The introduction of direct -acting antivirals has transformed kidney transplantation with hepatitis C virus -positive donors from a high -risk practice to a safe strategy for expanding the donor pool. This study aimed to highlight global research trends, collaborations, and shifts in hepatitis C virus -positive donor kidney transplant before and after the direct -acting antiviral era. We conducted a thorough search of the Web of Science database, focusing on research output with relevant key words related to the hepatitis C virus and kidney transplant, resulting in 414 pertinent research items. We analyzed these items using bibliometric parameters. Over the past 2 decades, notable shifts have occurred in the research trajectory, with a peak in publications observed in 2018 and 2019 following the introduction of direct -acting antivirals, followed by a decline in subsequent years. The United States generated the highest research output, followed by France and Spain. The journals Transplantation and American Journal of Transplantation dominated in terms of citations. The University of Toulouse, the University of Pennsylvania, and the University of Miami were the leading institutional contributors. The introduction of direct -acting anti -virals coincided with a rapid rise in research activity and global collaboration, reflecting the transition of hepatitis C virus -positive donor kidney transplant from a high -risk practice to routine clinical adoption.
Passenger lymphocyte syndrome (PLS) is a rare immune-mediated haemolytic complication of solid organ transplantation caused by donor-derived lymphocytes producing antibodies against recipient red blood cell (RBC) antigens. Multiple alloantibodies and concomitant autoantibody formation are uncommon, particularly in ABO-identical liver transplantation. A 56-year-old male underwent ABO-identical but D- and Kell-non-identical liver transplantation. Approximately, 3 weeks posttransplantation, haemoglobin decreased to 81 g/L, and indirect antiglobulin testing identified anti-D and anti-E antibodies, while direct antiglobulin testing confirmed IgG-coated RBCs. Subsequently, anti-K alloantibodies and transient pan-reactive IgG autoantibodies were detected, resulting in positive crossmatches and complicated transfusion support. Because most transfused RBC units before antibody detection were D+, E+ and K+, anti-E was interpreted as probable recipient-derived transfusion-associated alloimmunisation, whereas anti-D and anti-K were consistent with donor-derived PLS. Transfusion support was subsequently restricted to D-, E- and K- RBC units. The patient remained clinically stable despite haemoglobin decline with serologic evidence of immune-mediated RBC sensitization consistent with PLS. During 4 years of follow-up, anti-D and anti-K antibodies disappeared, while only weak residual anti-E reactivity persisted. The simultaneous occurrence of donor-derived alloantibodies, probable recipient-derived alloimmunisation and transient pan-reactive autoantibodies suggests broader posttransplant humoral immune activation than typically observed in classical PLS. Although clinically significant autoimmune haemolytic anaemia did not develop, the coexistence of multiple antibody specificities substantially complicated serologic interpretation and transfusion management. This case highlights complex posttransplant humoral immune dysregulation involving donor-derived alloantibodies, probable recipient alloimmunisation and transient autoantibody formation after ABO-identical liver transplantation. The coexistence of multiple antibodies significantly complicated serologic testing and transfusion support.
Clinically significant hemolysis and device thrombosis are uncommon with the Impella 5.5, and presentation with predominant direct hyperbilirubinemia has not been described. A 57-year-old man with refractory cardiogenic shock underwent Impella 5.5 placement as a bridge to transplant. He developed severe direct-predominant hyperbilirubinemia (total bilirubin 18.4 mg/dL; direct 11.7 mg/dL) with rising lactate dehydrogenase (1,395 U/L) and undetectable haptoglobin, despite normal purge pressures and no device alarms. Duplex ultrasonography excluded biliary obstruction. Device exchange revealed a large, organized thrombus in the motor/outflow housing, after which hemolysis was resolved, and biochemical improvement followed, allowing successful bridging to heart transplantation. Occult Impella thrombosis may present as direct-predominant hyperbilirubinemia, an atypical pattern that can mimic hepatobiliary disease and confound the diagnostic evaluation. Direct hyperbilirubinemia during Impella support should prompt evaluation for subclinical device thrombosis. Timely device exchange can reverse hemolysis and preserve transplant candidacy.
Kidney transplantation using hepatitis C virus (HCV) nucleic acid test-positive donors for HCV-negative recipients (D+/R-) has expanded in the direct-acting antiviral (DAA) era, but real-world outcomes with short-course prophylaxis remain limited. We report the largest cohort to date managed with a 7-d perioperative prophylactic DAA strategy. Single-center prospective observational study of 204 consecutive HCV nucleic acid test-positive donor to HCV-negative recipient kidney transplants performed between December 2018 and August 2025. All recipients received sofosbuvir/velpatasvir 400 of 100 mg daily for 7 d beginning on the day of transplantation. HCV RNA was monitored through 90 d posttransplant. Breakthrough viremia triggered full-course DAA therapy. Donor-derived breakthrough viremia occurred in 15 of 204 recipients (7.4%; 95% confidence interval, 4.2%-11.9%). Most cases (93.3%) were detected by postoperative day 28. Nonstructural protein 5A resistance-associated substitutions were identified in 4 of 8 tested breakthrough cases. First-line retreatment achieved sustained virologic response (SVR) at 12 wk in 14 of 15 (93.3%); 1 patient required salvage therapy, yielding overall SVR at 12 wk of 15 of 15 (100%), although 93% required insurance prior authorization (median delay 36 d). One-year patient and graft survival were 96.6% and 94.1%, respectively, with stable graft function through 12 mo (mean estimated glomerular filtration rate 53.0 ± 22.0 mL/min/1.73 m2). Seven-day perioperative sofosbuvir/velpatasvir prophylaxis achieved SVR after prophylaxis alone in >92% of D+/R- kidney transplant recipients, with favorable 1-y clinical outcomes. Given the nonstructural protein 5A resistance-associated substitutions observed, we have transitioned to 7-d glecaprevir/pibrentasvir prophylaxis; outcomes will be reported via the REFORM-HEPC registry. These findings provide real-world evidence supporting the feasibility of short-course antiviral prophylaxis in HCV-viremic donor kidney transplantation.
To explore the clinical features, serological test, and blood transfusion protocols of hemolytic anemia caused by passenger lymphocyte syndrome (PLS) with multiple antibodies after ABO-incompatible liver transplantation. The hemoglobin (Hb) and bilirubin levels were monitored in a patient (O blood type donor to B blood type) post-liver transplantation in our hospital. The ABO blood group typing, unexpected antibody screening and identify test, direct anti-globulin test (DAT) and acid elution test were performed respectively in blood samples of the patient to identify the serum and erythrocyte membrane sensitized antibodies. The patient's Hb showed a decreasing trend on the day 6 post-operation, reaching the lowest level of 37 g/L on day 12, while her serum bilirubin increased. The patient's ABO blood group did not match. The DAT and the irregular antibody screening test were positive. Anti-B, anti-E, anti-Jkb, and anti-Mur antibodies were detected in the serum, and the anti-B antibodies were detected in the elution liquid. After intermittent infusion of 9 U O type washed red blood cells after day 12, the Hb level increased steadily but the bilirubin level decreased gradually. The patient was discharged with improved conditions on day 38 after surgery. For patients undergoing ABO-incompatible liver transplantation, monitoring the Hb, blood type antibodies, and DAT is essential to timely diagnose PLS and adjust the treatment plan including transfusion strategy. 肝移植术后过客淋巴细胞综合征合并多重抗体的血清学特征与输血. 探讨ABO血型不合肝移植术后发生过客淋巴细胞综合征合并多重抗体导致溶血性贫血的临床特征、血清学检测与输血策略。. 监测本院1例肝移植（O型供B型）患者术后血红蛋白及胆红素等溶血指标变化并采用血清学方法分别进行ABO血型鉴定、意外抗体筛选及鉴定试验、直接抗球蛋白试验（DAT）和酸放散试验等，检测患者血清及红细胞膜致敏的抗体。. 患者术后d 6血红蛋白呈逐渐降低趋势，d 12达最低值37 g/L，同时血清胆红素呈升高趋势；ABO血型鉴定结果为正反定型不符，DAT阳性，抗体筛选试验阳性，血清中检出抗-B、抗-E、抗-Jkb、抗-Mur抗体，放散液中检出抗-B抗体。d 12后间断输注配血相合的O型洗涤红细胞9 U后，血红蛋白稳步上升，胆红素逐渐下降，并于术后d 38病情好转出院。. 对于ABO血型不合的肝移植患者，应定期监测血红蛋白、血型抗体、DAT，以及时诊断过客淋巴细胞综合征并调整包括输血策略在内的治疗方案。.
Xenotransplantation offers a promising solution to the shortage of human organs for transplantation but requires overcoming numerous immune responses-particularly those mediated by the innate immune system through natural killer (NK) cells and macrophages. This review examines advances demonstrating that the expression of human leukocyte antigen E (HLA-E) on porcine cells contributes to reduce cellular xenograft rejection. HLA-E expression partially inhibits both direct NK cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC), while also attenuating macrophage-mediated lysis. Furthermore, perfusion of transgenic porcine organs expressing HLA-E with human blood resulted in significantly less tissue damage compared to wild-type counterparts, thereby confirming the protective effect of HLA-E against innate immunity. Inhibition of NK cell activation can be further enhanced by co-expression of HLA-G and HLA-E. These findings confirm the potential of HLA-E and HLA-G expression as a complementary strategy in the design of immune-compatible porcine organs for clinical xenotransplantation.
Passenger lymphocyte syndrome (PLS) is a rare but recognized cause of immune-mediated hemolytic anemia in solid organ transplant recipients, most often occurring in the setting of minor ABO incompatibility but also described with non-ABO red cell antibodies. We present the case of a 48-year-old male with alcohol-related cirrhosis who developed PLS following orthotopic liver transplantation. His postoperative hospital course was complicated by acute kidney injury, delirium, and severe anemia requiring intensive care unit readmission. Diagnostic workup demonstrated hemolysis with an acute hemoglobin drop, elevated lactate dehydrogenase, indirect hyperbilirubinemia, undetectable haptoglobin, a positive direct antiglobulin test, and anti-B antibodies in the recipient serum. Management included donor-type packed red blood cell transfusions, supportive care, close hemolysis monitoring, and adjustment of immunosuppressive therapy. This case underscores the importance of early recognition of PLS in postliver transplant patients with an acute hemoglobin decline and highlights the need for multidisciplinary coordination among transplant surgery, hematology, and transfusion medicine teams.
Fertility preservation for women undergoing gonadotoxic treatments remains a critical clinical challenge. Ovarian tissue(OT) cryopreservation and transplantation are promising strategies. This review aims to map the biomaterials used in OT culture and cryopreservation, identify key knowledge gaps, and outline future research directions. Following the Arksey&O'Malley (2005) framework and the PRISMA-ScR guidelines, a literature search was conducted on PubMed and Web of Science. The review protocol was prospectively registered on the Open Science Framework (OSF.IO/NRZM7). Of 3,217 studies, 41 were included in the analysis: 32 were in vivo studies, 8 were in vitro, and 1 was clinical. The main biomaterials used for OT culture and cryopreservation included fibrin, alginate, collagen, hyaluronic acid, and extracellular matrix. Key preservation strategies involve encapsulating OT within biomaterial-based systems and enriching culture media with biomaterials. Hydrogels have demonstrated advantages by providing structural scaffolding and facilitating the diffusion of oxygen, nutrients, and bioactive supplements, thereby promoting angiogenesis and supporting OT functional restoration. Growing interest was noted in combinatorial approaches that integrate multiple biomaterials with stem cells, plasma proteins, and growth or antioxidant factors to enhance folliculogenesis and restore oestrous cycles. Despite progress, critical challenges persist, including capsule disintegration and the associated risk of immune sensitisation, as well as limited understanding of long-term tissue revascularisation and OT-biomaterial interactions. Overall, biobased materials strategies, particularly hydrogels, show promise for improving OT preservation and functionality, but further research is needed to optimise these materials and understand their long-term implications for fertility outcomes. Among the included studies, only one was a clinical study; the rest consisted of in vivo animal models and in vitro experiments. This limitation should be recognised, as it prevents direct application of the results to clinical practice. Consequently, further clinical research is crucial to confirm these strategies and facilitate their safe and effective implementation in fertility preservation protocols.
Cell replacement therapy is a promising strategy for treating Huntington's disease. Advances in cell reprogramming now allow the generation of clinically relevant cells; however, conventional delivery methods can compromise long-term cell survival and maturation. Hydrogels have emerged as supportive three-dimensional scaffolds that better mimic the in vivo environment. This study examined whether encapsulating human-induced lateral ganglionic eminence precursor cells (hiLGEPs) in gelatin methacryloyl (GelMA) hydrogel enhanced differentiation after transplantation into the striatum of the quinolinic acid lesion rat model of Huntington's disease. hiLGEPs were delivered either in cell culture medium (n = 5) or in a pre-crosslinked GelMA solution (n = 4) prior to transplantation. GelMA was polymerized in situ using a visible-light optical fibre system, and grafts were assessed 4 weeks later. Transplanted cells survived in all animals. Notably, GelMA-encapsulated hiLGEPs produced significantly more protein gene product 9.5 (PGP9.5+) neurons than those delivered in cell culture medium. Transplanted cells in both groups differentiated into microtubule-associated protein 2 (MAP2+) and GABA+ phenotypes, with no detectable differences in graft volume. These findings provide the first evidence that encapsulating hiLGEPs in GelMA enhances early neuronal differentiation following transplantation, supporting GelMA hydrogel as a promising delivery scaffold for cell replacement therapy in Huntington's disease.
Hypopituitarism is associated with adverse body composition and steatotic liver disease, particularly when the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is disturbed. Progression to decompensated cirrhosis is uncommon, and published reports do not establish a direct causal relationship. A 37-year-old woman presented with jaundice, massive ascites, splenomegaly, thrombocytopenia, hypoalbuminemia, coagulopathy, and hyponatremia. She had undergone pituitary adenoma surgery at approximately 12 years of age, followed by amenorrhea and more than two decades without regular endocrine follow-up or hormone replacement. The clinical and biochemical profile supported long-standing panhypopituitarism. Possible central HPA-axis dysfunction was present; secondary adrenal insufficiency was clinically probable but not dynamically confirmed. Other features included central hypothyroidism, hypogonadotropic hypogonadism, low prolactin, central diabetes insipidus, and severe GH/IGF-1 axis disturbance. GH stimulation testing was not performed, and interpretation of the GH/IGF-1 axis was confounded by advanced liver disease. Common viral, autoimmune, alcohol-related, drug-related, and overt cardiac causes were not supported. However, transferrin saturation was 94.6%, and iron overload, Wilson disease, alpha-1 antitrypsin deficiency, and histological metabolic steatohepatitis were not fully excluded. Liver biopsy supported advanced fibrosis/cirrhosis, and explant pathology showed micronodular cirrhosis with hepatocellular cholestasis. She underwent liver transplantation in May 2026. Aminotransferase levels subsequently declined, but persistent thrombocytopenia, pulmonary infection, and acute kidney injury requiring hemodialysis developed. She progressed to septic shock and died more than 20 days after transplantation. Long-standing untreated panhypopituitarism may have contributed to metabolic and fibrogenic risk in this patient, but incomplete etiological evaluation precluded a definitive causal link. Lifelong endocrine follow-up and attention to liver health are warranted after pituitary surgery.
Non-HLA antibodies have emerged as important contributors to antibody-mediated rejection and long-term graft dysfunction in kidney transplantation, including in patients without detectable donor-specific antibodies against human leukocyte antigens (HLA-DSAs). This review summarizes current evidence on major non-HLA antibody targets, including angiotensin II type 1 receptor, endothelin A receptor, perlecan fragment LG3, vimentin, major histocompatibility complex class I chain-related molecule A, collagen, fibronectin, natural antibodies, and glutathione S-transferase theta 1, and highlights their mechanisms of formation, pathogenic roles, and clinical associations. These antibodies can arise through alloimmune or autoimmune processes, often driven by endothelial injury, ischemia-reperfusion injury, and inflammatory signaling, which may expose cryptic antigens and promote loss of self-tolerance. Mechanistically, non-HLA antibodies can mediate graft injury through complement activation, Fc receptor-dependent immune responses, and direct signaling effects on endothelial and vascular cells, leading to inflammation, microvascular injury, and fibrosis. Importantly, they can act synergistically with HLA-DSA, amplifying immune responses, and contributing to worse transplant outcomes. However, findings across studies remain inconsistent due to heterogeneity in detection methods, lack of standardized thresholds for positivity, and variability in patient populations. Additionally, temporal dynamics in antibody development and fluctuations over time suggest that static measurements may not fully capture their clinical relevance. The presence of non-HLA antibodies in healthy populations further complicates interpretation and highlights the need to better define clinically meaningful thresholds. Given the wide diversity in antigen targets, biological functions, and mechanisms of action, a one-size-fits-all approach is insufficient. Instead, individual non-HLA antibodies should be investigated through targeted mechanistic and clinical studies to clarify their specific roles in transplant outcomes. Future research should prioritize large-scale, multicenter prospective studies with standardized methodologies, alongside mechanistic investigations, to improve risk stratification and advance understanding of their impact on long-term kidney transplant success.
Abernethy malformation is a rare congenital vascular anomaly defined by the absence or severe hypoplasia of the portal vein, resulting in portosystemic shunting. The metabolic and immunologic consequences such as hepatic encephalopathy and pulmonary complications are well recognized. However, renal involvement of Abernethy malformation has been reported rarely . We report a 13-year-old boy who presented with severe anemia, pneumonia and nephrotic-range proteinuria (14.18 g/24 h). Imaging demonstrated type Ib Abernethy malformation, with complete agenesis of the portal vein and direct drainage into the inferior vena cava. Kidney biopsy showed immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) with a"full house" immunofluorescence pattern and hypocomplementemia. Biomarkers for autoimmune disease, infection and monoclonal gammopathy were negative. The patient showed a limited response to methylprednisolone, cyclophosphamide and intravenous immunoglobulin. However, proteinuria declined to 1.2 g/24 h four weeks after liver transplantation,. The complement and hemoglobin levels also normalized. The patient currently has negative proteinuria on tacrolimus monotherapy. This case illustrates a potential association between Abernethy malformation and membranoproliferative glomerulonephritis (MPGN). It also highlights the importance of vascular imaging in patients with unexplained glomerulonephritis and hypocomplementemia accompanied by hepatic anomalies.
Background: Advancing age is incorporated as a strong risk variable in EuroSCORE II and is consistently associated with adverse outcomes after conventional coronary artery bypass grafting (CABG). Whether minimally invasive direct coronary artery bypass (MIDCAB)-which avoids both sternotomy and cardiopulmonary bypass-modifies this age-related risk in patients with single-vessel or LAD-predominant coronary artery disease remains insufficiently characterised. Methods: We retrospectively analysed 350 consecutive patients who underwent MIDCAB at Hannover Medical School between July 1999 and April 2025 (follow-up to April 2025). Elderly patients (age ≥70 years; n = 117) were compared with younger patients (age <70 years; n = 233) before and after 1:1 propensity score matching using greedy nearest-neighbour matching with a caliper of 0.2 × SD of the logit propensity score; age was excluded from the propensity model as it represented the exposure variable. A pre-specified sensitivity propensity model that additionally excluded EuroSCORE II (because EuroSCORE II contains an age component) was also evaluated. The primary endpoint was all-cause long-term mortality; secondary endpoints included perioperative complications and in-hospital outcomes. Long-term survival was assessed by Kaplan-Meier analysis and multivariable Cox proportional hazards regression, with a pre-specified parsimonious Cox model (age, LVEF, renal impairment) and cluster-robust standard errors on matched-pair identifiers. Results: Matching produced 109 pairs with excellent covariate balance (all standardized mean differences < 0.20). MIDCAB was completed without intraoperative conversion in all patients. No 30-day mortality, perioperative stroke, or new postoperative dialysis was observed in either age stratum (Clopper-Pearson 95% CI 0.00-3.33% for each zero-event outcome). Perioperative complications-including new-onset atrial fibrillation, re-exploration for bleeding, and intensive care unit and hospital length of stay-did not differ significantly between elderly and younger patients in the matched cohort (Newcombe 95% CI for risk differences all crossing zero; McNemar's exact tests non-significant for all matched-pair binary endpoints; Hodges-Lehmann median difference for hospital length of stay +1.0 day, bootstrap 95% CI 0.0-1.0 days). At a median follow-up of 19.0 years (IQR 11.5-24.3; reverse Kaplan-Meier potential median 19.7 years), all-cause mortality was higher in the elderly (20.2% vs. 5.5%, p = 0.002; log-rank p = 0.001; exact McNemar's p = 0.0025 for the matched-pair mortality endpoint). After multivariable adjustment, elderly age (≥70 years) was independently associated with long-term mortality (adjusted hazard ratio 4.48, 95% CI 1.79-11.20, p = 0.001), as was EuroSCORE II (HR 2.40 per unit, p = 0.034); a pre-specified parsimonious model (age, LVEF, renal impairment) with pair-cluster robust standard errors yielded an essentially identical adjusted HR for elderly age of 4.08 (95% CI 1.65-10.04, p = 0.002), and a sensitivity propensity model without EuroSCORE II yielded HR 3.95 (95% CI 1.68-9.29, p = 0.002). Conclusions: In this propensity-matched analysis with a median follow-up of ~19 years, MIDCAB was associated with excellent observed perioperative outcomes in appropriately selected elderly patients (no 30-day mortality, stroke, or new dialysis observed; upper 95% CI 3.3%) and no evidence of an excess of major in-hospital complications compared with younger patients within the statistical resolution of the cohort. The long-term mortality excess in the elderly is consistent with age-related life-expectancy curves in the source population; cause-specific mortality was not available in this cohort. External benchmarks from large MIDCAB cohorts in which long-term survival approximates that of the age-matched general population support this interpretation indirectly. These findings support MIDCAB as a feasible revascularization strategy associated with favourable observed early outcomes and long-term survival consistent with published MIDCAB literature, in appropriately selected elderly patients with single-vessel or LAD-predominant coronary artery disease treated at experienced centres.
Hepatic artery thrombosis (HAT) is one of the most severe complications following liver transplantation (LT). Its prevention requires balancing the risks of bleeding and embolism. Due to the incomplete recovery of the coagulation and fibrinolytic system function in LT patients and considerable individual variability, there is currently no standardized protocol for HAT prevention. This report presents a case of HAT in a patient with liver failure following LT. Following surgical thrombectomy and hepatic artery resection and anastomosis, the patient received combined antiplatelet and parenteral anticoagulant therapy during hospitalization. At discharge, sequential therapy was transitioned to direct oral anticoagulants (DOACs) for long-term prevention of HAT recurrence, resulting in favorable outcomes. This study also reviews relevant studies on HAT following LT and summarizes the current evidence-based treatment and antithrombotic prophylaxis strategies for HAT. Antithrombotic strategies vary according to the center. Although antiplatelet therapy has the highest level of evidence for HAT prevention, recent clinical experience also suggests a role for anticoagulants in selected patient populations. Regimen selection requires balancing thrombotic and hemorrhagic risks. In this case, we found that novel biomarkers (e.g., thrombin-antithrombin and plasmin-α2-plasmin inhibitor complexes) may guide anticoagulation decisions, and DOACs represent a promising long-term option for HAT prevention.
The avascular and alymphatic nature of articular cartilage severely limits its intrinsic repair capacity. Even when spontaneous healing occurs, it inevitably culminates in fibrocartilage formation, which lacks the biomechanical functionality of native hyaline cartilage. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic candidate owing to their regenerative potential. However, direct intra-articular transplantation exposes MSCs to a hostile microenvironment characterized by excessive reactive oxygen species and pro-inflammatory cytokines, leading to extensive apoptosis and substantially compromised therapeutic efficacy. Cell-derived decellularized extracellular matrix (dE) has been shown to enhance chondrogenic potential, yet it fails to suppress hypertrophic differentiation during chondrogenic induction, a major hurdle in cartilage engineering. To overcome this bottleneck, we integrated ascorbic acid (AA) with dE preconditioning. Notably, concurrent dE and AA combination synergistically enhanced antioxidant capacity during expansion, while significantly attenuating hypertrophic markers and matrix catabolism (MMP13, IL-1β) during chondrogenic induction. Mechanistically, this strategy sustained TGF-β receptor I expression alongside endogenous TGF-β1 ligand downregulation, optimizing canonical signaling without pathological overactivation. Strikingly, antecedent AA priming reversed these benefits, compromising chondrogenic potential and exacerbating hypertrophy during chondrogenic induction, underscoring a stringent temporal dependency. Collectively, this biomaterial-guided preconditioning strategy generates chondroprogenitors with reduced hypertrophic markers and improved hyaline phenotype in vitro, warranting further preclinical in vivo investigation.
Static cold storage of cardiac allografts at 4-8 °C or 10 °C has yielded promising heart transplant outcomes compared with ice storage. However, direct comparisons between these 2 preservation temperatures are lacking. This dual-center study is the first to compare adult heart transplant outcomes using allografts preserved at 10 °C versus 4-8 °C static cold storage. All single-organ, donation-after-brain-death adult heart transplants performed at 2 high-volume centers between January 2020 and April 2025 were retrospectively analyzed. Multiorgan, adult congenital, and donation-after-circulatory-death cases were excluded. A 3:1 nearest-neighbor propensity score matching was applied using a standardized mean difference <20% to create balanced cohorts. Firth logistic regression and quantile regression were used to evaluate categorical and continuous outcomes in unmatched and matched cohorts. Among 365 recipients, 113 received allografts preserved at 10 °C and 252 at 4-8 °C. The 10 °C group had higher donor and recipient risk profiles, including older donors (37 [28-43] versus 31 [24-39] years; P=0.004), greater donor-recipient sex mismatch, and more frequent donor undersizing by predicted heart mass ratio. Recipients in this cohort were older and had more re-sternotomies and higher serum creatinine levels at transplant. Patients in the 4-8 °C group were more often listed as Status 2. After matching, 10 °C preservation was associated with less primary graft dysfunction (2 [2.9%] versus 19 [14.6%]; P=0.008), less left and right ventricular dysfunction, reduced new intraaortic balloon pump use, and improved 1-year survival (95.7% versus 86.2%; P=0.02). Other outcomes, including cardiac indices and posttransplant length of stay, were not significantly different between groups. Preservation of cardiac allografts at 10 °C may yield superior early graft function compared with 4-8 °C static cold storage. However, further prospective studies are required to delineate the optimal donor heart preservation temperature.
Donation after circulatory death has emerged worldwide as a safe and effective alternative pathway to increase the donor pool. However, organs undergo a variable period of warm ischemia during the agonal phase and the cardiac arrest before graft procurement, and the heart is particularly vulnerable to injury provoked by warm ischemia and subsequent reperfusion. Several reperfusion strategies are currently available for the recovery and assessment of heart function in these donors, with promising early and long-term results. Nevertheless, each technique implies specific financial, logistical and ethical challenges, translating into a heterogeneous landscape of protocols across European and non-European countries. Additionally, no randomized clinical trials have been published to assess the superiority of one technique over the other, and current clinical evidence is based on retrospective registry data and single-center observational studies.
Laparoscopy is a minimally invasive surgical approach that can reduce morbidity compared with open surgery in appropriately selected patients. However, patients with a history of intra-abdominal solid organ transplantation may have postoperative adhesions and altered anatomy, leading to more complex and variable anatomy. It remains unclear whether prior transplantation increases the risk of complications during laparoscopy. This study aimed to evaluate the incidence of complications in patients undergoing laparoscopy following intra-abdominal solid organ transplantation. A systematic search of PubMed, EMBASE, and Google Scholar was conducted through October 2023 to identify studies on laparoscopy in postintra-abdominal solid organ transplant recipients. Two independent reviewers identified 30 relevant articles, of which 19 (including case reports, case-control, and cohort studies) met the inclusion criteria. Risk of bias was assessed using the Newcastle-Ottawa scale by two independent reviewers. The study protocol was registered with PROSPERO (CRD42023477254). Four studies included direct comparisons between transplant and nontransplant patients. The mean postoperative length of stay was 3.5 days among 1402 transplant patients, compared with 2.3 days among 2,640,340 nontransplant patients. Two studies reported a lower rate of wound infection in nontransplant patients compared with posttransplant patients (1.7% vs. 4.8%). Rates of other infections, seroma formation, ileus, and disease recurrence were comparable between groups, although each was reported by only one small study. Two of the four studies were assessed as having a low risk of bias. Direct comparisons between patients with and without a history of intra-abdominal solid organ transplantation suggest that laparoscopy is generally safe, with a modest increase in hospital stay and wound infection risk in posttransplant patients.
Cutaneous manifestations of chronic lymphocytic leukemia (CLL) are heterogeneous and may result from leukemic infiltration, secondary malignancies, infectious complications, or reactive inflammatory processes. Reactive angioendotheliomatosis (RAE) is a rare vascular proliferation that has only infrequently been reported in association with hematologic malignancies. We describe a 58-year-old man with high-risk relapsed/refractory CLL harboring TP53 mutation and del(17p) who developed rapidly enlarging, fungating cutaneous lesions involving the right thumb, upper arm, and additional sites despite multiple prior therapies, including fludarabine, cyclophosphamide, rituximab, ibrutinib, and venetoclax. Histopathologic evaluation demonstrated dermal vascular proliferation with endothelial marker positivity (CD31, CD34, ERG, and vimentin), consistent with RAE and without evidence of leukemic infiltration. The lesions were refractory to local supportive measures but showed marked regression following treatment with CD19-directed chimeric antigen receptor (CAR) T-cell therapy using lisocabtagene maraleucel. Notably, cutaneous remission despite persistent measurable residual disease and eventual systemic relapse requiring allogeneic hematopoietic cell transplantation. This discordance suggests that regression of RAE may be mediated through immune modulation and alteration of inflammatory or angiogenic pathways rather than direct elimination of cutaneous leukemia. To our knowledge, this is among the first reports describing resolution of paraneoplastic RAE following CAR T-cell therapy in CLL, and it highlights the broader immunomodulatory effects of cellular immunotherapy beyond direct antitumor activity. The authors have confirmed clinical trial registration is not needed for this submission.
Despite effective antiretroviral therapy, HIV-1 persists as a viral reservoir and remains a major barrier to a durable cure. Reservoir size and dynamics are central determinants of the success of cure strategies. Efforts to characterize and target the HIV-1 reservoir have primarily focused on people with HIV-1 subtype B in Western Europe and North America. This emphasis has limited our understanding of reservoir size and dynamics in individuals with non-B subtypes, which account for most infections globally, particularly in high-burden regions such as sub-Saharan Africa. This systematic review synthesizes evidence on HIV-1 reservoir size in individuals with non-B subtypes and compiles reported reservoir outcomes alongside demographic and clinical metadata. PubMed and EMBASE were searched for studies quantifying the HIV-1 reservoir in peripheral blood from individuals with non-B subtypes. Eligible studies quantified reservoir size in at least three non-B samples stratified by subtype or directly compared measurements between subtypes. Data were extracted on subtype, reservoir size, statistical comparisons thereof, and key demographic and clinical data. Study quality was assessed using a pre-defined, custom set of criteria. Data were synthesized by organizing within-study statistical comparisons by subtype in a schematic overview to indicate the direction of effect. Of 1589 unique records, 40 studies quantifying HIV-1 reservoir size in individuals with non-B subtypes were included. Records excluded at full-text screening commonly lacked viral subtype determination and/or subtype-stratified outcomes. Comparisons between subtype B and pooled non-B subtypes suggest a larger reservoir for subtype B. Substantial differences in study design, (meta)data reporting, and comparability limited direct comparison across studies. Strengthening knowledge on the HIV-1 subtype-specific reservoir is essential for the development of effective and globally relevant cure strategies. The available data point toward possible differences in reservoir size between subtype B and non-B subtypes. To improve further assessment, we developed recommendations urging studies to use standardized subtyping methods, report viral subtype according to Los Alamos guidelines, and provide detailed individual-level outcomes and metadata, including disease stage at treatment initiation, ART duration, and viral suppression status. Furthermore, we strongly recommend using multi-subtype reservoir assays that are cross-validated to enhance comparability across studies. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251074799, identifier CRD420251074799.