213 results on '"Heimbach JK"'
Search Results
2. Perioperative management of patients undergoing combined heart-liver transplantation
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Barbara, DW, Rehfeldt, KH, Heimbach, JK, Rosen, CB, Daly, RC, and Findlay, JY
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- 2014
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3. Contrast in cytokine expression between patients with monoclonal gammopathy of undetermined significance or multiple myeloma
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Donovan, KA, Lacy, MQ, Kline, MP, Ahmann, GJ, Heimbach, JK, Kyle, RA, and Lust, JA
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- 1998
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4. Imaging for the diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis
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Roberts, LR, Sirlin, CB, Zaiem, F, Almasri, J, Prokop, LJ, Heimbach, JK, Murad, MH, and Mohammed, K
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Adult ,Male ,Gastroenterology & Hepatology ,Carcinoma ,Liver Neoplasms ,Clinical Sciences ,Immunology ,Contrast Media ,Reproducibility of Results ,Hepatocellular ,Middle Aged ,Medical Biochemistry and Metabolomics ,Magnetic Resonance Imaging ,Multimodal Imaging ,X-Ray Computed ,Computer-Assisted ,Humans ,Female ,Image Interpretation ,Tomography - Abstract
Multiphasic computed tomography (CT) and magnetic resonance imaging (MRI) are both used for noninvasive diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. To determine if there is a relative diagnostic benefit of one over the other, we synthesized evidence regarding the relative performance of CT, extracellular contrast-enhanced MRI, and gadoxetate-enhanced MRI for diagnosis of HCC in patients with cirrhosis. We also assessed whether liver biopsy versus follow-up with the same versus alternative imaging is best for CT-indeterminate or MRI-indeterminate liver nodules in patients with cirrhosis. We searched multiple databases from inception to April 27, 2016, for studies comparing CT with extracellular contrast-enhanced MRI or gadoxetate-enhanced MRI in adults with cirrhosis and suspected HCC. Two reviewers independently selected studies and extracted data. Of 33 included studies, 19 were comprehensive, while 14 reported sensitivity only. For all tumor sizes, the 19 comprehensive comparisons showed significantly higher sensitivity (0.82 versus 0.66) and lower negative likelihood ratio (0.20 versus 0.37) for MRI over CT. The specificities of MRI versus CT (0.91 versus 0.92) and the positive likelihood ratios (8.8 versus 8.1) were not different. All three modalities performed better for HCCs ≥2 cm. Performance was poor for HCCs
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- 2018
5. Prevalence and clinical consequences of Hepatitis E in patients who underwent liver transplantation for chronic Hepatitis C in the United States
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Koning, Ludi, Charlton, MR, Pas, Suzan, Heimbach, JK, Osterhaus, Ab, Watt, KD, Janssen, HLA, de Knegt, Rob, Baltissen - van der Eijk, Annemiek, Koning, Ludi, Charlton, MR, Pas, Suzan, Heimbach, JK, Osterhaus, Ab, Watt, KD, Janssen, HLA, de Knegt, Rob, and Baltissen - van der Eijk, Annemiek
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Background: Infection with hepatitis E virus (HEV) in immunocompromised patients can lead to severe liver disease. Treatment options for HEV include peginterferon or ribavirin, routinely also used for the treatment of hepatitis C virus (HCV) infection. We determined the prevalence and clinical consequences of HEV in United States (US) based patients who underwent liver transplantation (LT) for chronic HCV. Methods: Seroprevalence of HEV in 145 US LT recipients with a history of chronic HCV was determined pre-LT, 1, 3 and 5 years post-LT. All last available samples and all samples in IgM positive patients and post-LT IgG seroconverters were tested for HEV RNA. Results: Overall anti-HEV seroprevalence was 42 %. Five patients were HEV IgM positive pre-LT, one patient had IgM seroconversion post-LT and eight patients had IgG seroconversion post-LT. None of the tested samples were positive for HEV RNA. Eight out of nine of the post-LT seroconverters had been treated for HCV recurrence before or at the moment of seroconversion. Conclusions: LT recipients in the US are at risk of acquiring HEV. Post-LT HCV treatment with interferons and/or ribavirin may have protected patients against chronic HEV. With the arrival of new direct antiviral agents for the treatment of HCV and the elimination of peginterferon and ribavirin from HCV treatment regimens, the prevalence of chronic HEV in this population may rise again.
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- 2015
6. Free fatty acid storage in human visceral and subcutaneous adipose tissue: role of adipocyte proteins.
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Ali AH, Koutsari C, Mundi M, Stegall MD, Heimbach JK, Taler SJ, Nygren J, Thorell A, Bogachus LD, Turcotte LP, Bernlohr D, Jensen MD, Ali, Asem H, Koutsari, Christina, Mundi, Manpreet, Stegall, Mark D, Heimbach, Julie K, Taler, Sandra J, Nygren, Jonas, and Thorell, Anders
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ENZYME metabolism ,ADIPOSE tissues ,ANTIGENS ,BODY composition ,FAT cells ,FATTY acids ,OBESITY ,RESEARCH funding ,TRANSFERASES - Abstract
Objective: Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat.Research Design and Methods: Elective surgery patients received a bolus of [1-(14)C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured.Results: Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol · kg adipose lipid(-1) · min(-1), P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity.Conclusions: Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation. [ABSTRACT FROM AUTHOR]- Published
- 2011
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7. Successful liver transplantation for hilar cholangiocarcinoma.
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Heimbach JK
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- 2008
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8. Liver transplantation for hepatocellular carcinoma.
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Heimbach JK
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Liver transplantation has emerged as an optimal treatment for stage I and II hepatocellular carcinoma for patients with underlying cirrhosis as it provides a treatment for the underlying liver disease as well as a reduced incidence of recurrent cancer. The current system of organ allocation in the United States allows an opportunity for liver transplantation for patients with tumor burden within the Milan criteria (a single tumor 2-5 cm or up to 3 lesions with none >3 cm). Outcomes of patients receiving transplants within these criteria approach outcomes for patients receiving transplants for all indications (85.9%, 74.8%, and 64.1% actuarial survival at 1, 3, and 5 years, respectively, for those with HCC receiving transplants compared with 82%, 73%, and 67% for the entire cohort). Transarterial chemoembolization, radiofrequency ablation, and other pretransplant treatment modalities aimed to slowing tumor growth for patients on a transplant waiting list are commonly used, although the impact on pretransplant disease progression or posttransplant survival remains uncertain. There is continued controversy over expanding patient selection criteria, in particular for those who have undergone downstaging of tumors. In addition, the role of certain immunosuppressive agents such as sirolimus in the reducing HCC recurrence posttransplant remains unclear. [ABSTRACT FROM AUTHOR]
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- 2008
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9. Neoadjuvant therapy and liver transplantation for hilar cholangiocarcinoma: is pretreatment pathological confirmation of diagnosis necessary?
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Rosen CB, Darwish Murad S, Heimbach JK, Nyberg SL, Nagorney DM, and Gores GJ
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- 2012
10. Management and Long-Term Outcomes of Patients With Hepatic Epithelioid Hemangioendothelioma.
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Sawma T, Sultan A, Abdulmoneim S, Grotz T, Rosen CB, Taner T, Heimbach JK, Warner SG, Siontis BL, Ho TP, Robinson SI, and Thiels CA
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Background and Objectives: Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular neoplasm characterized by variable clinical behavior. Our aim was to describe the therapeutic approach for HEHE at diagnosis and define clinicopathological characteristics associated with tumor progression and long-term survival., Methods: This is a retrospective study that includes patients with HEHE who received treatment at Mayo Clinic Rochester between 1984 and 2023., Results: Eighty patients were included in the study (median age: 44 years; 62.5% female), 24 underwent liver transplantation, 26 underwent liver resection, and 30 were managed medically. The 3-year overall survival rates were 86.7%, 80.9%, and 51.1%, respectively. Notably, 26 patients had extrahepatic metastases at the time of diagnosis, four (16.7%) in the transplantation group, four (15.4%) in the resection group, and 18 (69.2%) in the nonsurgical group. On multivariable modeling, bone metastasis was independently associated with long-term mortality (HR 6.3, p < 0.001) while lung metastasis and surgical intervention were not associated with long-term mortality (HR 0.8, p = 0.8; HR 1.1, p = 0.9, respectively)., Conclusion: Bone metastasis emerged as a strong predictor of poor survival. Hence, aggressive surgical intervention may not be advantageous in patients with skeletal metastases but can still be offered for those with other extrahepatic metastases., (© 2024 Wiley Periodicals LLC.)
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- 2024
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11. Transplantation Within 6 Months of Registration does not Enhance Survival for Patients with Perihilar Cholangiocarcinoma.
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Nasser-Ghodsi N, Eaton JE, Smith BH, Venkatesh SK, Heimbach JK, Taner T, Welle CL, Ilyas SI, Gores GJ, and Rosen CB
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Objectives: Determine if timing of transplantation affects patient mortality., Background: Neoadjuvant therapy and liver transplantation has emerged as an excellent treatment option for select patients with perihilar cholangiocarcinoma (pCCA). However, the optimal timing of transplantation is not known., Methods: We reviewed all patients registered for a standardized pCCA protocol between 1996 - 2020 at our center. After adjusting for confounders, we examined the association of waiting time with patient mortality in an intention-to-treat cohort (n=392) and those who received a liver transplant (n=256)., Results: The median (interquartile range) time from registration to transplant or drop out was 5.74 (3.25-7.06) months. Compared to a short wait time (0-3 months), longer waiting times did not affect all-cause mortality: (3-6 months) hazard ratio (HR) 0.98; 95% CI 0.52-1.84; (6-9 months) HR 0.80; 95% CI 0.39-1.65; (9-12 months) HR 0.56; 95% CI 0.26-1.22. Subgroups with a shorter waiting time had similar survival to those with long waiting times: living donor available HR 0.97; 95% CI 0.67-1.42; AB or B blood group HR 0.93; 95% CI 0.62-1.39. Longer waiting times were associated with decreased all-cause mortality after transplantation (HR 0.92; 95% CI 0.87-0.97). This benefit began after a 6 month waiting time minimum (HR 0.53; 95% CI 0.26-1.10) and increased further after 9 months (HR; 0.43 95% CI 0.20-0.93). Waiting time was not associated with residual adenocarcinoma in the explant (odds ratio 0.99; 95% CI 0.98-1.00)., Conclusions: A waiting time of at least 6 months will optimize results with transplantation without affecting overall (intention-to-treat) patient survival., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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12. Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.
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Li Z, Rammohan A, Gunasekaran V, Hong S, Chih-Yi Chen I, Kim J, Hervera Marquez KA, Hsu SC, Kirimker EO, Akamatsu N, Shaked O, Finotti M, Yeow M, Genedy L, Dutkowski P, Nadalin S, Boehnert MU, Polak WG, Bonney GK, Mathur A, Samstein B, Emond JC, Testa G, Olthoff KM, Rosen CB, Heimbach JK, Taner T, Wong TC, Lo CM, Hasegawa K, Balci D, Cattral M, Sapisochin G, Selzner N, Jeng LB, Broering D, Joh JW, Chen CL, Suh KS, Rela M, and Clavien PA
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- Humans, Male, Female, Retrospective Studies, Middle Aged, Adult, Risk Factors, Follow-Up Studies, Prognosis, Anastomotic Leak etiology, Biliary Tract Diseases etiology, Incidence, Survival Rate, Liver Transplantation adverse effects, Living Donors, Postoperative Complications etiology, Graft Survival
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In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2024
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13. Outcomes of bariatric surgery in the setting of compensated advanced chronic liver disease associated with clinically significant portal hypertension: a multicenter, retrospective, cohort study on feasibility and safety.
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Temime V, Ghanem OM, Heimbach JK, Diwan TS, Tranchart H, Abdallah H, Blanchard C, Lontrichard M, Reche F, Borel AL, Belluzzi A, Foletto M, Manno E, Poghosyan T, Chierici A, and Iannelli A
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- Humans, Retrospective Studies, Female, Male, Middle Aged, Adult, Feasibility Studies, Treatment Outcome, Postoperative Complications epidemiology, Postoperative Complications etiology, Chronic Disease, Aged, Liver Diseases surgery, Liver Diseases complications, Bariatric Surgery adverse effects, Bariatric Surgery methods, Hypertension, Portal complications, Hypertension, Portal surgery
- Abstract
Background: The obesity epidemic has led to an increase in the proportion of patients with chronic liver disease due to metabolic associated steatosic liver disease and in the prevalence of obesity in patients with cirrhosis. Metabolic and bariatric surgery (MBS) has been proven to determine weight loss, obesity-related medical problems remission, and liver steatosis, inflammation, and fibrosis improvement. However, cirrhosis and portal hypertension are well-known risk factors for increased morbidity and mortality after surgery. The aim of this study is to evaluate the safety of MBS in patients with compensated advanced chronic liver disease (cALCD) and clinically significant portal hypertension (CSPH)., Material and Methods: This is an international, multicentric, retrospective study on 63 individuals affected by obesity with cALCD and CSPH who underwent MBS in tertiary referral centers with experts hepatobiliary surgeons between January 2010 and October 2022. The primary endpoint was postoperative mortality at 90 days. The secondary endpoints included postoperative weight loss at last follow-up and postoperative complication rate. In addition, the authors performed subgroup analyses of Child-Pugh (A vs. B) score, MELD (≤9 vs. >9) score, and type of surgery., Results: One patient (1.6%) experienced gastric leakage and mortality. There were three (5%) reported cases of portal vein thrombosis, two (3%) postoperative acute renal failure, and one (1.6%) postoperative encephalopathy. Child-Pugh score A resulted to be a protective factor for intraoperative bleeding requiring transfusion at univariate analysis (OR: 0.73, 95% CI: 0.55-0.97, P =0.046) but not at multivariate analysis. MELD>9 score and the type of surgery did not result to be a risk factor for any postoperative complication., Conclusion: MBS is safe in patients with cALCD and CSPH performed in tertiary bariatric referral centers with hepatobiliary expert surgeons. Larger, prospective studies with longer follow-up periods are needed to confirm these results., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)
- Published
- 2024
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14. Improved Prioritization of the Liver Transplant Waitlist: Weighing the Risks.
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Heimbach JK and Allen AM
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- Humans, Risk Assessment, Risk Factors, Health Priorities, Patient Selection, Tissue and Organ Procurement, Liver Transplantation adverse effects, Waiting Lists
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- 2024
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15. One step closer to equity in liver transplant: The National Liver Review Board and the partnership that made it possible.
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Heimbach JK and Taner T
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- Humans, Liver, Liver Transplantation adverse effects, Tissue and Organ Procurement
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- 2024
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16. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma.
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Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, and Taddei TH
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- Humans, Contrast Media, Tomography, X-Ray Computed, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular prevention & control, Liver Neoplasms diagnosis, Liver Neoplasms prevention & control
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- 2023
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17. Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.
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Li Z, Rammohan A, Gunasekaran V, Hong S, Chen IC, Kim J, Hervera Marquez KA, Hsu SC, Kirimker EO, Akamatsu N, Shaked O, Finotti M, Yeow M, Genedy L, Dutkowski P, Nadalin S, Boehnert MU, Polak WG, Bonney GK, Mathur A, Samstein B, Emond JC, Testa G, Olthoff KM, Rosen CB, Heimbach JK, Taner T, Wong TC, Lo CM, Hasegawa K, Balci D, Cattral M, Sapisochin G, Selzner N, Bin Jeng L, Broering D, Joh JW, Chen CL, Suk KS, Rela M, and Clavien PA
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- Adult, Humans, Living Donors, Benchmarking, Treatment Outcome, Retrospective Studies, Severity of Illness Index, Graft Survival, Liver Transplantation, End Stage Liver Disease surgery, Liver Diseases complications, Thrombosis
- Abstract
Objective: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT)., Background: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments., Methods: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians., Results: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%)., Conclusions: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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18. Liver transplantation in the patient with physical frailty.
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Tandon P, Zanetto A, Piano S, Heimbach JK, and Dasarathy S
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- Humans, Liver Cirrhosis, Obesity, Liver Transplantation, Sarcopenia complications, Sarcopenia epidemiology, Frailty complications, Frailty epidemiology
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Frailty is a decline in functional reserve across multiple physiological systems. A key component of frailty is sarcopenia, which denotes a loss of skeletal muscle mass and impaired contractile function that ultimately result in physical frailty. Physical frailty/sarcopenia are frequent and contribute to adverse clinical outcomes before and after liver transplantation. Frailty indices, including the liver frailty index, focus on contractile dysfunction (physical frailty), while cross-sectional image analysis of muscle area is the most accepted and reproducible measure to define sarcopenia. Thus, physical frailty and sarcopenia are interrelated. The prevalence of physical frailty/sarcopenia is high in liver transplant candidates and these conditions have been shown to adversely impact clinical outcomes including mortality, hospitalisations, infections, and cost of care both before and after transplantation. Data on the prevalence of frailty/sarcopenia and their sex- and age-dependent impact on outcomes are not consistent in patients on the liver transplant waitlist. Physical frailty and sarcopenic obesity are frequent in the obese patient with cirrhosis, and adversely affect outcomes after liver transplantation. Nutritional interventions and physical activity remain the mainstay of management before and after transplantation, despite limited data from large scale trials. In addition to physical frailty, there is recognition that a global evaluation including a multidisciplinary approach to other components of frailty (e.g., cognition, emotional, psychosocial) also need to be addressed in patients on the transplant waitlist. Recent advances in our understanding of the underlying mechanisms of sarcopenia and contractile dysfunction have helped identify novel therapeutic targets., (Copyright © 2023. Published by Elsevier B.V.)
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- 2023
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19. Corrigendum to 'Assessment of long-term outcomes post living liver donation highlights the importance of scientific integrity when presenting transplant registry data' [American Journal of Transplantation. Volume 22, Issue 6, March 2023, Pages 1519-1522].
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Emamaullee J, Heimbach JK, Olthoff KM, Pomfret EA, Roberts JP, and Selzner N
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- 2023
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20. Timing is everything: sleeve gastrectomy and liver transplantation.
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Ryan RJ, Heimbach JK, and Diwan TD
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- Humans, Gastrectomy adverse effects, Liver Transplantation adverse effects, Obesity, Morbid surgery, Laparoscopy
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- 2023
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21. Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.
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Sawinski D, Lai JC, Pinney S, Gray AL, Jackson AM, Stewart D, Levine DJ, Locke JE, Pomposelli JJ, Hartwig MG, Hall SA, Dadhania DM, Cogswell R, Perez RV, Schold JD, Turgeon NA, Kobashigawa J, Kukreja J, Magee JC, Friedewald J, Gill JS, Loor G, Heimbach JK, Verna EC, Walsh MN, Terrault N, Testa G, Diamond JM, Reese PP, Brown K, Orloff S, Farr MA, Olthoff KM, Siegler M, Ascher N, Feng S, Kaplan B, and Pomfret E
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- Female, Humans, Healthcare Disparities, Kidney, Tissue Donors, United States, Waiting Lists, Frailty, Organ Transplantation, Tissue and Organ Procurement
- Abstract
Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed., (Copyright © 2022 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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22. Human Obesity Attenuates Cardioprotection Conferred by Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells.
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Yu S, Klomjit N, Jiang K, Zhu XY, Ferguson CM, Conley SM, Obeidat Y, Kellogg TA, McKenzie T, Heimbach JK, Lerman A, and Lerman LO
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- Humans, Mice, Animals, Infant, Newborn, Myocardium, Obesity, Adipose Tissue, Cardiomyopathies, Hypertension, Mesenchymal Stem Cells, Mesenchymal Stem Cell Transplantation methods
- Abstract
To explore the impact of obesity on reparative potency of adipose tissue-derived mesenchymal stromal/stem cells (A-MSC) in hypertensive cardiomyopathy, A-MSC were harvested from subcutaneous fat of obese and age-matched non-obese human subjects during bariatric or kidney donation surgeries, and then injected into mice 2 weeks after inducing renovascular hypertension (RVH) or sham surgery. Two weeks later, left ventricular (LV) function and deformation were estimated in vivo by micro-magnetic resonance imaging and myocardial damage ex vivo. Blood pressure and myocardial wall thickening were elevated in RVH + Vehicle and normalized only by lean-A-MSC. Both A-MSC types reduced LV mass and normalized the reduced LV peak strain radial in RVH, yet obese-A-MSC also impaired LV systolic function. A-MSC alleviated myocardial tissue damage in RVH, but lean-A-MSC decreased oxidative stress more effectively. Obese-A-MSC also showed increased cellular inflammation in vitro. Therefore, obese-A-MSC are less effective than lean-A-MSC in blunting hypertensive cardiomyopathy in mice with RVH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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23. Temporal Trends in Portopulmonary Hypertension Model for End-stage Liver Disease Exceptions and Outcomes.
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Del Valle KT, Krowka MJ, Heimbach JK, Taner T, and DuBrock HM
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Model for end-stage liver disease (MELD) exception criteria for portopulmonary hypertension (POPH) were created to prioritize patients for liver transplant before POPH progression. Little is known about trends in POPH exception frequency, disease severity, pulmonary hypertension treatment patterns, or outcomes since the POPH MELD exception began., Methods: Using data from the Organ Procurement and Transplantation Network database, we describe the frequency of POPH MELD exceptions between 2006 and 2019, compare baseline patient characteristics, and characterize trends in liver disease and POPH severity' as well as POPH treatment and outcomes' over time. To facilitate comparison, we divided this 14-y period into 3 "eras" (2006-2010, 2011-2015, and 2016-2019)., Results: Between 2006 and 2019, 504 unique POPH MELD exceptions were granted. Both liver disease severity and patient age have increased over time ( P = 0.04 and P = 0.006, respectively). Posttreatment hemodynamic values (mean pulmonary arterial pressure and pulmonary vascular resistance) have significantly improved ( P < 0.001 and P = 0.008, respectively). Treatment with endothelin receptor antagonists has become more prevalent, whereas use of parenteral therapy and monotherapy regimens has decreased ( P < 0.001). Neither waitlist nor liver transplant mortality outcomes have significantly changed over the eras analyzed., Conclusions: In conclusion, 504 patients have received POPH MELD exceptions between 2006 and 2019. Since 2010, nearly all patients granted POPH MELD exceptions have met hemodynamic criteria for POPH. Over time, there has been a trend toward older age and higher MELD scores with significant changes in pulmonary arterial hypertension treatment patterns and an improvement in posttreatment hemodynamics without major change in outcomes., Competing Interests: H.M.D. has served on advisory boards for Janssen. The other authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
- Published
- 2022
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24. Liver Transplantation as a New Standard of Care in Patients With Perihilar Cholangiocarcinoma? Results From an International Benchmark Study.
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Breuer E, Mueller M, Doyle MB, Yang L, Darwish Murad S, Anwar IJ, Merani S, Limkemann A, Jeddou H, Kim SC, López-López V, Nassar A, Hoogwater FJH, Vibert E, De Oliveira ML, Cherqui D, Porte RJ, Magliocca JF, Fischer L, Fondevila C, Zieniewicz K, Ramírez P, Foley DP, Boudjema K, Schenk AD, Langnas AN, Knechtle S, Polak WG, Taner CB, Chapman WC, Rosen CB, Gores GJ, Dutkowski P, Heimbach JK, and Clavien PA
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- Benchmarking, Humans, Standard of Care, Bile Duct Neoplasms, Cholangiocarcinoma surgery, Klatskin Tumor pathology, Klatskin Tumor surgery, Liver Transplantation
- Abstract
Objective: To define benchmark values for liver transplantation (LT) in patients with perihilar cholangiocarcinoma (PHC) enabling unbiased comparisons., Background: Transplantation for PHC is used with reluctance in many centers and even contraindicated in several countries. Although benchmark values for LT are available, there is a lack of specific data on LT performed for PHC., Methods: PHC patients considered for LT after Mayo-like protocol were analyzed in 17 reference centers in 2 continents over the recent 5-year period (2014-2018). The minimum follow-up was 1 year. Benchmark patients were defined as operated at high-volume centers (≥50 overall LT/year) after neoadjuvant chemoradiotherapy, with a tumor diameter <3 cm, negative lymph nodes, and with the absence of relevant comorbidities. Benchmark cutoff values were derived from the 75th to 25th percentiles of the median values of all benchmark centers., Results: One hundred thirty-four consecutive patients underwent LT after completion of the neoadjuvant treatment. Of those, 89.6% qualified as benchmark cases. Benchmark cutoffs were 90-day mortality ≤5.2%; comprehensive complication index at 1 year of ≤33.7; grade ≥3 complication rates ≤66.7%. These values were better than benchmark values for other indications of LT. Five-year disease-free survival was largely superior compared with a matched group of nodal negative patients undergoing curative liver resection (n=106) (62% vs 32%, P <0.001)., Conclusion: This multicenter benchmark study demonstrates that LT offers excellent outcomes with superior oncological results in early stage PHC patients, even in candidates for surgery. This provocative observation should lead to a change in available therapeutic algorithms for PHC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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25. Disparities in curative treatments and outcomes for early stage intrahepatic cholangiocarcinoma in the United States.
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Lee YT, Singal AG, Lauzon M, Agopian VG, Luu M, Noureddin M, Todo T, Kim IK, Friedman ML, Kosari K, Nissen NN, Roberts LR, Heimbach JK, Gores GJ, and Yang JD
- Subjects
- Bile Ducts, Intrahepatic pathology, Bile Ducts, Intrahepatic surgery, Early Detection of Cancer, Humans, Prognosis, United States epidemiology, Bile Duct Neoplasms diagnosis, Bile Duct Neoplasms surgery, Cholangiocarcinoma diagnosis, Cholangiocarcinoma surgery
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Background: Curative surgical treatments afford the best prognosis for patients with intrahepatic cholangiocarcinoma (iCCA); however, the comparative effectiveness of treatment options and factors associated with curative treatment receipt for early stage iCCA remain unknown., Methods: The authors identified patients who were diagnosed with early stage iCCA, defined as a unifocal tumor <3 cm, during 2004-2018 from the National Cancer Database. Multivariable logistic and Cox regression analyses were used to identify the factors associated with curative treatment and overall survival (OS), respectively., Results: The proportion of patients with early stage iCCA increased from 4.5% in 2004 to 7.3% in 2018, with the odds of early stage detection increasing by 3.1% per year (odds ratio [OR], 1.031; 95% CI, 1.015-1.049). Of 1093 patients who had early stage iCCA, 464 (42.5%) underwent resection, 113 (10.3%) underwent ablation, 62 (5.7%) underwent liver transplantation, and 454 (41.5%) received noncurative treatments. Hispanic patients (adjusted OR [aOR], 0.57; 95% CI, 0.33-0.97) and Black patients (aOR, 0.47; 95% CI, 0.28-0.77) were less likely to receive curative treatments than White patients. Compared with patients who underwent surgical resection, those who underwent liver transplantation had a trend toward improved OS (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.37-1.08), whereas those who underwent local ablation (aHR, 1.39; 95% CI, 1.01-1.92) and noncurative treatments (aHR, 3.97; 95% CI, 3.24-4.88) experienced worse OS., Conclusions: More than one third of patients with early stage iCCA did not receive curative treatment, with Hispanic and Black patients being less likely to receive curative treatments than White patients. Surgical resection and liver transplantation were associated with improved survival compared with local ablation. Future studies should investigate disparities in curative treatment receipt and outcomes for early stage iCCA., (© 2022 American Cancer Society.)
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- 2022
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26. The role of preoperative optimization of the nutritional status on the improvement of short-term outcomes after liver transplantation? A review of the literature and expert panel recommendations.
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Victor DW 3rd, Zanetto A, Montano-Loza AJ, Heimbach JK, Towey J, Spiro M, Raptis DA, and Burra P
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- Humans, Retrospective Studies, Obesity, Observational Studies as Topic, Nutritional Status, Liver Transplantation
- Abstract
Background: Malnutrition is a known risk factor for postoperative morbidity and mortality in patients awaiting liver transplantation (LT). Malnutrition is a potentially reversible risk factor, though there are no clear guidelines on the best mechanism for an improvement. It also remains unclear if preoperative nutritional interventions have benefits to post-transplant outcomes for transplant recipients., Objectives: Primary objective: To identify if preoperative optimization of nutritional status is associated with improved short-term outcomes after LT., Secondary Objectives: To determine if preoperative improvement of malnutrition improves short-term outcomes after LT, as well as if weight loss in obese patients affects short-term outcomes after LT., Data Sources: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central., Methods: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. POSPERO Protocol ID: CRD42021237450 RESULTS: 3851 records were identified in searching the databases, 3843 records were excluded by not fulfilling eligibility criteria. Seven full-text articles were included for the final analysis of which three were randomized controlled trials, one was prospective observational studies, and three were retrospective observational studies. No appreciable difference in mortality, post-transplant complication rate was noted across the studies. Length of stay (LOS) was noted to be shorter in two observational studies of Vitamin D deficiency in liver transplant patients., Conclusions: We have made a weak recommendation supporting pre-transplant nutritional supplementation due to possible benefit in reducing LOS as well as the lack of harm (Quality of Evidence low | Grade of Recommendation; Weak). No effective conclusions were reached for the secondary objectives due to the conflicting evidence., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)
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- 2022
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27. Inflammatory conditions play a role in recurrence of PSC after liver transplantation: An international multicentre study.
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Visseren T, Erler NS, Heimbach JK, Eaton JE, Selzner N, Gulamhusein A, van der Heide F, Porte RJ, van Hoek B, Alwayn IPJ, Metselaar HJ, IJzermans JNM, and Darwish Murad S
- Abstract
Background & Aims: Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries., Methods: In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29-10.11) years post-LT., Results: In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5-5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08-2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC., Conclusions: An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se . Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC., Impact and Implications: Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC., Competing Interests: The authors who have taken part in this study declared that they do not have any conflict of interest with respect to this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)
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- 2022
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28. So Shines a Good Deed in a Weary World.
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Heimbach JK and Taner T
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- 2022
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29. Classification of Distinct Patterns of Ischemic Cholangiopathy Following DCD Liver Transplantation: Distinct Clinical Courses and Long-term Outcomes From a Multicenter Cohort.
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Croome KP, Mathur AK, Aqel B, Yang L, Taner T, Heimbach JK, Rosen CB, Paz-Fumagalli R, and Taner CB
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- Death, Graft Survival, Humans, Ischemia etiology, Necrosis etiology, Retrospective Studies, Tissue Donors, End Stage Liver Disease, Liver Transplantation methods, Tissue and Organ Procurement
- Abstract
Background: As the number of donation after circulatory death (DCD) liver transplants (LTs) performed in the United States continues to increase annually, there has been interest by policy makers to develop a more robust exception point safety net for patients who develop ischemic cholangiopathy (IC) following DCD LT. As such, there is a need for better understanding of the clinical course and long-term outcomes in patients who develop IC, as well as determining if IC can be classified into distinct categories with distinctly different clinical outcomes., Methods: All DCD LT performed at Mayo Clinic Florida, Mayo Clinic Arizona, and Mayo Clinic Rochester from January 1999 to March 2020 were included (N = 770). Outcomes were compared between 4 distinct radiologic patterns of IC: diffuse necrosis, multifocal progressive, confluence dominant, and minor form., Results: In total, 88 (11.4%) patients developed IC, of which 42 (5.5%) were listed for retransplantation of liver (ReLT). Patients with diffuse necrosis and multifocal progressive patterns suffered from frequent hospital admissions for cholangitis in the first year following DCD LT (median 3 and 2), were largely stent dependent (100% and 85.7%), and almost universally required ReLT. Patients with confluence dominant disease were managed with multiple stents and frequently recovered, ultimately becoming stent free without need for ReLT. Patients with the minor form IC did well with limited need for stent placement or repeat procedures and did not require ReLT. Graft survival was different between the 4 distinct IC patterns (P < 0.001)., Conclusions: The present analysis provides a detailed analysis on the natural history and clinical course of IC. Patients developing IC can be classified into 4 distinct patterns with distinct clinical courses., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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30. Assessment of long-term outcomes post living liver donation highlights the importance of scientific integrity when presenting transplant registry data.
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Emamaullee J, Heimbach JK, Olthoff KM, Pomfret EA, Roberts JP, and Selzner N
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- Humans, Liver, Living Donors, Registries, Liver Transplantation, Transplants
- Abstract
Living donor liver transplantation has expanded in recent years, particularly in North America. As experience with this procedure has matured over the last 25 years, centers are increasingly faced with potential living donors who are more medically complex. As donors move through the evaluation process, completing the informed consent process continues to be challenged by a paucity of granular data demonstrating long-term outcomes and overall safety specifically in the otherwise "healthy" living liver donor population. Two recently published studies examined long-term outcomes post-living liver donation using Korean registry data and reported similar results, with excellent overall survival when compared to appropriately matched controls. However, the authors of these studies were presented differently, with one reporting an alarmist view based on one aspect of a suboptimal analysis approach using an inappropriate comparator group. Herein, the North American Living Liver Donor Innovation Group (NALLDIG) consortium discusses these two studies and their potential impact on living liver donation in North America, ultimately highlighting the importance of scientific integrity in data presentation and dissemination when using transplant registry data., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2022
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31. Complications After Hand-Assisted Laparoscopic Living Donor Nephrectomy.
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Benavides X, Rogers RT, Tan EK, Merzkani MA, Thirunavukkarasu S, Yigitbilek F, Smith BH, Rule AD, Kukla A, Chow GK, Heimbach JK, Taner T, Dean PG, Prieto M, and Stegall MD
- Subjects
- Female, Humans, Living Donors, Male, Middle Aged, Nephrectomy adverse effects, Postoperative Complications epidemiology, Postoperative Complications etiology, Retrospective Studies, Hand-Assisted Laparoscopy adverse effects, Kidney Transplantation adverse effects
- Abstract
Objective: To study the complications of hand-assisted laparoscopic living donor nephrectomy (HALLDN) with an emphasis on complications occurring early after hospital discharge up to 120 days after surgery., Patients and Methods: We retrospectively categorized complications using the Clavien-Dindo classification in 3002 HALLDNs performed at 1 center from January 1, 2000, through December 31, 2019. In addition to overall summaries, modeling was used to identify correlates of complications before and after living donation., Results: Of these donors, 87% were White, 59% were female, the mean age was 45 years (range, 18-77 years), 30.3% had a body mass index of at least 30, and 36.3% had previous abdominopelvic surgery. There were no deaths related to the surgery. The incidence of major complications (intraoperative complications plus Clavien-Dindo grade ≥III postoperatively) was 2.5% (n=74). The overall complication rate was 12.4% (n=371), including 15 intraoperative, 76 postoperative before discharge, and 280 after discharge to 120 days. Reoperation was required in 1.8% of patients (n=54), and all but 1 of these were incision-related problems. Seventy-six percent of all complications occurred after discharge, including 85% of the reoperations. For major complications, no risk factor was found. Risk factors for any complication included paramedian incision (hazard ratio [HR], 2.54; 95% CI, 1.49 to 4.34; P<.001); a history of abdominopelvic surgery (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), male sex (HR, 1.37; 95% CI, 1.07 to 1.76; P=.01), non-White race (HR, 1.40; 95% CI, 1.05 to 1.88; P=.02), and early era of the experience., Conclusion: Most major complications of HALLDN occur after discharge, suggesting that close follow-up is warranted and that the current literature may underestimate the true incidence., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)
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- 2022
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32. Endoscopic Ultrasound-Guided Dual Ultrasound Hepatic Cyst Aspiration and Sclerotherapy to Ameliorate Portal Hypertension.
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Levy MJ, Bendel EC, Bjarnason H, Reisenauer CJ, Amer H, Codipilly DC, Dean PG, Gleeson FC, Heimbach JK, Kalra M, Prieto M, Stegall MD, Taner T, and Kamath PS
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- Humans, Liver Diseases, Sclerotherapy, Ultrasonography, Interventional, Cysts, Hypertension, Portal complications, Hypertension, Portal diagnostic imaging, Hypertension, Portal therapy
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- 2022
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33. When the Sun Sets, Who Doth Not Look for Night?
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Ryan RJ, Taner T, and Heimbach JK
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- Humans, Liver Transplantation
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- 2022
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34. PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and 68 Ga-PSMA-11 PET Using Cyclotron-Produced 68 Ga.
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Thompson SM, Suman G, Torbenson MS, Chen ZE, Jondal DE, Patra A, Ehman EC, Andrews JC, Fleming CJ, Welch BT, Kurup AN, Roberts LR, Watt KD, Truty MJ, Cleary SP, Smoot RL, Heimbach JK, Tran NH, Mahipal A, Yin J, Zemla T, Wang C, Fogarty Z, Jacobson M, Kemp BJ, Venkatesh SK, Johnson GB, Woodrum DA, and Goenka AH
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- Bile Ducts, Intrahepatic metabolism, Cyclotrons, Gallium Radioisotopes, Humans, Immunohistochemistry, Male, Positron Emission Tomography Computed Tomography methods, Positron-Emission Tomography, RNA, Messenger, Theranostic Nanomedicine, Bile Duct Neoplasms, Carcinoma, Hepatocellular diagnostic imaging, Liver Neoplasms diagnostic imaging, Prostatic Neoplasms metabolism
- Abstract
Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with
68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2,68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)- Published
- 2022
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35. DNA methylation profile of liver tissue in end-stage cholestatic liver disease.
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Cheung AC, Juran BD, Schlicht EM, McCauley BM, Atkinson EJ, Moore R, Heimbach JK, Watt KD, Wu TT, LaRusso NF, Gores GJ, Sun Z, and Lazaridis KN
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- DNA Methylation, Epigenome, Humans, Liver, Cholangitis, Sclerosing genetics, Liver Cirrhosis, Biliary genetics
- Abstract
Aims: In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes . Patients & methods: Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.
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- 2022
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36. Induced Pluripotent Stem Cells From Subjects With Primary Sclerosing Cholangitis Develop a Senescence Phenotype Following Biliary Differentiation.
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Jalan-Sakrikar N, De Assuncao TM, Navarro-Corcuera A, Hamdan FH, Loarca L, Kirkeby LA, Resch ZT, O'Hara SP, Juran BD, Lazaridis KN, Rosen CB, Heimbach JK, Taner T, Shah VH, LaRusso NF, and Huebert RC
- Subjects
- Adult, Aged, Cells, Cultured, Cholangitis, Sclerosing metabolism, Culture Media, Conditioned, Cytokines metabolism, Female, Fibroblasts, Humans, Male, Middle Aged, Phenotype, Sequence Analysis, RNA, Skin cytology, Cell Differentiation, Cellular Senescence, Cholangitis, Sclerosing pathology, Induced Pluripotent Stem Cells pathology
- Abstract
Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory disease of the biliary tract characterized by cellular senescence and periportal fibrogenesis. Specific disease features that are cell intrinsic and either genetically or epigenetically mediated remain unclear due in part to a lack of appropriate, patient-specific, in vitro models. Recently, our group developed systems to create induced pluripotent stem cell (iPSC)-derived cholangiocytes (iDCs) and biliary epithelial organoids (cholangioids). We use these models to investigate whether PSC cholangiocytes are intrinsically predisposed to cellular senescence. Skin fibroblasts from healthy controls and subjects with PSC were reprogrammed to pluripotency, differentiated to cholangiocytes, and subsequently grown in three-dimensional matrigel-based culture to induce formation of cholangioids. RNA sequencing (RNA-seq) on iDCs showed significant differences in gene expression patterns, including enrichment of pathways associated with cell cycle, senescence, and hepatic fibrosis, that correlate with PSC. These pathways also overlapped with RNA-seq analysis on isolated cholangiocytes from subjects with PSC. Exome sequencing on the subjects with PSC revealed genetic variants of unknown significance in the genes identified in these pathways. Three-dimensional culture revealed smaller size, lack of a central lumen, and increased cellular senescence in PSC-derived cholangioids. Congruent with this, PSC-derived iDCs showed increased secretion of the extracellular matrix molecule fibronectin as well as the inflammatory cytokines interleukin-6, and chemokine (C-C motif) ligand 2. Conditioned media (CM) from PSC-derived iDCs more potently activated hepatic stellate cells compared to control CM. Conclusion: We demonstrated efficient generation of iDCs and cholangioids from patients with PSC that show disease-specific features. PSC cholangiocytes are intrinsically predisposed to cellular senescence. These features are unmasked following biliary differentiation of pluripotent stem cells and have functional consequences in epithelial organoids., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
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- 2022
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37. Usefulness of Controlled Attenuation Parameter and Liver Stiffness Measurement for the Identification of Extended-criteria Donors and Risk-assessment in Liver Transplantation.
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Duarte-Rojo A, Heimbach JK, Borja-Cacho D, Barone GW, Shaheen MF, Lamps LW, Graham RP, Tan EK, Concepcion W, and Kim WR
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- Biopsy, Humans, Liver diagnostic imaging, Liver pathology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis surgery, ROC Curve, Elasticity Imaging Techniques methods, Liver Transplantation adverse effects, Non-alcoholic Fatty Liver Disease pathology
- Abstract
Background: Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) are noninvasive surrogates for hepatic steatosis and fibrosis, respectively, and could help identify extended criteria donors in liver transplantation (LT). We aimed to determine the accuracy of CAP/LSM in deceased donors along with post-LT changes., Methods: Accuracy of preprocurement CAP/LSM to grade/stage steatosis/fibrosis was determined using liver biopsy as reference. Transplant outcomes, including primary nonfunction (PNF) and early allograft dysfunction, were recorded. Recipients underwent CAP/LSM as outpatients. Areas under the receiver operating characteristic curve and regression models were constructed to analyze data., Results: We prospectively evaluated 160 allografts (138 transplanted). Same-probe paired baseline/post-LT CAP was 231 dB/m (181-277)/225 (187-261) (P = 0.61), and LSM 7.6 kPa (6.3-10.8)/5.9 (4.6-8.7) (P = 0.002), respectively. CAP reading was affected by BMI and LSM by ALT, race and bilirubin. Although CAP did not correlate with steatosis from frozen sections (ρ = 0.08, P = 0.47), it correlated with steatosis from permanent sections (ρ = 0.32, P < 0.001) and with oil red O histomorphometry (ρ = 0.35, P = 0.001). CAP identified moderate-to-severe steatosis with an areas under the receiver operating characteristic curve curve of 0.79 (0.66-0.91), for a negative predictive value of 100% at a cutoff value of 230 dB/m. LSM correlated with fibrosis staging (ρ = 0.22, P = 0.007) and it identified discarded allografts with advanced fibrosis/cirrhosis. Patients with no to minimal fibrosis had an LSM of 7.6 (6-10.1) kPa., Conclusions: Our results are proof-of-concept of the utility of CAP/LSM during organ procurement. Establishing the precise role of these noninvasive tools in the organ allocation process mandates confirmatory studies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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38. ICU and Hospital Outcomes in Patients with Hepatopulmonary Syndrome Undergoing Liver Transplantation.
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Aragon Pinto C, Iyer V, Almodallal YA, Albitar H, Dubrock H, Cajigas H, Heimbach JK, Rosen CB, Watt K, Taner T, Nyberg S, Vargas H, Cartin-Ceba R, Keaveny AP, Krowka M, and Gallo de Moraes A
- Subjects
- Adult, Female, Hospital Mortality, Hospitals, Humans, Male, Middle Aged, Respiration, Artificial, Retrospective Studies, Hepatopulmonary Syndrome etiology, Hepatopulmonary Syndrome surgery, Intensive Care Units, Liver Transplantation adverse effects
- Abstract
Purpose: There are limited data regarding hospital and intensive care unit (ICU) outcomes in patients with hepatopulmonary syndrome (HPS) following liver transplantation (LT)., Methods: Data were retrospectively collected from consecutive HPS adult patients who underwent LT and were immediately admitted to the ICU at three transplant centers with shared management protocols, from 2002 to 2018. Demographic, clinical, surgical, laboratory, and outcome data were extracted., Results: We identified 137 patients (74 male, 54%), with a median age at LT of 58 years (IQR: 52-63). One hundred and 31 (95.6%) patients were admitted to the ICU on invasive mechanical ventilation (MV). The median time on invasive MV in the ICU was 12 hours (IQR: 5-28) and 97 patients (74%) were extubated within 24 hours of ICU admission. The median highest positive end expiratory pressure and fraction of inspired oxygen (FiO
2 ) were 7 (IQR: 5-8) and 0.6 (IQR: 0.5-0.7), respectively. 7 patients (5%) developed severe post-transplant hypoxemia. Of all patients, 42 (30.4%) required vasopressors and the median ICU and hospital length of stay (LOS) were 3 (IQR: 1-5) and 10 (IQR: 7-20) days, respectively. The in-hospital mortality rate was 3.6% (5/137). HPS severity was not associated with hospital mortality., Conclusion: Most HPS patients have short durations of MV, ICU, and hospital LOS post-LT. HPS severity does not impact hospital mortality., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2022
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39. Posttransplant recurrence of calcium oxalate crystals in patients with primary hyperoxaluria: Incidence, risk factors, and effect on renal allograft function.
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Cornell LD, Amer H, Viehman JK, Mehta RA, Lieske JC, Lorenz EC, Heimbach JK, Stegall MD, and Milliner DS
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- Allografts, Calcium Oxalate, Humans, Incidence, Kidney, Risk Factors, Hyperoxaluria epidemiology, Hyperoxaluria etiology, Hyperoxaluria, Primary epidemiology, Hyperoxaluria, Primary etiology, Kidney Transplantation adverse effects
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Primary hyperoxaluria (PH) is a metabolic defect that results in oxalate overproduction by the liver and leads to kidney failure due to oxalate nephropathy. As oxalate tissue stores are mobilized after transplantation, the transplanted kidney is at risk of recurrent disease. We evaluated surveillance kidney transplant biopsies for recurrent calcium oxalate (CaOx) deposits in 37 kidney transplants (29 simultaneous kidney and liver [K/L] transplants and eight kidney alone [K]) in 36 PH patients and 62 comparison transplants. Median follow-up posttransplant was 9.2 years (IQR: [5.3, 15.1]). The recurrence of CaOx crystals in surveillance biopsies in PH at any time posttransplant was 46% overall (41% in K/L, 62% in K). Higher CaOx crystal index (which accounted for biopsy sample size) was associated with higher plasma and urine oxalate following transplant (p < .01 and p < .02, respectively). There was a trend toward higher graft failure among PH patients with CaOx crystals on surveillance biopsies compared with those without (HR 4.43 [0.88, 22.35], p = .07). CaOx crystal deposition is frequent in kidney transplants in PH patients. The avoidance of high plasma oxalate and reduction of CaOx crystallization may decrease the risk of recurrent oxalate nephropathy following kidney transplantation in patients with PH. This study was approved by the IRB at Mayo Clinic., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
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- 2022
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40. Impact of Advanced Renal Dysfunction on Posttransplant Outcomes After Living Donor Liver Transplantation in the United States.
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Bittermann T, Abt PL, Olthoff KM, Kaur N, Heimbach JK, and Emamaullee J
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- Graft Survival, Humans, Living Donors, Proportional Hazards Models, Retrospective Studies, Treatment Outcome, United States epidemiology, Liver Transplantation adverse effects
- Abstract
Background: Survival after living donor liver transplantation (LDLT) in the United States is excellent. However, the significance of pretransplant kidney disease on outcomes in this population is poorly understood., Methods: This was a retrospective cohort study of 2806 LDLT recipients nationally between January 2010 and June 2020. Recipients with estimated glomerular filtration rate <40 mL/min/1.73 m2 (eGFR-low) or requiring dialysis were compared. Multivariable survival analyses evaluated (1) eGFR-low as a predictor of post-LDLT survival and (2) the survival of LDLT versus deceased donor liver transplant (DDLT) alone with eGFR-low., Results: From 2010 to 2020, 140 (5.0%) patients had eGFR-low and 18 (0.6%) required dialysis pre-LDLT. The number of LDLTs requiring dialysis between 2017 and 2020 outnumbered the prior 7 y. Overall LDLT experience was greater at centers performing LDLT in recipients with renal dysfunction (P < 0.001). LDLT recipients with eGFR-low had longstanding renal dysfunction: mean eGFR 3-6 mo before LDLT 42.7 (±15.1) mL/min/1.73 m2. Nearly half (5/12) of eGFR-low recipients with active kidney transplant (KT) listing at LDLT experienced renal recovery. Five patients underwent early KT after LDLT via the new "safety net" policy. Unadjusted survival after LDLT was worse with eGFR-low (hazard ratio 2.12 versus eGFR ≥40 mL/min/1.73 m2; 95% confidence interval, 1.47-3.05; P < 0.001), but no longer so when accounting for mean eGFR 3-6 mo pre-LDLT (hazard ratio, 1.27; 95% confidence interval, 0.82-1.95; P = 0.3). The adjusted survival of patients with eGFR-low receiving LDLT versus deceased donor liver transplant alone was not different (P = 0.08)., Conclusions: Overall, outcomes after LDLT with advanced renal dysfunction are acceptable. These findings are relevant given the recent "safety net" KT policy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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41. MELD 3.0: The Model for End-Stage Liver Disease Updated for the Modern Era.
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Kim WR, Mannalithara A, Heimbach JK, Kamath PS, Asrani SK, Biggins SW, Wood NL, Gentry SE, and Kwong AJ
- Subjects
- Bilirubin blood, Biomarkers blood, Clinical Decision-Making, Creatinine blood, End Stage Liver Disease blood, End Stage Liver Disease mortality, End Stage Liver Disease surgery, Female, Healthcare Disparities, Humans, International Normalized Ratio, Male, Middle Aged, Predictive Value of Tests, Prognosis, Registries, Risk Assessment, Risk Factors, Severity of Illness Index, Sex Factors, Sodium blood, Time Factors, United States, Decision Support Techniques, End Stage Liver Disease diagnosis, Liver Transplantation adverse effects, Liver Transplantation mortality, Waiting Lists mortality
- Abstract
Background & Aims: The Model for End-Stage Liver Disease (MELD) has been established as a reliable indicator of short-term survival in patients with end-stage liver disease. The current version (MELDNa), consisting of the international normalized ratio and serum bilirubin, creatinine, and sodium, has been used to determine organ allocation priorities for liver transplantation in the United States. The objective was to optimize MELD further by taking into account additional variables and updating coefficients with contemporary data., Methods: All candidates registered on the liver transplant wait list in the US national registry from January 2016 through December 2018 were included. Uni- and multivariable Cox models were developed to predict survival up to 90 days after wait list registration. Model fit was tested using the concordance statistic (C-statistic) and reclassification, and the Liver Simulated Allocation Model was used to estimate the impact of replacing MELDNa with the new model., Results: The final multivariable model was characterized by (1) additional variables of female sex and serum albumin, (2) interactions between bilirubin and sodium and between albumin and creatinine, and (3) an upper bound for creatinine at 3.0 mg/dL. The final model (MELD 3.0) had better discrimination than MELDNa (C-statistic, 0.869 vs 0.862; P < .01). Importantly, MELD 3.0 correctly reclassified a net of 8.8% of decedents to a higher MELD tier, affording them a meaningfully higher chance of transplantation, particularly in women. In the Liver Simulated Allocation Model analysis, MELD 3.0 resulted in fewer wait list deaths compared to MELDNa (7788 vs 7850; P = .02)., Conclusion: MELD 3.0 affords more accurate mortality prediction in general than MELDNa and addresses determinants of wait list outcomes, including the sex disparity., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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42. Variation in opioid prescribing patterns after abdominal transplant surgery.
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Sussman J, Calderon E, Ubl DS, Croome KP, Taner CB, Heimbach JK, Moss A, Habermann EB, and Mathur AK
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- Aged, Humans, Length of Stay, Patient Discharge, Practice Patterns, Physicians', Retrospective Studies, Analgesics, Opioid therapeutic use, Pain, Postoperative drug therapy, Pain, Postoperative etiology
- Abstract
Background: Opioids are associated with negative transplant outcomes. We sought to identify patient and center effects on over-prescribing of opioids (> 200 OME (oral morphine equivalents))., Study Design: Clinical and opioid prescription data (2014-2017) were collected from three academic transplant centers for kidney (KT), liver (LT), and simultaneous liver-kidney transplant (SLK) patients. Multivariable models were used to identify predictors of opioid over-prescribing at discharge and the occurrence of refill prescriptions at 90 days., Results: Three-thousand seven-hundred and two patients underwent transplant in the cohort (KT: n = 2358, LT: n = 1221, SLK: n = 123). More than 80% of recipients were over-prescribed opioids at discharge (Median OME (mOME) = 300 (IQR 225-375). LT and SLK had the largest prescription size (LT mOME 338 (IQR 300-450); SLK mOME 338 (IQR 225-450) and refill rate (LT: 64%, SLK 59%) (all, P < .001). Multivariable analysis indicated that transplant center was a significant predictor of opioid over-prescription after KT and LT (all, P < .001); older age (in KT) and length of stay (LOS) (in LT) were protective factors (both, P < .05). Refill occurrence was associated with initial prescription size and was reduced by older age and initial LOS (all, P < .05)., Conclusions: The wide variation in opioid prescribing patterns has implications for transplant practice innovation, guideline development, and further study., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2021
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43. Response to letter to the editor.
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Anderson TL, Brandts HM, Gunderson T, Fazzio RT, Hunt KN, Heimbach JK, and Glazebrook KN
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- 2021
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44. Efficacy and Safety of Endoscopic Balloon Placement for Weight Loss in Patients With Cirrhosis Awaiting Liver Transplantation.
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Watt KD, Heimbach JK, Rizk M, Jaruvongvanich P, Sanchez W, Port J, Venkatesh SK, Bamlet H, Tiedtke K, Malhi H, Acosta Cardenas A, Grothe K, Clark M, Mundi MS, and Abu Dayyeh BK
- Subjects
- Aged, Humans, Liver Cirrhosis complications, Liver Cirrhosis diagnosis, Liver Cirrhosis surgery, Male, Severity of Illness Index, Weight Loss, Carcinoma, Hepatocellular, End Stage Liver Disease complications, End Stage Liver Disease surgery, Gastric Balloon adverse effects, Liver Neoplasms, Liver Transplantation adverse effects
- Abstract
The efficacy and safety of a fluid-filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m
2 and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End-Stage Liver Disease-sodium (MELD-Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD-Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short-term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow-up are required., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)- Published
- 2021
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45. Symptomatic Val122del mutated hereditary transthyretin amyloidosis: Need for early diagnosis and prioritization for heart and liver transplantation.
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Schettini AV, Llado L, Heimbach JK, Costello JG, Tranäng M, Van Caenegem O, Daly RC, Van den Bergh P, Casanovas C, Fabregat J, Poterucha JJ, Foguenne M, Ericzon BG, and Lerut J
- Subjects
- Early Diagnosis, Humans, Prealbumin genetics, Amyloid Neuropathies, Familial diagnosis, Amyloid Neuropathies, Familial genetics, Amyloid Neuropathies, Familial surgery, Cardiomyopathies diagnosis, Cardiomyopathies genetics, Cardiomyopathies surgery, Liver Transplantation
- Abstract
Background: Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils (i.e. amyloid). Apart from the common Val30Met mutation there is a very heterogeneous group of non-Val30Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy., Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed., Results: Three patients needed a staged (1 patient) or simultaneous (2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac (allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months., Conclusions: This is the first report in (liver) transplant literature about the rare Val122del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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46. Liver Transplantation After Bariatric Surgery: a Clinical Cohort Study.
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Fipps DC, Goetze RE, Clark MM, Mara K, Watt KD, Jowsey-Gregoire SG, Heimbach JK, and Grothe K
- Subjects
- Cohort Studies, Female, Humans, Male, Retrospective Studies, Severity of Illness Index, Bariatric Surgery, Depressive Disorder, Major, End Stage Liver Disease, Liver Transplantation, Obesity, Morbid surgery
- Abstract
Purpose: Individuals that undergo bariatric surgery are at higher risk for problematic alcohol use via pharmacokinetic changes in alcohol metabolism and cross addictions. Little data exists regarding post-bariatric surgery patients with alcohol-related liver disease (ALD) who ultimately require liver transplantation. The aim of this project was to better understand demographic, medical, and psychological characteristics of post-bariatric surgery patients who undergo liver transplantation due to ALD., Methods: This retrospective clinical cohort identified 1416 patients who underwent ALD liver transplantation over a 10-year timespan at three academic medical centers. Electronic medical records were reviewed for patient characteristics, including sex, age, body mass index, surgery dates, Model for End Stage Liver Disease (MELD) scores, medical history, psychiatric history, and mortality rates., Results: Within the sample of liver transplantation patients, 1.3% had undergone bariatric surgery prior to transplantation. Fifty percent of the post-bariatric surgery sample was female. The MELD score was higher and the median age at transplantation was younger in the post-bariatric surgery subgroup in comparison to that in the non-bariatric surgery patients. Mood and anxiety disorders were more common among those with a history of having bariatric surgery, with major depressive disorder having the largest difference between subgroups., Conclusions: Among patients who require a liver transplantation due to ALD, those with a history of bariatric surgery are more likely to be female, younger, and diagnosed with mood disorders. Further studies with larger and more diverse samples are necessary to better understand how to prevent development of alcohol use disorder in the bariatric surgery population., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2021
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47. Breast cancers observed in transplant patients in a single institution.
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Anderson TL, Brandts HM, Gunderson T, Fazzio RT, Hunt KN, Heimbach JK, and Glazebrook KN
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- Breast Density, Early Detection of Cancer, Female, Humans, Mammography, Middle Aged, Retrospective Studies, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology
- Abstract
Objective: Document occurrence of breast cancer in females after liver, kidney, or pancreas transplantation seen at a tertiary medical center., Methods: Medical records of adult female patients with liver, kidney, or pancreas transplants from 1/1/1995 to 4/4/2014 were retrospectively reviewed. Patients with a history of breast cancer, no mammogram post-transplant, or no research authorization were excluded. Mammogram findings and pathology results were reviewed and recorded. Cancer rates could not be measured in patients followed up outside the institution. Descriptive statistics summarized the cohort. Occurrence rates were estimated using Poisson regression., Results: 1095 women were included and 33 were diagnosed with breast cancer post-transplant. Median age at diagnosis was 58 years. Average interval from transplant to cancer diagnosis was 82.6 months. Observed occurrence of invasive and in-situ breast cancer (reported as per 100,000 person-years [95% confidence interval]) was 353 [243-496]. Liver transplant patients showed the lowest rate (181 [95% CI 73-372]), vs. kidney (476 [305-708]) or pancreas (467 [57-1688]). Patients with the highest breast density showed increased occurrence despite younger age (1001 [367-2178]) compared to those with lower breast density (range 239 [109-454] to 372 [186-666])., Conclusions: Female patients after organ transplant experienced increased breast cancer occurrence in this observational study. Those who developed breast cancer also had increased breast density. The findings underscore the importance of breast cancer screening in this population., (Copyright © 2021. Published by Elsevier Inc.)
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- 2021
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48. Surface color spectrophotometry in a murine model of steatosis: an accurate technique with potential applicability in liver procurement.
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Kanamori KS, Tarragó MG, Jones A, Cheek EH, Warner GM, Jenkins SM, Povero D, Graham RP, Mounajjed T, Chedid MF, Sabat BD, Torbenson MS, Heimbach JK, Chini EN, and Moreira RK
- Subjects
- Animals, Disease Models, Animal, Histological Techniques, Liver Transplantation, Male, Mice, Mice, Inbred C57BL, Spectrophotometry instrumentation, Fatty Liver diagnostic imaging, Fatty Liver pathology, Liver diagnostic imaging, Liver pathology, Spectrophotometry methods
- Abstract
Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement., (© 2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.)
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- 2021
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49. Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.
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Yohanathan L, Campioli CC, Mousa OY, Watt K, Friedman DZP, Shah V, Ramkissoon R, Hines AS, Kamath PS, Razonable RR, Badley AD, DeMartino ES, Joyner MJ, Graham R, Vergidis P, Simonetto DA, Sanchez W, Taner T, Heimbach JK, Beam E, and Leise MD
- Subjects
- Adolescent, Female, Humans, Pandemics, Polymerase Chain Reaction, SARS-CoV-2, COVID-19, Liver Failure, Acute etiology, Liver Failure, Acute surgery, Liver Transplantation adverse effects
- Abstract
Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2021
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50. Reply by Authors.
- Author
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Gargollo PC, Ahmed ME, Prieto M, Butaney M, Cramer CH, Joshi V, Heimbach JK, and Granberg CF
- Published
- 2021
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