The role of molecular chaperonins in warm ischemia and reperfusion injury in the steatotic liver: A proteomic study

BACKGROUND: The molecular basis of the increased susceptibility of steatotic livers to warm ischemia/reperfusion (I/R) injury during transplantation remains undefined. Animal model for warm I/R injury was induced in obese Zucker rats. Lean Zucker rats provided controls. Two dimensional differential gel electrophoresis was performed with liver protein extracts. Protein features with significant abundance ratios (p < 0.01) between the two cohorts were selected and analyzed with HPLC/MS. Proteins were identified by Uniprot database. Interactive protein networks were generated using Ingenuity Pathway Analysis and GRANITE software. RESULTS: The relative abundance of 105 proteins was observed in warm I/R injury. Functional grouping revealed four categories of importance: molecular chaperones/endoplasmic reticulum (ER) stress, oxidative stress, metabolism, and cell structure. Hypoxia up-regulated 1, calcium binding protein 1, calreticulin, heat shock protein (HSP) 60, HSP-90, and protein disulfide isomerase 3 were chaperonins significantly (p < 0.01) down-regulated and only one chaperonin, HSP-1was significantly upregulated in steatotic liver following I/R. CONCLUSION: Down-regulation of the chaperones identified in this analysis may contribute to the increased ER stress and, consequently, apoptosis and necrosis. This study provides an initial platform for future investigation of the role of chaperones and therapeutic targets for increasing the viability of steatotic liver allografts

Understanding the Impact of Pneumonia and Other Complications in Elderly Liver Transplant Recipients: An Analysis of NSQIP Transplant.

Despite an increasing demand for liver transplantation in older patients, our understanding of posttransplant outcomes in older recipients is limited to basic recipient and graft survival. Using National Surgical Quality Improvement Program Transplant, we tracked early outcomes after liver transplantation for patients &gt;65.MethodsWe conducted a retrospective analysis of patients in National Surgical Quality Improvement Program Transplant between March 1, 2017 and March 31, 2019. Recipients were followed for 1 y after transplant with follow-up at 30, 90, and 365 d. Data were prospectively gathered using standard definitions across all sites.ResultsOne thousand seven hundred thirty-one adult liver transplants were enrolled; 387 (22.4%) were &gt;65 y old. The majority of older recipients were transplanted for hepatocellular carcinoma. The older cohort had a lower lab Model for End-Stage Liver Disease and was less likely to be hospitalized at time of transplant. Overall, older recipients had higher rates of pneumonia but no difference in intensive care unit length of stay (LOS), total LOS, surgical site infection, or 30-d readmission. Subgroup analysis of patients with poor functional status revealed a significant difference in intensive care unit and total LOS. Pneumonia was even more common in older patients and had a significant impact on overall survival.ConclusionsBy targeting patients with hepatocellular carcinoma and lower Model for End-Stage Liver Diseases, transplant centers can achieve nearly equivalent outcomes in older recipients. However, older recipients with poor functional status require greater resources and are more likely to develop pneumonia. Pneumonia was strongly associated with posttransplant survival and represents an opportunity for improvement. By truly understanding the outcomes of elderly and frail recipients, transplant centers can improve outcomes for these higher-risk recipients

Extinguishing burnout: National analysis of predictors and effects of burnout in abdominal transplant surgery fellows

Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work \u3e100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P \u3c .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout

Extinguishing burnout: National analysis of predictors and effects of burnout in abdominal transplant surgery fellows

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163973/1/ajt16075_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163973/2/ajt16075.pd