Presentation 2

David Hull, MD, FACS

Director of TransplantationHartford Hospital

Co-Medical DirectorLifeChoice Donor Services

DONOR KIDNEY PUMPING FROM DONOR KIDNEY PUMPING FROM OPO / TRANSPLANT CENTER OPO / TRANSPLANT CENTER

PERSPECTIVEPERSPECTIVE

KIDNEY COLD STORAGE (CS) – PUMP PRESERVATION (PP)

• Dr. Najarian 1964 LR Kidney Transplant San Francisco

• Folkert Belzer, MD – Pump Preservation– 1967 ‘24 and 72 Canine

Kidney Preservation’– 1967 Human Kidney Tx 17

Hr Storage

Lancet Sept, 1967 536-39

KIDNEY PRESERVATION COLD STORAGE (CS)

• G.M. Collins, MD– UCLA – Lancet 1969 ‘Kidney

Preservation 30 Hours Ice Storage’ Canine Model

– Dog Kidneys From L.A.• Tel Aviv• Sydney• London

Lancet Dec. 1969 , 1219-22

WATERS RENAL PRESERVATION SYSTEM- RM3

• Belzer 1967 Lab & Clinical• Belzer & Truman (Moffin Hosp)

1971 Waters Company – Membrane Oxygenator

• 1971 Storage of a Kidney Shipped to Holland Tx 37 Hr

• UW Solution 1987 – Clinical– 1979 UW CS– 1984 Gluconate UW PP

• Characteristics Past & Present– PO2 & PCO2 Controlled– Ph Controlled at 4ºC– Microfiltration– Pulsatile Pump– Solution Gluconate UW 1984

• SRTR 1994-2003– 98,736 Deceased Donor Kidneys

• Pump Preservative (PP) – Less ECD Discards p < 0.0001– Less DGF

• Group - With High Risk Factors for DGF

• Prolonged Ischemic Times– 10 % Overall Decrease in

Discards With PP = +1500 Transplants / 10 year

– Slight Improvement in Survival

AJT 2005;5: 1681-88

LIFEPORT- ORGAN RECOVERY SYSTEM

• FDA Approved 2003

• Characteristics– Solution KPS-1

• UW Gluconate– Measurements

• Pressure Limit 30mm HG• 30 Beats/Min• Averages Pressure over 30 Beats• Measures Volume of Flow• Ω = Average Press / Flow• Data Base Downloads

– Battery• Charge 40-48 Hrs• Life 3 Years

– Back Up Cold Storage• 24 Hrs

Unadjusted Adjusted*

OR p OR p

Non-DCD 1.00 Ref 1.00 Ref

DCD 2.61 < 0.0001 3.11 < 0.0001

Not Pumped 1.00 Ref 1.00 Ref

Pumped by OPO only 0.99 0.94 0.70 0.0003

Pumped by Center only 0.99 0.94 0.80 0.0605

Pumped by OPO and Center 0.78 0.15 0.58 0.0005

Not Pumped During Transfer 1.00 Ref 1.00 Ref

Pumped During Transfer 0.86 0.21 0.89 0.3268

•Adjusted for donor age, sex, race, hypertension status• diabetic status, cause of death, creatinine and ECD status•, recipient age, sex, race, cause of ESRD and PRA, •HLA matching, ABO compatibility, shared status and cold ischemia time.


OR p OR p


DCD 2.43 < 0.0001 3.03 < 0.0001

Resistance

0-0.17 0.99 0.954 1.02 0.881

0.18-0.23 1.00 Ref 1.00 Ref

0.24-0.31 1.16 0.177 1.14 0.250

0.32-0.60 1.46 0.001 1.47 0.002

Missing 1.22 0.108 1.35 0.020

Unadjusted and Adjusted Models DCD Delayed Graft Function 7/1/04-5/1/06

n=16,889

n=4,226

SRTR

THE AGING KIDNEY

Age > 65 USA Population

2000 35 Million

2010 54 Million

Prevalence of Moderate to Severe Renal Failure = 20.6%

Without Hypertension and Diabetes = 10.8%

Brenner & Rector’s The Kidney 7th Ed

AGING AND GFR

Figure 53-13 Percentiles of glomerular filtration rate (GFR) and Cockcroft-Gault creatinine clearance (CCr) by age, plotted on the same graph as data by Davies and Shock[124] on inulin clearance in healthy men. Percentiles are calculated using a fourth-order polynomial weighted quantile regression. The solid line shows a polynomial regression to the inulin data. Dashed lines without symbols show the 5th and 95th percentiles for GFR estimates. (Reprinted with permission from Coresh J, Astor BC, Greene T, et al: Prevalence of chronic kidney disease and decreased kidney function in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 41:1–12, 2003.)

Brenner & Rector’s The Kidney 7th Ed 2004 Saunders

https://portal.harthosp.org/mdconsulthome/das/book/body/517104904/1201/1294.html#4-u1.0-B0-7216-0164-2..50057-4--bib124

THE AGING & EXTENDED CRITERIA DONOR KIDNEYS

• Decreased Renal Weight and Mass• Thickening Intra-Renal Vasculature

– Arteriolar Hyaline Thickening

• Glomerulosclerosis– Ischemia of Cortex

• Vascular Disease• Decreased Endothelial Growth Factors

– Numbers Decrease 30%-50% by Age 70

• Tubulointerstitial Fibrosis• Metabolic Derangements• Donation Process

Deceased Cardiac Donor (DCD)

• Profound Tissue Stresses – – Ischemia / Hypoxemia

• What Objective Measures Predict Transplant Outcomes In The Recipient??– Standardize Recording & Definitions of DCD Events– Understand The Tolerance Of Operative Procedures

Used In The Donation Process– Objective Measures ?

• Pump Preservation Characteristics– Simultaneously Limiting DGF & ? Improved Outcome

• Biopsy Analysis

DONATION AFTER CARDIAC DEATH INTRAOPERATIVE MANAGEMENT Enter OR Date / Time / / @ ______________EST

Withdrawal of support/ Time / / @ ______________EST

Agonal phase begins/ Time (SBP &/or O2 sat drops below 80) / / @ ______________EST

Cardiac Death / Time / / @ ______________EST

Incision Date / Time / / @ ______________EST

Abdominal Aortic Cannulation / Time / / @ ______________EST

Thoracic Aorta Cannulation / Time / / @ ______________EST

Portal Flush / Time / / @ ______________EST

Liver at the back table / Time / / @ ______________EST

Kidneys at the back table / Time / / @ ______________EST

Pancreas at the back table / Time / / @ ______________EST

Lungs at the back table / Time / / @ ______________EST

Exit OR Date / Time

/ /

@ ______________EST

Kidney Selection Process

• Know Parameters Reflective of Outcomes– SCD, DCD and ECD Characteristics– ? DCD / ECD and ? Unstable SCD

• Objective Data of Individual Kidneys– Preservation Time, etc– Performance on Pumping– Biopsy Findings

• Adequacy of Specimen – Sample Size• Alignment of Specimen for Processing

– Frozen Section and Permanent Slides

• Standardization of Reporting

Pumped Kidneys: Unadjusted and Adjusted Models for Delayed Graft Function, 7/1/04-

5/1/06Unadjusted Adjusted*

OR p OR p


DCD 2.43 < 0.0001 3.03 < 0.0001Resistance

0-0.17 0.99 0.954 1.02 0.881

0.18-0.23 1.00 Ref 1.00 Ref

0.24-0.31 1.16 0.177 1.14 0.250

0.32-0.60 1.46 0.001 1.47 0.002Missing 1.22 0.108 1.35 0.020

•Adjusted for donor age, sex, race, hypertension status, diabetic status, cause of death•, creatinine and ECD status, recipient age, sex, race, cause of ESRD and PRA,• HLA matching, ABO compatibility, shared status and cold ischemia time.

Non-DCD (n=15640) DCD (n=1249)

High Risk of Discard (HRD) Kidneys

Deceased Donor Kidneys with at Least Four of the Following:• DCD• Not Pumped• HCV Positive• Hepatitis B Core Antibody Positive• Creatinine Clearance < 62• Pumped with Resistance Greater Than 0.349• Donor Age 45 or Greater• Donor Creatinine > 2.0• Donor History of Diabetes• Donor Cause of Death CNS Tumor or Other• Percentage Glomerulosclerosis >5%• Donor History of Hypertension

DONOR QUALITY AND DISCARD RATE

SRTR 11-1-2003 to 10-31-2005

Number RecoveredNumber

TransplantedPercent

Discarded

Donor Type HRD?

1,277 1,098 14.0%DCD No

Yes 425 202 52.5%Total 1,702 1,300 23.6%

ECD HRD?

2,744 2,056 25.1%No

Yes

2,614 1,093 58.2%Total 5,358 3,149 41.2%

SCD HRD?

17,226 16,108 6.5%No

Yes

1,304 809 38.0%Total 18,530 16,917 8.7%

Total HRD?

21,247 19,262 9.3%No

Yes

4,343 2,104 51.6%Total 25,590 21,366 16.5%

ECD Kidneys Recovered For Transplant And Discarded

GS % Not Pumped

Pumped

0-5% 27.3 % 22.2 % P< 0.01

6-10% 37.9 % 29.5 % P< 0.01

11-15% 48.5 % 30.3 % P< 0.001

16-20% 63.6 % 46.5 % P< 0.001

> 20% 81.2 % 61.5 % P< 0.001

SRTR 2000-2004

LCDS SELECTIVE BX & PUMP PRESERVATION

• Pump Preservation 1971 – Present• Waters (RM3) 1971 – 2005• Lifeport ORS 2005 – Present• Pump Preservation

– DCD– ECD– OTHER SELECTIVE CASES– PROCEDURE

• DONOR KIDNEYS BIOPSIED• FROZEN SECTIONS READ AT DONOR HOSPITAL

– PATHOLOGIST AND SURGEON• IF ACCEPTABLE PLACED ON PUMP

– Ω - 0.25 Acceptable; 0.25-0.40 ? DGF, > 0.40 ? PNF• IF TRANSPLANTED PERMANENT SECTIONS REVIEWED POST

TRANSPLANT

LCDS SELECTIVE BX & PUMP PRESERVATION 2003*-06

DISCARD/TOTAL

Discard

% DISCARD/ TOTAL

Discard

%DISCARD/ TOTAL

Discard

%SCD 25/235 10.6 25/214 11.7 ZERO/

210.0

ECD 20/58 34.5 14/19 73.4 6/39 15.4

DCD 2/16 12.5 ZERO/ZERO

N/A 2/16 12.5

TOTAL 47/309 15.2 39/233 16.7 8/74 10.8

NOT PUMPED PUMPEDTOTAL

* ECD Defined

PUMP PRESERVATION

• Organ Procurement Organization– COST ?– PERSONEL ?– BENEFITS

TRANSPLANT CENTER vs OPO ?

• Transplant Center– INCREASED ORGAN

COSTS FROM SAC FEES ?

– BENEFITS PATIENT

AND CENTER• LESS DGF• LIMITS EFFECTS OF

CIT• DECREASED LOS• DECREASED COSTS

7/04-6/06 SRTR

Number LOS

DGF 4315 9

No DGF 15314 6

P<0.0001

UNIT COST $30,000* $36,000*

MAINTENCE

KIT

$500

N/A

CANULARS $4000 N/A

TRAINING $1000 $1400

TOTAL $35,500 $37,400

CASSETTE $800 $1100

SOLUTIONS

ADDITIVES

$234

$40

$468

N/A

STAFF TIME MONITORING ? EXTRA HR

TOTAL $1074 + $1600

BIOPSY $400 $400

TOTAL $1404 + $2000

* Based on 2 kidneys

WATERS RM3 LIFEPORT ORS

ONE TIME COSTS

COSTS FOR PUMPIMG 2 KIDNEYS

COSTS RELATED TO PUMP PRESERVATION

(LCDS)

ESTIMATED BENEFIT AND COSTS TO OPO WITH PUMP PRESERVATION AND

BIOPSY• Additional 6 Kidney Tx’s

– SAC $20,000 = $120,000– Pumping Costs = $4,800– Procurement Costs = $21,000– Biopsies = $2,400– Buy Out Costs = $3,036– TOTAL COSTS = $31,236

• OPO TOTAL = + $88,764

• ORS Disposables = $1600– 2 Kidneys– FTE Time

• Procurement Costs = $7000– 1 Donor = 2 Kidneys

• Buy Out Lifeport = $506– Cost Per Kidney

• Biopsy = $400– Per Kidney

Donor Type Number Recovered

Number Transplanted

Percent Discarded

DCD 1702 1300 23.6%

ECD 5,358 3,149 41.2%

SCD 18,530 16,917 8.7%

Total 25,590 21,366 16.5%

LCDS# LCDS

Discard

Rate

SRTR

Discard

Rate

% ∆

Of Discard

ADDED KIDNEYS

DCD 16 12.5% 23.6% 11.1% ≈ 2

ECD 58 34.5% 41.2% 6.7% ≈ 4

ESTIMATED BENEFIT AND COSTS TO OPO WITH PUMP PRESERVATION AND BIOPSY

METHODOLOGY• Additional 499 Kidney Tx’s

– SAC $20,000 = $10,980,000– Pumping Costs = $439,200– Procurement Costs = $1,925,000– Biopsies = $219,600– Buy Out Costs = $277,794– TOTAL COSTS = $2,861,594

• OPO TOTAL = + $8,118,406– 549 Additional Transplants

• ORS Disposables = $1600– 2 Kidneys– FTE Time

• Procurement Costs = $7000– 1 Donor = 2 Kidneys

• Buy Out Lifeports = $506– Cost Per Kidney

• Biopsy = $400– Per Kidney

SRTR 11-1-2003 to 10-31-2005

Donor Type

Number Recovered

Number Transplanted

Percent Discarded

DCD 1702 1300 23.6%

ECD 5,358 3,149 41.2%

SCD 18,530 16,917 8.7%

Total 25,590 21,366 16.5%

Donor Type

Number Recovered

Percent ∆* Discarded

Additional Kidneys

DCD 1702 11.1% 190

ECD 5,358 6.7% 359

Total 549

*Based on LCDS Discard Rates

CONCLUSIONS

• Cold Storage vs Pump Preservation– OUTCOME / DEBATE GOES ON

• Pump Preservation– Provides Objective Data– Decreased DGF (Decreased LOS)– Decreased Discard Rates / Increases Transplants– Financially Friendly to the OPO– Financially Friendly to the Transplant Center– Advantageous to the RECIPIENT

ACKNOWLEDGEMENTS

SURGEONS HARTFORD HOSPITAL &BAYSTATE MEDICAL CENTER

GEORGE LIPKOWITZ, MD

LIFECHOICE DONOR SERVICESDEB SAVARIA & LAINE KRISIUNAS

PRESERVATIONISTSDAN DURKIN

DONOR KIDNEY PUMPING FROM DONOR KIDNEY PUMPING FROM OPO / TRANSPLANT CENTER OPO / TRANSPLANT CENTER

PERSPECTIVEPERSPECTIVE

DATA FOR DCD AND DGF AND ΩTable 3.3: Sample Size and Number of Delayed Graft Function Events, 7/1/04-5/1/06

Status

Non-DCD (n=15640) DCD (n=1249)

Ndelaye

d% N delayed %

Not Pumped 12260 2955 24.1 403

177 43.9

Pumped by OPO only 994 234 23.5 506

209 41.3

Pumped by Center only 955 218 22.8 41 19 46.3

Pumped by OPO and Center 1431 213 14.9 299

128 42.8

Not Pumped During Transfer*

13493 3235 24.0 790

349 44.2

Pumped During Transfer* 2153 385 17.9 459

184 40.1

* According to OPO

1/2001 – 10/2005

Donor Type

Number Recovered

Number Transplanted

Percent Discarded

DCD 1702 1300 23.6%

ECD 5,358 3,149 41.2%

SCD 18,530 16,917 8.7%

Total 25,590 21,366 16.5%

Table 3.4: Unadjusted and Adjusted Models for Delayed Graft Function, 7/1/04-5/1/06


OR p OR p


DCD 2.61 < 0.0001 3.11 < 0.0001

Not Pumped 1.00 Ref 1.00 Ref

Pumped by OPO only 0.99 0.94 0.70 0.0003

Pumped by Center only 0.99 0.94 0.80 0.0605

Pumped by OPO and Center 0.78 0.15 0.58 0.0005

Not Pumped During Transfer

1.00 Ref 1.00 Ref

Pumped During Transfer 0.86 0.21 0.89 0.3268

•Adjusted for donor age, sex, race, hypertension status, diabetic status, cause of death•, creatinine and ECD status, recipient age, sex, race, cause of ESRD and PRA,• HLA matching, ABO compatibility, shared status and cold ischemia time.

Non-DCD (n=15640) DCD (n=1249)

Table 3.3: Sample Size and Number of Delayed Graft Function Events, 7/1/04-5/1/06

Status

Non-DCD (n=15640) DCD (n=1249)

Ndelaye

d% N delayed %

Not Pumped 12260 2955 24.1 403

177 43.9

Pumped by OPO only 994 234 23.5 506

209 41.3

Pumped by Center only 955 218 22.8 41 19 46.3

Pumped by OPO and Center 1431 213 14.9 299

128 42.8

Not Pumped During Transfer*

13493 3235 24.0 790

349 44.2

Pumped During Transfer* 2153 385 17.9 459

184 40.1

* According to OPO

SRTRSRTR

Pumping and Outcomes of Deceased Donor Kidneys: Review of

Recent SRTR Analyses

Laura L. Christensen, M.S.Scientific Registry of Transplant Recipients

Arbor Research Collaborative for HealthOctober 26, 2006

SRTRSRTR

Background

• OPTN Organ Availability Committee has long been interested in the benefits of pumping of kidneys

• SRTR has performed many analyses examining the relationship between pumping and:– Discard

– Delayed Graft Function (DGF)

– Graft Survival

SRTRSRTR

Ascertainment of Pumping Data

• Until recently, pumping of kidneys was only reported by the OPO

• Beginning July 1, 2004, transplant centers began to report pumping

SRTRSRTR

Analyses Based on OPO Pumping Only

SRTRSRTR

DCD Kidneys

0

20

40

60

80

100

32 OPOs, 7 w/ 0%

Perc

ent D

CD

s Pu

mpe

d

ECD Kidneys

0

20

40

60

80

100

57 OPOs, 25 w/ 0%

Perc

ent E

CD

s Pu

mpe

d

All Kidneys

0

20

40

60

80

100

58 OPOs, 20 w/ 0%

Per

cent

Pum

ped

SCD Kidneys

0

20

40

60

80

100

58 OPOs, 25 w/ 0%

Perc

ent S

CD

s Pu

mpe

d

Pulsatile Perfusion by OPO and Organ Type*

Range: 0-85%

Median: 8%

Discard Rate: 16.5%

Range: 0-84%

Median: 2.3%

Discard Rate: 8.7%

Range: 0-94%

Median: 18%

Discard Rate: 41.2%

Range: 0-100%

Median: 73%

Discard Rate:

23.5%

*13 OPOs w/ 0 DCDs, 13 OPOs w/ 1-4 DCDs

*Non-preemptive kidney-only transplants 7/1/04 – 6/30/05

SRTRSRTR

Complications of Varying OPO Pumping Practice

• OPOs that never pump give us no information about pumping outcomes

• OPOs that pump selectively appear to mostly pump kidneys perceived as poor quality

• OPOs that pump most kidneys appear to not pump the poorest organs

SRTRSRTR

SCD Kidneys: % DGF by OPO Pumping Practice

21.425.1

22.1 21.6

13.1

23.7

8.5

0

5

10

15

20

25

30

None 1-50% 51-100%Percent Transplanted SCD Kidneys

Pumped

Per

cent

SC

D w

/ DG

F

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

24

8377

30 6

13565 20 151 1569

OR for 100% vs. 0% pumped by OPO: 0.45; p < 0.0001

OR for kidney level pumped vs. not: 0.51; p < 0.0001

Among non-preemptive deceased donor transplants, January 1, 2001 to July 31, 2004

SRTRSRTR

DCD Kidneys: % DGF by OPO Pumping Practice

37.6

46.846.540.9 38.6

47.5

37.4

0

10

20

30

40

50

None 1-50% 51-100%Percent Transplanted DCD Kidneys

Pumped

Per

cent

DC

D w

/ DG

F

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

15

187

8 20

287 139 77 521

OR for 100% vs. 0% pumped by OPO: 0.64; p=0.11

OR for kidney level pumped vs. not: 0.76; p=0.12


SRTRSRTR

ECD Kidneys: % DGF by OPO Pumping Practice

38.933.8

37.0 36.2

29.328.6 27.2

0

10

20

30

40

None 1-50% 51-100%Percent Transplanted ECD Kidneys

Pumped

Per

cent

EC

D w

/ DG

F

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

27

1806

20 13

1425 514 302 662




SRTRSRTR

Adjusted Cox Regression for Graft Failure/Death

OPO Level (Testing % of Population Pumped by OPO)

Kidney Level (Testing Pumping of each Kidney)

Transplant Population

HR for 100% vs. 0%

p-value

HR p-value

All 0.905 0.4559 0.919 0.2310 SCD 0.933 0.5829 0.880 0.1539 DCD 1.23 0.2653 1.23 0.2807 ECD 0.86 0.2036 0.953 0.5837

Among deceased donor transplants, January 1, 2001 to July 31, 2004

SRTRSRTR

SCD Kidneys: % Discard by OPO Pumping Practice

7.5

20.7

7.4 7.89.3

13.9

4.9

0

5

10

15

20

25

None 1-50% 51-100%

Percent Recovered SCD Kidneys Pumped

Per

cent

SC

D D

isca

rded

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

22

8941

32 6

17592 831 1091 2139



Among deceased donor kidneys recovered for transplant, January 1, 2001 to July 31, 2004

SRTRSRTR

DCD Kidneys: % Discard by OPO Pumping Practice

16.6

41.5

22.917.0

20.517.7 17.4

05

1015202530354045

None 1-50% 51-100%

Percent Recovered DCD Kidneys Pumped

Per

cent

DC

D D

isca

rded

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

15

249

9 19

379 198 94 628




SRTRSRTR

ECD Kidneys: % Discard by OPO Pumping Practice

43.7

69.9

41.2 40.233.630.8

23.0

010203040506070

None 1-50% 51-100%

Percent Recovered ECD Kidneys Pumped

Per

cent

EC

D D

isca

rded

Not Pumped

Overall

Pumped

n OPOs:

n Kidneys:

22

2420

34 4

3728 1352 93 318




SRTRSRTR

Analyses Based on OPO and Center Pumping

SRTRSRTR

Pumping at the OPO and Center7/1/04 – 5/1/06

Center Pumped Not Pumped

Pumped 1431 (9.1%) 994 (6.4%) OPO

Not Pumped 955 (6.1%) 12260 (78.4%)

Center Pumped Not Pumped

Pumped 299 (23.9%) 506 (40.5%) OPO

Not Pumped 41 (3.2%) 403 (32.3%)

Non-DCD Kidneys

DCD Kidneys

SRTRSRTR

Relationship between Pumping and Delayed Graft Function7/1/04-5/1/06, n=16,889

AOR p DCD 3.11 < 0.0001 Pumped by OPO 0.70 0.0003 Pumped by Center 0.81 0.0413 Pumped During Transfer 0.89 0.3065 Adjusted for donor age, sex, race, hypertension status, diabetic status, cause of

death, creatinine and ECD status, recipient age, sex, race, cause of ESRD and PRA, HLA matching, ABO compatibility, cold ischemia time and shared status.

SRTRSRTR

Among Pumped Kidneys: Resistance and Delayed Graft Function

7/1/04-5/1/06, n=4,226

OR p DCD Status Non-DCD 1.00 Ref DCD 3.03 < 0.0001 Resistance 0-0.17 1.02 0.881 0.18-0.23 1.00 Ref 0.24-0.31 1.14 0.250 0.32-0.60 1.47 0.002 Missing 1.35 0.020

Adjusted for donor age, sex, race, hypertension status, diabetic status, cause of death, creatinine and ECD status, recipient age, sex, race, cause of ESRD and PRA, HLA matching, ABO compatibility, shared status and cold ischemia time.

SRTRSRTR

Conclusions

• Pumping practice varies widely by OPO for each type of kidney (SCD, DCD, ECD)

• Varying practices introduce selection bias

• Associations between pumping and discard/DGF vary by kidney type and pumping practice

• Analyses at OPO and kidney levels are not always consistent

• A randomized controlled trial is needed to determine whether pumping provides beneficial effects

Presentation 2

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