Search Results (3,112)

Background: Obesity is increasingly prevalent among kidney transplant candidates; however, its impact on graft outcomes in Asian populations is not well characterized. We evaluated the association between preoperative obesity and living-donor kidney transplantation outcomes in Japan. Methods: We analyzed 623 living-donor kidney transplants performed from 1998 to 2021 at six centers in northern Japan. Recipients were categorized by body mass index (BMI) at transplant, and multivariable Cox regression was employed for assessing graft outcomes. Results: Obesity (BMI, ≥30 kg/m²; n = 27 [4.3%]) was the strongest graft failure predictor (hazard ratio, 4.62) compared with normal-weight recipients. Moreover, overweight status (BMI, 25–29.9 kg/m²), acute rejection, and older donor age were independent risk factors. Despite similar rejection rates across the BMI groups, recipients with obesity exhibited persistently impaired kidney function from 1-week posttransplant to the 5-year follow-up. Patient survival was comparable across BMI groups; however, underweight status (BMI < 18.5 kg/m²) was associated with higher mortality. Conclusions: Preoperative obesity and overweight status were significant risk factors for graft failure in Japanese living-donor kidney transplant recipients. Meanwhile, the mortality rate was significantly higher in the patients with underweight status at transplant. Pre-transplant weight optimization and shared decision-making with candidates warrant consideration. Full article

Background: Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody directed against the 21–28 kd cell surface glycoprotein, CD52. Alemtuzumab is used as an organ anti-rejection therapy in transplant recipients. Neuro-ophthalmic adverse effects are rarely described, and, to our knowledge, accommodative spasm has not previously been reported in a transplant recipient. Case Description: A thirty-nine-year-old woman with genetically confirmed NPHP1-associated nephronophthisis, with stage F3 fibrosis, developed persistent bilateral blurred vision 72 h following alemtuzumab administration for a biopsy-proven acute cellular rejection, approximately six to seven weeks post-transplant. Initial attribution to hyperglycaemia and tacrolimus toxicity delayed recognition. Cycloplegic refraction confirmed a marked hyperopic shift (+2.75 D right eye, +2.50 D left eye) with significant improvement in visual acuity, consistent with accommodative spasm. Systemic evaluations excluded hyperglycaemia-related lens changes, calcineurin inhibitor neurotoxicity, and cytomegalovirus retinitis. MRI was not pursued in the absence of red flag neurological features, and because a definitive ophthalmic diagnosis had been made. Management and Outcome: The patient was managed expectantly, as cycloplegic refraction had already confirmed the diagnosis, and symptoms were improving. Therapeutic cycloplegia (e.g., atropine) was withheld to avoid impairing near vision and driving ability. Full resolution occurred within 4 to 6 weeks without intervention. Drug exposure to onset of symptoms was 72 h; onset of symptoms to diagnostic confirmation was 22 days; total symptom duration was 5.5 weeks, and recovery was 2 weeks after diagnosis. Conclusions: This case represents the first reported transplant case of alemtuzumab-associated accommodative spasm. Causality assessment supports a WHO-UMC classification of “Probable”, aligning with five Bradford–Hill considerations (temporality, biological plausibility, consistency, specificity, and analogy), but without statistical “strength of association” given that this is a single case report. Early cycloplegic refraction should be incorporated into the evaluation of post-alemtuzumab visual complaints, and clinicians should contribute to pharmacovigilance through structured reporting to capture these rare but important events. Full article

Background/Objectives: The gut microbiota is increasingly recognized as a key determinant of human health, playing a vital role in metabolism, immunity, and disease susceptibility. Dysbiosis, or microbial imbalance, is associated with gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and Clostridioides difficile infection (CDI), as well as extraintestinal conditions, including obesity, cardiovascular disease, and neuropsychiatric disorders. This review aims to provide an updated overview of emerging therapeutic strategies to modulate the gut microbiota to restore eubiosis and improve health outcomes. Methods: A narrative review of recent literature was conducted, focusing on preclinical and clinical studies investigating microbiota-targeted therapies. The review primarily covers innovative interventional approaches, including fecal microbiota transplantation (FMT), bacterial consortium transplantation (BCT), bacteriophage therapy and outer membrane vesicles (OMVs). Results: Evidence supports the role of probiotics, prebiotics, and synbiotics in remodeling microbial communities and improving host health, although their effects may be strain- and context-dependent. FMT has demonstrated high efficacy in the treatment of recurrent Clostridium difficile infections and is being studied for IBD, IBS and extraintestinal diseases, following the recent Food and Drug Administration approval of the first commercial FMT products. BCT offers a standardized alternative to donor-derived material, with early clinical successes such as FDA-approved SER-109. Phage therapy and OMVs represent promising frontiers, offering targeted microbial modulation and interactions with the immune system, although clinical data remain limited. Conclusions: Emerging gut microbiota modulation strategies offer new perspectives for precision medicine and could transform the prevention and treatment of many diseases, but further studies are needed to ensure their safety, standardization, and clinical application. Full article

Introduction: Cardiothoracic transplant surgery represents a critical intervention for patients with end-stage heart and/or lung failure. While advancements in surgical techniques and perioperative management have enhanced survival rates, these procedures remain associated with significant morbidity, extended hospitalizations, and complex recovery trajectories. Background/Objectives: Enhanced Recovery After Surgery (ERAS) protocols, originally developed for colorectal surgery, have shown promise in optimizing perioperative care across various surgical disciplines. However, their application in cardiac and thoracic transplantation is still emerging. This article evaluates recent advancements in ERAS protocols tailored to cardiac and thoracic transplant patients, focusing on preoperative, intraoperative, and postoperative interventions. Results: Evidence highlights the potential of ERAS to reduce complications, shorten hospital stays, and improve long-term outcomes. Key strategies include preoperative optimization through nutritional and psychosocial prehabilitation, intraoperative adoption of minimally invasive techniques and refined anesthesia practices, and postoperative protocols emphasizing opioid-sparing pain management, early mobilization, and nutritional recovery. Conclusions: This review identifies gaps in current research and offers recommendations for the broader implementation and standardization of ERAS protocols in cardiothoracic surgery, with emphasis on cardiothoracic transplantation, aiming to improve outcomes for this high-risk population. Full article

Background: Comparative real-world data on the pharmacokinetics of once-daily tacrolimus formulations in de novo kidney transplantation remain limited. We compared tacrolimus exposure and dosing requirements with Envarsus and Advagraf during the early post-transplant period. Methods: We conducted a prospective, observational, single-center study including adult de novo kidney transplant recipients treated with once-daily tacrolimus as either Envarsus or Advagraf. The immunosuppressive protocol was based on thymoglobulin induction, with delayed initiation of tacrolimus at an initial dose of 0.15 mg/kg/day, prednisone, and sirolimus as the third immunosuppressive agent. Trough concentrations (C0), daily dose, and dose-normalized trough exposure (C0/D) were assessed at 48 h and over 3 months (days 7, 14, 30, 60, and 90). Dose adjustments were guided by therapeutic drug monitoring and Bayesian individualization to achieve target trough ranges (6–10 ng/mL during month 1; 5–7 ng/mL thereafter). Clinical effectiveness and safety outcomes were evaluated through month 3. Results: Ninety recipients were included (Advagraf n = 43; Envarsus n = 47). At 48 h, Envarsus achieved higher trough concentrations and higher C0/D than Advagraf (C0: 10.7 vs. 7.7 ng/mL; C0/D: 1.30 vs. 0.75 (ng/mL)/mg; both p < 0.001). From week 1 to month 3, trough concentrations were similar between groups (week 1: 8.5 vs. 8.5 ng/mL, p = 0.968; month 3: 5.7 vs. 5.1 ng/mL, p = 0.234), but Envarsus required lower daily doses (week 1: 6.4 vs. 9.9 mg/day, p = 0.001; month 3: 3.2 vs. 4.1 mg/day, p = 0.021) and maintained higher C0/D (week 1: 1.53 vs. 1.00, p = 0.001; month 3: 1.94 vs. 1.57 (ng/mL)/mg, p = 0.012). At 48 h, infra-therapeutic troughs were less frequent with Envarsus (6.7% vs. 40.5%, p = 0.0001), while supra-therapeutic levels were more frequent (57.8% vs. 18.9%), and tacrolimus discontinuation due to high troughs occurred more often (23.4% vs. 7.0%, p = 0.032). Over 3 months, the proportion of measurements within the therapeutic range was similar (57.6% vs. 64.5%, p = 0.705). Efficacy and safety were similar between groups. Conclusions: In de novo kidney transplant recipients, Envarsus provides higher early tacrolimus exposure and consistently higher dose-normalized trough exposure than Advagraf, enabling lower maintenance doses while maintaining similar short-term effectiveness and safety. However, early overexposure was more frequent with Envarsus at 0.15 mg/kg/day, supporting careful early monitoring and consideration of lower starting doses. Full article

Kidney transplantation is considered the gold standard treatment for patients with end-stage kidney disease. Historically, outcomes in kidney transplantation have been focused on reducing rates of rejection as the dominant cause of graft loss. However, managing the risk of rejection with infection continues to be a delicate balancing act for transplant physicians. It has long been recognised that viruses are an important cause of morbidity and mortality in immunosuppressed patients with significant implications for kidney graft function and patient outcomes worldwide. This is a review article with literature selected from the PubMed database using relevant terms related to kidney transplantation and infectious diseases. This article focuses on the key viruses affecting kidney transplant recipients, including cytomegalovirus, polyoma virus, Epstein–Barr virus, varicella zoster virus, adenovirus, hepatitis B and C, and new emerging viruses. It examines differing epidemiology, diagnostic challenges, screening methods, and antiviral treatments. Key challenges for the international nephrology community include increased global mobility resulting in rapid shifts in viral epidemiology, increasing antimicrobial resistance, virus-associated malignancies, and suboptimal assays for screening donors and transplant recipients. Full article

As the rates of type 2 diabetes and obesity have increased globally, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic steatotic fatty liver disease (NAFLD), has risen concomitantly worldwide. MASLD is now the most common etiology of chronic liver disease and is the leading indication for liver transplantation in the United States. Patients with MASLD have an increased risk of progression to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, hepatocellular carcinoma, extrahepatic malignancies, as well as liver- and cardiovascular-related mortality. Diet and lifestyle modifications with a goal of ≥10% total body weight loss—required to reverse steatosis, steatohepatitis, and fibrosis—are often challenging and ineffective. Although novel pharmacotherapies have recently been approved and others are in development, cost, adherence, and adverse effects remain potential limitations. Bariatric surgery, including Roux-en-Y gastric bypass and sleeve gastrectomy, is highly efficacious and a cost-effective treatment for obesity and associated medical problems. However, bariatric surgery may be associated with morbidity and mortality. Endoscopic bariatric and metabolic therapy (EBMT) has recently emerged as a promising treatment modality and offers an alternative to surgery. Primary EBMTs include intragastric balloon placement, aspiration therapy, endoscopic sleeve gastroplasty, duodenal mucosal resurfacing, duodenal–jejunal bypass liner, and primary obesity surgery endoluminal (POSE 2.0). Secondary EBMTs include transoral outlet reduction, argon plasma coagulation of the anastomosis, and revisional endoscopic sleeve procedure. We review the recent literature on primary EBMTs and secondary EBMTs for the treatment of obesity and MASLD, the pathophysiologic mechanisms, efficacy, safety, and patient outcomes in MASLD in this narrative review. Full article

In recent decades, the rate of kidney transplantation has risen significantly, leading to better outcomes in terms of cardiovascular and overall mortality for patients with kidney failure. Although kidney transplantation represents the most effective therapeutic option, it is not devoid of the risk of failure. Immunological and non-immunological risk factors are involved. These factors often interact and may act synergistically, ultimately influencing graft longevity and patient survival. Both contribute to long-term transplant outcomes; however, non-immunological factors, representing a significant clinical challenge, will be the focus of our review. Of the numerous non-immunological risk factors, for clarity and to avoid overextending the discussion, only those most closely associated with chronic kidney disease have been considered: hypertension, anemia, diabetes mellitus, proteinuria, electrolyte and acid–base imbalances, and impaired bone mineralization. Hypertension is reported in approximately 90% of kidney transplant recipients, often related to immunosuppressive therapy and residual renal dysfunction, and it is strongly associated with reduced graft survival. Anemia affects approximately 20–51% of these patients, contributing to cardiovascular morbidity and a more rapid decline in graft function, as does pre-existing diabetes mellitus. Proteinuria has a prevalence ranging from 7.5% to 45%, depending on the established target, and is a significant negative prognostic factor. Metabolic complications are also frequent; for example, hyperkalemia has an incidence of 25–44%, and metabolic acidosis has a prevalence of 12–58%. In our review, each of these factors is analyzed in terms of clinical impact, etiopathogenic mechanism, and available therapeutic management. Full article

Background: Exercise-induced fatigue (EIF) impairs performance and recovery and may contribute to overreaching/overtraining and adverse health outcomes. Beyond classical explanations (substrate depletion, metabolite accumulation, oxidative stress), accumulating evidence indicates that the gut microbiota modulates fatigue-related physiology through metabolic, immune, barrier, and neurobehavioral pathways. Methods: We conducted a structured narrative review of PubMed and Web of Science covering 1 January 2015 to 30 November 2025 using predefined keywords related to EIF, gut microbiota, recovery, and nutritional interventions. Human studies, animal experiments, and mechanistic preclinical work (in vivo/in vitro) were included when they linked exercise load, microbial features (taxa/functions/metabolites), and fatigue-relevant outcomes. Results: Across models, high-intensity or prolonged exercise is consistently associated with disrupted gut homeostasis, including altered community structure, reduced abundance of beneficial taxa, increased intestinal permeability, and shifts in microbial metabolites (e.g., short-chain fatty acids). Evidence converges on four interconnected microbiota-mediated pathways relevant to EIF: (1) energy availability and metabolic by-product clearance; (2) redox balance and inflammation; (3) intestinal barrier integrity and endotoxemia risk; and (4) central fatigue and exercise motivation via microbiota–gut–brain signaling. Nutritional strategies—particularly targeted probiotics, prebiotics/plant polysaccharides, and selected bioactive compounds—show potential to improve fatigue biomarkers and endurance-related outcomes, although effects appear context-dependent (exercise modality, baseline fitness, diet, and baseline microbiota). Conclusions: Current evidence supports a mechanistic role of the gut microbiota in EIF and highlights microbiota-targeted nutrition as a promising adjunct for recovery optimization. Future work should prioritize causal validation (e.g., fecal microbiota transplantation and metabolite supplementation), athlete-focused randomized trials with standardized fatigue endpoints, and precision approaches that stratify individuals by baseline microbiome features and training load. Full article

Background: Colorectal liver metastases (CRLM) represent a major determinant of prognosis in patients with metastatic colorectal cancer and account for a substantial proportion of cancer-related mortality worldwide. Over the last decades, survival outcomes have improved significantly as a result of advances in systemic therapies, refinement of surgical techniques, and, most importantly, the widespread implementation of multidisciplinary management strategies. Within this evolving landscape, surgery remains the cornerstone of potentially curative treatment, although its optimal integration with systemic and locoregional therapies requires careful patient selection and individualized treatment planning. Methods: This narrative review explores the contemporary role of surgery within the multidisciplinary management of CRLM, emphasizing how surgical decision-making is integrated with medical oncology, radiology, interventional procedures, and emerging technologies. Results: The pivotal role of multidisciplinary team meetings in defining resectability, treatment sequencing, and therapeutic intent is highlighted. Key technical and oncological criteria guiding upfront resection, neoadjuvant or conversion strategies, and staged approaches are reviewed, including assessment of future liver remnant, optimization of liver volume and function, tumor burden, molecular profile, and dynamic prognostic models. In addition, the review summarizes current evidence supporting parenchyma-sparing liver surgery and the integration of local therapies such as thermal ablation, irreversible electroporation, stereotactic body radiotherapy, selective internal radiation therapy, and hepatic artery infusion chemotherapy within multimodal treatment algorithms. Complex clinical scenarios, including synchronous disease, extensive bilobar metastases, chemotherapy-associated liver injury, and the emerging role of liver transplantation in highly selected patients with liver-only disease, are also addressed. Conclusions: Modern CRLM management has evolved toward a highly individualized, biology-driven approach in which surgery is optimally integrated within a multidisciplinary framework to maximize curative potential and long-term survival. Full article

Background: Cultivated oral mucosal epithelial transplantation (COMET/CAOMECS) is an autologous, immunosuppression-sparing option for ocular surface reconstruction in limbal stem cell deficiency (LSCD). After two decades, indications, platforms and outcome definitions vary, and COMET’s position relative to limbal-derived epithelium remains uncertain. Methods: We conducted a PRISMA-ScR scoping review of human clinical studies (PubMed, 2000–30 December 2025) with hand-searching and regulatory sources. Eligible reports included COMET/CAOMECS series and comparative cohorts (CLET/ACLET, SLET, KLAL/CLAL). The primary outcome was anatomical success (stable epithelialised cornea without recurrent persistent epithelial defect, progressive conjunctivalisation or uncontrolled neovascularisation at last assessment). Given heterogeneity in definitions and analytic frames (fixed-time vs. Kaplan–Meier [KM]), results were synthesised narratively by indication and platform. Results: Twenty-five reports (893 eyes; 821 patients) were included. Aetiologies were predominantly burns and SJS/TEN. Across amniotic membrane-based mixed-aetiology series, 12-month anatomical success clustered around 55–70%. Aggregated descriptively across COMET eyes, 211/467 (45%) had a stable surface at last follow-up. Epithelialisation was generally rapid in quiet AM-based reconstructions and slower with severe adnexal disease or carrier-free platforms. Mean BCVA improved from 1.8 ± 0.7 to 1.4 ± 0.7 logMAR (471 eyes); ≥2-line gains occurred in 308/471 (65.4%). A matched comparison suggested better 12-month survival, less neovascularisation and better BCVA with substrate-free versus AM-carried COMET; a biomaterial-/feeder-free platform reconstructed most eyes but failed more often with four-quadrant symblepharon. Observational comparative cohorts suggested higher surface survival and average visual gain with limbal-derived epithelium, at the cost of systemic immunosuppression. Conclusions: In appropriately selected bilateral LSCD, COMET offers immunosuppression-sparing reconstruction with moderate, durable surface stability and clinically meaningful visual gains when performed on a quiet, optimised surface. Platform refinements—particularly substrate-free constructs—and prospective, indication-defined comparative studies with harmonised outcomes are needed to define COMET’s role relative to limbal-derived epithelium. Full article

Gastric cancer (GC), often diagnosed at advanced or metastatic stages, remains a significant clinical challenge requiring novel biomarkers for early detection, risk stratification, and effective, personalized treatment optimization. Emerging evidence underscores a strong association between gut microbiome dysbiosis and GC initiation, progression, and therapeutic outcomes. This review explores the potential of the advanced/metastatic gastric microbiome as a source of diagnostic and targetable biomarkers and its role in modulating responses to immunotherapy. Although Helicobacter pylori (H. pylori) is the most significant risk factor for GC, several other gastrointestinal taxa—including Fusobacterium nucleatum (F. nucleatum)—have been implicated in advanced GC (AGC). At its inception, microbial dysbiosis contributes to chronic inflammation and immune evasion, thereby influencing tumor behavior and treatment efficacy. Integrating microbiome-based biomarkers into risk stratification, GC staging, and targetable treatment frameworks may enhance early detection, inform immunotherapy strategies, and improve patient-specific treatment responses. Bifidobacterium and Lactobacillus rhamnosus GG have the potential to change the immunotherapy framework with their direct influence on dendritic cell (DC) and cytotoxic T cell (CTL) activity. However, clinical translation is impeded by methodological heterogeneity, causality limitations, and a lack of clinical trials. Nonetheless, the integration of microbiome profiling and the development of therapeutic microbiome modulation strategies, such as personalized probiotics regimens and fecal microbiota transplantation, hold substantial potential for improving clinical outcomes and reducing treatment-related toxicity in GC management. Full article

Gut microbiota influences colorectal cancer (CRC) development, tumor progression, and response to therapy. Fecal microbiota transplantation (FMT) has been proposed as a strategy to restore microbial balance and modulate treatment outcomes. We evaluated the effects of human fecal transplantation on gut microbiota composition, metabolites, tumor growth, and the efficacy of folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy in four CRC patient-derived xenograft (CRC PDX) models in NSG mice. Gut microbiota was profiled by 16S rRNA sequencing; short-chain fatty acids (SCFAs) and amino acids (AAs) were analyzed by mass spectrometry. Prolonged FMT significantly altered gut microbiota structure, increasing α-diversity and modifying β-diversity, and induced distinct changes in bacterial genera. FMT alone did not affect tumor growth. FOLFOX inhibited tumor progression in all CRC PDXs, with FMT enhancing therapeutic efficacy in two models. Despite substantial microbiota shifts, FMT exerted minimal or no effect on fecal SCFAs and AAs. FMT induced robust microbiota remodeling but did not modify selected stool metabolites or intrinsic tumor growth. However, FMT enhanced FOLFOX responsiveness in selected CRC PDXs, supporting a microbiota-mediated modulation of chemotherapy outcomes. Full article

Background: Second salvage autologous stem cell transplantation (SAT) is a therapeutic option for patients with multiple myeloma (MM) who relapse after a first autologous stem cell transplantation (ASCT) in the era of novel agents. However, the clinical context in which SAT provides benefit relative to contemporary salvage regimens remains unclear. Methods: We retrospectively analyzed 51 patients who underwent SAT after novel agent-based induction and first ASCT, and salvage re-induction, and compared outcomes with 113 patients treated with salvage carfilzomib–lenalidomide–dexamethasone (KRd) without SAT. Results: Median interval from first ASCT to relapse was 27 months. In the SAT cohort, median progression-free survival (PFS) and overall survival (OS) from initiation of salvage therapy were 30 and 99 months, respectively. A time to relapse ≥18 months after first ASCT and receipt of SAT as second-line of therapy were associated with significantly longer PFS and OS. In multivariate analysis, administration of SAT at later lines was independently associated with inferior outcomes, while a time to relapse ≥18 months after first ASCT was associated with significantly longer OS. Compared with the KRd-only cohort, SAT was associated with longer OS, whereas PFS was numerically longer without statistical significance. Among patients who had received both a proteasome inhibitor and an immunomodulatory drug as salvage induction, SAT was associated with longer PFS and OS. Conclusions: SAT may provide clinical benefit in selected patients with MM, particularly those with a durable response to first ASCT and those undergoing SAT at an earlier line of relapse in the novel agent era. Full article

Background: Cancer patients admitted to the bone marrow transplant (BMT) unit face life-threatening medical conditions. Consequently, their family members experience uncertainty, resulting in high levels of anxiety and depression (AD). Limited updates and communication from medical staff exacerbate these emotional burdens. To address these challenges, we developed a mobile health (mHealth) intervention, FamCarePlus, and evaluated its feasibility, usability, and efficacy. We hypothesized that the FamCarePlus application would demonstrate a high degree of feasibility and usability and would reduce AD compared to a control group relying solely on traditional communication through the nurses’ station. Methods: We employed a quasi-experimental pretest/posttest non-randomized, non-blinded self-report design over 3 weeks, with an experimental group (n = 10) using FamCarePlus and a control group (n = 9). We selected participants via convenience sampling using the electronic medical record to identify eligible patients and families, guided by inclusion and exclusion criteria. We used descriptive statistics and the Hospital Anxiety and Depression Scale (HADS) guidelines to analyze the data. Feasibility was defined by a retention rate > 80%, with usability testing using the System Usability Scale (SUS) and NASA Task Load Index (NASA-TLX) surveys. The HADS measured AD, comparing baseline to Week 3. Results: We met our feasibility criteria of >80%. All SUS and NASA scores were in the higher index, suggesting a significant degree of usability and low workload demand on participants. For efficacy, we compared baseline mean scores, with the experimental group reporting lower AD levels at Week 1 (41.9% and 27.8%, respectively) than the control group (55.2% and 34.2%, respectively). From Week 1 to Week 3, the percentage change showed an 8.6% decrease in anxiety in the experimental group, compared to a 12.8% decrease in anxiety in the control group. These results were consistent when analyzed according to HADS guidelines. Conclusions: The findings of this study provide preliminary evidence that the FamCarePlus intervention is feasible and usable, while also demonstrating that its use may be associated with a sustained reduction in AD levels among family members of patients admitted to the BMT unit. These outcomes underscore the potential of digital interventions to address disparities in patient health information access and psychosocial support. Full article