Post-pancreatectomy acute pancreatitis after pancreatoduodenectomy: Analysis of a clinically-relevant complication in a single-center retrospective study.

BACKGROUND: /Objectives: This study aimed to evaluate the frequency, clinical impact, and risk factors of post-pancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD) according to the definition proposed by the International Study Group for Pancreatic Surgery (ISGPS). METHODS: patients undergoing PD between 2010 and 2021 were retrospectively analyzed. PPAP was defined according to the ISGPS criteria, including elevated serum amylase for 48 h and concurring pancreatitis alterations on a CT scan. RESULTS: 272 patients were finally included in the study. PPAP occurred in 40 (14.7 %) patients, and it was significantly related to higher rates of clinically-relevant postoperative pancreatic fistula (CR-POPF) (p < 0.001), post-pancreatectomy hemorrhage (PPH) (p < 0.001) and major complications (Clavien-Dindo ≥ 3a) (p < 0.001). Moreover, PPAP in the absence of CR-POPF (n = 18) was significantly related to longer hospital stay (p < 0.001), PPH (p < 0.001), major complications (Clavien-Dindo≥ 3a, p = 0.001) and higher intensive care unit costs (p = 0.029) compared to patients not developing PPAP. In the univariable and multivariable analysis, the duct size (p = 0.004) and high-risk pathologies (p = 0.004) but not intraoperative bleeding (p = 0.066) represented independent risk factors for PPAP. In the same analysis, patients receiving a bridging therapy with low molecular-weight heparin showed significantly lower rates of PPAP (p = 0.045). CONCLUSIONS: PPAP represents a relevant complication after PD. Its risk factors are similar to those for CR-POPF, while anticoagulants could represent a possible prevention strategy.

Impact of citrulline substitution on clinical outcome after liver transplantation in carbamoyl phosphate synthetase 1 and ornithine transcarbamylase deficiency.

Carbamoyl phosphate synthetase 1 (CPS1) and ornithine transcarbamylase (OTC) deficiencies are rare urea cycle disorders, which can lead to life-threatening hyperammonemia. Liver transplantation (LT) provides a cure and offers an alternative to medical treatment and life-long dietary restrictions with permanent impending risk of hyperammonemia. Nevertheless, in most patients, metabolic aberrations persist after LT, especially low plasma citrulline levels, with questionable clinical impact. So far, little is known about these alterations and there is no consensus, whether l-citrulline substitution after LT improves patients' symptoms and outcomes. In this multicentre, retrospective, observational study of 24 patients who underwent LT for CPS1 (n = 11) or OTC (n = 13) deficiency, 25% did not receive l-citrulline or arginine substitution. Correlation analysis revealed no correlation between substitution dosage and citrulline levels (CPS1, p = 0.8 and OTC, p = 1). Arginine levels after liver transplantation were normal after LT independent of citrulline substitution. Native liver survival had no impact on mental impairment (p = 0.67). Regression analysis showed no correlation between l-citrulline substitution and failure to thrive (p = 0.611) or neurological outcome (p = 0.701). Peak ammonia had a significant effect on mental impairment (p = 0.017). Peak plasma ammonia levels correlate with mental impairment after LT in CPS1 and OTC deficiency. Growth and intellectual impairment after LT are not significantly associated with l-citrulline substitution.

Assessment of Mitochondrial Respiration During Hypothermic Storage of Liver Biopsies Following Normothermic Machine Perfusion.

Organ quality can be assessed prior to transplantation, during normothermic machine perfusion (NMP) of the liver. Evaluation of mitochondrial function by high-resolution respirometry (HRR) may serve as a viability assessment concept in this setting. Freshly collected tissue is considered as optimal sample for HRR, but due to technical and personnel requirements, more flexible and schedulable measurements are needed. However, the impact of cold storage following NMP before processing biopsy samples for mitochondrial analysis remains unknown. We aimed at establishing an appropriate storage protocol of liver biopsies for HRR. Wedge biopsies of 5 human livers during NMP were obtained and assessed by HRR. Analysis was performed after 0, 4, 8, and 12 h of hypothermic storage (HTS) in HTK organ preservation solution at 4°C. With HTS up to 4 h, mitochondrial performance did not decrease in HTS samples compared with 0 h (OXPHOS, 44.62 [34.75-60.15] pmol·s-1·mg wet mass-1 vs. 43.73 [40.69-57.71], median [IQR], p > 0.999). However, at HTS beyond 4 h, mitochondrial respiration decreased. We conclude that HTS can be safely applied for extending the biopsy measurement window for up to 4 h to determine organ quality, but also that human liver respiration degrades beyond 4 h HTS following NMP.

The BAR Score Predicts and Stratifies Outcomes Following Liver Retransplantation: Insights From a Retrospective Cohort Study.

Liver retransplantation (reLT) yields poorer outcomes than primary liver transplantation, necessitating careful patient selection to avoid futile reLT. We conducted a retrospective analysis to assess reLT outcomes and identify associated risk factors. All adult patients who underwent a first reLT at the Medical University of Innsbruck from 2000 to 2021 (N = 111) were included. Graft- and patient survival were assessed via Kaplan-Meier plots and log-rank tests. Uni- and multivariate analyses were performed to identify independent predictors of graft loss. Five-year graft- and patient survival rates were 64.9% and 67.6%, respectively. The balance of risk (BAR) score was found to correlate with and be predictive of graft loss and patient death. The BAR score also predicted sepsis (AUC 0.676) and major complications (AUC 0.720). Multivariate Cox regression analysis identified sepsis [HR 5.179 (95% CI 2.575-10.417), p < 0.001] as the most significant independent risk factor for graft loss. At a cutoff of 18 points, the 5 year graft survival rate fell below 50%. The BAR score, a simple and easy to use score available at the time of organ acceptance, predicts and stratifies clinically relevant outcomes following reLT and may aid in clinical decision-making.

The Predictive Value of Graft Viability and Bioenergetics Testing Towards the Outcome in Liver Transplantation.

Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.

Liver Transplantation after Successful Downstaging of a Locally Advanced Hepatocellular Carcinoma with Systemic Therapy.

INTRODUCTION: Liver transplantation (LT) is potentially curative for patients with cirrhosis and hepatocellular carcinoma (HCC). However, this procedure is usually reserved for patients with early tumor stages or after successful downstaging with local regional therapies. In patients with locally advanced HCC, current guidelines recommend locoregional and palliative systemic therapies for tumor stages Barcelona Clinic Liver Cancer (BCLC) B and C, respectively. CASE REPORT: In this article, we describe a 63-year-old male patient with locally advanced HCC (BCLC C) and hepatitis C-associated cirrhosis. Following systemic treatment with the immune checkpoint inhibitor atezolizumab and the anti-VEGF antibody bevacizumab, significant downstaging to a tumor stage within the Milan criteria was achieved after which LT was successfully performed. CONCLUSION: As more effective systemic therapies become available, LT and potential curative treatment could become feasible for selected patients with locally advanced HCC.

Liver Transplantation in Recipients With a Positive Crossmatch: A Retrospective Single-Center Match-Pair Analysis.

A positive crossmatch (XM+) is considered a contraindication to solid abdominal organ transplantation except liver transplantation (LT). Conflicting reports exist regarding the effects of XM+ on post-transplant outcomes. The goal of this retrospective single-center analysis is to evaluate the influence of XM+ on relevant outcome parameters such as survival, graft rejection, biliary and arterial complications. Forty-nine adult patients undergoing LT with a XM+ between 2002 and 2017 were included. XM+ LT recipients were matched 1:2 with crossmatch negative (XM-) LT recipients based on the balance of risk (BAR) score. Patient and graft survival were compared using Kaplan-Meier survival analysis and the log-rank test. Comparative analysis of clinical outcomes in XM+ and XM- groups were conducted. Patient and graft survival were similar in XM+ and XM- patients. Rejection episodes did not differ either. Recipients with a strong XM+ were more likely to develop a PCR+ CMV infection. A XM+ was not associated with a higher incidence of biliary or arterial complications. Donor age, cold ischemia time, PCR+ CMV infection and a rejection episode were associated with the occurrence of ischemic type biliary lesions. A XM+ has no effects on patient and graft survival or other relevant outcome parameters following LT.

Bioenergetic and Cytokine Profiling May Help to Rescue More DCD Livers for Transplantation.

The majority of organs used for liver transplantation come from brain-dead donors (DBD). In order to overcome the organ shortage, increasingly donation after circulatory death (DCD) organs are also considered. Since normothermic machine perfusion (NMP) restores metabolic activity and allows for in-depth assessment of organ quality and function prior to transplantation, such organs may benefit from NMP. We herein compare the bioenergetic performance through a comprehensive evaluation of mitochondria by high-resolution respirometry in tissue biopsies and the inflammatory response in DBD and DCD livers during NMP. While livers were indistinguishable by perfusate biomarker assessment and histology, our findings revealed a greater impairment of mitochondrial function in DCD livers after static cold storage compared to DBD livers. During subsequent NMPs, DCD organs recovered and eventually showed a similar performance as DBD livers. Cytokine expression analysis showed no differences in the early phase of NMP, while towards the end of NMP, significantly elevated levels of IL-1ß, IL-5 and IL-6 were found in the perfusate of DCD livers. Based on our results, we find it worthwhile to reconsider more DCD organs for transplantation to further extend the donor pool. Therefore, donor organ quality criteria must be developed, which may include an assessment of bioenergetic function and cytokine quantification.

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12-24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = -0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

Influence of early biliary complications on survival rates after pediatric liver transplantation-A positive outlook.

BACKGROUND: Early biliary complications (EBC) constitute a burden after pediatric liver transplantation frequently requiring immediate therapy. We aimed to assess the impact of EBC on short- and long-term patient and graft survival as well as post-transplant morbidity. METHODS: We analyzed 121 pediatric liver transplantations performed between 1984 and 2019 at the Medical University of Innsbruck for the occurrence of early (<90 days) biliary complications and investigated the influence of EBC on patient and graft survival. RESULTS: Early biliary complications occurred in 30 (24.8%) out of the 121 pediatric liver transplant recipients. Patient survival at 15 years (89.2% vs. 84.2%, p = .65) and all-cause (82.5% vs. 74.0%) and death-censored graft survival (82.5% vs. 75.1%, p = .71) at 10 years were similar between the EBC and the non-EBC group. The EBC group had a significantly longer ICU (25 vs. 16 days, p < .001) and initial hospital stay (64 vs. 42 days, p = .002). Livers of patients with EBC were characterized by multiple bile ducts (33.3% vs. 13.2%, p = .027), and patients with EBC had a higher risk to develop late biliary complications (OR 2.821 [95% CI 1.049-7.587], p = .044) and bowel obstruction/perforation (OR 4.388 [95% CI 1.503-12.812], p = .007). CONCLUSION: Early biliary complications after pediatric liver transplantation is frequent. The occurrence of EBC significantly increased post-transplant morbidity without affecting mortality. Multiple bile ducts were the only risk factor for the development of EBC in our cohort.

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs.

Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

Donor cardiac arrest and cardiopulmonary resuscitation: impact on outcomes after simultaneous pancreas-kidney transplantation - a retrospective study.

Donor cardiac arrest and cardiopulmonary resuscitation (CACPR) has been considered critically because of concerns over hypoperfusion and mechanical trauma to the donor organs. We retrospectively analyzed 371 first simultaneous pancreas-kidney transplants performed at the Medical University of Innsbruck between 1997 and 2017. We evaluated short- and long-term outcomes from recipients of organs from donors with and without a history of CACPR. A total of 63 recipients received a pancreas and kidney graft from a CACPR donor. At 1, and 5-years, patient survival was similar with 98.3%, and 96.5% in the CACPR and 97.0%, and 90.2% in the non-CACPR group (log rank P = 0.652). Death-censored pancreas graft survival was superior in the CACPR group with 98.3%, and 91.4% compared to 86.3%, and 77.4% (log rank P = 0.028) in the non-CACPR group, which remained statistically significant even after adjustment [aHR 0.49 (95% CI 0.24-0.98), P = 0.044]. Similar relative risks for postoperative complications Clavien Dindo > 3a, pancreatitis, abscess, immunologic complications, delayed pancreas graft function, and relative length of stay were observed for both groups. Donors with a history of CACPR are, in the current practice, safe for transplantation. Stringent donor selection and short CPR durations may allow for outcomes surpassing those of donors without CACPR.

Restoring Mitochondrial Function While Avoiding Redox Stress: The Key to Preventing Ischemia/Reperfusion Injury in Machine Perfused Liver Grafts?

Mitochondria sense changes resulting from the ischemia and subsequent reperfusion of an organ and mitochondrial reactive oxygen species (ROS) production initiates a series of events, which over time result in the development of full-fledged ischemia-reperfusion injury (IRI), severely affecting graft function and survival after transplantation. ROS activate the innate immune system, regulate cell death, impair mitochondrial and cellular performance and hence organ function. Arresting the development of IRI before the onset of ROS production is currently not feasible and clinicians are faced with limiting the consequences. Ex vivo machine perfusion has opened the possibility to ameliorate or antagonize the development of IRI and may be particularly beneficial for extended criteria donor organs. The molecular events occurring during machine perfusion remain incompletely understood. Accumulation of succinate and depletion of adenosine triphosphate (ATP) have been considered key mechanisms in the initiation; however, a plethora of molecular events contribute to the final tissue damage. Here we discuss how understanding mitochondrial dysfunction linked to IRI may help to develop novel strategies for the prevention of ROS-initiated damage in the evolving era of machine perfusion.

Heart Failure Stimulates Tumor Growth by Circulating Factors.

BACKGROUND: Heart failure (HF) survival has improved, and nowadays, many patients with HF die of noncardiac causes, including cancer. Our aim was to investigate whether a causal relationship exists between HF and the development of cancer. METHODS: HF was induced by inflicting large anterior myocardial infarction in APCmin mice, which are prone to developing precancerous intestinal tumors, and tumor growth was measured. In addition, to rule out hemodynamic impairment, a heterotopic heart transplantation model was used in which an infarcted or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ. After 6 weeks, tumor number, volume, and proliferation were quantified. Candidate secreted proteins were selected because they were previously associated both with (colon) tumor growth and with myocardial production in post-myocardial infarction proteomic studies. Myocardial gene expression levels of these selected candidates were analyzed, as well as their proliferative effects on HT-29 (colon cancer) cells. We validated these candidates by measuring them in plasma of healthy subjects and patients with HF. Finally, we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large, prospective general population cohort. RESULTS: The presence of failing hearts, both native and heterotopically transplanted, resulted in significantly increased intestinal tumor load of 2.4-fold in APCmin mice (all P<0.0001). The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016, respectively). We identified several proteins (including serpinA3 and A1, fibronectin, ceruloplasmin, and paraoxonase 1) that were elevated in human patients with chronic HF (n=101) compared with healthy subjects (n=180; P<0.001). Functionally, serpinA3 resulted in marked proliferation effects in human colon cancer (HT-29) cells, associated with Akt-S6 phosphorylation. Finally, elevated cardiac and inflammation biomarkers in apparently healthy humans (n=8319) were predictive of new-onset cancer (n=1124) independently of risk factors for cancer (age, smoking status, and body mass index). CONCLUSIONS: We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors. A diagnosis of HF may therefore be considered a risk factor for incident cancer.

Live Confocal Tissue Assessment With SYTO16/PI and WGA Staining Visualizes Acute Organ Damage and Predicts Delayed Graft Function in Kidney Transplantation.

OBJECTIVE: The aim of our prospective clinical trial was to test a tissue staining technique (real-time confocal analysis [RTCA]) as a rapid assessment tool for donor kidney quality and function in human kidney transplantation. SUMMARY BACKGROUND DATA: Tools for objective graft tissue viability assessment before kidney transplantation are lacking. RTCA has recently been established and tested in a pilot study using rodent kidneys. METHODS: RTCA was performed in kidney biopsies stained with SYTO16/PI and WGA. A score between -3 (100% nonviable) and +3 (100% viable) describes the sum of viable cells divided by the number of nonviable cells per examined area (glomerulus, proximal, and distal tubules). The primary study endpoint was the delayed graft function (DGF). RESULTS: Seventy-one kidney transplant recipients were transplanted. The median recipient and donor age were 58.5 and 57 years, respectively. Cold ischemia time was 13.6 ±â€Š4.7 hours; anastomosis time was 30.8 ±â€Š8.7 minutes (mean ±â€ŠSD). Overall, 23 (33.8%) patients developed DGF. The RTCA score was significantly lower in kidneys developing DGF -0.43 ±â€Š1.78 versus no DGF 0.91 ±â€Š2.17, P = 0.01. The Remuzzi score did not differ between DGF and no DGF, P = 0.13. Remuzzi score and RTCA score correlate inversely significantly; P = 0.004. In the multivariate analysis, solely RTCA score was revealed as a significant independent factor predicting DGF; P = 0.015, Wald = 5.95, odds ratio = 0.72, 95% confidence interval = 0.55 to 0.94. CONCLUSIONS: Our data demonstrate that RTCA is feasible and clinically meaningful. The RTCA score predicts DGF and is a valid option to be applied in renal transplantation.

Sex matching does not impact the outcome after simultaneous pancreas-kidney transplantation.

BACKGROUND: Several studies in solid organ transplantation have shown a correlation between donor and recipient sex mismatch and risk of graft loss. In this study, we aimed to analyze the impact of donor and recipient sex matching on patient and pancreas graft survival in a large single-center cohort. METHODS: We retrospectively analyzed all first simultaneous pancreas-kidney transplants performed between 1979 and 2017 at the Medical University of Innsbruck. RESULTS: Of 452 patients, 54.6% (247) received a sex-matched transplant. Patient survival (P = .86), death-censored pancreas graft survival (dcPGS, P = .26), and death-censored kidney graft survival (dcKGS, P = .24) were similar between the sex-matched and sex-mismatched groups. Patient survival and dcPGS at 1, 5, and 15 years were 95.9%, 90.0%, and 62.1% and 86.1%, 77.1%, and 56.7% in the sex-matched group and 93.6%, 86.2%, and 62.4% and 83.1%, 73.3%, and 54.3% in the sex-mismatched group. Sex matching led to a lower odds of severe postoperative complications (41.2% vs 49.0%; OR 0.57, 95%CI 0.33-0.97; P = .038); however, no increased odds of other adverse postoperative outcomes was detected. CONCLUSION: Our study demonstrates that sex matching reduced the odds of postoperative complications but did not impact other early and late outcome parameters in our cohort.

Successful management of recurrent focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.

Late recurrent bleeding episodes from duodenojejunostomy after pancreas transplantation.

In response to a number of late, repetitive bleeding episodes from the site of the enteric anastomosis, we herein analyze the clinical courses and etiologies of 379 consecutively performed pancreas transplants between January 2000 and December 2016. Duodenojejunostomies for enteric drainage were performed at the upper jejunum in a side to side, double layer fashion. Five patients (1.3%) developed recurrent late hemorrhagic episodes originating from the graft duodenal anastomosis. Bleeding from the anastomotic site was associated with hematochezia, hemodynamic instability and decrease in serum hemoglobin. Mean onset was 6.4(±2.8) years after transplantation. Bleeding was recurrent (mean 5.2 ± 2.6) and required 9(±2.5) interventions. Hypervascularization, mucosal vulnerability, and bleeding at the site of the enteric anastomosis could be identified in all cases. In four patients, the enteric pancreas anastomosis was resected and a new duodenojejunostomy was performed. No pancreas graft loss occurred due to bleeding. In two patients, hepatic cirrhosis and portal hypertension were identified, one patient had a liver fibrosis as putative cause for the repetitive bleeding episodes. Late anastomotic hemorrhage is a rare but severe complication following pancreas transplantation. The treatment is challenging and includes endoscopy, interventional radiology, and surgery. Hepatic conditions with an increased portal pressure may be the underlying cause.

Donor brain death leads to differential immune activation in solid organs but does not accelerate ischaemia-reperfusion injury.

A comparative analysis of inflammation between solid organs following donor brain death (BD) is still lacking and the detailed influence of BD accelerating ischaemia-reperfusion injury (IRI) post-transplantation remains to be addressed. Applying a murine model of BD, we demonstrated that 4 h after BD organs were characterized by distinct inflammatory expression patterns. For instance, lipocalin 2 (LCN2), a marker of acute kidney injury, was selectively induced in BD livers but not in kidneys. BD further resulted in significantly reduced frequencies of CD3(+) CD4(+) , CD3(+) CD8(+) T cells and NKp46(+) NK cells in the liver, whereas BD kidneys and hearts were characterized by significantly lower frequencies of conventional dendritic cells (cDCs). Syngeneic models of kidney (KTx) and heart transplantation (HTx) illustrated stronger gene expression in engrafted BD hearts only, but 20 h post-transplantation both organs displayed comparable intragraft lymphocyte frequencies, except for NK cells and graft function. Moreover, the complement factor C3d deposit detected in small vessels and capillaries in cardiac syngrafts did not significantly differ between BD and sham-transplanted groups. Finally, no further influence of donor BD on graft survival was detected in an allogeneic heart transplantation setting (C57BL/6 grafts into BALB/c recipients). We show for the first time that BD organs are characterized by a varying inflammatory profile; however, BD does not accelerate IRI in syngeneic KTx and HTx.