Introduction While the benefits of deceased donor kidney transplant versus dialysis are clear, the impact of graft longevity remains unclear. Research Questions This study assessed survival between patients with failed grafts and patients who remained on dialysis alone. Design Utilizing the Organ Procurement and Transplant Network database, adults on dialysis listed for deceased donor kidney transplant between 1/2005 and 12/2017 were identified ( n = 265 280; n = 129 062 [48.7%] transplant; n = 136 218 [51.3%] dialysis alone, not transplanted). A multivariable Cox proportional hazards model incorporating confounding covariates and utilizing transplant status (dialysis alone, functioning graft, failed graft) as a time-varying covariate was constructed. Representative patients were then fit to this model to assess survival probability. Results Patients who underwent transplant experienced a 65% reduction in mortality compared to those remaining on dialysis. However, graft failure ( n = 19 389, 15.0% of transplants) was associated with a 47% increase in hazard rate compared to dialysis. When an average-risk patient was fit to this model, with transplant 4 years after dialysis initiation, a graft required longevity of 3 years to convey a survival probability benefit at 5 years postoperatively (9 years from waitlisting, 35%) over remaining on dialysis through the same time point (9 years from waitlisting, 32%). Conclusions These results argue for scrutiny of anticipated graft longevity and its expected impact on individual outcomes and advocate for 3-year graft survival as a critical clinical measure for transplant programs.

Background:Deceased donor multiorgan transplants utilizing kidneys (MOTs) can improve outcomes for multiorgan recipients but reduces kidneys for chronic renal failure patients. Methods:We reviewed the Organ Procurement and Transplantation Network database from 2015 through 2019, for adult deceased donor kidney transplants. Recipients were classified as kidney transplant alone (KTA) (n = 62,252) or MOTs pancreas-kidney, simultaneous pancreas-kidney (n = 3,976), liver-kidney, simultaneous liver-kidney (n = 3,212), heart-kidney, simultaneous heart-kidney (n = 808), and "other"-kidney, simultaneous "other" kidney (n = 73). Results:Liver, heart, and lung-alone transplants were at least 7 times more frequent than their MOT correlate, whereas the inverse was true with pancreas transplantation with SPKs being by far the most common pancreas transplant type. On average, KTA recipients waited between 2.8 and 21.4 times longer than MOTs, with SPKs waiting the longest of the MOT types. Predialysis initiation transplants were less frequent in KTAs compared with MOTs. Use of high-quality grafts according to Kidney Donor Profile Index < 35% was frequent among MOTs, but uncommon in KTAs who had an Estimated Post Transplant Survival score (EPTS) of >20%. For recipients older than 65, SPKs and SOKs were rare, but SLKs and SHKs had a higher fraction of recipients than KTAs and were much more likely to use a Kidney Donor Profile Index <35% kidney. SPKs and KTAs with an EPTS ≤20% had the best kidney graft survival. KTAs with an EPTS ≤80% had better kidney graft survival than SLKs, SHKs, and SOKs. Conclusions:This study highlights disparities in access to deceased donor kidneys for kidney-alone candidates versus MOTs and suggests opportunities to improve allocation.

BackgroundSurgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients.MethodsBetween the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed.ResultsSSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo >= 3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6).ConclusionElective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.

Mahvash disease is an exceedingly rare genetic disorder of glucagon signaling characterized by hyperglucagonemia, hyperaminoacidemia, and pancreatic α-cell hyperplasia. Although there is no known definitive treatment, octreotide has been used to decrease systemic glucagon levels. We describe a woman who presented to our medical center after three episodes of small-volume hematemesis. She was found to have hyperglucagonemia and pancreatic hypertrophy with genetically confirmed Mahvash disease and also had evidence of portal hypertension (recurrent portosystemic encephalopathy and variceal hemorrhage) in the absence of cirrhosis. These findings established a diagnosis of portosinusoidal vascular disease, a presinusoidal type of portal hypertension previously known as noncirrhotic portal hypertension. Liver transplantation was followed by normalization of serum glucagon and ammonia levels, reversal of pancreatic hypertrophy, and resolution of recurrent encephalopathy and bleeding varices.

Background. Organ donors supported by extracorporeal membrane oxygenation (ECMO) have historically been considered high-risk and are judiciously utilized. This study examines transplant outcomes using renal allografts from donors supported on ECMO for nondonation purposes. Methods. Retrospective review of the Gift of Life (Pennsylvania, New Jersey, Delaware) organ procurement organization database, cross-referenced to the Organ Procurement and Transplantation Network database, assessed kidney transplants using donors supported on venoarterial (VA) and venovenous (VV) ECMO for nondonation purposes. Transplants using VA- and VV-ECMO donors were compared with Kidney Donor Profile Index (KDPI)-stratified non-ECMO donors. Regression modeling of the entire ECMO and non-ECMO populations assessed ECMO as predictive of graft survival. Additional regression of the ECMO population alone assessed for donor features associated with graft survival. Results. Seventy-eight ECMO donors yielded 128 kidney transplants (VA: 80, VV: 48). Comparing outcomes using these donors to kidney transplants using organs from KDPI-stratified non-ECMO donors, VA- and VV-ECMO donor grafts conferred similar rates of delayed graft function and posttransplant renal function to KDPI-matched non-ECMO counterparts. VA-ECMO kidneys demonstrated superior graft survival compared with the lowest-quality (KDPI 86%–100%) non-ECMO kidneys and similar graft survival to KDPI <85% non-ECMO kidneys. VV-ECMO showed inferior graft survival to all but the lowest-quality (KDPI 86%–100%) non-ECMO kidneys. VV-ECMO, but not VA-ECMO, was associated with increased risk of graft loss on multivariable regression (hazard ratios—VA: 1.02, VV: 2.18). Higher KDPI, advanced age, increased body mass index, hypertension, and diabetes were identified as high-risk features of ECMO donors. Conclusions. Kidney transplantation using appropriately selected ECMO donors can safely expand the donor pool. Ongoing studies are necessary to determine best practice patterns using kidneys from these donors.

BACKGROUND Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required ECMO support. METHODS We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ procuring organization database for transplants performed using donors supported on ECMO for non-donation purposes. These were cross-referenced to the Organ Procurement and Transplantation Network database, and outcomes of liver transplants using donors on ECMO support were compared to those not requiring ECMO. Organ use and non-use patterns were then evaluated in ECMO-supported donors, identifying factors associated with non-use compared to factors associated with graft failure. RESULTS Thirty-nine of 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary non-function were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. CONCLUSION Livers from donors supported on ECMO prior to donation appear safe to use in select transplant settings. Better understanding the impact of pre-donation ECMO on liver allograft function will help guide optimal use of these scarcely used donors.

Background In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients.Methods From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor.Findings We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. Interpretation This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

Liver transplantation continues to face significant organ shortages and efficient utilization of marginal donors is paramount. This study evaluates the practice patterns and outcomes in liver transplantation when utilizing allografts from marginal donors who required extracorporeal membrane oxygenation (ECMO) support. We performed a retrospective review of the Gift of Life (PA, NJ, DE) organ-procuring organization database for transplants performed using donors supported on ECMO for nondonation purposes. These were cross-referenced to the transplant recipients within the Organ Procurement and Transplantation Network database, and the outcomes of liver transplants using donors on ECMO support were compared with those not requiring ECMO. Organ use and nonuse patterns were then evaluated in ECMO-supported donors, identifying the factors associated with nonuse compared with the factors associated with graft failure. Thirty-nine of the 84 ECMO-supported donors contributing at least one intra-abdominal organ for transplant donated a liver. Graft survival and patient survival up to 5 years were comparable between transplants from ECMO and non-ECMO-supported donors, and no cases of primary nonfunction were seen in the ECMO group. ECMO support was not associated with 1-year graft failure on regression modeling. Additional regression analyses within the ECMO donor population identified bacteremia (HR: 19.81) and elevated total bilirubin at donation (HR: 2.44) as predictive of post-transplant graft failure. Livers from donors supported on ECMO before donation appear safe to use in select transplant settings. Better understanding of the impact of predonation ECMO on liver allograft function will help guide the optimal use of these scarcely used donors.

Garcinia cambogia, a weight control herbal, can cause mild liver toxicity with nonspecific histologic changes. Herein, we reported a case of herbal-induced fulminant cholestatic giant cell hepatitis due to garcinia cambogia use. A 65-year-old woman with breast cancer treated 18 years earlier was admitted for obstructive jaundice for 2 weeks. She started using garcinia cambogia 3 months ago for weight loss. Physical exam showed scleral icterus. Serum studies excluded Wilson's disease, systemic infection including COVID-19 (coronavirus disease 2019), autoimmune hepatitis, and metabolic or toxicologic causes. An urgent liver biopsy showed severe giant cell hepatitis in absence of HSV-1/2, cytomegalovirus, HBsAg and HBcAg (immunostain), and EBV (in situ hybridization). Despite supportive therapy, the patient developed grade 2-3 hepatic encephalopathy and necessitated liver transplant. The explanted liver was markedly atrophy, in which the most striking histologic finding was diffuse distribution of multinucleated giant hepatocytes with syncytial pattern in a background of extensive zone-1 accentuated, geographic, hemorrhagic, confluent hepatocytic necrosis, along with remarkable hepatocytic and canalicular cholestasis. Marked hepatocellular and sinusoidal iron orverload present. The patient recovered uneventfully.

Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) has become the second leading cause of HCC-related liver transplantation in the United States. This study investigated post-transplant recurrence and survival for patients transplanted for NASH-related HCC compared to non-NASH HCC etiologies. Retrospective review of the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) database identified 7,461 patients with HCC—1,405 with underlying NASH and 6,086 with non-NASH underlying diseases. After propensity score matching (PSM) to account for patient- and tumor-related confounders 1,175 remained in each group. Primary outcomes assessed were recurrence rate and recurrence-free survival. Recurrent malignancy at 5 years post-transplant was lower in NASH compared to non-NASH patients (5.80 vs. 9.41%, p = 0.01). Recurrence-free survival, however, was similar at 5 years between groups. Patients with NASH-related HCC were less likely to have post-transplant recurrence than their non-NASH counterparts, although recurrence-free survival was similar at 5 years.

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) affects both recipient and donor populations in liver transplantation. Presently, it is unclear whether transplantation of macrosteatotic allografts is affected by the metabolic milieu of liver transplant recipients. This study investigates fatty liver disease at the intersection of donor and recipient. A retrospective review of the Organ Procurement and Transplantation database identified 5167 NASH and 26,289 non‐NASH transplant recipients who received transplants from January 1, 2004, to June 12, 2020. A total of 12,569 donors had allografts with no macrosteatosis (<5%), 16,140 had mild macrosteatosis (5%‐29%), and 2747 had moderate to severe macrosteatosis (≥30%). Comparing recipients with NASH to propensity score–matched (PSM) recipients without NASH demonstrated noninferior graft and patient survival up to 10 years in patients with NASH. Similar trends were observed in subgroup analyses of transplants within each strata of allograft macrosteatosis. Assessing allograft macrosteatosis specifically in the NASH population demonstrated that allografts with ≥30% macrosteatosis were associated with reduced early graft survival (30 days, 93.32% versus 96.54% [P = 0.02]; 1 year, 84.53% versus 88.99% [P = 0.05]) compared with PSM grafts with <30% macrosteatosis. Long‐term graft survival at 5 and 10 years, however, was similar. The use of carefully selected macrosteatotic allografts can be successful in both recipients with NASH and recipients without NASH. The metabolic environment of patients with NASH does not appear to adversely affect outcomes with regard to the allograft when controlled for numerous confounders. It is, however, important to remain cognizant of the potential for high‐risk macrosteatotic allografts to negatively affect outcomes.

Rates of simultaneous liver kidney (SLK) transplantation in the United States have progressively risen. On 8/10/17, the Organ Procurement and Transplantation Network implemented a policy defining criteria for SLK, with a “Safety Net” to prioritize kidney allocation to liver recipients with ongoing renal failure. We performed a retrospective review of the United Network for Organ Sharing (UNOS) database to evaluate policy impact on SLK, kidney after liver (KAL) and kidney transplant alone (KTA). Rates and outcomes of SLK and KAL transplants were compared, as was utilization of high-quality kidney allografts with Kidney Donor Profile Indices (KDPI) <35%. Here, SLK transplants comprised 9.0% and 4.5% of total postpolicy liver and kidney transplants compared to 10.2% and 5.5% prior. Policy enactment did not affect 1-year graft or patient survival for SLK and KAL populations. Less postpolicy SLK transplants utilized high-quality kidney allografts; in all transplant settings, outcomes using high-quality grafts remained stable. These findings suggest that policy implementation has reduced kidney allograft use in SLK transplantation, although both SLK and KAL rates have recently increased. Despite decreased high-quality kidney allograft use, SLK and KAL outcomes have remained stable. Additional studies and long-term follow-up will ensure optimal organ access and sharing.

Urine protein excretion is a prerequisite test for evaluation of living kidney donor candidates. According to Kidney Disease: Improving Global Outcomes (KDIGO) living kidney donor guidelines, initial evaluation of donor albuminuria (screening) should be performed using random urine albumin-to-creatinine ratio (ACR).1 Donor albuminuria should be confirmed using albumin excretion rate (AER, mg/d) in a timed urine specimen. Urine AER <30 mg/d is considered an acceptable level for donation.

Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1-4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P > .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response. © RSNA, 2020.

INTRODUCTION: Immunosuppressed patients are at risk of fungal infections associated with high morbidity and mortality. Invasive aspergillosis (IA) leading to vertebral osteomyelitis, intracardiac and renal aspergillomas in the post-transplant setting is a rare infectious complication. CASE DESCRIPTION/METHODS: A 64-year-old former prison nurse, with a history of alcohol dependence and COPD, presented to our university medical center with fulminant hepatitis A requiring urgent orthotopic liver transplantation (OLT). Intra-operatively, she was noted to have focal ischemic colitis of the cecum and proximal ascending colon with mucosal necrosis, necessitating a right hemicolectomy and primary ileocolostomy. She received induction immunosuppression with basiliximab, followed by maintenance tacrolimus and mycophenolate mofetil. Post-operatively, she received antimicrobial and antifungal prophylaxis and was discharged to a rehab unit on post-op day 11. Her post-OLT course was further complicated by failure to thrive and de novo cytomegalovirus (CMV) viremia at 2 months (CMV D+/R−). > 90 days post OLT she developed fevers and lower back pain. MRI of the spine demonstrated lumbar discitis/osteomyelitis and abdominal CT scan showed a right renal nodule. Biopsies of the L-spine and right kidney revealed septated fungi and tissue cultures were positive for Aspergillus fumigatus. Immunosuppression was stopped and she was treated with amphotericin B, but later switched to isavuconazole and anidulafungin. Despite aggressive medical therapy, she continued to deteriorate clinically, and a TEE and CT chest revealed multi-chamber intracardiac and left ventricular free wall involvement by IA that had progressed. The prognosis was felt to be extremely poor, and she later died in hospice, 5 months post-OLT. DISCUSSION: IA has been recognized as one of the most highly lethal opportunistic fungal infections in organ transplant recipients. In this unique case, late-onset IA (>90 days post-OLT) manifested with vertebral, intracardiac, and renal involvement. Her risk factors included immunosuppression, hemodialysis, and CMV infection. Early initial treatment of IA involves immunosuppression minimization and systemic antifungal therapy using a combination of an azole with or without echinocandin. Surgical resection of an aspergilloma may be indicated prior to starting medical therapy. However, despite aggressive therapy, there is generally <35% survival from IA in this high-risk population.Figure 1.: CT chest showing intracardiac masses in the left atrium (white arrow; left image). CT abdomen showing a right renal nodule that was biopsied (white arrow; right image).

Bevilacqua, Lisa A. MD; Pace, Devon J. MD; Aka, Allison A. MD; Latona, Jessica MD; Koenig, George J. DO; Marks, Joshua A. MD; Cohen, Murray J. MD; Maley, Warren R. MDAuthor Information