Austinbjerrum4861
In the recipient perspective ethical questions regarding organ procurement techniques occur.
Ethical decision-making on DCD-HTx is complex, but it can be processed in a structured way by applying the decision diagrams that we have developed.
Ethical decision-making on DCD-HTx is complex, but it can be processed in a structured way by applying the decision diagrams that we have developed.
Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs.
We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters.
The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejectionpairment.
During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment.
Endomyocardial biopsy remains the gold standard for distinguishing types of immunologic injury-acute versus antibody-mediated rejection (AMR). Exosomes are tissue-specific extracellular microvesicles released by many cell types, including transplanted heart. Circulating transplant heart exosomes express donor-specific human leukocyte antigen (HLA) I molecules. As AMR is mediated by antibodies to donor HLAs, we proposed that complement deposition that occurs with AMR at tissue level would also occur on circulating donor heart exosomes.
Plasma exosomes in 4 patients were isolated by column chromatography and ultracentrifugation. Donor heart exosomes were purified using anti-donor HLA I antibody beads and complement C4d protein expression was assessed in this subset as marker for AMR.
Three patients had no rejection episodes. Circulating donor heart exosomes showed troponin protein and mRNA expression at all follow-up time points. One patient developed AMR on day 14 endomyocardial biopsy that was treated with rituximab, IVIG/plasmapheresis. Time-specific detection of C4d protein was seen in donor heart exosome subset in this patient, which resolved with treatment. C4d was not seen in other 3 patients' donor exosomes.
Anti-donor HLA I specificity enables characterization of circulating donor heart exosomes in the clinical setting. Further characterization may open the window to noninvasively diagnose rejection type, such as AMR.
Anti-donor HLA I specificity enables characterization of circulating donor heart exosomes in the clinical setting. Further characterization may open the window to noninvasively diagnose rejection type, such as AMR.
Over the past decades, there has been a rapid change in the gender ratio of medical doctors, whereas gender differences in academia remain apparent. In transplantation research, a field already understaffed with female doctors and researchers, there is little published data on the development in proportion, citations, and funding of female researchers over the past years.
To evaluate the academic impact of female doctors in transplantation research, we conducted a bibliometric analysis (01 January 1999 to 31 December 2018) of high-impact scientific publications, subsequent citations, and funding in this field. Web of Science data was used in combination with software R-Package "Gender," to predict gender by first names.
For this study, 15 498 (36.2% female; 63.8% male) first and 13 345 (30.2% female; 69.8% male) last author gender matches were identified. An increase in the percentage of female first and last authors is seen in the period 1999-2018, with clear differences between countries (55.1% femaleorting and funding rewarding.
This is the first analysis of gender bias in scientific publications, subsequent citations, and funding in transplantation research. We show ongoing differences between male and female authors in citation rates and rewarded funding in this field. This requires an active approach to increase female representation in research reporting and funding rewarding.
Whole pancreas transplantation (Tx) is a successful treatment for type 1 diabetes resulting in independence from antidiabetic therapies. Transplant-related factors contributing to pancreatic islet failure are largely unknown; both recurring insulitis and pancreatitis have been implicated. The aim was to determine if cellular changes in islets and exocrine tissue are evident early in Tx, which could contribute to eventual graft failure using well-preserved tissue of grafts explanted from largely normoglycemic recipients.
Histological specimens of explants (n = 31), Tx duration 1 day-8 years (median 29 d), cold ischemia time 7.2-17.3 hours (median 11.1 h), donor age 13-54 years (median 38 y) were examined; sections were labeled for inflammation, islet amyloidosis, and tissue fibrosis, and morphometry performed on immunolabeled insulin and glucagon positive islet cells. Data were related to clinical details of donor, recipient, and features of Tx.
Islet inflammation consistent with recurrent insulitis was on sustainability of islet function.
Explant histological changes after short-term Tx are similar to those seen in type 2 diabetes and occur in the absence of immunologic rejection without causing hyperglycemia. This suggests that factors associated with Tx affect islet stability; persistent deterioration of islet integrity and exocrine tissue fibrosis could impact on sustainability of islet function.
Changing opinions on the alcohol abstinence requirement have led to increased liver transplantation (LT) for alcoholic hepatitis (AH). We aimed to determine the trend in LT for AH in the United States and overall and graft survival rates.
Adult liver-alone and liver-kidney registrations added to the Organ Procurement and Transplantation Network waiting list between 2004 and 2018 were divided into 3 periods (2004-2009, 2010-2013, 2014-2018). Kaplan-Meier survival models illustrated patient and graft survival.
Between 2004 and 2018, 529 AH patients were registered for and 254 received LT. By periods, 116, 73, and 340 patients were registered for and 49, 17, and 188 patients received LT, respectively, indicating a increase in LT for AH from 2014 to 2018. Yearly registrants from 2014 to 2018 were 32, 47, 51, 70, and 140, and recipients were 16, 24, 24, 38, and 88, respectively, indicating increases of 338% and 450% in registrants and recipients, respectively, since 2014. AH patients had the highest 1- and 3-year posttransplant survival (93.2% and 87.3%, respectively) and graft survival (90.4% and 84.8%, respectively) comparing to other LT recipients.
LT for AH in the United States is at an all-time high with an increased overall patient and graft survival.
LT for AH in the United States is at an all-time high with an increased overall patient and graft survival.Alagille syndrome (AGS) is a disorder that affects the liver, heart, kidneys, and skeleton. Development of hepatocellular carcinoma (HCC) is rare in AGS. A 41-y-old male with AGS presented with a 6 × 8-cm HCC and underwent transarterial chemoembolization (TACE) followed by right hepatic lobectomy. One year later, he developed HCC recurrence within Milan's criteria and received a deceased donor liver transplant. An interposition donor iliac artery graft from the supraceliac aorta to the donor hepatic artery was needed due to celiac axis occlusion noted on TACE. He subsequently underwent a Roux-en-Y hepaticojejunostomy for a bile leak. Surveillance imaging for HCC revealed a 3-cm pseudoaneurysm of his aortoiliac vascular anastomosis, 3 mo posttransplant. An infrarenal aortic jump graft to the donor hepatic artery and ligation of supraceliac aortic conduit was performed, followed by aortic stent-graft placement to occlude the pseudoaneurysm. He received a deceased donor kidney transplant 13 mo after the liver transplant. He remains HCC free with excellent liver and renal allograft function. Adults with AGS undergoing liver transplantation for HCC need special consideration due to related vascular, cardiac, and renal anomalies.Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown.
We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Terfenadine mouse Waitlist dropout and LT were analyzed using competing risk regression.
Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58,
< 0.001) with more women (50.0 versus 23.6%,
< 0.001), Hispanic ethnicity (40.5 versus 17.7%,
= 0.001), obesity (69.0 versus 29.9%,
< 0.001), diabetes mellitus (59.5 versus 27.8%,
< 0.01), insulin-dependence (23.8 versus 10.2%,
= 0.007), hyperlipidemia (40.5 versus 10.5,
< 0.001), and statin use (33.3 versus 5.3%,
< 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% cions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.Our aim was to determine whether hyponatremia is associated with waiting list or posttransplantation mortality in children having liver transplantation (LT).
A retrospective analysis of the united network for organ sharing/organ procurement transplantation network database on pediatric LT performed between 1988 and 2016 was conducted. Hyponatremia was defined as a serum sodium of 130 mEq/L or below. Subjects were divided into 2 age groups I (0-6 y old) and II (7-18 y old). Patient survival before and after LT, as well as graft survival, were compared in patients with and without hyponatremia. Multivariable Cox proportional hazards models were constructed for perioperative mortality.
Data from 6606 children were available for analysis of waiting list mortality, and 4478 for postoperative mortality. The prevalence of hyponatremia at the time of registration was 2.8% and 3.7% at the time of LT. Waiting list mortality in patients with hyponatremia was significantly higher in group I (
< 0.001) but not in ased on our findings.The prevalence of alcohol use disorder (AUD) and alcohol-associated liver disease is increasing in the United States. Efficacious AUD pharmacotherapies, while available, are, for protean reasons, underutilized. Hepatology providers may be in a position to bridge the pharmacotherapeutic gap between availability and utilization of AUD pharmacotherapies. Our aim was to ascertain the current practice, knowledge and attitudes of hepatology physicians in the United States, and identify opportunities on how to increase AUD medication prescribing.
A web-based survey, developed by an expert panel, was administered to hepatology physicians working at all transplant centers in the United States.
The survey response rate was 131/658 (20%). There was significant support (two-thirds of respondents) for hepatology providers prescribing AUD medications; however, only 1 in 4 was comfortable prescribing these medications. The majority felt additional education is needed to prescribe AUD medications. The practice of hepatology providers prescribing AUD medications is common, with >50% of respondents having done so.