HIT), and management during combination MCS support. The use of a heparinized, dextrose-containing purge solution is critical for optimal device function, and a bicarbonate-based purge solution may be an alternative in certain situations. Likewise, intravenous (i.e. systemic) anticoagulation with heparin is often necessary, although evidence supporting the optimal assay and target range for monitoring the level of anticoagulation is generally lacking. Patients treated with an Impella MCS device may develop HIT, which is more difficult to evaluate and treat in this setting. Lastly, the use of Impella with extracorporeal membrane oxygenation or for biventricular support creates additional anticoagulation challenges. Pharmacy Griebe KM, Hencken LN, Efta J, Patel N, Stine JJ, Bott B, El-Khoury C, and MacDonald NC. An electronic tool for health systems to assess and communicate discharge medication access. Am J Health Syst Pharm 2021; Epub ahead of print. PMID: 34636856. Full Text Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI, USA. Community Care Services, Ambulatory Pharmacy, Henry Ford Hospital, Detroit, MI, USA. Community Care Services, Ambulatory Pharmacy, Henry Ford Health System, Detroit, MI, USA. DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The purpose of this study was to describe how the discharge medication cost inquiry (DMCI) consult order and workflow were created and used to communicate transition of care needs and medication access barriers before discharge. SUMMARY: Health-system pharmacists collaborated with the information technology department to develop the DMCI consult order and workflow. This institutional review board-approved retrospective case study evaluated use of the DMCI consult order throughout the health system. Outcomes that could not be retrieved electronically were collected for every third patient encounter using manual chart review. The DMCI consult order was used at each hospital in the health system. Physicians placed the most DMCI consult orders; however, pharmacists at the large academic tertiary hospital utilized the DMCI consult order the most. The DMCI

consult order was sent most frequently for anticoagulants. Although most medications were covered by insurance, the tool and workflow identified barriers to medication access. Almost 90% of the patients with a DMCI consult order had at least one prescription generated on discharge. CONCLUSION: The DMCI consult order is a novel electronic tool to aid in communicating discharge medication needs. When incorporated into care transition planning, the DMCI consult order and workflow provide a model to ensure patients have access to medications. It can also be used to document and evaluate the role of pharmacy in transitions of care in the health system. Pharmacy Hachem SN, Thomson JM, Heigham MK, and MacDonald NC. Improving pediatric pharmacy services in a primarily adult emergency department. Am J Health Syst Pharm 2021; Epub ahead of print. PMID: 34597368. Full Text Department of Pharmacy Services, St. Joseph Mercy Oakland Hospital, Pontiac, MI, USA. Department of Pharmacy Services, Henry Ford Hospital, Detroit, MI, USA. Department of Pharmacy Services, St. Louis Children's Hospital, St. Louis, MO, USA. DISCLAIMER: In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The American Society of Health-System Pharmacists (ASHP) and Pediatric Pharmacy Advocacy Group (PPAG) guidelines for providing pediatric pharmacy services in hospitals and health systems can be used to improve medication safety wherever pediatric patients receive care, including in the emergency department (ED). The purpose of this initiative was to improve compliance with these guidelines in a primarily adult ED. METHODS: This quality improvement initiative was conducted in a level 1 trauma center ED between October 2019 and March 2020. The ASHP-PPAG guidelines were used to create practice elements applicable to the ED. An initial compliance assessment defined elements as noncompliant, partially compliant, fully compliant, or not applicable. Investigators identified interventions to improve compliance for noncompliant or partially compliant elements and then reassessed compliance following implementation. Data were expressed using descriptive statistics. This initiative was exempt from institutional review board approval. RESULTS: Ninety-three ED practice elements were identified within the 9 standards of the ASHP-PPAG guidelines. At the initial compliance assessment, the majority (59.8%) of practice elements were fully compliant; however, various service gaps were identified in 8 of the standards, and 16 interventions were implemented to improve compliance. At the final compliance assessment, there was a 19.5% increase in full compliance. Barriers to achieving full compliance included technology restrictions, time constraints, financial limitations, and influences external to pharmacy. CONCLUSION: This quality improvement initiative demonstrated that the ASHP-PPAG guidelines can be used to improve ED pediatric pharmacy services in a primarily adult institution. The initiative may serve as an example for other hospitals to improve compliance with the guidelines. Plastic Surgery Engel R, Greenberg Y, and Rozzelle A. Subglossopalatal Membrane With Associated Cleft Palate, Cardiovascular, and Neurologic Anomalies. J Craniofac Surg 2021; Epub ahead of print. PMID: 34643601. Full Text Wayne State University School of Medicine Division of Plastic Surgery, Henry Ford Hospital Department of Plastic Surgery, Children's Hospital of Michigan, Detroit, MI. Subglossopalatal membrane (or subglossopalatal synechia) is a rare clinical entity that can lead to respiratory distress and feeding difficulty due to oral obstruction. Here, the authors present a case of subglossopalatal membrane with associated cleft palate and cardiovascular and neurologic anomalies that was treated with surgical excision and lip-tongue adhesion. Etiology of these membranes is believed to be intrauterine fetal insult. Membranes should be treated with excision, whereas taking care to ensure

patency of the airway. Presence of a subglossopalatal membrane should prompt thorough examination for additional congenital anomalies. Public Health Sciences Arena SK, Wilson CM, Boright L, and Peterson E. Impact of the HOP-UP-PT program on older adults at risk to fall: a randomized controlled trial. BMC Geriatr 2021; 21(1):520. PMID: 34598692. Full Text Physical Therapy Program, Oakland University, School of Health Sciences, Human Health Bldg, 433 Meadowbrook Road, Rochester, MI, 48309-4401, USA. arena@oakland.edu. Physical Therapy Program, Oakland University, School of Health Sciences, Human Health Bldg, 433 Meadowbrook Road, Rochester, MI, 48309-4401, USA. Henry Ford Health System, Department of Public Health Sciences, Detroit, MI, USA. BACKGROUND: Reduced falls and fall risks have been observed among older adults referred to the HOP-UP-PT (Home-based Older Persons Upstreaming Prevention-Physical Therapy) program. The purpose of this study was to describe outcomes of HOP-UP-PT program participants and then to compare these outcomes to non-participants. METHODS: Six Michigan senior centers referred adults ≥65 years who were at-risk for functional decline or falls. 144 participants (n = 72 per group) were randomized to either the experimental group (EG) or the control group (CG). Physical therapists (PTs) delivered physical, environmental, and health interventions to the EG over nine encounters (six in-person, three telerehabilitation) spanning seven months. The CG participants were told to continue their usual physical activity routines during the same time frame. Baseline and re-assessments were conducted at 0-, 3-, and 7-months in both groups. Descriptions and comparisons from each assessment encounter were analyzed. RESULTS: Participants ages were: EG = 76.6 (7.0) years and CG = 77.2 (8.2). Baseline measures were not significantly different apart from the Short Physical Performance Battery (SPPB) which favored the EG (P = 0.02). While no significant differences were identified in the survey outcomes or home environment assessments, significant differences in favor of the EG were identified in common fall risk indicators including the Timed Up and Go (P = 0.04), Four Test Balance Scale (P = 0.01), and the modified SPPB (P = 0.02) at the 3-month assessment visit. However, these differences were not sustained at the 7-month assessment as, notably, both groups demonstrated positive improvements in the Four Test Balance Score and SPPB. For individuals at a moderate/high fall risk at baseline, 47.8% of CG reported falling at seven months; whereas, only 6.3% of EG participants meeting the same criteria reported a fall after HOP-UP-PT participation. CONCLUSIONS: A prevention-focused multimodal program provided by PTs in older adults' homes proved beneficial and those with the highest fall risk demonstrated a significant decrease in falls. A collaboration between PTs and community senior centers resulted in upstreaming care delivery that may reduce both the financial and personal burdens associated with falls in an older adult population. TRIAL REGISTRATION: This study was retrospective registered at Clinical Trials.gov , TRN: NCT04814459 on 24/03/2021. Public Health Sciences Fonseca W, Malinczak CA, Fujimura K, Li D, McCauley K, Li J, Best SKK, Zhu D, Rasky AJ, Johnson CC, Bermick J, Zoratti EM, Ownby D, Lynch SV, Lukacs NW, and Ptaschinski C. Maternal gut microbiome regulates immunity to RSV infection in offspring. J Exp Med 2021; 218(11). PMID: 34613328. Request Article Department of Pathology, University of Michigan, Ann Arbor, MI. Department of Medicine-Gastroenterology, University of California, San Francisco, San Francisco, CA. Department of Public Health Sciences, Henry Ford Health System, Detroit, MI. Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan, Ann Arbor, MI. Division of Allergy and Clinical Immunology, Department of Medicine, Henry Ford Health System, Detroit, MI. Department of Pediatrics, Augusta University, Augusta, GA. Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI. Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with

persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates. Public Health Sciences Law RH, Larrabee KA, Van Harn M, and Singer MC. Parathyroid Gland Autofluorescence Characteristics in Patients With Primary Hyperparathyroidism. Laryngoscope 2021; Epub ahead of print. PMID: 34612528. Full Text Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, Detroit, Michigan, U.S.A. Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, U.S.A. OBJECTIVE: Near-infrared imaging for intraoperative parathyroid gland (PG) detection has recently commanded significant attention. The PTeye (Medtronic, Minneapolis, MN) is a probe-based system for near-infrared autofluorescent evaluation of PGs. This study was designed to evaluate the capabilities of the PTeye in the setting of surgery for primary hyperparathyroidism. STUDY DESIGN: Prospective, Cohort study. METHODS: This single-institution, prospective cohort study included all patients undergoing parathyroidectomy for primary hyperparathyroidism with presumed single gland disease from June 2020 to December 2020. Absolute intensity and intensity ratios, with the thyroid as the control tissue, were obtained for the adenoma, ipsilateral normal PG, and adjacent tissue. The ability of the PTeye to function when not in direct contact with tissue was measured. RESULTS: Twenty-two patients were included. The median intensity ratio for the in situ adenomas was 4.38 (interquartile range [IQR]: 2.03-5.87), ipsilateral normal PGs 6.17 (IQR: 3.83-7.67), strap muscle 0.47 (IQR: 0.30-0.60), and fat 0.20 (IQR: 0.17-0.47). All normal PGs and 21/22 adenomas demonstrated autofluorescence above the detection threshold. The PTeye functioned at a maximum distance of separation of 10 mm through saline medium and 6 mm through clear solid medium. CONCLUSION: This study confirms the PTeye's ability to recognize PGs with a high degree of precision. The device was found to function properly even with the probe not in direct contact with the tissue. Although adenomatous PGs appear to demonstrate altered autofluorescent properties from normal PGs, additional research is required to determine if these differences are clinically useful. LEVEL OF EVIDENCE: 3 Laryngoscope, 2021. Public Health Sciences Prescott SL, Wegienka G, Kort R, Nelson DH, Gabrysch S, Hancock T, Kozyrskyj A, Lowry CA, Redvers N, Poland B, Robinson J, Moubarac JC, Warber S, Jansson J, Sinkkonen A, Penders J, Erdman S, Nanan R, van den Bosch M, Schneider K, Schroeck NJ, Sobko T, Harvie J, Kaplan GA, Moodie R, Lengnick L, Prilleltensky I, Celidwen Y, Berman SH, Logan AC, and Berman B. Project Earthrise: Proceedings of the Ninth Annual Conference of inVIVO Planetary Health. Int J Environ Res Public Health 2021; 18(20). PMID: 34682400. Full Text NOVA Institute for Health of People, Places and Planet, 1407 Fleet Street, Baltimore, MD 21231, USA. School of Medicine, University of Western Australia, Nedlands, WA 6009, Australia. ORIGINS Project, Telethon Kids Institute at Perth Children's Hospital, Nedlands, WA 6009, Australia. Department of Family and Community Medicine, Center for Integrative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI 48202, USA. Department of Molecular Cell Biology, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands. ARTIS_Micropia, Plantage Kerklaan 38-40, 1018 CZ Amsterdam, The Netherlands.

Independent Researcher, Woodstock, ON N4S 6Y9, Canada. Heidelberg Institute of Global Health, Heidelberg University, 69120 Heidelberg, Germany. Potsdam Institute for Climate Impact Research (PIK), Member of the Leibniz Association, 14412 Potsdam, Germany. Institute of Public Health, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany. School of Public Health and Social Policy, University of Victoria, Victoria, BC V8W 2Y2, Canada. Department of Pediatrics, Faculty of Medicine & Dentistry, Alberta, Edmonton Clinic Health Academy, Edmonton, AB T6G 1C9, Canada. Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA. School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202, USA. Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada. Department of Landscape, The University of Sheffield, Sheffield S10 2TN, UK. Department of Nutrition, Faculty of Medicine, University of Montréal, Montreal, QC H3T 1J4, Canada. Department of Family Medicine, University of Michigan, Ann Arbor, MI 48109, USA. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, DC 99352, USA. Natural Resources Institute Finland, Itäinen Pitkäkatu 4, 20520 Turku, Finland. Department of Medical Microbiology, School for Nutrition & Translational Research in Metabolism (NUTRIM) and Care and Public Health Research Institute (CAPHRI), Maastricht UMC+ [University Medical Centre], 6202 AZ Maastricht, The Netherlands. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Sydney Medical School-Nepean, University of Sydney, Camperdown, NSW 2006, Australia. School of Population and Public Health, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Existential-Humanistic Institute, San Francisco, CA 94901, USA. Department of Humanistic and Clinical Psychology, Saybrook University, Pasadena, CA 91103, USA. Teachers College, Columbia University, New York, NY 10027, USA. School of Law, University of Detroit Mercy, 651 East Jefferson Ave., Detroit, MI 48226, USA. School of Biological Sciences, University of Hong Kong, Hong Kong, China. Institute for a Sustainable Future, Duluth, MN 55802, USA. School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA. School of Population and Global Health (MSPGH), University of Melbourne, Parkville, VIC 3010, Australia. Cultivating Resilience, LLC, Asheville, NC 28805, USA. School of Education and Human Development, University of Miami, Coral Gables, FL 33124, USA. Independent Researcher, New York, NY 10017, USA. The "Earthrise" photograph, taken on the 1968 Apollo 8 mission, became one of the most significant images of the 20th Century. It triggered a profound shift in environmental awareness and the potential for human unity-inspiring the first Earth Day in 1970. Taking inspiration from these events 50 years later, we initiated Project Earthrise at our 2020 annual conference of inVIVO Planetary Health. This builds on the emergent concept of planetary health, which provides a shared narrative to integrate rich and diverse approaches from all aspects of society towards shared solutions to global challenges. The acute catastrophe of the COVID-19 pandemic has drawn greater attention to many other interconnected global health, environmental, social, spiritual, and economic problems that have been underappreciated or neglected for decades. This is accelerating opportunities for greater collaborative action, as many groups now focus on the necessity of a "Great Transition". While ambitious integrative efforts have never been more important, it is imperative to apply these with mutualistic value systems as a compass, as we seek to make wiser choices. Project Earthrise is our contribution to this important process. This underscores the imperative for creative ecological solutions to challenges in all systems, on all scales with advancing global urbanization in the digital age-for personal, environmental, economic and societal health alike. At the same time, our agenda seeks to equally consider our social and spiritual ecology as it does natural ecology. Revisiting the inspiration of "Earthrise", we welcome diverse perspectives from across all dimensions of the arts and the sciences, to explore novel solutions and new normative values. Building on academic rigor, we seek to place greater value on imagination, kindness and mutualism as we address our greatest challenges, for the health of people, places and planet.

Public Health Sciences Rapp A, Fall G, Radomsky AC, and Santarossa S. Child Maltreatment During the COVID-19 Pandemic: A Systematic Rapid Review. Pediatr Clin North Am 2021; 68(5):991-1009. PMID: 34538308. Full Text Department of Public Health Sciences, Henry Ford Health System, 1 Ford Place, Detroit, MI 48202, USA. Electronic address: arapp2@hfhs.org. Department of Public Health Sciences, Henry Ford Health System, 1 Ford Place, Detroit, MI 48202, USA. Wayne State University, School of Medicine, 540 E Canfield Street, Detroit, MI 48210, USA. The present study is systematic rapid review on the nature of the relationship between the COVID-19 pandemic and child maltreatment. Database searches on December 28, 2020, identified 234 unique citations; 12 were ultimately included in our analysis. Included articles measured child maltreatment inclusive of physical, psychological, and sexual abuse, and child neglect during the COVID-19 pandemic. Compared with the prepandemic period, 5 articles found an increase in child maltreatment, 6 articles found a decrease, and 1 study found no difference. There existed variation in geography of study location, age of child maltreatment victims, and types of child maltreatment assessed. Public Health Sciences Richey BF, Obrock RS, Gee ZM, Lu DY, Jacobsen G, and Richards SC. Smoking, Rural Residence and Diabetes as Risk Factors for Presumed Ocular Histoplasmosis Syndrome. Retina 2021; Epub ahead of print. PMID: 34690340. Full Text Weber State University, Ogden, Utah The Retinal Institute, Fort Wayne, Indiana Des Moines University, Des Moines, Iowa Henry Ford Hospital Department of Ophthalmology, Detroit, Michigan Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan. PURPOSE: To investigate the relationship of smoking, urbanicity and diabetes to presumed ocular histoplasmosis syndrome (POHS) and associated choroidal neovascularization (CNV). METHODS: Medical records of 751 adult patients with POHS were reviewed, including 603 patients without CNV and 148 patients with CNV. Age- and gender-matched controls were randomly selected from the same practice for comparison. Statistical comparisons of smoking history, urbanicity, and diabetic history were performed using Chi-Square and conditional logistic regression analyses. RESULTS: Increased rates of current or former smoking, rural residence, and diabetes were found in patients with POHS compared with controls. POHS patients with CNV had increased rates of current or former smoking and rural residence as compared with controls. CONCLUSIONS: A history of current or past smoking is associated with an increased risk of developing both POHS alone and POHS with CNV. We did not find a significant additional risk of smoking on the development of CNV in patients with POHS. Patients living in rural locations are more likely than those in urban locations to develop both POHS and POHS with CNV. Diabetics may be more likely to develop POHS than non-diabetics. Public Health Sciences Ritzwoller DP, Meza R, Carroll NM, Blum-Barnett E, Burnett-Hartman AN, Greenlee RT, Honda SA, Neslund-Dudas C, Rendle KA, and Vachani A. Evaluation of Population-Level Changes Associated With the 2021 US Preventive Services Task Force Lung Cancer Screening Recommendations in Community-Based Health Care Systems. JAMA Netw Open 2021; 4(10). PMID: 34636916. Full Text Institute for Health Research, Kaiser Permanente Colorado, Aurora. Department of Epidemiology, University of Michigan, Ann Arbor. Marshfield Clinic Research Institute, Marshfield, Wisconsin. Center for Integrated Healthcare Research, Kaiser Permanente Hawaii, Oahu. Henry Ford Health System and Henry Ford Cancer Institute, Detroit, Michigan. Perelman School of Medicine, University of Pennsylvania, Philadelphia. IMPORTANCE: The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history

from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups. OBJECTIVE: To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded. EXPOSURES: Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history. MAIN OUTCOMES AND MEASURES: Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests. RESULTS: As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations. CONCLUSIONS AND RELEVANCE: This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer. Public Health Sciences Shipp GM, Weatherspoon LJ, Norman GS, Alexander GL, Kelleher D, and Kerver JM. Understanding Factors Influencing Breastfeeding Outcomes in a Sample of African American Women. Matern Child Health J 2021; Epub ahead of print. PMID: 34637064. Full Text Michigan State University, East Lansing, USA. shippgay@msu.edu. Michigan State University, East Lansing, USA. Wayne State University, Detroit, USA. Henry Ford Health System, Detroit, USA. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA. OBJECTIVES: Persistent disparities in breastfeeding rates among African American (AA) women compared to other population groups have motivated researchers to understand factors influencing breastfeeding choices using a variety of methods. Quantitative surveys are more commonly reported, however, qualitative work that amplifies voices of AA women is limited. METHODS: Participants were recruited from a randomized controlled feasibility trial focused on breastfeeding support for AA women in Detroit, MI. Thirteen women were enrolled in the qualitative portion of the study described here. Using the Socioecological model (SEM) as the theoretical foundation, semi-structured qualitative interviews were conducted to explore perceived facilitators and barriers to breastfeeding. Interviews were digitally recorded, transcribed, and analyzed using Theoretical thematic analysis. RESULTS: Women reported factors ranging from micro to macro SEM levels that discouraged or reinforced breastfeeding. Key challenges included breastfeeding-related discouragement issues, including factors that decreased

confidence and led women to terminate breastfeeding (e.g., problems with latching, pumping, lack of comfort with breastfeeding in public, and work constraints). Facilitators included perceived mother and infant benefits, perseverance/commitment/self-motivation, pumping ability, and social support. Participant suggestions for expanding breastfeeding promotion and support included: (1) tangible, immediate, and proactive support; (2) positive non-judgmental support; (3) "milk supply" and "use of pump" education; and (4) self-motivation/willpower/perseverance. CONCLUSIONS FOR PRACTICE: Despite the identification of common facilitators, findings reveal AA women face many obstacles to meeting breastfeeding recommendations. Collaborative discussions between women and healthcare providers focused on suggestions provided by AA women should be encouraged. Public Health Sciences Su WK, Coleman CM, Bossick AS, Lee-Griffith M, and Wegienka G. Racial Differences in Planned Hysterectomy Procedure Route. J Womens Health (Larchmt) 2021; Epub ahead of print. PMID: 34637634. Request Article Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA. Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA. Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan, USA. inVIVO Planetary Health, Worldwide Universities Network, West New York, New Jersey, USA. Background: Hysterectomies can be performed with a minimally invasive surgical (MIS) approach or a laparotomic (abdominal) approach. The objective of this study was to assess any racial differences in the likelihood of having a planned MIS hysterectomy. Materials and Methods: A prospective cohort study of women undergoing hysterectomy at Henry Ford Health System was conducted where laparotomic and MIS approaches are available to all patients. All procedures were performed between October, 2015, and August, 2017. For this study, women were asked to report demographic and insurance information and complete validated questionnaires from 2 weeks before hysterectomy and up to six additional times in the year after hysterectomy. Clinical and operative characteristics were collected from electronic health records. Logistic regression and multinomial logistic regression models were applied to assess the association between race and the surgical approach. Results: Analyses included 235 White women and 196 Black women. Black women were less likely to have any MIS planned for their hysterectomy (odds ratio [OR] = 0.46, 95% confidence interval [CI] 0.3-0.71, p < 0.05), a laparoscopic hysterectomy (relative risk ratio [RRR] = 0.46, 95% CI 0.29-0.73, p < 0.05), or a vaginal hysterectomy (RRR = 0.45, 95% CI 0.25-0.81, p = 0.01) compared with White women. After adjusting for confounders, uterine weight and indication for surgery was fibroids, these racial differences did not remain statistically significant (MIS vs. abdominal [adjusted odds ratio {aOR} = 0.93, 95% CI 0.55-1.57, p = 0.79], laparoscopic vs. abdominal [adjusted relative risk ratio {aRRR} = 0.89, 95% CI 0.52-1.51, p = 0.54], and vaginal vs. abdominal [aRRR = 1.22, 95% CI 0.61-2.45, p = 0.58]). The associations were not confounded by the baseline survey data from standardized questionnaires on depression, financial distress, and satisfaction with their decision. Conclusions: Black women were not less likely than White women to have planned an MIS hysterectomy after controlling for important confounding variables. These results emphasize the importance of considering all important confounders when examining racial differences. Public Health Sciences Zhang J, Buller BA, Zhang ZG, Zhang Y, Lu M, Rosene DL, Medalla M, Moore TL, and Chopp M. Exosomes derived from bone marrow mesenchymal stromal cells promote remyelination and reduce neuroinflammation in the demyelinating central nervous system. Exp Neurol 2021; 347:113895. PMID: 34653510. Full Text Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America. Electronic address: jingz@neuro.hfh.edu. Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America. Public Health Sciences, Henry Ford Health System, Detroit, Michigan, United States of America. Department of Anatomy and Neurobiology, Boston University, Boston, Massachusetts, United States of America; Center for Systems Neuroscience, Boston University, Boston, Massachusetts, United States of America.

Department of Neurology, Henry Ford Health System, Detroit, Michigan, United States of America; Department of Physics, Oakland University, Rochester, Michigan, United States of America. Injury of oligodendrocytes (OLs) induces demyelination, and patients with neurodegenerative diseases exhibit demyelination concomitantly with neurological deficit and cognitive impairment. Oligodendrocyte progenitor cells (OPCs) are present in the adult central nervous system (CNS), and they can proliferate, differentiate, and remyelinate axons after damage. However, remyelination therapies are not in clinical use. Multiple sclerosis (MS) is a major demyelinating disease in the CNS. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic promise in animal models and in clinical trials of MS. Exosomes are nanoparticles generated by nearly all cells and they mediate cell-cell communication by transferring cargo biomaterials. Here, we hypothesize that exosomes harvested from MSCs have a similar therapeutic effect on enhancement of remyelination as that of MSCs. In the present study we employed exosomes derived from rhesus monkey MSCs (MSC-Exo). Two mouse models of demyelination were employed: 1) experimental autoimmune encephalomyelitis (EAE), an animal model of MS; and 2) cuprizone (CPZ) diet model, a toxic demyelination model. MSC-Exo or PBS were intravenously injected twice a week for 4 weeks, starting on day 10 post immunization in EAE mice, or once a week for 2 weeks starting on the day of CPZ diet withdrawal. Neurological and cognitive function were tested, OPC differentiation and remyelination, neuroinflammation and the potential underlying mechanisms were investigated using immunofluorescent staining, transmission electron microscopy and Western blot. Data generated from the EAE model revealed that MSC-Exo cross the blood brain barrier (BBB) and target neural cells. Compared with the controls (p < 0.05), treatment with MSC-Exo: 1) significantly improved neurological outcome; 2) significantly increased the numbers of newly generated OLs (BrdU(+)/APC(+)) and mature OLs (APC(+)), and the level of myelin basic protein (MBP); 3) decreased amyloid-β precursor protein (APP)(+) density; 4) decreased neuroinflammation by increasing the M2 phenotype and decreasing the M1 phenotype of microglia, as well as their related cytokines; 5) inhibited the TLR2/IRAK1/NFκB pathway. Furthermore, we confirmed that the MSC-Exo treatment significantly improved cognitive function, promoted remyelination, increased polarization of M2 phenotype and blocked TLR2 signaling in the CPZ model. Collectively, MSC-Exo treatment promotes remyelination by both directly acting on OPCs and indirectly by acting on microglia in the demyelinating CNS. This study provides the cellular and molecular basis for this cell-free exosome therapy on remyelination and modulation of neuroinflammation in the CNS, with great potential for treatment of demyelinating and neurodegenerative disorders. Pulmonary and Critical Care Medicine Simoff MJ, Pritchett MA, Reisenauer JS, Ost DE, Majid A, Keyes C, Casal RF, Parikh MS, Diaz-Mendoza J, Fernandez-Bussy S, and Folch EE. Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System. BMC Pulm Med 2021; 21(1):322. PMID: 34656103. Full Text Bronchoscopy and Interventional Pulmonology, Lung Cancer Screening Program, Department of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University School of Medicine, 2799 West Grand Blvd, Detroit, MI, 48202, USA. MSimoff1@hfhs.org. Pulmonary Department, Pinehurst Medical Clinic, Pinehurst, NC, USA. Pulmonary Department, First Health Moore Regional Hospital, Pinehurst, NC, USA. Department of Pulmonary Medicine and Thoracic Surgery, Mayo Clinic, Rochester, MN, USA. Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Thoracic Surgery and Interventional Pulmonology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Department of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Bronchoscopy and Interventional Pulmonology, Lung Cancer Screening Program, Department of Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University School of Medicine, 2799 West Grand Blvd, Detroit, MI, 48202, USA. Department of Pulmonary Medicine, Mayo Clinic, Jacksonville, FL, USA.

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were < 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB's functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019. Radiation Oncology Hall WA, Dawson LA, Hong TS, Palta M, Herman JM, Evans DB, Tsai S, Ferrone CR, J BF, Chang DT, Crane C, Koong AC, Oar A, Parikh P, Erickson B, Hoffe S, and Goodman KA. Value of Neoadjuvant Radiation Therapy in the Management of Pancreatic Adenocarcinoma. J Clin Oncol 2021; Epub ahead of print. PMID: 34623894. Full Text Medical College of Wisconsin, Department of Radiation Oncology and the LaBahn Pancreatic Cancer Program, Milwaukee, WI. Medical College of Wisconsin, Department of Surgery and the LaBahn Pancreatic Cancer Program, Milwaukee, WI. Radiation Medicine Program, Princess Margaret Cancer Centre; Department of Radiation Oncology, University of Toronto, Toronto, Canada. Massachusetts General Hospital, Department of Radiation Oncology, Boston, MA. Duke University, Department of Radiation Oncology, Durham, NC. Northwell Health, Department of Radiation Oncology, New Hyde Park, NY. Massachusetts General Hospital, Department of Surgery, Boston, MA. Moffitt Cancer Center, Department of Surgery, Tampa, FL. Stanford Health Care, Department of Radiation Oncology, Stanford, CA. Memorial Sloan-Kettering Cancer Center, Department of Radiation Oncology, New York, NY. MD Anderson Cancer Center, Department of Radiation Oncology, Houston, TX. Gold Coast University Hospital, Gold Coast, Queensland, Australia. Henry Ford Health System, Department of Radiation Oncology, Detroit, MI. Mount Sinai Hospital, Department of Radiation Oncology, New York, NY. Radiation Oncology Jagsi R, Griffith KA, Moran JM, Matuszak MM, Marsh R, Grubb M, Abu-Isa E, Dilworth JT, Dominello MM, Heimburger D, Lack D, Walker EM, Hayman JA, Vicini F, and Pierce LJ. Comparative Effectiveness Analysis of 3D-Conformal Radiotherapy versus Intensity Modulated Radiotherapy (IMRT) in a Prospective Multicenter Cohort of Breast Cancer Patients. Int J Radiat Oncol Biol Phys 2021; Epub ahead of print. PMID: 34634437. Full Text University of Michigan, Ann Arbor, MI. Electronic address: rjagsi@med.umich.edu. University of Michigan, Ann Arbor, MI.

University of Michigan, Ann Arbor, MI; Providence Ascension, Novi, MI. Beaumont Health, Royal Oak, MI. Karmanos Cancer Center, Wayne State University, Detroit, MI. Munson Healthcare, Traverse City, MI. Henry Ford Health System, Detroit, MI. GenesisCare, Farmington Hills, MI. PURPOSE: Simple intensity modulation of radiation therapy reduces acute toxicity compared to two-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiotherapy (IMRT) offers an advantage over forward-planned, three-dimensional conformal radiotherapy (3DCRT). METHODS AND MATERIALS: Using prospective data regarding patients receiving adjuvant whole breast RT without nodal irradiation at 23 institutions from 2011-2018, we compared incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting (IPTW), adjusting for treatment facility as a random effect. RESULTS: Of 1,185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly-segmented forward-planned IMRT, 458 (59.2%) did; of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1,296 patients treated with hypofractionation and 3DCRT 432 (33.3%) experienced acute toxicity; of 709 treated with highly-segmented forward-planned IMRT, 227 (32.0%) did; of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with IPTW, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% CI, 0.45-0.91) with conventional fractionation and 0.41 (95% CI, 0.26-0.65) with hypofractionation. CONCLUSIONS: This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared to 3DCRT in reducing acute toxicity of breast radiotherapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness. Radiation Oncology Jagsi R, Griffith KA, Vicini FA, Abu-Isa E, Bergsma D, Bhatt A, Dilworth JT, Dominello M, Franklin S, Heimburger DK, Kaufman I, Kocheril PG, Kretzler AE, Paximadis P, Radawski JD, Walker EM, and Pierce L. Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort. Int J Radiat Oncol Biol Phys 2021; Epub ahead of print. PMID: 34718094. Full Text University of Michigan. Electronic address: rjagsi@med.umich.edu. University of Michigan. 21st Century Oncology, Michigan Healthcare Professionals. University of Michigan; Ascension Providence Hospital. University of Michigan; Mercy Health Radiation Oncology. Karmanos Cancer Institute at McLaren Greater Lansing. Beaumont Radiation Oncology. Wayne State University, Department of Radiation Oncology; Karmanos Cancer Center. Karmanos Cancer Institute at McLaren Macomb, Ted B. Wahby Cancer Center. Munson Medical Center. Karmanos Cancer Institute at McLaren Northern. Genesys Hurley Cancer Institute. Henry Ford Health System. Lakeland Radiation Oncology. West Michigan Cancer Center. PURPOSE: Questions remain about whether moderately hypofractionated whole breast irradiation is appropriate for patients with triple-negative breast cancer. METHODS: Using a prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared

outcomes using the product-limit estimation method of Kaplan and Meier with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. RESULTS: The sample included 538 patients treated at 18 centers in one state in the United States, of whom 307 received conventionally fractionated whole breast irradiation and 231 received moderately hypofractionated whole breast irradiation. The median follow-up time was 5.0 years (95% CI 4.77-5.15). The 5-year IPTW estimates for FFLR were 93.6% (95% CI 87.8%-96.7%) in the moderately hypofractionated group and 94.4% (95% CI 90.3%-96.8%) in the conventionally fractionated group. The hazard ratio was 1.05 (95% CI 0.51-2.17), p=0.89. The 5-year IPTW estimates for RFS were 87.8% (95% CI 81.0%-92.4%) in the moderately hypofractionated group and 88.4% (95% CI 83.2%-92.1%) in the conventionally fractionated group. The hazard ratio was 1.02 (95% CI 0.62-1.67), p=0.95. The 5-year IPTW estimates for OS were 96.6% (95% CI 92.0%-98.5%) in the moderately hypofractionated group and 93.4% (95% CI 88.7%-96.1%) in the conventionally fractionated group. The hazard ratio was 0.65 (95% CI 0.30-1.42), p=0.28. CONCLUSION: Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole breast irradiation reveals no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease. Radiation Oncology Xu Y, Brovold N, Cyriac J, Bossart E, Padgett K, Butkus M, Diwanj T, King A, Dal Pra A, Abramowitz M, Pollack A, and Dogan N. Assessment of Knowledge-Based Planning for Prostate Intensity Modulated Proton Therapy. Int J Part Ther 2021; 8(2):62-72. PMID: 34722812. Full Text Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA. Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA. PURPOSE: To assess the performance of a proton-specific knowledge based planning (KBPP) model in creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of patients with prostate cancer. MATERIALS AND METHODS: Forty-five patients with localized prostate cancer, who had previously been treated with volumetric modulated arc therapy, were selected and replanned with robustly optimized IMPT. A KBPP model was generated from the results of 30 of the patients, and the remaining 15 patient results were used for validation. The KBPP model quality and accuracy were evaluated with the model-provided organ-at-risk regression plots and metrics. The KBPP quality was also assessed through comparison of expert and KBPP-generated IMPT plans for target coverage and organ-at-risk sparing. RESULTS: The resulting R (2) (mean ± SD, 0.87 ± 0.07) between dosimetric and geometric features, as well as the χ(2) test (1.17 ± 0.07) between the original and estimated data, showed the model had good quality. All the KBPP plans were clinically acceptable. Compared with the expert plans, the KBPP plans had marginally higher dose-volume indices for the rectum V65Gy (0.8% ± 2.94%), but delivered a lower dose to the bladder (-1.06% ± 2.9% for bladder V65Gy). In addition, KBPP plans achieved lower hotspot (-0.67Gy ± 2.17Gy) and lower integral dose (-0.09Gy ± 0.3Gy) than the expert plans did. Moreover, the KBPP generated better plans that demonstrated slightly greater clinical target volume V95 (0.1% ± 0.68%) and lower homogeneity index (-1.13 ± 2.34). CONCLUSIONS: The results demonstrated that robustly optimized IMPT plans created by the KBPP model are of high quality and are comparable to expert plans. Furthermore, the KBPP model can generate more-robust and more-homogenous plans compared with those of expert plans. More studies need to be done for the validation of the proton KBPP model at more-complicated treatment sites. Surgery Davidson GH, Flum DR, Monsell SE, Kao LS, Voldal EC, Heagerty PJ, Fannon E, Lavallee DC, Bizzell B, Lawrence SO, Comstock BA, Krishnadasan A, Winchell RJ, Self WH, Thompson CM, Farjah F, Park PK, Alam HB, Saltzman D, Moran GJ, Kaji AH, DeUgarte DA, Salzberg M, Ferrigno L, Mandell KA, Price TP, Siparsky N, Glaser J, Ayoung-Chee P, Chiang W, Victory J, Chung B, Carter DW, Kutcher ME, Jones A, Holihan J, Liang MK, Faine BA, Cuschieri J, Evans HL, Johnson J, Patton JH, Coleman N, Fischkoff K, Drake FT, Sanchez SE, Parsons C, Odom SR, Kessler LG, and Talan DA. Antibiotics versus Appendectomy for Acute Appendicitis - Longer-Term Outcomes. N Engl J Med 2021; Epub ahead of print. PMID: 34694761. Full Text

From University of Washington Medical Center-UW Medicine (G.H.D., D.R.F., E.F., D.C.L., B.B., S.O.L., F.F., L.G.K.), University of Washington (S.E.M., E.C.V., P.J.H., B.A.C.), Swedish Medical Center (K.A.M.), and Harborview Medical Center-UW Medicine (J.C., H.L.E.), Seattle, and Providence Regional Medical Center, Everett (J.G.) - all in Washington; McGovern Medical School, University of Texas Health Science Center (L.S.K.), Lyndon B. Johnson General Hospital, University of Texas (J.H., M.K.L.), and HCA Healthcare Kingwood, University of Houston (M.K.L.) - all in Houston; BC Academic Science Health Network, Vancouver, BC, Canada (D.C.L.); Olive View-UCLA Medical Center (A.K., D.S., G.J.M., D.A.T.), Harbor-UCLA Medical Center (A.H.K., D.A.D.), and UCLA Ronald Reagan Medical Center (D.A.T.), Los Angeles, and the University of California, San Francisco (J.C.) - all in California; Weill Cornell Medical Center (R.J.W.), Tisch Hospital, NYU Langone Medical Center (P.A.-C., W.C., J.V.), Bellevue Hospital Center, NYU School of Medicine (W.C.), and Columbia University Medical Center (N.C., K.F.) - all in New York; Vanderbilt University Medical Center, Nashville (W.H.S., C.M.T.); University of Utah, Salt Lake City (C.M.T.); University of Michigan Medical Center, Ann Arbor (P.K.P., H.B.A.), and Henry Ford Health System, Detroit (J.J., J.H.P.) - both in Michigan; UCHealth, University of Colorado Hospital, Denver (M.S., L.F.); Rush University Medical Center, Chicago (T.P.P., N.S.); Morehouse School of Medicine, Atlanta (P.A.-C.); Maine Medical Center, Portland (B.C., D.W.C.); University of Mississippi Medical Center, Jackson (M.E.K., A.J.); University of Iowa Hospitals and Clinics, Iowa City (B.A.F.); Medical University of South Carolina, Charleston (H.L.E.); and Boston University Medical Center (F.T.D., S.E.S.) and Beth Israel Deaconess Medical Center (C.P., S.R.O.) - both in Boston. Surgery Eng MH, Qintar M, Apostolou D, and O'Neill WW. Alternative Access for Transcatheter Aortic Valve Replacement: A Comprehensive Review. Interv Cardiol Clin 2021; 10(4):505-517. PMID: 34593113. Full Text Division of Cardiology, Banner- University Medical Center Phoenix, 1111 East McDowell Road, Phoenix, AZ 85006, USA. Electronic address: Marvin.eng@bannerhealth.com. Division of Cardiology, Sparrow Hospital, 1215 East Michigan Avenue, Lansing, MI 48912, USA. Division of Cardiothoracic Surgery, Department of Surgery, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Division of Cardiology, Center for Structural Heart Disease, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA. Transfemoral is the most widely used access to perform transcatheter aortic valve replacement (TAVR). However, alternative access is needed in up to 21% of patients with TAVR because of a myriad of factors. The authors provide a comprehensive review on alternative access for TAVR, discussing the relevant data and providing the pros and cons of each access route. Surgery Ivanics T, Nelson W, Patel MS, Claasen M, Lau L, Gorgen A, Abreu P, Goldenberg A, Erdman L, and Sapisochin G. The Toronto Post Liver Transplant Hepatocellular Carcinoma Recurrence Calculator: A Machine Learning Approach. Liver Transpl 2021; Epub ahead of print. PMID: 34626159. Full Text Multi-Organ Transplant Program, Division of General Surgery, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada. Department of Surgery, Henry Ford Hospital, Detroit, Michigan, United States of America. Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden. Centre for Data Science and Digital Health, Hamilton Health Sciences, Hamilton, ON, Canada. Department of Statistical Sciences, University of Toronto, Toronto, ON, Canada. Department of Surgery, Erasmus MC, University Medical Center Rotterdam, the Netherlands. SickKids Research Institute, University of Toronto, Toronto, Canada. Center for Computational Medicine, SickKids Research Institute, Toronto, Canada. BACKGROUND: Liver transplant (LT) listing criteria for hepatocellular carcinoma (HCC) remain controversial. To optimize the utility of limited donor organs, this study aims to leverage machine learning to develop an accurate post-transplant HCC recurrence prediction calculator. METHODS: HCC patients

listed for LT from 2000-2016 were identified, with 739 patients who underwent LT used for modeling. Data included serial imaging, alpha-fetoprotein (AFP), locoregional therapies, treatment response, and post-transplant outcomes. We compared the CoxNet (regularized Cox regression), Survival Random Forest, Survival Support Vector Machine (SVM), and DeepSurv machine learning algorithms via the mean cross-validated concordance index. We validated the selected CoxNet model by comparing it to other currently available recurrence risk algorithms on a held-out test set (AFP, MORAL, and HALT-HCC score). RESULTS: The developed CoxNet-based recurrence prediction model showed a satisfying overall concordance score of 0.75 (95% CI 0.64 - 0.84). In comparison, the recalibrated risk algorithms' concordance scores were: AFP score 0.64 (outperformed by the CoxNet model, one-sided 95% CI >0.006; p=0.04) and MORAL score 0.64 (outperformed by the CoxNet model one-sided 95% CI >0.015; p=0.03). The recalibrated HALT-HCC score performed well with a concordance of 0.72 (95% CI 0.63-0.81) and was not significantly outperformed (one-sided 95% CI >-0.05; p=0.29). CONCLUSIONS: Developing a comprehensive post-transplant HCC recurrence risk calculator using machine learning is feasible and can yield higher accuracy than other available risk scores. Further research is needed to confirm the utility of machine learning in this setting. Surgery Martens K, Pester BD, Hecht LM, Herb Neff KM, Clark-Sienkiewicz SM, Hamann A, Carlin AM, and Miller-Matero LR. Adherence to Post-operative Appointments Is Associated with Weight Loss Following Bariatric Surgery. Obes Surg 2021; Epub ahead of print. PMID: 34651288. Full Text Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Kmarten2@hfhs.org. Department of Surgery, Henry Ford Health System, Detroit, MI, 48202, USA. Behavioral Health, Henry Ford Health System, Detroit, MI, 48202, USA. Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, 48202, USA. Surgery Park WD, Kim DY, Mai ML, Reddy KS, Gonwa T, Ryan MS, Herrera Hernandez LP, Smith ML, Geiger XJ, Turkevi-Nagy S, Cornell LD, Smith BH, Kremers WK, and Stegall MD. Progressive decline of function in renal allografts with normal one year biopsies: Gene expression studies fail to identify a classifier. Clin Transplant 2021; Epub ahead of print. PMID: 34717009. Full Text Mayo Clinic Rochester. Henry Ford. Mayo Clinic Florida. Mayo Clinic Arizona. University of Szegad. Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = 0.59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and 0.58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e. those with a relatively normal 1-year biopsy and eGFR >40) remains difficult. This article is protected by copyright. All rights reserved.

Surgery Rajendran L, Ivanics T, Mpaw C, Muaddi H, and Sapisochin G. THE MANAGEMENT OF POST-TRANSPLANTATION RECURRENCE OF HEPATOCELLULAR CARCINOMA. Clin Mol Hepatol 2021; Epub ahead of print. PMID: 34610652. Request Article Division of General Surgery, University of Toronto, Toronto, Ontario, Canada. Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. Department of Surgery, Henry Ford Hospital, Detroit, MI, USA. Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden. Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The annual incidence of hepatocellular carcinoma (HCC) continues to rise. Over the last two decades, liver transplantation (LT) has become the preferable treatment of HCC, when feasible and strict selection criteria are met. With the rise in HCC-related liver transplantation, compounded by downstaging techniques and expansion of transplant selection criteria, a parallel increase in number of post-transplantation HCC recurrence is expected. Additionally, in the context of an immunosuppressed transplant host, recurrences may behave aggressively and more challenging to manage, resulting in poor prognosis. Despite this, no consensus or best practice guidelines for post-transplantation cancer surveillance and recurrence management for HCC currently exist. Studies with adequate population sizes and high-level evidence are lacking, and the role of systemic and locoregional therapies for graft and extrahepatic recurrences remains under debate. This review seeks to summarize the existing literature on post-transplant HCC surveillance and recurrence management. It highlights the value of early tumour detection, re-evaluating the immunosuppression regimen, and staging to differentiate disseminated recurrence from intrahepatic or extrahepatic oligo-recurrence. This ultimately guides decision-making and maximizes treatment effect. Treatment recommendations specific to recurrence type are provided based on currently available locoregional and systemic therapies. Urology Butaney M, Chan EM, and Rambhatla A. Editorial Comment. J Urol 2021; Epub ahead of print. PMID: 34633222. Full Text Department of Urology, Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan. Urology Jamil M, Rakic N, Sood A, Keeley J, Modonutti D, Novara G, Jeong W, Menon M, Rogers CG, and Abdollah F. Impact of Lymphovascular Invasion on Overall Survival in Patients With Prostate Cancer Following Radical Prostatectomy: Stage-per-Stage Analysis. Clin Genitourin Cancer 2021; 19(5):e319-e325. PMID: 34154946. Full Text Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Vattikuti Urology Institute, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202 USA. Department of Surgery, Oncology, and Gastroenterology - Urology Clinic, University of Padua, Italy. Vattikuti Urology Institute Center for Outcomes Research, Analytics and Evaluation (VCORE), Vattikuti Urology Institute, Henry Ford Health System, 2799 W Grand Blvd, Detroit, MI 48202 USA. Electronic address: firas.abdollah@gmail.com. BACKGROUND: The detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa. METHODS: We examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n = 232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b). RESULTS: Of the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P = .0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable

analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P = .2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P = .02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI. CONCLUSIONS: Our report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology. Urology Pilling A, Kim SH, and Hwang C. Androgen receptor negatively regulates mitotic checkpoint signaling to induce docetaxel resistance in castration-resistant prostate cancer. Prostate 2021; Epub ahead of print. PMID: 34672379. Full Text Department of Internal Medicine, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, Michigan, USA. Department of Urology, Henry Ford Health System, Detroit, Michigan, USA. BACKGROUND: Despite multiple treatment advances for castration-resistant prostate cancer (CRPC), there are currently no curative therapies and patients ultimately to succumb to the disease. Docetaxel (DTX) is the standard first-line chemotherapy for patients with metastatic CRPC; however, drug resistance is inevitable and often develops rapidly, leading to disease progression in nearly all patients. In contrast, when DTX is deployed with androgen deprivation therapy in castration-sensitive disease, more durable responses and improved outcomes are observed, suggesting that aberrant androgen receptor (AR) signaling accelerates DTX resistance in CRPC. In this study, we demonstrate that AR dysregulates the mitotic checkpoint, a critical pathway involved in the anticancer action of DTX. METHODS: Androgen-dependent and independent cell lines were used to evaluate the role of AR in DTX resistance. Impact of drug treatment on cell viability, survival, and cell-cycle distribution were determined by plate-based viability assay, clonogenic assay, and cell-cycle analysis by flow cytometry, respectively. Mitotic checkpoint kinase signal transduction and apoptosis activation was evaluated by Western blotting. Pathway gene expression analysis was evaluated by RT-PCR. A Bliss independence model was used to calculate synergy scores for drug combination studies. RESULTS: Activation of AR in hormone-sensitive cells induces a rescue phenotype by increasing cell viability and survival and attenuating G2/M arrest in response to DTX. Analysis of mitotic checkpoint signaling shows that AR negatively regulates spindle checkpoint signaling, resulting in premature mitotic progression and evasion of apoptosis. This phenotype is characteristic of mitotic slippage and is also observed in CRPC cell lines where we demonstrate involvement of AR splice variant AR-v7 in dysregulation of checkpoint signaling. Our findings suggest that DTX resistance is mediated through mechanisms that drive premature mitotic exit. Using pharmacologic inhibitors of anaphase-promoting complex/cyclosome and polo-like kinase 1, we show that blocking mitotic exit induces mitotic arrest, apoptosis, and synergistically inhibits cell survival in combination with DTX. CONCLUSION: Our results suggest that targeting the mechanisms of dysregulated mitotic checkpoint signaling in AR-reactivated tumors has significant clinical potential to extend treatment benefit with DTX and improve outcomes in patients with lethal prostate cancer.

Conference Abstracts

Administration Caldwell MT, Goyal N, Dudley A, Dehlendorf C, Scott J, Parke D, Vallee P, Daniels G, Manteuffel J, Thomas CSD, Hambrick N, Guetterman TC, Misra D, and Joseph CLM. ENGAGING CLINICIANS IN A PRE-IMPLEMENTATION ASSESSMENT OF THE WOMEN & PERSON-EMPOWERED COMMUNITY ACCESS FOR REPRODUCTIVE EQUITY (WE CARE) INTERVENTION. Contraception 2021; 104(4):468-468. PMID: Not assigned. Full Text [Caldwell, M. T.] Henry Ford Hlth Syst, Detroit, MI USA. Behavioral Health Services/Psychiatry/Neuropsychology Huang Y, Chen D, Levin A, Ahmedani B, Frank C, Wang Q, and Gui H. TU88. INVESTIGATION OF OPIOID USE DISORDER ON RISK OF SUICIDAL ATTEMPT: A MENDELIAN RANDOMIZATION STUDY. European Neuropsychopharmacology 2021; 51:e143-e144. PMID: Not assigned. Full Text Background: Suicide is a major public health concern that accounts for more than 800,000 deaths each year around the world. Known risk factors for suicide are mental health conditions and their related clinical variables. Among them, opioid use disorder (OUD) significantly increases risk for suicidal ideation, attempts, and death. In spite of their co-occurrence and reported association from observational findings, it remains to be elucidated whether suicidal behaviors are a cause or consequence of opioid use. Both suicide attempt and OUD are heritable (heritability at 0.55 and 0.34, respectively) and each has been previously investigated individually through genome-wide association studies (GWAS). When combined, existing GWAS data from both phenotypes also provides a means (i.e., Mendelian randomization [MR]) to infer a possible causal relationship between them outside of a clinical trial setting. Methods: GWAS summary statistics for suicidal attempt were collected from two resources: 1) the UK Biobank analysis (Neale Lab, round 2) that was accessible through the IEU OpenGWAS project and 2) a Danish iPSYCH study (Erlangsen et al. 2020). Fixed-effect meta-analysis was used to combine the two datasets for suicide. Genetic variants present in both datasets showing no heterogeneity were retained. In addition, GWAS summary statistics for OUD were downloaded from Psychiatric Genomic Consortium (Polimanti et al. 2020) that studied both opioid dependence and opioid exposure. For both suicide attempt and OUD GWAS, studies included only individuals of principally European ancestry, and no overlapping individuals were identified between suicide attempt GWAS and OUD GWAS. Variants were also harmonized to have consistent strand and allele coding. Genotypes from 1000 Genome CEU population (n=183) and another subset of healthy controls (n =70,000) in the UK Biobank project were used as reference. MR inference was then conducted by TwoSampleMR and MR-PRESSO R packages. Results: TwoSampleMR analyses indicated moderate but significant causal relationship from opioid dependence to suicide attempt (inverse-variance weighted [IVW]: OR=1.043; PIVW < 0.001); Weighted median: OR= 1.048, Pweighted-median =0.002; MR-Egger: OR =1.029, PMR-Egger =0.409). Heterogeneity tests showed no significant horizontal pleiotropy effects exist between the two phenotypes (P > 0.05 from MR-Egger intercept test and MR-PRESSO global test). As a comparison, no such causal relationship was found from opioid exposure to suicide attempt (IVW: OR = 0.975, PIVW = 0.591; weighted median: OR = 1.011, PIVW = 0.870; MR-Egger: OR =0.930, PMR-Egger = 0.486). Discussion: In summary, this MR study reveals a possible causal effect of opioid dependence on suicidal attempt. Another larger OUD GWAS dataset from the Million Veteran Program is being used to replicate this finding. In addition, approaches for transcriptomic-wide association studies (e.g., SMR, FUSION and KGGSEE) will be adopted to infer potential molecular-level mechanistic explanations (i.e., shared causal SNPs and genes) for this cross-phenotype relationship. Disclosure: Nothing to disclose. Cardiology/Cardiovascular Research Yahya J, Henkin D, Montecalvo J, and Abdulla RK. Prisoner of the Heart - Primary Unresectable Cardiac Angiosarcoma in an African American Man. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S128-S130. PMID: Not assigned. [Yahya, Jehan] Oregon Hlth & Sci Univ, OHSU, Portland, OR 97201 USA. [Henkin, David] UT Hlth, Houston, TX USA. [Montecalvo, Joseph; Abdulla, Rami Khoury] Henry Ford Hosp, Detroit, MI USA.

Center for Health Policy and Health Services Research Huang Y, Chen D, Levin A, Ahmedani B, Frank C, Wang Q, and Gui H. TU88. INVESTIGATION OF OPIOID USE DISORDER ON RISK OF SUICIDAL ATTEMPT: A MENDELIAN RANDOMIZATION STUDY. European Neuropsychopharmacology 2021; 51:e143-e144. PMID: Not assigned. Full Text Background: Suicide is a major public health concern that accounts for more than 800,000 deaths each year around the world. Known risk factors for suicide are mental health conditions and their related clinical variables. Among them, opioid use disorder (OUD) significantly increases risk for suicidal ideation, attempts, and death. In spite of their co-occurrence and reported association from observational findings, it remains to be elucidated whether suicidal behaviors are a cause or consequence of opioid use. Both suicide attempt and OUD are heritable (heritability at 0.55 and 0.34, respectively) and each has been previously investigated individually through genome-wide association studies (GWAS). When combined, existing GWAS data from both phenotypes also provides a means (i.e., Mendelian randomization [MR]) to infer a possible causal relationship between them outside of a clinical trial setting. Methods: GWAS summary statistics for suicidal attempt were collected from two resources: 1) the UK Biobank analysis (Neale Lab, round 2) that was accessible through the IEU OpenGWAS project and 2) a Danish iPSYCH study (Erlangsen et al. 2020). Fixed-effect meta-analysis was used to combine the two datasets for suicide. Genetic variants present in both datasets showing no heterogeneity were retained. In addition, GWAS summary statistics for OUD were downloaded from Psychiatric Genomic Consortium (Polimanti et al. 2020) that studied both opioid dependence and opioid exposure. For both suicide attempt and OUD GWAS, studies included only individuals of principally European ancestry, and no overlapping individuals were identified between suicide attempt GWAS and OUD GWAS. Variants were also harmonized to have consistent strand and allele coding. Genotypes from 1000 Genome CEU population (n=183) and another subset of healthy controls (n =70,000) in the UK Biobank project were used as reference. MR inference was then conducted by TwoSampleMR and MR-PRESSO R packages. Results: TwoSampleMR analyses indicated moderate but significant causal relationship from opioid dependence to suicide attempt (inverse-variance weighted [IVW]: OR=1.043; PIVW < 0.001); Weighted median: OR= 1.048, Pweighted-median =0.002; MR-Egger: OR =1.029, PMR-Egger =0.409). Heterogeneity tests showed no significant horizontal pleiotropy effects exist between the two phenotypes (P > 0.05 from MR-Egger intercept test and MR-PRESSO global test). As a comparison, no such causal relationship was found from opioid exposure to suicide attempt (IVW: OR = 0.975, PIVW = 0.591; weighted median: OR = 1.011, PIVW = 0.870; MR-Egger: OR =0.930, PMR-Egger = 0.486). Discussion: In summary, this MR study reveals a possible causal effect of opioid dependence on suicidal attempt. Another larger OUD GWAS dataset from the Million Veteran Program is being used to replicate this finding. In addition, approaches for transcriptomic-wide association studies (e.g., SMR, FUSION and KGGSEE) will be adopted to infer potential molecular-level mechanistic explanations (i.e., shared causal SNPs and genes) for this cross-phenotype relationship. Disclosure: Nothing to disclose. Diagnostic Radiology Liang E, Greer G, Burmeister C, Massa P, Dragovic J, and Parikh P. Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S55. PMID: Not assigned. [Liang, Evan; Greer, Garret; Burmeister, Charlotte; Massa, Peter; Dragovic, Jadranka; Parikh, Parag] Henry Ford Hlth Syst, Detroit, MI USA. Emergency Medicine Caldwell MT, Goyal N, Dudley A, Dehlendorf C, Scott J, Parke D, Vallee P, Daniels G, Manteuffel J, Thomas CSD, Hambrick N, Guetterman TC, Misra D, and Joseph CLM. ENGAGING CLINICIANS IN A PRE-IMPLEMENTATION ASSESSMENT OF THE WOMEN & PERSON-EMPOWERED COMMUNITY ACCESS FOR REPRODUCTIVE EQUITY (WE CARE) INTERVENTION. Contraception 2021; 104(4):468-468. PMID: Not assigned. Full Text [Caldwell, M. T.] Henry Ford Hlth Syst, Detroit, MI USA.

Gastroenterology Kirsch C, Schaff E, Parikh P, Movsas B, Siddiqui F, Kwon D, Li P, Khan G, and Shah R. Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S54. PMID: Not assigned. [Kirsch, Celina] Henry Ford Canc Inst, Detroit, MI USA. [Schaff, Eric; Parikh, Parag; Kwon, David; Li, Pin; Khan, Gazala; Shah, Rupen] Henry Ford Hlth Syst, Detroit, MI USA. [Movsas, Benjamin; Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Gastroenterology Schaff E, Kirsch C, Parikh P, Chuong M, Herrera R, Asbun H, Jimenez R, Siddiqui F, Khan G, Aparo S, De Zarraga F, Ucar A, Shah R, Li P, Movsas B, and Kwon D. Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S57-S57. PMID: Not assigned. [Schaff, Eric; Kirsch, Celina; Parikh, Parag; Khan, Gazala; Shah, Rupen; Li, Pin; Kwon, David] Henry Ford Hlth Syst, Detroit, MI USA. [Chuong, Michael; Herrera, Roberto; Asbun, Horacio; Jimenez, Ramon; Aparo, Santiago; De Zarraga, Fernando; Ucar, Antonio] Miami Canc Inst, Miami, FL USA. [Siddiqui, Farzan; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Hematology-Oncology Abu Rous F, Singh SRK, Li P, Elgamal M, Abunafeesa H, Chacko R, Vuyyala S, Alkhatib Y, and Kuriakose P. Satisfaction of hem/onc patients with video visits during the COVID-19 pandemic at a tertiary care center in Michigan. Journal of Clinical Oncology 2021; 39(28):4. PMID: Not assigned. Full Text [Abu Rous, Fawzi; Singh, Sunny R. K.; Li, Pin; Elgamal, Mohamed; Abunafeesa, Hussna; Chacko, Rebecca; Vuyyala, Sowjanya; Alkhatib, Yaser; Kuriakose, Philip] Henry Ford Hlth Syst, Detroit, MI USA. Hematology-Oncology Bazhenova L, Girard N, Minchom A, Ou S, Gadgeel S, Trigo JM, Viteri S, Londhe A, Mahadevia P, and Bauml J. P08.04 Comparative Clinical Outcomes Between EGFR Exon20ins and Wildtype NSCLC Treated with Immune Checkpoint Inhibitors. Journal of Thoracic Oncology 2021; 16(10):S992-S993. PMID: Not assigned. Full Text Introduction: Mutation of the epidermal growth factor receptor (EGFR) is a major oncogenic driver in non-small cell lung cancer (NSCLC), and up to 12% of all EGFR-mutant NSCLCs harbor Exon 20 insertion mutations (Exon20ins). The insensitivity of Exon20ins to EGFR tyrosine kinase inhibitors has been well documented, but the activity of immune checkpoint inhibitors (ICIs) has not been closely examined due to the frequent exclusion of patients with EGFR mutations from large immunotherapy-based NSCLC trials. Methods: We conducted a retrospective study to compare clinical outcomes of ICI-treated patients with EGFR Exon20ins and wildtype NSCLC (wt-NSCLC, defined as EGFR, ALK test negative). Patients with advanced NSCLC with non-squamous histology from the Flatiron Health database from 2015 to 2020 were included in this analysis. Real-world time to next therapy (rwTTNT) was the primary endpoint and analyzed using multivariable Cox proportional hazards model (covariates: age, time from advanced diagnosis to index date, time from initial to advanced diagnosis, sex, ECOG performance status, smoking history, and practice type) stratified by ICI initiation line of therapy. Overall survival was the secondary endpoint. Both endpoints were summarized by Kaplan-Meier method. Results: Clinical outcomes of ICI therapy were assessed in 5365 with wt-NSCLC against 59 patients with Exon20ins NSCLC. ICI treatment was received as first or second-line therapy in 25% and 41% of Exon20ins and 39% and 42% of wt-NSCLC patients, respectively. The most common ICIs received by Exon20ins and wt-NSCLC patients were nivolumab (64% and 51%) and pembrolizumab (32% and 42%), respectively. Patients with Exon20ins had a 58% increased risk of shorter time to next-line therapy compared to wt-NSCLC (adjusted hazard ratio of 1.58 [95% CI, 1.2–2.1]; p=0.0012). The median rwTTNT was 3.7 months (95%

CI, 3.0–4.9) for Exon20ins compared with 5.8 months (95% CI, 5.6–6.0) for wt-NSCLC (Figure). At 12-months, 10% of Exon20ins patients remained on ICIs compared with 31% of wt-NSCLC patients. No meaningful difference in survival between the Exon20ins and wt-NSCLC groups was observed. Conclusion: ICI therapy was less effective for patients with Exon20ins compared with wt-NSCLC, although the sample size for Exon20ins NSCLC was smaller. The limited effectiveness of current treatment options for patients with EGFR Exon20ins NSCLC stress the need for new targeted therapies. [Formula presented] Keywords: EGFR Exon 20 Insertion, Real world, immune checkpoint inhibitor Hematology-Oncology Gadgeel S, Izano M, Sweetnam C, Rybkin I, Hendawi M, Weese J, Patel A, Reding D, Treisman J, Stafford A, Wolf F, Zhang C, and Brown T. P10.03 Pembrolizumab With or Without Chemotherapy for Advanced Lung Cancer: A Real-World Analysis of Key Prognostic Factors. Journal of Thoracic Oncology 2021; 16(10):S999. PMID: Not assigned. Full Text Introduction: Immune checkpoint inhibitors alone or in combination with chemotherapy have become standard of care for patients with advanced non-small cell lung cancer (aNSCLC) without driver mutations. This study investigates the real-world performance of immunotherapies in the treatment of patients with aNSCLC. Methods: Data on patients diagnosed with aNSCLC between 1/2016 and 9/2020 who received frontline treatment with pembrolizumab alone (IO) or in combination with platinum-based chemotherapy (IO+C) within community health systems were extracted from electronic health records. The Kaplan-Meier estimator was used to assess overall survival (OS) and time-to-next treatment or death (TTNT). Results: Of 739 patients, 82% were White and 12% were Black; 79% had non-squamous histology. Brain and liver metastases were documented in 25% and 10% of patients, respectively; 83% of patients’ tumors were tested for PD(L)-1, 80% for EGFR, and 74% for ALK. Among patients tested for PD(L)-1, 98% (295) of IO and 69% (217) of IO+C patients’ tumors were positive. A greater proportion of IO than IO+C patients were female (52% vs 44%) and fewer had performance status (PS) <2 (44% vs 53%). During the median follow-up of 10 months, 24% of patients received second line therapy and 57% died. IO patients had longer median OS than IO+C patients (Table 1; p=0.02). Median OS was longer for non-squamous than squamous histology in both groups. patients with brain metastases, patients with liver metastases, and patients with PS ≥2 treated with IO had a longer median OS than patients treated with IO+C. TTNT followed a similar pattern. In Cox proportional hazards models adjusted for age, sex, race, year and stage of diagnosis, histology, brain and liver metastasis, smoking, PS, comorbidity and tumor proportion score (TPS), treatment with IO was associated with reduced mortality [HR 0.8; 95% Confidence Interval, (0.6, 1.0); p=0.02] and reduced hazard of initiating next treatment [HR 0.8 (0.7, 1.0); p=0.08]. [Formula presented] Conclusion: In this real-world analysis, frontline IO was associated with longer survival than IO+C. Real-world benefits of IO and IO+C were more modest than reported in clinical trials, particularly in squamous patients. While these findings must be replicated in analyses that control for imbalances in patients characteristics between the two treatment arms, real-world data provide a powerful tool for assessing treatment efficacy outside of the clinical trial setting. Keywords: Immune checkpoint inhibitors, Real-world data, Survival analysis Hematology-Oncology Khaddour L, Zhang C, Ali F, Gadgeel S, Tadesse E, Thompson M, Reding D, Treisman J, Berry A, Izano M, Sweetnam C, Stafford A, Wolf F, Brown T, and Rybkin I. P10.04 Immunotherapy-Treated Non-Small Cell Lung Cancer Patients With Sensitizing Gene Alterations: A Real World Survival Analysis. Journal of Thoracic Oncology 2021; 16(10):S999-S1000. PMID: Not assigned. Full Text Introduction: Mutation-specific tyrosine kinase inhibitors (TKIs) have demonstrated efficacy among patients (pts) with advanced non-small cell lung cancer (aNSCLC) with sensitizing gene alterations (GA). It is unclear how effective immune checkpoint inhibitor (ICI) therapy is among NSCLC pts with sensitizing GA, particularly after TKI failure or resistance. Methods: Pts with aNSCLC (stages IIIB/IV at diagnoses, or progression to metastatic disease) diagnosed 01/01/2014-06/01/2020 with sensitizing GA in EGFR, ALK, ROS1, BRAF, NTRK1/2/3, MET, or RET genes were identified in community health systems, with data extracted from electronic health records. All pts were treated with at least one line of TKI. This cohort was assessed for overall survival (OS) in pts who did or did not receive ICI (either as a single agent or in combination with chemotherapy) at any time during their disease course. Sub-analyses were performed

for pts with sensitizing GA in EGFR, and for pts treated with ICI after TKI therapy. Results: 371 TKI-treated aNSCLC pts with sensitizing GA were included in the analysis, among whom 97 (26%) were treated with ICIs. Sensitizing GA were identified in EGFR (77%), ALK (15%), ROS1 (3%), BRAF (4%), NTRK1/2/3 (<1%), MET (3%), and RET (1%) genes. Pts who were in the ICI-treated vs ICI-naive groups had similar baseline characteristics with respect to histology (non-squamous vs squamous), initial stage at diagnosis, race/ethnicity, and never-smoking history. ICI-treated pts were younger (median age 62 vs 69), and more likely to be men (41% vs 34%). Compared to ICI-naive pts, those with ICI treatment anytime had greater OS for all pts with sensitizing GA (log-rank P=0.125), as well as for pts with EGFR GA (log-rank P=0.016) (Table). Compared to ICI-naive pts, those with ICI treatment after TKI therapy also had greater OS for all pts with sensitizing GA (log-rank P=0.179), as well as for pts with EGFR GA (log-rank P=0.025). [Formula presented] Conclusion: Longer OS was observed in TKI-treated aNSCLC pts with sensitizing GA who received ICI compared to those who did not receive ICI at any point. This was seen within pts with any sensitizing GA, and especially within the subset of pts with EGFR GA. Further analyses into determinants of treatment response in these real world pts should be explored, along with pursuing prospective clinical trials for ICI therapy in pts with aNSCLC and sensitizing GA. Keywords: Immune checkpoint inhibitors, Real-world data, Survival analysis Hematology-Oncology Kirsch C, Schaff E, Parikh P, Movsas B, Siddiqui F, Kwon D, Li P, Khan G, and Shah R. Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S54. PMID: Not assigned. [Kirsch, Celina] Henry Ford Canc Inst, Detroit, MI USA. [Schaff, Eric; Parikh, Parag; Kwon, David; Li, Pin; Khan, Gazala; Shah, Rupen] Henry Ford Hlth Syst, Detroit, MI USA. [Movsas, Benjamin; Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Hematology-Oncology Schaff E, Kirsch C, Parikh P, Chuong M, Herrera R, Asbun H, Jimenez R, Siddiqui F, Khan G, Aparo S, De Zarraga F, Ucar A, Shah R, Li P, Movsas B, and Kwon D. Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S57-S57. PMID: Not assigned. [Schaff, Eric; Kirsch, Celina; Parikh, Parag; Khan, Gazala; Shah, Rupen; Li, Pin; Kwon, David] Henry Ford Hlth Syst, Detroit, MI USA. [Chuong, Michael; Herrera, Roberto; Asbun, Horacio; Jimenez, Ramon; Aparo, Santiago; De Zarraga, Fernando; Ucar, Antonio] Miami Canc Inst, Miami, FL USA. [Siddiqui, Farzan; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Hematology-Oncology Smeltzer M, Bunn B, Choi YS, Coate L, Corona-Cruz J, Drilon A, Duma N, Edelman M, Fidler MJ, Gadgeel S, Goto Y, Herbst R, Hesdorffer M, Higgins K, Labdi B, Leal T, Liu S, Mazotti J, Novello S, Patel S, Popat S, Ramirez R, Reckamp K, Reguart N, Soo R, Tan A, Wolf J, Yano S, Stiles B, and Baird A. OA17.04 The Global Impact of COVID-19 on Telehealth and Care for Persons With Thoracic Cancers. Journal of Thoracic Oncology 2021; 16(10):S879. PMID: Not assigned. Full Text Introduction: The COVID-19 pandemic has resulted in countless challenges and changes in health-systems and healthcare delivery around the world. Face-to-face consultation became the exception rather than the norm. Many people at risk of, and living with, thoracic malignancies experienced significant barriers to accessing care. Telehealth was employed by many providers to engage and monitor patients remotely, thus providing some continuity of care. The aim of this project was to assess the use of telehealth during the pandemic and the wider impact on thoracic cancer care from the perspective of healthcare professionals. Methods: An English language survey was developed by the IASLC communications committee, and administered using Qualtrics software from April 12, 2021 through May 31, 2021. It was disseminated via the IASLC and others, through multiple modalities. The 24-question survey included multiple choice, Likert scale, and free-response questions: covering two broad themes concerning the impact of the pandemic on (i) the use of telehealth and (ii) lung cancer/mesothelioma

care. Some general information was also gathered such as location and primary speciality. Statistical analyses included summary statistics reported for each question by region and provider specialty, compared with Chi-Square tests. Types of Analysis and Data Reporting: Full survey results will be reported for the two study themes (i) the use of telehealth and (ii) impact on lung cancer and mesothelioma care. We will present overall results and stratify by region of the world and provider type. Statistical comparisons across groups will also be reported. Finally, free-response data will be summarized and most frequent themes identified will be reported. Results: The 141 respondents were most frequently male (63.8%), between 41-50 years old (32.6%), medical oncologists (50.7%), with majority based at academic centres (84.2%). Responses were primarily from North America (37.6%), Europe (31.2%), and Asia (14.9%). During the pandemic most used telehealth for the first time (65.2%) and billing (where appropriate) at normal rates (48.2%); the majority felt that telehealth is here to stay (48.2%). Telehealth visits were conducted by phone call (29.2%) and mixed platforms (35.7%), however ‘Video via e-medical record’ was the preferred method (42.5%). The most common barriers to adoption of telehealth were lack of resources for patients (66.1%) and regulatory limitations (56.2%), with patient interest and lack of institutional resources not rated as barriers (43.1% and 41.4%;, respectively). The top advantages for providers/patients were continuity of care and maintenance of contact with patients (88%-92% of respondents). Top disadvantages for providers were lack of human contact (72.9%), lack of patient internet access/tech knowledge (71.3%) and missing informal aspects of face-to-face visits (71.3%); these also ranked as top concerns for patients (74.8%,74%, 76.1% and 68.4%, respectively). Providers felt that telehealth was most appropriate during surveillance (94.1%) and least so for initial diagnosis (69.8%). Most felt that patients were receptive to telehealth (55.3%), however there was a worry that its use would increase healthcare disparities (29.7%). Overall, most felt that the pandemic had a negative impact on care (68%), with impacts on accessing diagnostics (i.e. biopsy), clinical trials (i.e. reduction in trials), basic/translational research (i.e. decrease in activity) as well as care (i.e. surgery). There was also a decrease in numbers accessing lung cancer screening (86.9%). Conclusion: Much will need to be done to counteract the negative impacts on care, clinical trials, and research during the COVID-19 pandemic. Although, telehealth has been widely adopted, issues remain such as healthcare access, point of use in the care pathway and telehealth platform selection. Keywords: telemedicine, covid-19 Hospital Medicine Song M, Haymart B, Kong X, Ali M, Kozlowski J, Krol G, Kaatz S, Froehlich J, and Barnes G. Combination antithrombotic therapy and bleeding risk: Comparing atrial fibrillation and venous thromboembolism. Vascular Medicine 2021; 26(5):NP10. PMID: Not assigned. Full Text M. Song, University of Michigan, Ann Arbor, MI, United States Background: Existing studies regarding combination anticoagulant- antiplatelet management have focused on patients with atrial fibrillation (AF). It is unknown if the combination of anticoagulant-antiplatelet therapy presents a comparable risk of bleeding for patients with venous thromboembolism (VTE). Methods: Adult patients initiating warfarin at six anticoagulation clinics in Michigan from 2009 to 2020 were enrolled via a registry-based cohort study. Participants were stratified based on sole indication for anticoagulation: AF or VTE. Two propensity score-matched cohorts were generated based on demographics, comorbidities, antiplatelet use, and follow-up time. Survival analysis and Cox proportional hazards were used to examine adverse events. Results: Propensity score matching generated two wellbalanced cohorts of 1593 patients each. Bleeding risk was significantly higher in patients treated for VTE compared to AF (see Fig.). After adjusting for the number of antiplatelet agents, being anticoagulated for VTE remained significantly associated with increased bleeding risk (hazard ratio: 1.23; 95% CI: 1.08-1.42). Conclusion: Patients anticoagulated for VTE have a significantly higher bleeding risk compared to similarly matched patients with AF. As most guidelines regarding antithrombotic management have focused on patients with AF, further research is needed to tailor these recommendations to the unique VTE population.

Internal Medicine Song M, Haymart B, Kong X, Ali M, Kozlowski J, Krol G, Kaatz S, Froehlich J, and Barnes G. Combination antithrombotic therapy and bleeding risk: Comparing atrial fibrillation and venous thromboembolism. Vascular Medicine 2021; 26(5):NP10. PMID: Not assigned. Full Text M. Song, University of Michigan, Ann Arbor, MI, United States Background: Existing studies regarding combination anticoagulant- antiplatelet management have focused on patients with atrial fibrillation (AF). It is unknown if the combination of anticoagulant-antiplatelet therapy presents a comparable risk of bleeding for patients with venous thromboembolism (VTE). Methods: Adult patients initiating warfarin at six anticoagulation clinics in Michigan from 2009 to 2020 were enrolled via a registry-based cohort study. Participants were stratified based on sole indication for anticoagulation: AF or VTE. Two propensity score-matched cohorts were generated based on demographics, comorbidities, antiplatelet use, and follow-up time. Survival analysis and Cox proportional hazards were used to examine adverse events. Results: Propensity score matching generated two wellbalanced cohorts of 1593 patients each. Bleeding risk was significantly higher in patients treated for VTE compared to AF (see Fig.). After adjusting for the number of antiplatelet agents, being anticoagulated for VTE remained significantly associated with increased bleeding risk (hazard ratio: 1.23; 95% CI: 1.08-1.42). Conclusion: Patients anticoagulated for VTE have a significantly higher bleeding risk compared to similarly matched patients with AF. As most guidelines regarding antithrombotic management have focused on patients with AF, further research is needed to tailor these recommendations to the unique VTE population.. Neurology LeWitt P, Klepitskaya O, Bahroo LB, Liang GS, Rattana S, Trotter J, and Serbin M. OPTI-on: A longitudinal real-world study of opicapone in patients with parkinson's disease and motor fluctuations. Annals of Neurology 2021; 90(SUPPL 27):S148. PMID: Not assigned. Full Text P. LeWitt, Henry Ford Hospital and Department of Neurology, Wayne State University, School of Medicine, West Bloomfield, MI, United States Background: Motor fluctuations and wearing-off of medications are common complications as Parkinson's disease (PD) progresses. Opicapone is an oral once-daily catechol-Omethyltransferase (COMT) inhibitor for adjunctive treatment to carbidopa/levodopa (CD/LD) in patients with PD and OFF-episodes. The efficacy and safety of opicapone was demonstrated in two phase 3 studies that were conducted in Europe and Asia (BIPARK-1 BIPARK-2). An observational phase 4 study in the United States (US), OPTI-ON (Opicapone Treatment Initiation Open-Label Study [NCT04787965]), is currently underway. This study examines treatment patterns, clinical outcomes, safety and tolerability of opicapone as an adjunctive treatment to CD/LD in patients with PD who are experiencing OFF-episodes. Methods: OPTI-ON is an ongoing, prospective, multicenter open-label study of opicapone as an adjunctive treatment to CD/LD. Approximately 250 clinically eligible patients with PD and OFF-episodes are being enrolled at about 50 sites in the US. Participation in the study is expected to continue for up to 6 months. Assessments include patient demographics and clinical history, opicapone treatment decisions (reasons for initiation or discontinuation), use of other PD medications, and changes in PD medications. Clinician- and patient-rated outcomes (PROs) include: Clinician Global Impression of Change; MDS-Unified Parkinson's Disease Rating Scale, Parts 1A and 4 (clinician) Parts 1B and 2 (patient); Patient Global Impression of Change; Patient Global Impression of Severity in ON- and OFF-states; and 8-item Parkinson's Disease Questionnaire. This is also the first longitudinal study to implement the new clinician- and patient-rated Non-Motor Fluctuation Assessment. Assessments are completed online by patients (electronic PROs) and performed by clinicians during office visits or via telemedicine. Results: Up-to-date findings will be presented. Conclusions: Results from the OPTI-ON study are expected to provide real-world information about the patterns of use and outcomes with adjunctive opicapone for treatment of PD in clinical practices throughout the US. These results will expand upon findings from the phase 3 clinical trials which established the efficacy and safety of once-daily opicapone in patients with PD and OFF-episodes.

Neurology Monternier PA, Singh J, Gluais P, Moller D, and Bozec S. Validation of direct AMP kinase (AMPK) activation for treatment of X-linked Adrenoleukodystrophy. Journal of the Neurological Sciences 2021; 429. PMID: Not assigned. Full Text Background and aims: X-linked Adrenoleukodystrophy (ALD and adrenomyeloneuropathy - AMN) is a neurologic peroxisomal disorder, caused by ABCD1-gene mutations, leading to Very Long Chain Fatty Acid (VLCFA; C26:0) accumulation, AMPK downregulation, inflammation, mitochondrial impairment and demyelination. We investigated PXL770, a clinical-stage new direct AMPK activator, in AMN/ALD models. Methods: AMN/ALD patient-derived fibroblasts/lymphocytes and ABCD1-KO mouse glial cells were exposed to PXL770 for 7 days. Phospho-AMPK was measured by Western-blot, VLCFA content by LC-MS, selected gene expression by RT-qPCR and oxygen consumption with a Seahorse Analyzer. PXL770 (oral 75 mg/kg, BID, 12 weeks) was administered to ABCD1-KO mice. VLCFA content was measured by LC-MS, sciatic nerve axonal morphology by electronic microscopy, and locomotor function by beam balance test. Results: In AMN fibroblasts PXL770 reduced C26:0 levels (−90%, p = 0.0001), increased compensatory ABCD2 mRNA levels (9-fold), and improved mitochondrial function by increasing basal and ATP-linked respiration (14% and 112%, respectively) and decreasing proton leak (−25%). Similar profile was achieved in ALD fibroblasts, ALD/AMN lymphocytes and ABCD1-KO mice glial cells. In ALD lymphocytes, PXL770 decreased mRNAs encoding pro-inflammatory proteins including NF-κB, iNOS and CCR3 (2.9-fold, 8.2-fold, 5.9-fold, respectively). In ABCD1-KO mice treated with PXL770, C26:0 levels were decreased in the spinal cord by 29% (greater VLCFA decrease was also observed in brain/plasma). Sciatic nerve axons showed less myelin invaginations (−61%) and neurologic function was improved compared to untreated mice. Conclusions: We established preclinical validation for the potential utility of direct AMPK activators as a treatment for X-ALD, supporting further development of PXL770 for this debilitating neurometabolic disease. Obstetrics, Gynecology and Women’s Health Services Cook A, Ghanem A, Hijaz M, Burmeister C, and Elshaikh M. Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S13-S14. PMID: Not assigned. [Cook, Andrew] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ghanem, Ahmed; Hijaz, Miriana; Elshaikh, Mohamed] Henry Ford Canc Inst, Detroit, MI USA. [Burmeister, Charlotte] Henry Ford Hlth Syst, Detroit, MI USA. Otolaryngology – Head and Neck Surgery Engel R, Etta P, Gahzi T, Williams A, Tam S, Momin S, Chang S, Ghanem T, Walker D, Siddiqui F, Ali H, Wu V, Sheqwara J, and Carlson M. Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S81-S81. PMID: Not assigned. [Engel, Ricardo; Etta, Patrick] Wayne State Univ, Sch Med, Detroit, MI 48202 USA. [Gahzi, Talha] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Tam, Samantha; Momin, Suhael; Chang, Steven; Ghanem, Tamer; Wu, Vivian] Henry Ford Canc Inst, Dept Otolaryngol, Detroit, MI USA. [Walker, Diana] Henry Ford Hlth Syst, Speech Language Pathol & Otolaryngol, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ali, Haythem; Sheqwara, Jawad] Henry Ford Canc Inst, Dept Hematol Oncol, Detroit, MI USA. [Carlson, Megan] Henry Ford Hlth Syst, Speech Language Pathol, Detroit, MI USA. Otolaryngology – Head and Neck Surgery Goosmann M, Chang S, Williams A, and Tam S. Sex Differences in Health Related Quality of Life in Head & Neck Cancer One Year After Treatment. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S82-S82. PMID: Not assigned.

[Goosmann, Madeline; Chang, Steven] Henry Ford Hosp, Detroit, MI 48202 USA. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Tam, Samantha] Henry Ford Canc Inst, Dept Otolaryngol, Detroit, MI USA. Otolaryngology – Head and Neck Surgery Riley J, Williams A, Best K, Tripathi N, Chang S, Ghanem T, Momin S, Siddiqui F, Wu V, and Tam S. Evaluating Quality of Life and Functional Outcomes in Salvage Surgery for Head and Neck Cancer. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S87-S87. PMID: Not assigned. [Riley, John] Henry Ford Macomb Hosp, Clinton, MI USA. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Best, Keisha; Tripathi, Nitika] Wayne State Univ, Sch Med, Detroit, MI USA. [Chang, Steven; Ghanem, Tamer; Momin, Suhael; Wu, Vivian; Tam, Samantha] Henry Ford Canc Inst, Dept Otolaryngol, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiation Oncol, Detroit, MI USA. Otolaryngology – Head and Neck Surgery Williams A, Olex M, Miller MK, Gilbert M, and Siddiqui F. Expanding Our Understanding of Adherence: The Role of Health Literacy and Cognitive Function in Adherence and Outcomes in Head and Neck Cancer. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S89-S90. PMID: Not assigned. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Olex, Maria] Med Coll Wisconsin, Wauwatosa, WI USA. [Miller, Mary Kate] UMass Mem Med Ctr, Worcester, MA USA. [Gilbert, Marissa] Henry Ford Hlth Syst, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Pathology and Laboratory Medicine Engel R, Etta P, Gahzi T, Williams A, Tam S, Momin S, Chang S, Ghanem T, Walker D, Siddiqui F, Ali H, Wu V, Sheqwara J, and Carlson M. Assessing Oral Intake Outcomes in Head and Neck Cancer Patients Treated with Definitive Radiation with or Without Chemotherapy. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S81-S81. PMID: Not assigned. [Engel, Ricardo; Etta, Patrick] Wayne State Univ, Sch Med, Detroit, MI 48202 USA. [Gahzi, Talha] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Tam, Samantha; Momin, Suhael; Chang, Steven; Ghanem, Tamer; Wu, Vivian] Henry Ford Canc Inst, Dept Otolaryngol, Detroit, MI USA. [Walker, Diana] Henry Ford Hlth Syst, Speech Language Pathol & Otolaryngol, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ali, Haythem; Sheqwara, Jawad] Henry Ford Canc Inst, Dept Hematol Oncol, Detroit, MI USA. [Carlson, Megan] Henry Ford Hlth Syst, Speech Language Pathol, Detroit, MI USA. Pathology and Laboratory Medicine Yahya J, Henkin D, Montecalvo J, and Abdulla RK. Prisoner of the Heart - Primary Unresectable Cardiac Angiosarcoma in an African American Man. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S128-S130. PMID: Not assigned. [Yahya, Jehan] Oregon Hlth & Sci Univ, OHSU, Portland, OR 97201 USA. [Henkin, David] UT Hlth, Houston, TX USA. [Montecalvo, Joseph; Abdulla, Rami Khoury] Henry Ford Hosp, Detroit, MI USA. Public Health Sciences Abu Rous F, Singh SRK, Li P, Elgamal M, Abunafeesa H, Chacko R, Vuyyala S, Alkhatib Y, and Kuriakose P. Satisfaction of hem/onc patients with video visits during the COVID-19 pandemic at a tertiary care center in Michigan. Journal of Clinical Oncology 2021; 39(28):4. PMID: Not assigned. Full Text

[Abu Rous, Fawzi; Singh, Sunny R. K.; Li, Pin; Elgamal, Mohamed; Abunafeesa, Hussna; Chacko, Rebecca; Vuyyala, Sowjanya; Alkhatib, Yaser; Kuriakose, Philip] Henry Ford Hlth Syst, Detroit, MI USA. Public Health Sciences Caldwell MT, Goyal N, Dudley A, Dehlendorf C, Scott J, Parke D, Vallee P, Daniels G, Manteuffel J, Thomas CSD, Hambrick N, Guetterman TC, Misra D, and Joseph CLM. ENGAGING CLINICIANS IN A PRE-IMPLEMENTATION ASSESSMENT OF THE WOMEN & PERSON-EMPOWERED COMMUNITY ACCESS FOR REPRODUCTIVE EQUITY (WE CARE) INTERVENTION. Contraception 2021; 104(4):468-468. PMID: Not assigned. Full Text [Caldwell, M. T.] Henry Ford Hlth Syst, Detroit, MI USA. Public Health Sciences Cook A, Ghanem A, Hijaz M, Burmeister C, and Elshaikh M. Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S13-S14. PMID: Not assigned. [Cook, Andrew] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ghanem, Ahmed; Hijaz, Miriana; Elshaikh, Mohamed] Henry Ford Canc Inst, Detroit, MI USA. [Burmeister, Charlotte] Henry Ford Hlth Syst, Detroit, MI USA. Public Health Sciences Dawkins BA, Garman L, Cejda N, Pezant N, Rasmussen A, Rybicki BA, Levin AM, Benchek P, Hawn TR, Seshadri C, Iannuzzi MC, Stein CM, and Montgomery CG. Individuals of african ancestry share HLA alleles protective against tuberculosis and sarcoidosis. Genetic Epidemiology 2021; 45(7):751-752. PMID: Not assigned. Full Text B.A. Dawkins, Genes and Human Disease, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Tuberculosis (TB) and sarcoidosis are distinct granulomatous disorders with numerous genetic associations. Human leukocyte antigen (HLA) is important in susceptibility and progression in both diseases. Although TB is caused by Mycobacterium tuberculosis, HLA associations in case control TB studies are highly variable, potentially due to phenotype heterogeneity, limited allelic resolution, and narrow analytical methods that exclude more complex associations common to biological data. Using four digit HLA alleles and applying more inclusive feature selection methodology, we provide the first HLA association analysis in TB that compares latent and active TB to individuals who display no evidence of infection and maintain negative diagnostic tests over a long term period of exposure to individuals with active TB. To detect a more comprehensive array of statistical effects, we introduce a novel application of nearest neighbor feature selection that uses a consensus approach across three input neighborhood algorithms to define allelic importance for classifying outcomes. This nearest neighbor approach is generally applicable in the context of binary classification and regression, with either categorical or continuous predictors. We compare our findings to sarcoidosis, both persistent and resolving. We provide the first comparison between TB and sarcoidosis resistance phenotypes, showing that HLA-DRB1 alleles ∗01:02, ∗03:02, ∗12:01, and ∗13:02 are associated with both resolving sarcoidosis in African Americans and long term resistance to latent or active TB in Ugandans. Public Health Sciences Kirsch C, Schaff E, Parikh P, Movsas B, Siddiqui F, Kwon D, Li P, Khan G, and Shah R. Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S54. PMID: Not assigned. [Kirsch, Celina] Henry Ford Canc Inst, Detroit, MI USA. [Schaff, Eric; Parikh, Parag; Kwon, David; Li, Pin; Khan, Gazala; Shah, Rupen] Henry Ford Hlth Syst, Detroit, MI USA. [Movsas, Benjamin; Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA.

Public Health Sciences Liang E, Greer G, Burmeister C, Massa P, Dragovic J, and Parikh P. Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S55. PMID: Not assigned. [Liang, Evan; Greer, Garret; Burmeister, Charlotte; Massa, Peter; Dragovic, Jadranka; Parikh, Parag] Henry Ford Hlth Syst, Detroit, MI USA. Public Health Sciences Natour AK, Shepard A, Nypaver T, Rteil A, Corcoran P, Tang XQ, and Kabbani L. Impact of Preoperative Anemia in Patients Undergoing Peripheral Vascular Intervention. Journal of Vascular Surgery 2021; 74(4):E370-E371. PMID: Not assigned. [Natour, Abdul Kader; Shepard, Alexander; Nypaver, Timothy; Rteil, Ali; Corcoran, Paul; Tang, Xiaoqin; Kabbani, Loay] Henry Ford Hlth Syst, Vasc Surg, Detroit, MI USA. Public Health Sciences Pezant N, Garman L, Pelikan RC, Rasmussen A, Li C, Rybicki BA, Iannuzzi MC, and Montgomery CG. Unique TGF-ß signaling pathway in African Americans with fibrotic sarcoidosis. Genetic Epidemiology 2021; 45(7):782. PMID: Not assigned. Full Text N. Pezant, Genes and Human Disease, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas in any number of organs, but with pulmonary manifestation in most patients. Progressive pulmonary disease (PPD), likely including pulmonary fibrosis (PF), leads to worse clinical outcomes and prognosis. Previous genome-wide association studies of PPD in sarcoidosis patients of European ancestry (EA) identified multiple associations with genes in the TGF-ß signaling pathway, specifically TGFß1, TGFß2, TGFß3, GREM1, and ANXA11. This is important as TGF-ß is widely accepted as a master regulator of fibrosis. The involvement of TGF-ß signaling has not previously been investigated in patients of African Ancestry (AA) nor has it been investigated beyond variant association. In this study we aimed to identify genetic and genomic factors influencing fibrotic disease in a cohort of AA patients with PF compared to non-fibrotic sarcoidosis patients using whole genome sequencing and cell-type specific expression data. We identified suggestive associations between variants in the region of TGFß3 as well as other TGF-ß pathway genes PARS2, LTBP1, PVT1, SLC29A3, OTX2-AS1/EXOC5, and SPOP; all of which are primarily involved in TGF-ß signaling and fibrosis or play a regulatory role. Single-cell RNA sequencing data were obtained and cell-type specific expression quantitative trait loci (eQTL) are being identified to better understand the role risk variants play in the mechanism of fibrotic development. Our findings support both the role of TGF-ß signaling in the development of PF as well as differences in the dysregulation of TGF-ß signaling by ancestry. Pulmonary and Critical Care Medicine Devpura S, Feldman A, Rusu S, Brown S, Cook A, Movsas A, Sun Z, Vance S, Simoff M, Ajlouni M, Siddiqui MS, Movsas B, and Chetty I. The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S11-S11. PMID: Not assigned. [Devpura, Suneetha; Feldman, Aharon; Rusu, Samuel; Brown, Stephen; Movsas, Avielle; Sun, Zhen; Vance, Sean; Simoff, Michael; Ajlouni, Munther; Siddiqui, M. Salim; Chetty, Indrin] Henry Ford Canc Inst, HFHS, Detroit, MI USA. [Cook, Andrew; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA.

Radiation Oncology Cook A, Ghanem A, Hijaz M, Burmeister C, and Elshaikh M. Survival Outcomes and Patterns of Recurrence After Adjuvant Vaginal Cuff Brachytherapy and Chemotherapy in Early-Stage Uterine Serous Carcinoma. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S13-S14. PMID: Not assigned. [Cook, Andrew] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ghanem, Ahmed; Hijaz, Miriana; Elshaikh, Mohamed] Henry Ford Canc Inst, Detroit, MI USA. [Burmeister, Charlotte] Henry Ford Hlth Syst, Detroit, MI USA. Radiation Oncology Devpura S, Feldman A, Rusu S, Brown S, Cook A, Movsas A, Sun Z, Vance S, Simoff M, Ajlouni M, Siddiqui MS, Movsas B, and Chetty I. The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S11-S11. PMID: Not assigned. [Devpura, Suneetha; Feldman, Aharon; Rusu, Samuel; Brown, Stephen; Movsas, Avielle; Sun, Zhen; Vance, Sean; Simoff, Michael; Ajlouni, Munther; Siddiqui, M. Salim; Chetty, Indrin] Henry Ford Canc Inst, HFHS, Detroit, MI USA. [Cook, Andrew; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Radiation Oncology Dragovic J, Aldridge K, and Doemer A. Magnetic Resonance Guided Accelerated Partial Breast Irradiation - Single Institution Experience Using ViewRay Technology. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S39-S40. PMID: Not assigned. [Dragovic, Jadranka] Henry Ford Hlth Syst, Detroit, MI USA. [Aldridge, Kate] Henry Ford Hosp, Detroit, MI 48202 USA. [Doemer, Anthony] Henry Ford Canc Inst, Detroit, MI USA. Radiation Oncology Kirsch C, Schaff E, Parikh P, Movsas B, Siddiqui F, Kwon D, Li P, Khan G, and Shah R. Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S54. PMID: Not assigned. [Kirsch, Celina] Henry Ford Canc Inst, Detroit, MI USA. [Schaff, Eric; Parikh, Parag; Kwon, David; Li, Pin; Khan, Gazala; Shah, Rupen] Henry Ford Hlth Syst, Detroit, MI USA. [Movsas, Benjamin; Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Radiation Oncology Laucis A, Hochstedler K, Schipper M, Paximadis P, Boike T, Bergsma D, Movsas B, Ajlouni M, Kretzler A, Spratt D, Dess R, Mietzel M, Dominello M, Matuszak M, Jagsi R, Hayman J, Pierce L, and Jolly S. Racial Differences in Treatments and Toxicity in Non-Small Cell Lung Cancer Patients Treated with Thoracic Radiation Therapy. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S25-S25. PMID: Not assigned. [Laucis, Anna; Hochstedler, Kimberly; Pierce, Lori; Jolly, Shruti] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Schipper, Matthew; Dess, Robert; Mietzel, Melissa; Matuszak, Martha; Jagsi, Reshma; Hayman, James] Univ Michigan, Ann Arbor, MI 48109 USA. [Paximadis, Peter] Lakeland Radiat Oncol, St Joseph, MO USA. [Boike, Thomas] 21st Century Oncol, Ft Myers, FL USA. [Bergsma, Derek] Mercy Hlth St Marys, Dept Radiat Oncol, Grand Rapids, MI USA. [Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. [Ajlouni, Munther] Henry Ford Canc Inst, HFHS, Detroit, MI USA. [Kretzler, Annette] Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI USA. [Dominello, Michael] Wayne State Univ, Detroit, MI 48202 USA.

Radiation Oncology Liang E, Gilbert M, and Siddiqui F. Recurrence of Primary Mucosal Head and Neck Squamous Cell Carcinoma in Solid Organ Transplant Recipients. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S85-S85. PMID: Not assigned. [Liang, Evan; Gilbert, Marissa] Henry Ford Hlth Syst, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Radiation Oncology Liang E, Greer G, Burmeister C, Massa P, Dragovic J, and Parikh P. Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S55. PMID: Not assigned. [Liang, Evan; Greer, Garret; Burmeister, Charlotte; Massa, Peter; Dragovic, Jadranka; Parikh, Parag] Henry Ford Hlth Syst, Detroit, MI USA. Radiation Oncology Riley J, Williams A, Best K, Tripathi N, Chang S, Ghanem T, Momin S, Siddiqui F, Wu V, and Tam S. Evaluating Quality of Life and Functional Outcomes in Salvage Surgery for Head and Neck Cancer. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S87-S87. PMID: Not assigned. [Riley, John] Henry Ford Macomb Hosp, Clinton, MI USA. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Best, Keisha; Tripathi, Nitika] Wayne State Univ, Sch Med, Detroit, MI USA. [Chang, Steven; Ghanem, Tamer; Momin, Suhael; Wu, Vivian; Tam, Samantha] Henry Ford Canc Inst, Dept Otolaryngol, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiation Oncol, Detroit, MI USA. Radiation Oncology Schaff E, Kirsch C, Parikh P, Chuong M, Herrera R, Asbun H, Jimenez R, Siddiqui F, Khan G, Aparo S, De Zarraga F, Ucar A, Shah R, Li P, Movsas B, and Kwon D. Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S57-S57. PMID: Not assigned. [Schaff, Eric; Kirsch, Celina; Parikh, Parag; Khan, Gazala; Shah, Rupen; Li, Pin; Kwon, David] Henry Ford Hlth Syst, Detroit, MI USA. [Chuong, Michael; Herrera, Roberto; Asbun, Horacio; Jimenez, Ramon; Aparo, Santiago; De Zarraga, Fernando; Ucar, Antonio] Miami Canc Inst, Miami, FL USA. [Siddiqui, Farzan; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Radiation Oncology Williams A, Olex M, Miller MK, Gilbert M, and Siddiqui F. Expanding Our Understanding of Adherence: The Role of Health Literacy and Cognitive Function in Adherence and Outcomes in Head and Neck Cancer. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S89-S90. PMID: Not assigned. [Williams, Amy] Henry Ford Hosp, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. [Olex, Maria] Med Coll Wisconsin, Wauwatosa, WI USA. [Miller, Mary Kate] UMass Mem Med Ctr, Worcester, MA USA. [Gilbert, Marissa] Henry Ford Hlth Syst, Detroit, MI USA. [Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Surgery Kirsch C, Schaff E, Parikh P, Movsas B, Siddiqui F, Kwon D, Li P, Khan G, and Shah R. Stereotactic MRI-guided Adaptive Radiation Therapy for Non-metastatic Pancreatic Cancer; Outcomes and Toxicity Analysis for Patients Treated in an Underserved Urban Center. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S54-S54. PMID: Not assigned.

[Kirsch, Celina] Henry Ford Canc Inst, Detroit, MI USA. [Schaff, Eric; Parikh, Parag; Kwon, David; Li, Pin; Khan, Gazala; Shah, Rupen] Henry Ford Hlth Syst, Detroit, MI USA. [Movsas, Benjamin; Siddiqui, Farzan] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA. Surgery Mohammad F, Kabbani L, Henke P, Battaglia M, Mouawad N, Osborne N, Corriere M, and Nypaver T. Single-state Transcarotid Artery Revascularization Experience: Outcomes and Impact on Carotid Procedural and Operative Volumes. Journal of Vascular Surgery 2021; 74(4):E395-E395. PMID: Not assigned. [Mohammad, Farah; Nypaver, Timothy] Henry Ford Hosp, Div Vasc Surg, Detroit, MI 48202 USA. [Kabbani, Loay] Henry Ford Hosp, Detroit, MI 48202 USA. [Henke, Peter; Osborne, Nick; Corriere, Matt] Univ Michigan, Ann Arbor, MI 48109 USA. [Battaglia, Michael] Methods Consultants Ann Arbor, Ann Arbor, MI USA. [Mouawad, Nicolas] McLaren Thumb Reg Hosp, Bay City, MI USA. Surgery Natour AK, Shepard A, Nypaver T, Rteil A, Corcoran P, Tang XQ, and Kabbani L. Impact of Preoperative Anemia in Patients Undergoing Peripheral Vascular Intervention. Journal of Vascular Surgery 2021; 74(4):E370-E371. PMID: Not assigned. [Natour, Abdul Kader; Shepard, Alexander; Nypaver, Timothy; Rteil, Ali; Corcoran, Paul; Tang, Xiaoqin; Kabbani, Loay] Henry Ford Hlth Syst, Vasc Surg, Detroit, MI USA. Surgery Natour AK, Shepard A, Nypaver T, Weaver M, Peshkepija A, and Kabbani L. Socioeconomic Disparities Do Not Affect Outcomes in Acute Limb Ischemia. Journal of Vascular Surgery 2021; 74(4):E372-E373. PMID: Not assigned. [Natour, Abdul Kader; Shepard, Alexander; Nypaver, Timothy; Weaver, Mitchell; Peshkepija, Andy; Kabbani, Loay] Henry Ford Hlth Syst, Vasc Surg, Detroit, MI USA. Surgery Schaff E, Kirsch C, Parikh P, Chuong M, Herrera R, Asbun H, Jimenez R, Siddiqui F, Khan G, Aparo S, De Zarraga F, Ucar A, Shah R, Li P, Movsas B, and Kwon D. Surgery After Neoadjuvant Stereotactic MRI Guided Adaptive Radiation in Pancreatic Cancer: Multi-institutional Toxicity and Survival Outcomes. American Journal of Clinical Oncology-Cancer Clinical Trials 2021; 44(10):S57-S57. PMID: Not assigned. [Schaff, Eric; Kirsch, Celina; Parikh, Parag; Khan, Gazala; Shah, Rupen; Li, Pin; Kwon, David] Henry Ford Hlth Syst, Detroit, MI USA. [Chuong, Michael; Herrera, Roberto; Asbun, Horacio; Jimenez, Ramon; Aparo, Santiago; De Zarraga, Fernando; Ucar, Antonio] Miami Canc Inst, Miami, FL USA. [Siddiqui, Farzan; Movsas, Benjamin] Henry Ford Canc Inst, Dept Radiat Oncol, Detroit, MI USA.

HFHS Publications on COVID-19

Dermatology Torres AE, Ozog DM, and Hruza GJ. Coronavirus Disease 2019 and Dermatology Practice Changes. Dermatol Clin 2021; 39(4):587-597. PMID: 34556248. Full Text

Hematology-Oncology Abu Rous F, Singh SRK, Li P, Elgamal M, Abunafeesa H, Chacko R, Vuyyala S, Alkhatib Y, and Kuriakose P. Satisfaction of hem/onc patients with video visits during the COVID-19 pandemic at a tertiary care center in Michigan. Journal of Clinical Oncology 2021; 39(28):4. PMID: Not assigned. Conference Abstract. Full Text Hematology-Oncology Smeltzer M, Bunn B, Choi YS, Coate L, Corona-Cruz J, Drilon A, Duma N, Edelman M, Fidler MJ, Gadgeel S, Goto Y, Herbst R, Hesdorffer M, Higgins K, Labdi B, Leal T, Liu S, Mazotti J, Novello S, Patel S, Popat S, Ramirez R, Reckamp K, Reguart N, Soo R, Tan A, Wolf J, Yano S, Stiles B, and Baird A. OA17.04 The Global Impact of COVID-19 on Telehealth and Care for Persons With Thoracic Cancers. Journal of Thoracic Oncology 2021; 16(10):S879. PMID: Not assigned. Conference Abstract. Full Text Hospital Medicine Bossone E, Cademartiri F, AlSergani H, Chianese S, Mehta R, Capone V, Ruotolo C, Tarrar IH, Frangiosa A, Vriz O, Maffei V, Annunziata R, Galzerano D, Ranieri B, Sepe C, Salzano A, Cocchia R, Majolo M, Russo G, Longo G, Muto M, Fedelini P, Esposito C, Perrella A, Guggino G, Raiola E, Catalano M, De Palma M, Romano L, Romano G, Coppola C, Mauro C, and Mehta RH. Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era. J Cardiovasc Dev Dis 2021; 8(10). PMID: 34677195. Full Text

Hospital Medicine Mann CZ, Abshire C, Yost M, Kaatz S, Swaminathan L, Flanders SA, Prescott HC, and Gagnon-Bartsch JA. Derivation and external validation of a simple risk score to predict in-hospital mortality in patients hospitalized for COVID-19: A multicenter retrospective cohort study. Medicine (Baltimore) 2021; 100(40). PMID: 34622851. Full Text Neurosurgery Siddiqui MS, Jimenez-Shahed J, Mari Z, Walter BL, De Jesus S, Panov F, Schwalb JM, York MK, Sarva H, Bertoni JM, Patel N, Zhang L, McInerney J, and Rosenow JM. North American survey on impact of the COVID-19 pandemic shutdown on DBS care. Parkinsonism Relat Disord 2021; 92:41-45. PMID: 34688029. Full Text

Orthopedics/Bone and Joint Center Sims BM, Patel AD, Garnica BG, Faraj MT, Tang A, Parsons T, Hoegler JJ, and Day CS. Effect of elective surgery cancellations during the COVID-19 pandemic on patients' activity, anxiety and pain. Br J Surg 2021; Epub ahead of print. PMID: 34611698. Full Text Public Health Sciences Abu Rous F, Singh SRK, Li P, Elgamal M, Abunafeesa H, Chacko R, Vuyyala S, Alkhatib Y, and Kuriakose P. Satisfaction of hem/onc patients with video visits during the COVID-19 pandemic at a tertiary care center in Michigan. Journal of Clinical Oncology 2021; 39(28):4. PMID: Not assigned. Conference Abstract. Full Text Public Health Sciences Prescott SL, Wegienka G, Kort R, Nelson DH, Gabrysch S, Hancock T, Kozyrskyj A, Lowry CA, Redvers N, Poland B, Robinson J, Moubarac JC, Warber S, Jansson J, Sinkkonen A, Penders J, Erdman S, Nanan R, van den Bosch M, Schneider K, Schroeck NJ, Sobko T, Harvie J, Kaplan GA, Moodie R,

Lengnick L, Prilleltensky I, Celidwen Y, Berman SH, Logan AC, and Berman B. Project Earthrise: Proceedings of the Ninth Annual Conference of inVIVO Planetary Health. Int J Environ Res Public Health 2021; 18(20). PMID: 34682400. Full Text Public Health Sciences Rapp A, Fall G, Radomsky AC, and Santarossa S. Child Maltreatment During the COVID-19 Pandemic: A Systematic Rapid Review. Pediatr Clin North Am 2021; 68(5):991-1009. PMID: 34538308. Full Text