Evaluating Islet Cell Isolation and Transplantation From Donors Following Medical Assistance in Dying.

Background: Limited information is available regarding outcomes of islet cell isolation (ICI) and transplantation (ITx) using medical assistance in dying (MAiD) donors. We aimed to assess the feasibility and outcomes of ICI and ITx in MAiD donors. Methods: ICI and ITx from MAiD were compared with donation after circulatory death (DCD) type III between 2016 and 2023. Differences of isolated islet equivalents (IEQs), numeric viability and other quantitative in vitro metabolic measures were assessed. Results: Overall, 81 ICIs were available of whom 34 (42%) and 47 (58%) from MAiD and DCD-III, respectively. There were no differences of pancreas and digested tissue weight and islets viability among the 2 groups; however, cold ischemic time was longer in MAiD (11.5 versus 9.1 h; P = 0.021). The IEQ (P < 0.001) and percent trapped (P < 0.001) were higher in the DCD-III; however, MAiD islets demonstrated a higher purity (P = 0.020). Overall, 15 ITx were performed of whom 3 (8.8%) and 12 (25.5%) from MAiD and DCD-III, respectively (P = 0.056). Patients had a median fasting C-peptide of 0.51 ng/mL (interquartile range, 0.30-0.76 nmol/L), with no differences between groups (MAiD = 0.52 versus DCD-III = 0.51; P = 0.718). The median HbA1c was 6.2% (interquartile range, 5.7%-7%) (MAiD = 6.3% versus DCD-III = 6.1%; P = 0.815) and BETA2 scores (MAiD = 7.4 versus DCD-III = 12.8; P = 0.229) did not differ. Conclusions: ICI from MAiD donor pancreas may be successfully transplanted with comparable outcomes to DCD-III and may be used for research. These results justify additional efforts to consider MAiD as another valuable source of grafts for ITx. Further multicenter studies and larger clinical experience are needed to validate our findings.

Incidence of clinically relevant postoperative pancreatic fistula in patients undergoing open and minimally invasive pancreatoduodenectomy: a population-based study.

Purpose: Postoperative pancreatic fistula (POPF) remains a devastating complication of pancreatoduodenectomy (PD). Minimally invasive PD (MIPD), including laparoscopic (LPD) and robotic (RPD) approaches, have comparable POPF rates to open PD (OPD). However, we hypothesize that the likelihood of having a more severe POPF, as defined as clinically relevant POPF (CR-POPF), would be higher in an MIPD relative to OPD. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted pancreatectomy dataset (2014-2020) was reviewed for any POPF after OPD. Propensity score matching (PSM) compared MIPD to OPD, and then RPD to LPD. Results: Among 3,083 patients who developed a POPF, 2,843 (92.2%) underwent OPD and 240 (7.8%) MIPD; of these, 25.0% were LPD (n = 60) and 75.0% RPD (n = 180). Grade B POPF was observed in 45.4% (n = 1,400), and grade C in 6.0% (n = 185). After PSM, MIPD patients had higher rates of CR-POPF (47.3% OPD vs. 54.4% MIPD, p = 0.037), as well as higher reoperation (9.1% vs. 15.3%, p = 0.006), delayed gastric emptying (29.2% vs. 35.8%, p = 0.041), and readmission rates (28.2% vs. 35.1%, p = 0.032). However, CR-POPF rates were comparable between LPD and RPD (56.8% vs. 49.3%, p = 0.408). Conclusion: The impact of POPF is more clinically pronounced after MIPD than OPD with a more complex postoperative course. The difference appears to be attributed to the minimally invasive environment itself as no difference was noted between LPD and RPD. A clear biological explanation of this clinical observation remains missing. Further studies are warranted.

Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.

INTRODUCTION: Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications. METHODS AND ANALYSIS: The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC. ETHICS AND DISSEMINATION: All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.

Small graft size and hepatocellular carcinoma outcomes in living donor liver transplantation: a retrospective multicentric cohort study.

INTRODUCTION: This study examined associations between the graft-to-recipient weight ratio (GRWR) for adult-to-adult living donor liver transplantation (LDLT) and HCC outcomes. MATERIALS AND METHODS: Data from patients in the Korean Organ Transplantation Registry who underwent LDLT for HCC from 2014-2021 were retrospectively reviewed. Patients were categorized using the cutoff GRWR for HCC recurrence determined by an adjusted cubic spline (GRWR<0.7% vs. GRWR≥0.7%). Recurrence-free survival (RFS) and HCC recurrence were analyzed in the entire and a 1:5 propensity-matched cohort. RESULTS: The eligible cohort consisted of 2005 LDLT recipients (GRWR<0.7 [n=59] vs. GRWR≥0.7 [n=1946]). In the entire cohort, 5-year RFS was significantly lower in the GRWR<0.7 than in the GRWR≥0.7 group (66.7% vs. 76.7%, P =0.019), although HCC recurrence was not different between groups (77.1% vs. 80.7%, P =0.234). This trend was similar in the matched cohort ( P =0.014 for RFS and P =0.096 for HCC recurrence). In multivariable analyses, GRWR<0.7 was an independent risk factor for RFS (adjusted HR [aHR] 1.89, P =0.012), but the result was marginal for HCC recurrence (aHR 1.61, P =0.066). In the pretransplant tumor burden subgroup analysis, GRWR<0.7 was a significant risk factor for both RFS and HCC recurrence only for tumors exceeding the Milan criteria (aHR 3.10, P <0.001 for RFS; aHR 2.92, P =0.003 for HCC recurrence) or with MoRAL scores in the fourth quartile (aHR 3.33, P <0.001 for RFS; aHR 2.61, P =0.019 for HCC recurrence). CONCLUSIONS: A GRWR<0.7 potentially leads to lower RFS and higher HCC recurrence after LDLT when the pretransplant tumor burden is high.

Cost-competitive decentralized ammonia fertilizer production can increase food security.

The current centralized configuration of the ammonia industry makes the production of nitrogen fertilizers susceptible to the volatility of fossil fuel prices and involves complex supply chains with long-distance transport costs. An alternative consists of on-site decentralized ammonia production using small modular technologies, such as electric Haber-Bosch or electrocatalytic reduction. Here we evaluate the cost-competitiveness of producing low-carbon ammonia at the farm scale, from a solar agrivoltaic system, or using electricity from the grid, within a novel global fertilizer industry. Projected costs for decentralized ammonia production are compared with historical market prices from centralized production. We find that the cost-competitiveness of decentralized production relies on transport costs and supply chain disruptions. Taking both factors into account, decentralized production could achieve cost-competitiveness for up to 96% of the global ammonia demand by 2030. These results show the potential of decentralized ammonia technologies in revolutionizing the fertilizer industry, particularly in regions facing food insecurity.

Efficiency of machine perfusion in pediatric liver transplantation.

Liver transplantation is the only life-saving procedure for children with end-stage liver disease. The field is however heterogenic with various graft types, recipient age, weight, and underlying diseases. Despite recently improved overall outcomes and the expanded use of living donors, waiting list mortality remains unacceptable, particularly in small children and infants. Based on the known negative effects of elevated donor age, higher body mass index, and prolonged cold ischemia time, the number of available donors for pediatric recipients is limited. Machine perfusion has regained significant interest in the adult liver transplant population during the last decade. Ten randomized controlled trials are published with an overall advantage of machine perfusion techniques over cold storage regarding postoperative outcomes, including graft survival. The concept of hypothermic oxygenated perfusion (HOPE) was the first and only perfusion technique used for pediatric liver transplantation today. In 2018 the first pediatric candidate received a full-size graft donated after circulatory death with cold storage and HOPE, followed by a few split liver transplants after HOPE with an overall limited case number until today. One series of split procedures during HOPE was recently presented by colleagues from France with excellent results, reduced complications, and better graft survival. Such early experience paves the way for more systematic use of machine perfusion techniques for different graft types for pediatric recipients. Clinical reports of pediatric liver transplants with other perfusion techniques are awaited. Strong collaborative efforts are needed to explore the effect of perfusion techniques in this vulnerable population impacting not only the immediate posttransplant outcome but the development and success of an entire life.

Routine utilization of machine perfusion in liver transplantation: Ready for prime time?

The last decade has been notable for increasing high-quality research and dramatic improvement in outcomes with dynamic liver preservation. Robust evidence from numerous randomized controlled trials has been pooled by meta-analyses, providing the highest available evidence on the protective effect of machine perfusion (MP) over static cold storage in liver transplantation (LT). Based on a protective effect with less complications and improved graft survival, the field has seen a paradigm shift in organ preservation. This editorial focuses on the role of MP in LT and how it could become the new "gold standard". Strong collaborative efforts are needed to explore its effects on long-term outcomes.

Data-driven models and digital twins for sustainable combustion technologies.

We highlight the critical role of data in developing sustainable combustion technologies for industries requiring high-density and localized energy sources. Combustion systems are complex and difficult to predict, and high-fidelity simulations are out of reach for practical systems because of computational cost. Data-driven approaches and artificial intelligence offer promising solutions, enabling renewable synthetic fuels to meet decarbonization goals. We discuss open challenges associated with the availability and fidelity of data, physics-based numerical simulations, and machine learning, focusing on developing digital twins capable of mirroring the behavior of industrial combustion systems and continuously updating based on newly available information.

Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Clinical outcomes after transplantation of domino grafts or standard deceased donor livers: a systematic review and meta-analysis.

BACKGROUND AND AIM: Domino liver transplantation (DLT) utilizes otherwise discarded livers as donor grafts for another recipients. It is unclear whether DLT has less favorable outcomes compared to deceased donor liver transplantation (DDLT). We aimed to assess the outcomes of DLT compared to DDLT. METHODS: MEDLINE, Embase, and Web of Science database were searched to identify studies comparing outcomes after DLT with DDLT. Data were pooled using random-effects modeling, evaluating odds ratios (OR) or mean difference (MD) for outcomes including waiting list time, severe hemorrhage, intensive care unit (ICU), length hospital stay (LOS), rejection, renal, vascular, and biliary events, and recipient survival at 1, 3, 5, and 10 years. RESULTS: Five studies were identified including 945 patients (DLT = 409, DDLT = 536). The DLT recipients were older compared to the DDLT group (P = 0.04), and both cohorts were comparable regarding lab MELD, hepatocellular carcinoma, and waitlist time. There were no differences in vascular (OR: 1.60, P = 0.39), renal (OR: 0.62, P = 0.24), biliary (OR: 1.51, P = 0.21), severe hemorrhage (OR: 1.09, P = 0.86), rejection (OR: 0.78, P = 0.51), ICU stay (MD: 0.50, P = 0.21), or LOS (MD: 1.68, P = 0.46) between DLT and DDLT. DLT and DDLT were associated with comparable 1-year (78.9% vs 80.4%; OR: 1.03, P = 0.89), 3-year (56.2% vs 54.1%; OR: 1.35, P = 0.07), and 10-year survival (6.5% vs 8.5%; OR: 0.8, P = 0.67) rates. DLT was associated with higher 5-year survival (41.6% vs 36.4%; OR: 1.70; P = 0.003) compared to DDLT, which was not confirmed at sensitivity analysis. CONCLUSION: This meta-analysis of the best available evidence (Level 2a) demonstrated that DLT and DDLT have comparable outcomes. As indications for liver transplantation expand, future high-quality research is encouraged to increase the DLT numbers in clinical practice, serving the growing waiting list candidates, with the caveat of uncertain de novo disease transmission risks.

Meta-analysis of fenestrating versus reconstituting subtotal cholecystectomy in the management of difficult gallbladder.

AIMS: To evaluate comparative outcomes of fenestrating and reconstituting subtotal cholecystectomy (STC) in patients with difficult gallbladder. METHODS: A systematic search of electronic data sources and bibliographic reference lists were conducted. All comparative studies reporting outcomes of laparoscopic fenestrating and reconstituting STC were included and their risk of bias were assessed using ROBINS-I tool. RESULTS: Seven comparative studies were included enrolling 590 patients undergoing laparoscopic STC using either fenestrating (n = 353) or reconstituting (n = 237) approaches. Although fenestrating STC was associated with a significantly higher rate of bile leak (OR: 2.47, p = 0.007) compared to reconstituting STC, both approaches were comparable in terms of resolution of bile leak without (RD: -0.02, p = 0.86) or with (OR: 1.84, p = 0.40) postoperative ERCP. Moreover, there was no significant difference in development of bile duct injury (RD: -0.02, p = 0.16), need for postoperative ERCP (OR: 1.36, p = 0.49), wound infection (RD: 0.03, p = 0.27), re-operation (OR: 0.95, p = 0.95), gallbladder remnant cholecystitis (OR: 0.21, p = 0.09) or need for completion cholecystectomy (RD: 0.01, p = 0.59) between two groups. CONCLUSIONS: Fenestrating STC is associated with a higher risk of bile leak than the reconstructing technique. This issue can be mitigated by routine use of drains, delayed drain removal, and in selected cases endoscopic therapy. We encourage the fenestrating approach considering trends in improved short- and long-term outcomes.

Improving reduced-order models through nonlinear decoding of projection-dependent outputs.

A fundamental hindrance to building data-driven reduced-order models (ROMs) is the poor topological quality of a low-dimensional data projection. This includes behavior such as overlapping, twisting, or large curvatures or uneven data density that can generate nonuniqueness and steep gradients in quantities of interest (QoIs). Here, we employ an encoder-decoder neural network architecture for dimensionality reduction. We find that nonlinear decoding of projection-dependent QoIs, when embedded in a dimensionality reduction technique, promotes improved low-dimensional representations of complex multiscale and multiphysics datasets. When data projection (encoding) is affected by forcing accurate nonlinear reconstruction of the QoIs (decoding), we minimize nonuniqueness and gradients in representing QoIs on a projection. This in turn leads to enhanced predictive accuracy of a ROM. Our findings are relevant to a variety of disciplines that develop data-driven ROMs of dynamical systems such as reacting flows, plasma physics, atmospheric physics, or computational neuroscience.

Global land and water limits to electrolytic hydrogen production using wind and solar resources.

Proposals for achieving net-zero emissions by 2050 include scaling-up electrolytic hydrogen production, however, this poses technical, economic, and environmental challenges. One such challenge is for policymakers to ensure a sustainable future for the environment including freshwater and land resources while facilitating low-carbon hydrogen production using renewable wind and solar energy. We establish a country-by-country reference scenario for hydrogen demand in 2050 and compare it with land and water availability. Our analysis highlights countries that will be constrained by domestic natural resources to achieve electrolytic hydrogen self-sufficiency in a net-zero target. Depending on land allocation for the installation of solar panels or wind turbines, less than 50% of hydrogen demand in 2050 could be met through a local production without land or water scarcity. Our findings identify potential importers and exporters of hydrogen or, conversely, exporters or importers of industries that would rely on electrolytic hydrogen. The abundance of land and water resources in Southern and Central-East Africa, West Africa, South America, Canada, and Australia make these countries potential leaders in hydrogen export.

Risk factors for postoperative complications after adrenalectomy for phaeochromocytoma: multicentre cohort study.

BACKGROUND: To determine the incidence and risk factors for postoperative complications and prolonged hospital stay after adrenalectomy for phaeochromocytoma. METHODS: Demographics, perioperative outcomes and complications were evaluated for consecutive patients who underwent adrenalectomy for phaeochromocytoma from 2012 to 2020 in nine high-volume UK centres. Odds ratios were calculated using multivariable models. The primary outcome was postoperative complications according to the Clavien---Dindo classification and secondary outcome was duration of hospital stay. RESULTS: Data were available for 406 patients (female n = 221, 54.4 per cent). Two patients (0.5 per cent) had perioperative death, whilst 148 complications were recorded in 109 (26.8 per cent) patients. On adjusted analysis, the age-adjusted Charlson Co-morbidity Index ≥3 (OR 8.09, 95 per cent c.i. 2.31 to 29.63, P = 0.001), laparoscopic converted to open (OR 10.34, 95 per cent c.i. 3.24 to 36.23, P <0.001), and open surgery (OR 11.69, 95 per cent c.i. 4.52 to 32.55, P <0.001) were independently associated with postoperative complications. Overall, 97 of 430 (22.5 per cent) had a duration of stay ≥5 days and this was associated with an age-adjusted Charlson Co-morbidity Index ≥3 (OR 4.31, 95 per cent c.i. 1.08 to 18.26, P = 0.042), tumour size (OR 1.15, 95 per cent c.i. 1.05 to 1.28, P = 0.006), laparoscopic converted to open (OR 32.11, 95 per cent c.i. 9.2 to 137.77, P <0.001), and open surgery (OR 28.01, 95 per cent c.i. 10.52 to 83.97, P <0.001). CONCLUSION: Adrenalectomy for phaeochromocytoma is associated with a very low mortality rate, whilst postoperative complications are common. Several risk factors, including co-morbidities and operative approach, are independently associated with postoperative complications and/or prolonged hospitalization, and should be considered when counselling patients.

The impact of center volume on the utilization and outcomes of machine perfusion technology in liver transplantation: An international survey.

INTRODUCTION: Machine perfusion (MP) was developed to expand the donor pool and improve liver transplantation (LT) outcomes. Despite optimal results in clinical trials, the real-world MP benefit in centers with low-/mid-volume activity (LVCs) is still being determined. METHODS: Online survey on MP for LT, distributed to worldwide LT-centers representatives. Variables of interest included logistics, technicalities, and outcomes. Responders were grouped into high-volume centers (HVCs) (>60 LTs/year) and LVCs and results compared. RESULTS: Sixty-seven centers were included, 36 HVCs and 31 LVCs. Significant differences in MP regarded: (I) existence of an established program (80.6% vs. 41.9%; p = 0.02), (II) presence of a dedicated perfusionist (58.3% vs. 22.6%; p = 0.006), (III) duration (>4 h: 47.2% vs. 16.1%; p = 0.01), (IV) routine use (20%-40% vs. 5%-20%; p = 0.002), (V) graft utilization (>50%: 75% vs. 51.6%; p = 0.009), (VI) 90-day patient-survival (90%-100% vs. 50%-90%; p = 0.001) and (VII) subjectively perceived benefit (always vs. only in selected ECD; p = 0.009). Concordance was found for indications, type, viability tests, graft-salvage, 90-day graft-loss, and major-complications. CONCLUSIONS: This study captured a picture of MP in real-world LT-practice. Significant disparities have surfaced between LVCs and HVCs regarding logistics, utilization, and results. To close this gap, efforts should be made to more efficiently deliver dedicated support, training and mentoring to LVC teams adopting MP technology.

Risk Factors for the Development of Early Recurrence in Patients with Primary Retroperitoneal Sarcoma.

BACKGROUND: Disease recurrence after retroperitoneal sarcoma (RPS) surgery is common, and resection may offer no benefit for patients who experience recurrence early. This study examined the incidence of early recurrence (EREC) in RPS patients, and the association between EREC and prognosis, aiming to identify the factors associated with EREC. METHODS: Patients undergoing surgery for primary RPS from 2008 to 2019 at two tertiary RPS centers were analyzed. The study defined EREC as any evidence of local recurrence and/or distant metastases on the CT scan up to 6 months after surgery. Overall survival (OS) was calculated using the Kaplan-Meier method. A multivariable analysis was performed to identify independent predictors of EREC. RESULTS: Of the 692 patients who underwent surgery during the study period, 657 were included in the analysis. Sixty-five of these patients (9.9%; 95% confidence interval [CI], 7.7-12.4%) developed EREC. Five-year OS was 3% for the patients with EREC versus 76% for those without EREC (p < 0.001). Patient characteristics were compared between the EREC and non-EREC patients, and EREC was found to be significantly associated with Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.006), tumor histology (p = 0.002), tumor grading (p < 0.001), radiotherapy (p = 0.04), and postoperative complications measured as a comprehensive complications index value (p = 0.003). However, the only significant independent predictor of EREC in the multivariable analysis was grade 3 tumors, with an odds ratio of 14.8 (95% CI, 4.44-49.2; p < 0.001). CONCLUSION: Early recurrence is associated with a poor prognosis, and a high tumor grade is an independent predictor for the development of EREC. Patients with EREC may benefit the most from new therapeutic options such as neoadjuvant chemotherapy.