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In a multicenter, controlled trial, patients undergoing transplantation of a liver from a donor after circulatory death were randomly assigned to receive the liver after hypothermic oxygenated machine perfusion or conventional static cold storage. Hypothermic perfusion led to a lower risk of post-transplantation nonanastomotic biliary strictures.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality. Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

We aimed to systematically review published data on the effectiveness of Institut Georges Lopez-1 (IGL-1) as a preservation solution for kidney and pancreas grafts. A systematic literature search of PubMed, Embase, Web of Science, and the Cochrane Library databases was performed. Human studies evaluating the effects of IGL-1 preservation solution in kidney and/or pancreas transplantation were included. Outcome data on kidney and pancreas graft function were extracted. Of 1513 unique articles identified via the search strategy, four articles could be included in the systematic review. Of these, two retrospective studies reported on the outcome of IGL-1 compared to University of Wisconsin (UW) solution in kidney transplantation. These show kidneys preserved in IGL-1 had improved early function (2 weeks post-transplant) compared to UW. Follow-up was limited to 1 year and showed similar graft and patient survival rates when reported. Two case series described acceptable early outcomes (up to 1 month) of simultaneous kidney pancreas transplantation after storage in IGL-1. As only four clinical papers were identified, we widened our search to include four eligible large animal studies. Three compared IGL-1 with UW in pig kidney transplant models with inconclusive or mildly positive results. One pig pancreas transplant study suggested better early outcome with IGL-1 compared to UW. Too few published data are available to allow any firm conclusions to be drawn on the effectiveness of IGL-1 as a preservation solution of kidney and pancreas grafts. The limited available data show satisfactory early outcomes though no medium to long-term outcomes have been described. Further well-designed clinical studies are needed.

A 67-year-old woman with malabsorption and malnourishment was referred for possible intestinal transplantation. CT showed small-bowel dilatation along with a whirl sign and numerous collateral veins, suggestive of a midgut volvulus, shown in a video. A 67-year-old woman with a 6-month history of malabsorption and malnourishment was referred for possible intestinal transplantation. She had a body-mass index (the weight in kilograms divided by the square of the height in meters) of 19. The patient was receiving only parenteral nutrition because of a long-standing history of jejunal diverticulosis with bacterial overgrowth that was resistant to long-term antibiotic treatment. Six years earlier, a small-bowel derotation and cecopexy had been performed after she had had an episode of gastrointestinal obstruction; however, nausea and diarrhea remained. During the 2 years before the current presentation, she had reported having frequent . . .

The scientific community must urgently and proactively facilitate the shift from conventional, “one-size-fits-all” clinical research to more personalized methodologies that thoroughly consider genetic, environmental, and lifestyle factors in a person-centered approach. [...]Annema et al. address the often-overlooked topic of prehabilitation for transplant candidates, advocating a multimodal strategy that emphasizes exercise, nutrition, and psychosocial support to improve outcomes. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The farnesoid X receptor (FXR) is abundantly expressed in the ileum, where it exerts an enteroprotective role as a key regulator of intestinal innate immunity and homeostasis, as shown in pre-clinical models of inflammatory bowel disease. Since intestinal ischemia reperfusion injury (IRI) is characterized by hyperpermeability, bacterial translocation and inflammation, we aimed to investigate, for the first time, if the FXR-agonist obeticholic acid (OCA) could attenuate intestinal ischemia reperfusion injury. In a validated rat model of intestinal IRI (laparotomy + temporary mesenteric artery clamping), 3 conditions were tested (n = 16/group): laparotomy only (sham group); ischemia 60min+ reperfusion 60min + vehicle pretreatment (IR group); ischemia 60min + reperfusion 60min + OCA pretreatment (IR+OCA group). Vehicle or OCA (INT-747, 2*30mg/kg) was administered by gavage 24h and 4h prior to IRI. The following end-points were analyzed: 7-day survival; biomarkers of enterocyte viability (L-lactate, I-FABP); histology (morphologic injury to villi/crypts and villus length); intestinal permeability (Ussing chamber); endotoxin translocation (Lipopolysaccharide assay); cytokines (IL-6, IL-1-β, TNFα, IFN-γ IL-10, IL-13); apoptosis (cleaved caspase-3); and autophagy (LC3, p62). It was found that intestinal IRI was associated with high mortality (90%); loss of intestinal integrity (structurally and functionally); increased endotoxin translocation and pro-inflammatory cytokine production; and inhibition of autophagy. Conversely, OCA-pretreatment improved 7-day survival up to 50% which was associated with prevention of epithelial injury, preserved intestinal architecture and permeability. Additionally, FXR-agonism led to decreased pro-inflammatory cytokine release and alleviated autophagy inhibition. Pretreatment with OCA, an FXR-agonist, improves survival in a rodent model of intestinal IRI, preserves the gut barrier function and suppresses inflammation. These results turn FXR into a promising target for various conditions associated with intestinal ischemia.

De novo malignancy (DNM) is the primary cause of mortality after liver transplantation (LT) for alcohol-related liver disease (ALD). However, data on risk factors for DNM development after LT are limited, specifically in patients with ALD. Therefore, we retrospectively analyzed all patients transplanted for ALD at our center before October 2016. Patients with a post-LT follow-up of <12 months, DNM within 12 months after LT, patients not on tacrolimus in the 1st year post-LT, and unknown smoking habits were excluded. Tacrolimus drug exposure level (TDEL) was calculated by area under the curve of trough levels in the 1st year post-LT. 174 patients received tacrolimus of which 19 (10.9%) patients developed a DNM between 12 and 60 months post-LT. Multivariate cox regression analysis identified TDEL [HR: 1.710 (1.211–2.414); p = 0.002], age [1.158 (1.076–1.246); p < 0.001], number of pack years pre-LT [HR: 1.021 (1.004–1.038); p = 0.014] and active smoking at LT [HR: 3.056 (1.072–8.715); p = 0.037] as independent risk factors for DNM. Tacrolimus dose minimization in the 1st year after LT and smoking cessation before LT might lower DNM risk in patients transplanted for ALD.

In September 2022, Belgium implemented a nationally reimbursed HMP service for all ECD and DCD kidneys procured and transplanted within the country. We retrospectively analyzed data from 242 kidney transplantations preserved with continuous HMP between October 2022 and September 2023. Active oxygenation (HMPO 2 ) was applied in DCD donors aged >50 years. One-year outcomes for all HMP kidneys included delayed graft function (DGF) in 14.4%, estimated glomerular filtration rate of 50 mL/min/1.73 m 2 , 10.1% acute rejection, 96.3% death-censored graft survival, and 98.3% patient survival. DGF rates were lower in ECD kidneys (9.1%) and in DCD ≤50 years (9.5%), while higher in DCD >50 years (19.6%). National transplantation rates of DCD kidneys significantly increased from 90 to 175 per year (p < 0.0001), but not for ECD kidneys (from 45 to 54 per year (p = 0.2965) post-HMP implementation without affecting kidney export. The annual cost savings from reduced dialysis requirements were estimated at €3.59 million. The national implementation of a centralized HMP service in Belgium led to excellent one-year transplant outcomes, increased utilization of ECD and DCD kidneys, and substantial healthcare cost savings. These findings support HMP, and where appropriate HMPO 2 , as the new standard of care for kidney preservation in Belgium, with potential implications for broader international collaboration.

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05–1.83)), chronic lung disease (HR 1.71 (95% CI 1.13–2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61–4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66–17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75–7.19)), corticosteroid use (OR 2.93 (95% CI 1.03–2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65–17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type.