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In post-transplant phase, liver transplant (LT) recipients may experience anemia or hemolysis due to various immune or non-immune reasons and require prompt intervention and timely management. One such instance is when recipients of minor ABO-incompatible LT (ABOiLT) experience delayed hemolysis mediated by lymphocytes present in the graft known as passenger lymphocyte syndrome (PLS). We present a case report of a PLS in a 6-month-old child who underwent ABOiLT. On postoperative day 14, there was a drop in patient's hemoglobin, and anti-human globulin crossmatch was incompatible with recipient group (A positive) red cells. No standardized consensus exists on screening for PLS in post-LT recipients. In transplant settings, it is imperative to streamline the workflow for timely recognition and management of PLS early to prevent adverse outcomes and minimize invasive therapy. We present this case of PLS in a post-LT child to highlight the need for right algorithm of immuno-hematological workup in case of post-transplant hemolysis.

Central venous catheters (CVCs) are essential in transplantation but can rarely fracture and embolize, with donor-to-recipient transmission of catheter fragments scarcely described. A 62-year-old woman with hepatitis C-related cirrhosis and hepatocellular carcinoma underwent orthotopic liver transplantation from a brain-dead donor with a left subclavian multi-lumen CVC in situ at procurement. Postoperative chest radiography identified a new curvilinear opacity at the left hilum, and contrast-enhanced computed tomography showed a 5 cm radiopaque structure in a segmental branch of the left lower lobe pulmonary artery, consistent with an embolized CVC tip. All recipient vascular access devices were removed intact, strongly suggesting a donor-origin catheter fragment transplanted with the liver graft. Alternative explanations, including unrecognized recipient catheter fracture and pre-existing foreign body, were considered but deemed less likely given the temporal relationship, imaging findings, and systematic device inspection. Percutaneous endovascular retrieval via femoral venous access was attempted but failed because of the fragment's distal location and probable endothelialization. Therapeutic anticoagulation was considered but not commenced because there was no radiological evidence of thrombus formation or pulmonary embolism, and substantial competing postoperative bleeding risk. The patient remained asymptomatic, and conservative management with clinical and imaging surveillance was adopted; at 6 months, she had excellent graft function and no cardiopulmonary sequelae. However, an uneventful short-term follow-up does not establish long-term safety, and early retrieval remains the preferred strategy whenever technically feasible and clinically safe. This case represents, to our knowledge, a previously unreported mechanism of donor-to-recipient CVC fragment transmission in liver transplantation, with the most plausible explanation being unrecognized transection of the donor catheter during heart procurement with subsequent lodgment in hepatic venous outflow, although definitive proof is not possible in the absence of direct intraoperative recognition. It highlights an important systems-level vulnerability at the interface between donor procurement, graft preparation, and recipient implantation. Modern multiorgan retrieval frequently involves multiple independent procedural teams, overlapping operative fields, and rapid transitions, creating fragmented responsibility for confirming removal and integrity of vascular access devices. This case underscores the importance of standardized vascular access reconciliation, careful inspection of donor venous structures, and early postoperative imaging. Structured vascular access reconciliation and verification protocols, analogous to surgical instrument counts and implant verification systems, may represent an important patient-safety intervention in transplantation.

Glycans constitute a structurally diverse and immunologically instructive layer that shapes how transplanted tissues are interpreted by the host immune system. Although glycoengineering approaches and glycocalyx-focused strategies have gained momentum, the mechanistic pathways through which immune cells decode glycan information remain underexplored in transplantation biology. This hybrid Perspective integrates selected mechanistic foundations with a broader conceptual framework that positions glycans as upstream immune checkpoints governing graft recognition and early innate-adaptive integration. We synthesize advances across four major axes of glycan-regulated immunity: Siglec (Sialic acid-binding immunoglobulin-type lectin)-mediated inhibitory circuits that calibrate macrophage, neutrophil, and NK-cell activation; C-type lectin receptor pathways that program antigen-presenting cells and govern antigen routing; NK-cell glycan-sensing mechanisms shaped by sialylation density, glycan topology, and ischemia-reperfusion-induced glycocalyx collapse; and complement regulation through Factor H, which interprets sialic acid motifs to restrain alternative pathway amplification. We further examine how these innate pathways intersect with glycan-dependent modulation of direct, indirect, and semi-direct allorecognition, including effects on MHC stability, exosomal transfer, antigen uptake, and T-cell intrinsic glycan checkpoints. Together, these mechanisms reveal that glycans function as a pre-recognition code that precedes and conditions classical protein-centric checkpoints by initiating, amplifying and sustaining the classical pathways, and influencing whether grafts are classified as self-like, stressed, or foreign. By consolidating these pathways into a unified model, this Perspective highlights glycan composition and architecture as a foundational design parameter for next-generation immune-compatible organ modifications and outlines mechanistic priorities for advancing glycan-informed strategies in transplantation.

BACKGROUND Autoimmune hemolytic anemia (AIHA) is characterized by immune-mediated premature red blood cell destruction. Although AIHA has been reported after solid organ transplantation, it remains uncommon, and very late-onset presentations occurring decades after transplantation are rare. Both warm and cold AIHA have been reported after transplant. Reported etiologies include immune dysregulation, infections, post-transplant lymphoproliferative disorders, and medication-associated immune hemolysis, including calcineurin inhibitor-related effects. CASE REPORT A 30-year-old woman with orthotopic liver transplantation at age 9 for biliary atresia, on long-term tacrolimus, presented 21 years after transplant with exertional dyspnea and symptomatic anemia. Laboratory evaluation revealed severe anemia with biochemical evidence of hemolysis, including undetectable haptoglobin and reticulocytosis. A direct antiglobulin test was positive for IgG, confirming warm autoimmune hemolytic anemia. Antibody identification revealed a warm autoantibody, and crossmatch-compatible red blood cells were transfused without reaction. Extensive evaluation excluded gastrointestinal bleeding, infection including Epstein-Barr virus, post-transplant lymphoproliferative disorder, and thrombotic microangiopathy. She was treated with high-dose corticosteroids with partial response, followed by early rituximab due to persistent hemoglobin instability. The tacrolimus dose was modestly reduced but not discontinued. Bone marrow biopsy excluded hematolymphoid malignancy. The patient achieved complete remission with normalization of hemoglobin and hemolysis markers after 4 rituximab doses and steroid tapering. CONCLUSIONS Warm autoimmune hemolytic anemia can present decades after solid organ transplantation and should be considered in transplant recipients with unexplained anemia. Remission can be achieved with corticosteroids and early rituximab without discontinuation of tacrolimus. Further studies are needed to clarify optimal treatment strategies for late-onset post-transplant AIHA, including the role of early rituximab.

Kidney transplantation from Hepatitis C virus (HCV) positive donors to HCV-negative recipients has emerged as a viable strategy to expand the donor pool, made possible by advances in antiviral therapy and post-transplant management. Notably, access to the necessary drug regimen in this study was guaranteed through a public-private partnership with the Washington D.C. municipal government. In this retrospective cohort study, we analyzed 58 kidney transplant recipients, including 29 HCV-negative patients who received organs from HCV-positive donors and 29 matched controls who received kidneys from HCV-negative donors. Variables collected included metrics detailing time to transplant, donor graft function, and transplant outcomes. Given the small sample size, non-parametric statistical methods were used. Recipients from HCV-positive donors demonstrated a trend toward shorter waiting times compared to controls (median, 1402 vs. 2276 days; p = .053), with no difference in listing times (p = .785). Donor kidney quality was similar between groups in terms of allograft eGFR (94 vs. 113 mL/min/1.73m², p = .715), cold ischemia time (18.9 vs. 15.7 hours, p = .142), and donor age (32 vs. 34 years, p = .432). Acute rejection rates were similar (34.5% vs. 31.0%; p = .78) as were IFTA scores (0.1 vs. 0.05; p = .37). Allograft loss occurred in 0% of recipients from HCV-positive donors compared to 3.4% in the control group. At one year, patient survival was 100% in both groups. A novel public-private collaboration allowed us to increase kidney transplantation access in an underserved community through transplantation of kidneys from HCV-positive donors into HCV-negative recipients with trending decreases in wait times, and without differences in graft function and clinical outcomes. Prophylactic direct-acting antiviral therapy (DAAT) allows our patients to never experience hepatitis C viremia. These findings support adoption of innovative healthcare partnerships to broaden access to life-saving therapies, especially as poor patients and marginalized communities continue to have significant obstacles to organ transplantation.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent liver-centred manifestation of systemic metabolic dysfunction. The gut-liver axis provides a biologically credible therapeutic rationale because intestinal dysbiosis, impaired barrier integrity, microbial metabolites, bile acid signalling, short-chain fatty acids, and trimethylamine N-oxide may influence hepatic steatosis, inflammation, and fibrogenesis. This narrative review critically evaluates dietary patterns, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT) as microbiome-directed strategies in MASLD. The comparative framework prioritises disease-specific human evidence, clinically meaningful endpoints, trial duration and sample size, reproducibility, safety, and feasibility. Dietary optimisation remains the most clinically grounded intervention, whereas probiotics and synbiotics show modest and heterogeneous signals on biochemical or metabolic surrogate endpoints. Prebiotics are mechanistically coherent but supported by limited liver-centred trials. Postbiotics and microbiome-mediated bioactives remain early-stage and require stricter definitional boundaries. FMT is investigational and should not be extrapolated from its established role in recurrent Clostridioides difficile infection. Most available evidence across all intervention categories relies principally on surrogate endpoints-including aminotransferases, insulin resistance indices, lipid parameters, and microbiome compositional shifts-rather than on validated liver-centred outcomes such as histological improvement or quantitative liver fat assessment; this constrains the strength of conclusions that can currently be drawn. Across all categories, microbiome modulation does not by itself establish liver disease modification, and no microbiome-targeted nutritional intervention has yet demonstrated histological benefit in MASLD. Future trials in this field should prioritise validated hepatic endpoints, phenotype-stratified patient enrolment, adequate follow-up duration, and direct comparisons between intervention categories to determine which microbiome-directed strategies, if any, deliver measurable and reproducible hepatic benefit beyond surrogate markers.

Electrical storm in Chagas disease represents a life-threatening scenario, particularly in Latin America. A 62-year-old man developed recurrent ventricular tachycardia a decade after implantable cardioverter-defibrillator placement for Chagas cardiomyopathy. Despite optimized therapy, arrhythmia control was not achieved, culminating in refractory electrical storm. He underwent heart transplantation. Severe primary graft dysfunction developed intraoperatively. Peripheral venoarterial extracorporeal membrane oxygenation was initiated, unloading with an intra-aortic balloon pump and direct left atrial drainage, achieving successful recovery. Management of refractory electrical storm is complex and may require mechanical circulatory support. Heart transplantation is a therapeutic option. When primary graft dysfunction occurs, venoarterial extracorporeal membrane oxygenation provides effective support, particularly when combined with active unloading. Heart transplantation should be considered for refractory electrical storm in Chagas disease. Severe primary graft dysfunction is a major complication that could be reversed with structured, physiology-guided support.

This study systematically elucidated the microecological mechanisms underlying Atractylodes macrocephala geoherbalism via integrated transplantation experiments across China's four major producing regions. Data showed that soil from Pan'an significantly enhanced the accumulation of bioactive compounds in A. macrocephala sourced from Bozhou. 16S rRNA gene sequencing revealed that geographic transplantation significantly restructured the rhizosphere microbial community and markedly increased its α-diversity. Functional metabolic analysis indicated that transplantation to Pan'an regulated various pathways and enhanced secondary metabolism in the rhizosphere microbiome. Co-occurrence network analysis revealed 11 upregulated keystone genera that potentially promoted secondary metabolism in A. macrocephala, and were positively correlated with root growth and bioactive compound accumulation. These results demonstrate that direct soil nutrient supply, microbiome-mediated C/N metabolism remodeling, and resource reallocation collectively drive A. macrocephala geo-authenticity. It will lay the groundwork for the use of microbiome biofertilizers and the cross-regional eco-cultivation of geo-authentic herbs.

The routine mass applications of human pluripotent stem (hPS) cell-derived progenies for regenerative medicine or high-throughput drug screenings will depend on the standardized supply of high-quality cells via controlled, efficient bioprocesses. Recent suspension culture (three-dimensional, 3D) strategies for hPS cell production in stirred-tank bioreactors (STBR) support this development. However, bioprocess inoculation still depends on adherent (two-dimensional, 2D) preculture, which is labor intensive, resource demanding and poorly controlled and limits process automation. Here we describe the controlled in-process production and dissociation of 3D cultured hPS cell aggregates directly in STBRs, tackling these challenges. The resulting cells can be used for the generation of high-density cryostocks, subsequently enabling the direct inoculation of 3D cultures, thereby entirely omitting the need for 2D preculture and the associated limitations. A key feature of this Protocol is the nonenzymatic, EDTA-based hPS cell aggregate dissociation approach in STBRs, enabling the impeller-based mechanical control of the dissociation process. The resulting cell suspension can be used for process reinoculation and seed train-based upscaling, as well as for the cryopreservation of produced hPS cells, ideally via controlled-rate freezing. Together, the protocol enables the efficient and flexible hPS cell suspension culture over multiple passages, maintaining karyotype stability and pluripotency. This Protocol can be easily implemented by any cell culture-educated scientist without extensive bioprocess training. Cell thawing requires 1 h, the 2D preculture requires 9 days, 2D cell passaging requires 1 h, bioreactor preparation requires 2 days, (direct) bioreactor inoculation requires 1.5 h, 3D STBR cultivation requires 3-4 days and STBR-based aggregate dissociation requires 2 h.

Reports about relevance of three common and linked ABCB1 polymorphisms (c.2677G>T/A, c.1236C>T, c.3435C>T) for exposure to- and functional outcomes in tacrolimus-treated renal transplant patients are inconsistent. Tacrolimus morning troughs/dose-corrected troughs and serum creatinine/estimated glomerular filtration rate (eGFR) were measured on 6th-7th and 8th-10th postoperative day in tacrolimus-mycophenolate-treated renal transplant patients. Exposure was defined as the number of ABCB1 variant alleles (three levels; 0-1 variant = control) or as diplotypes (three levels, wild-type = control). Four target trials were emulated (2 exposure definitions × 2 outcome categories) contrasting exposed and controls for ln-transformed outcomes, and for creatinine/eGFR also on natural scales. Complementary mediation analysis related exposure, troughs, and eGFR. The 173 enrolled patients provided 316 paired trough and creatinine/eGFR values. After correction for strong residual confounding, all GMRs (95% CrI) for troughs remained within the 0.75-1.33 range. All GMRs (95% CrI) for ln-trasformed creatinine/eGFR were within the 0.75-1.33 range. On the natural scale, creatinine/eGFR differences were within -26.5 to 26.5 μmol/L and -5.0 to 5.0 mL/min/1.73 m2, respectively. In mediation analysis, direct, indirect, and total effects were within the same ranges. Renal transplant recipients subsetted by genotypes across the three common ABCB1 polymorphisms display closely similar tacrolimus troughs and graft function early after transplantation.

Hematopoietic stem cell transplantation (HSCT) is a curative treatment for hematologic malignancies, yet access in Indonesia remains limited due to high costs and its exclusion from the national health insurance scheme. This study determined the unit cost of allogeneic HSCT at Dr. Kariadi General Hospital using the activity-based costing (ABC) approach. A mixed-method design combined retrospective cost data from three donor-recipient pairs that received HSCT during the January 2023 - December 2024 period and thematic analysis of qualitative interviews with clinical and administrative staff. Costs were categorized as direct and indirect, mapped along the HSCT clinical pathway, and analyzed descriptively. The total unit cost of allogeneic HSCT was IDR 377,978,399, comprising IDR 297,063,048 for recipients and IDR 80,915,351 for donors. Post-transplant care was the major cost driver among recipients (IDR 157,843,439), while harvesting represented the highest donor-related cost (IDR 37,819,185). However, comparison with current hospital tariffs demonstrated CRRs of 218.8-239.0% for recipients and 113.7-123.6% for donors, suggesting that existing tariff packages exceed the estimated unit costs and may generate a financial surplus. The ABC method effectively identified major cost components and financial gaps, highlighting the need for updated reimbursement models and BPJS coverage inclusion to ensure long-term HSCT program sustainability in Indonesia.

The practice of living donor kidney transplantation has evolved through innovations in logistics, technology, and clinical practice. In the United States, Good Samaritan donation, a historical label exclusive to nondirected donors, now incorporates voucher-based models. To determine how voucher-based nondirected living kidney donation has influenced the volume and practice of Good Samaritan living kidney donation in the United States, we analyzed living donor kidney transplants from 2000 to 2024 using data from the National Kidney Registry (103 transplant centers) and the Scientific Registry of Transplant Recipients. Temporal trends were derived by linear regression. We identified 4662 Good Samaritan living donor kidney transplants, defined as historical nondirected and novel voucher-based nondirected donations. Of 2131 Good Samaritan living donor kidney transplants facilitated by the National Kidney Registry, donors had a median age of 43 y, were predominantly of White race (93%), and were women (60%). Recipients had a median age of 52 y and were racially and ethnically diverse (63% White, 14% Black, and 10% Hispanic). Annual Good Samaritan donation counts in the United States increased from 17 in 2000 to 439 in 2024, corresponding to a growth rate of 14.5%. Voucher-based nondirected donations increased from 2 in 2015 to 314 in 2024, comprising 72% of all Good Samaritan donations in that year. The advent of voucher-based nondirected donation correlated with growth in Good Samaritan donation volume. Given the prevalence of voucher-based donations, connecting local kidney paired donation practices to voucher-based nondirected donation may improve access to and participation in living kidney donation.

As the cross talk of the parasympathetic nervous system, the vagus nerve exerts organ-specific regulatory effects on hepatic and pancreatic endocrine homeostasis, yet its divergent innervation patterns and their implications for post-transplant functional recovery remain understudied. This review summarizes the anatomical and functional differences of the vagus nerve in the liver and pancreas, and discusses how surgical denervation and incomplete re-innervation affect endocrine recovery after liver and pancreatic transplantation. At the anatomical level, vagus nerve fibers in the liver are relatively sparse and travel along the portal tripa, mainly terminating in the perihilar blood vessels and biliary tract ecological loci, with limited direct parenchymal synapses. This structure is conducive to metabolic perception and indirect regulation of liver glucose flux, bile acid-dependent signaling, and inflammatory tension. In contrast, pancreatic vagus nerve input enters through periarterial/periductal channels and is relays through pancreatic ganglia, forming dense cholinergic efferent control over pancreatic islet α/β/δ cells, supporting rapid and precise insulin-glucagon coordination and counterregulation responses. Clinically, recent preclinical trials and translational studies demonstrate that vagal nerve integrity-often compromised during transplant surgery-serves as a pivotal prognostic marker for endocrine recovery: Preserved vagal innervation is associated with accelerated glucose metabolism normalization and reduced post-transplant complications (e.g., insulin resistance, graft rejection). Notably, frontier strategies such as intraoperative vagal nerve-sparing techniques, targeted neuromodulation (e.g., vagus nerve stimulation), and stem cell-derived neurotrophic factor delivery have shown promising potential in mitigating denervation-induced endocrine dysfunction. This review emphasizes that deciphering the organ-specific vagal innervation mechanisms holds great promise for optimizing precision transplant surgery and developing novel neuromodulatory therapies, which may revolutionize the prognosis of liver and pancreatic transplant recipients.

Autologous stem cell transplantation (ASCT) remains a cornerstone therapy for eligible multiple myeloma (MM) patients, but its use in older adults is debated due to concerns about toxicity and cost-effectiveness (CE). This study aimed to evaluate the CE of upfront ASCT compared with non-transplant therapy in newly diagnosed MM patients aged 65-69 years within a single-payer healthcare system. Using nationwide claims data from the Korean Health Insurance Review and Assessment Service (HIRA database, 2009-2024; study enrollment period, 2017-2024), we conducted a CE analysis of 735 patients, of whom 458 received bortezomib-thalidomide-dexamethasone induction followed by ASCT and 277 received non-transplant therapy. A state-transition semi-Markov model estimated life-years (LYs), quality-adjusted life-years (QALYs), and direct medical costs from a healthcare system perspective. Inverse probability of treatment weighting reduced confounding bias, and deterministic and probabilistic sensitivity analyses assessed parameter uncertainty. ASCT yielded superior overall survival (4-year: 67.8% vs. 55.0%; HR 0.62, P = 0.001) and longer time-to-next-treatment (29.8 vs. 19.7 months, P < 0.001), with 0.71 additional QALYs at an incremental cost of $21,378. The incremental CE ratio was $30,251 per QALY, remaining below Korea's willingness-to-pay threshold of $37,453. Probabilistic sensitivity analysis demonstrated a 70.3% likelihood of CE at this threshold. Upfront ASCT is a cost-effective consolidation strategy for appropriately selected MM patients aged 65-69 years within Korea's single-payer healthcare system, supporting fitness-based rather than age-based transplant eligibility criteria.

Faecal microbiota transplantation (FMT) is increasingly used. However, no systematic approach exists to assess infectious risks after FMT, leading to underreporting. We evaluated infectious complications at the Netherlands Donor Feces Bank (NDFB) and proposed a structured biovigilance approach aligned with the EU Regulation on Substances of Human Origin (SoHO). We conducted a prospective observational cohort study of all patients receiving frozen donor faecal suspensions from the NDFB (May 2016-December 2023) for recurrent Clostridioides difficile infection (rCDI) or via an extended access programme (EAP) for non-CDI indications. (Serious) adverse events ((S)AEs) were reported by physicians and recorded at 3&#xa0;weeks, 3&#xa0;months, and 6&#xa0;months. Serious adverse reactions (SARs) were defined as SAEs probably or definitely related to FMT. We included 290 rCDI patients (322 FMTs) and 35 EAP patients (75 FMTs). FMT efficacy was favourable overall: 92% of rCDI patients remained free of rCDI within 8&#xa0;weeks, and 49% of EAP patients achieved at least a partial response. Sixty-one per cent of rCDI patients and 34% of EAP patients had mild gastrointestinal AEs. AE incidences were comparable across groups (rCDI: 5.1 vs. EAP: 4.4 per 100 patient-weeks). SAEs were more frequent in EAP patients (0.66 vs. 0.28 per patient), reflecting higher immunosuppression and comorbidity. FMT-attributable SARs occurred after 6 of 322 FMTs (1.9%) in the rCDI group and after 3 of 75 FMTs (4.0%) in the EAP group. Two donor-derived Escherichia coli infections in EAP patients with predisposing conditions were confirmed, consistent with early donor-strain colonisation rather than a direct FMT effect. Most SAEs were unrelated. In this 7-year cohort, donor-derived infections were rare but present, particularly in non-CDI patients with substantial comorbidity, whereas overall safety remained favourable. A SoHO-compliant biovigilance protocol incorporating microbiological investigation and donor/sample traceability is essential for the safe clinical use of FMT and faecal microbiota products.

Liver transplantation (LT) has achieved excellent short-term outcomes; however, long-term survival remains limited by cardiovascular disease, now a leading cause of late mortality in transplant recipients. Immunosuppressive therapy is a major contributor to this risk through both direct vascular toxicity and indirect metabolic effects. This review examines the clinical impact of immunosuppression-associated vascular remodeling and strategies to reduce cardiovascular complications after LT. Calcineurin inhibitors remain central to post-transplant immunosuppression but are strongly associated with hypertension, endothelial dysfunction, nephrotoxicity, and progressive vascular injury. Corticosteroids further increase cardiovascular risk by promoting insulin resistance, dyslipidemia, weight gain, and blood pressure elevation, supporting widespread adoption of steroid-sparing protocols. Mammalian target of rapamycin inhibitors may limit vascular smooth muscle proliferation and intimal hyperplasia and are frequently used to facilitate calcineurin inhibitor minimization, though careful patient selection is required due to metabolic and thrombotic concerns. Antimetabolites are generally vascularly well tolerated and play a key role in combination regimens. Subclinical vascular injury can be detected using noninvasive measures such as pulse wave velocity, carotid intima-media thickness, and flow-mediated dilation, enabling earlier identification of patients at increased cardiovascular risk. Host factors including metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, diabetes mellitus, and pre-existing cardiovascular disease further modify outcomes and should guide individualized immunosuppressive planning. Prospective studies incorporating vascular endpoints are needed to refine immunosuppressive strategies and improve long-term outcomes after LT.

Alcohol-related liver disease (ALD) is a major indication for liver transplantation (LT) and post-LT alcohol relapses remain a key concern. We evaluated the risk and predictors in a nationwide ALD cohort using phosphatidylethanol (PEth), a direct biomarker of alcohol consumption. We retrospectively analyzed all adults transplanted for ALD in Finland 2018-2023. Alcohol relapse was defined as any relapse (PEth &#x2265; 0.03&#x2009;&#xb5;mol/L) or severe relapse (PEth &#x2265; 0.30&#x2009;&#xb5;mol/L). Cumulative incidence was estimated using competing-risk time-to-event methods, and predictors were examined using univariable Cox proportional hazards models. Among 95 patients (median post-LT follow-up 4.3&#x2009;years), 29 (31%) experienced any relapse and 13 of those (14%) severe relapse. Limited social support (HR 2.81, 95% CI 1.32-5.95) and insufficient assessment of alcohol use disorder (AUD) (HR 2.93, 95% CI 1.34-6.41) were associated with increased risk of any relapse, while involvement of a relative during LT evaluation (HR 0.28, 95% CI 0.10-0.72) and a formal diagnosis of alcohol dependence (HR 0.15, 95% CI 0.03-0.76) were protective. Older age reduced the risk of severe relapse (HR 0.93 per year, 95% CI 0.88-0.99). Among those transplanted within &#x2264;6&#x2009;months of pre-transplant abstinence (n&#x2009;=&#x2009;9), 78% experienced any relapse and 44% developed severe relapse. In this national Finnish ALD cohort, approximately one third of LT recipients experienced alcohol relapse. Short pre-transplant abstinence and indicators of limited support and suboptimal AUD assessment were associated with higher relapse risk, underscoring the need for sustained addiction treatment and consistent support post-LT.

Chronic lung allograft dysfunction significantly impairs long-term lung transplant survival. Bronchiolitis obliterans syndrome is a chronic lung allograft dysfunction phenotype characterized by fibroproliferative changes in noncartilaginous airways. We previously demonstrated that the tyrosine kinase inhibitor nintedanib reduces chronic airway changes in murine tracheal allografts. In this study, we investigated whether delayed treatment, similar to the clinical scenario following lung transplantation, would still be beneficial. Recipient CBA/JRj mice received orthotopic tracheal transplants from donor C57BL/6JRj mice. A dosage of 60&#x2009;mg/kg of nintedanib was administered orally to transplanted mice every day between days 14 and 29 after transplantation. Histological and immunofluorescence analyses, as well as intragraft gene expression measurements, were performed after 14 and 30 d. Delayed-treated tracheal allografts (nintedanib 14-30) exhibited less evidence of chronic rejection than untreated allografts on day 30 (control 30). This is demonstrated by an increased epithelium-to-lamina propria ratio (0.62&#x2005;&#xb1;&#x2005;0.16 [nintedanib 14-30] versus 0.50&#x2005;&#xb1;&#x2005;0.01 [control 30]; P&#x2005;<&#x2005;0.05), with a reduction in CD4+ T cell, dendritic cell, and macrophage infiltration. Furthermore, intragraft gene expression of inflammatory cytokines, adhesion molecules, and growth factors was also lowered. While allografts treated immediately (nintedanib 30) demonstrated a comparable epithelium-to-lamina propria ratio to the nintedanib 14-30 group, earlier treatment resulted in considerably lower infiltration of CD4+ and CD8+ T cells as well as alpha smooth muscle actin expression. Even delayed nintedanib therapy has an attenuating effect on chronic inflammation but is less effective regarding the fibroproliferative changes that are considered a sign of chronic airway changes after murine tracheal transplantation. Thus, it may serve as supportive therapy in the clinical setting after lung transplantation, but earlier initiation might be more effective.

Identifying an optimally matched donor is a critical determinant of outcomes following liver transplantation (LT). Several donor- and recipient-related factors have been shown to influence posttransplant survival. However, the impact of donor-recipient sex mismatch (DRSM) on long-term outcomes remains controversial, with inconsistent findings reported across prior studies. This study aimed to further clarify the contemporary role of DRSM in LT outcomes. We conducted a single-center retrospective cohort study including 1146 adult patients who underwent LT at the Ajmera Transplant Centre, Toronto, between January 2014 and January 2022. Donor and recipient characteristics, including age, sex, and donor type, were analyzed. The primary outcome was patient survival up to 10 y of follow-up. Comparative analyses were performed between recipients with mismatch (DRSM+) and those without (DRSM-), as well as relevant subgroup analyses. In unadjusted survival analysis, recipients in the DRSM+ group demonstrated slightly higher survival compared with DRSM- recipients up to 10 y following LT (P&#x2005;=&#x2005;0.018). However, after multivariable adjustment and propensity score matching, survival was comparable between groups, and DRSM was not identified as an independent predictor of mortality. Subgroup analyses showed no adverse effect of DRSM in deceased donor transplantation (P&#x2005;=&#x2005;0.547), while a survival difference was observed in the living donor cohort (P&#x2005;<&#x2005;0.001). In addition, female recipients exhibited improved survival compared with male recipients, irrespective of DRSM. DRSM does not appear to be an independent risk factor for reduced long-term survival after LT. Moreover, the composition of favorable recipient and donor characteristics seems to be the main factors influencing long-term survival. These findings suggest that DRSM alone should not preclude donor selection in clinical practice.