Kidney transplantation is the preferred therapy for end-stage kidney disease (ESKD), but long-term success is greatly influenced by the selection and safety of immunosuppressants. Local data on prescribing patterns and the incidence of drug side effects in Indonesia are still limited. Therefore, this study aims to evaluate induction therapy patterns, immunosuppressant maintenance, and the incidence of drug-related side effects among kidney transplant recipients at a tertiary hospital in Yogyakarta, Indonesia. Materials and methods: This was a retrospective cohort study of recipients aged ≥18 years who underwent outpatient follow-up between January 2017 and July 2024. Complete medical records were analyzed descriptively, with variables including recipient and donor characteristics, induction and maintenance immunosuppressive regimens, and adverse drug reactions such as infections and non-infections during the 12 months post-transplantation. A total of 57 among the 87 recipients met the inclusion criteria, comprising 70.2% male, 56.1% aged 18-39 years, 98.2% with a history of dialysis, 77.2% with hypertension, and all living donors. Basiliximab induction was administered to all recipients (100%) in combination with triple therapy of tacrolimus, mycophenolate sodium (MPS) or mycophenolate mofetil (MMF) and steroids. Maintenance therapy was predominantly tacrolimus, MPS, steroids 43/57 (75.4%), and tacrolimus, MMF, steroids 14/57 (24.6%). The most common adverse drug events were urinary tract infections (31.6%), followed by cytomegalovirus (CMV, 5.3%) and herpes zoster (3.5%). Non-infectious events included diarrhea (7%), tremor (3.5%), dyslipidemia (3.5%), and new-onset diabetes after transplantation (NODAT) (3.5%). Basiliximab induction and tacrolimus-mycophenolate-steroid maintenance therapy were the predominant immunosuppressive regimens and were associated with an acceptable first-year safety profile. Close monitoring for opportunistic infections, optimization of tacrolimus levels, and structured pharmacovigilance are required to maintain graft function.
Subcutaneous transplantation of islets into small-pore macroencapsulation devices that prevent immune cell passage can inhibit allorejection in rodents. However, there are no reports of euglycemia in humans using this technology. This report further develops these macroencapsulation devices. We compared the ability of macroencapsulation transplant devices containing transformed mouse islet cells (MIN-6) with varying polymer membranes, pore sizes, and hydrophilicity to inhibit allorejection and maintain glycemic control in diabetic mice. We found that 10 μm pore planar polytetrafluoroethylene (PTFE) devices do not inhibit allorejection; 1-2 μm pore devices allow only partial protection; and 0.4 μm devices prevent long-term allorejection. A more hydrophilic PTFE membrane (PTFE-HP) improves device function. Devices constructed with nylon and, secondly, PTFE-HP membranes serve as transplant devices better than those constructed with polyvinylidene fluoride (PVDF), fluorinated ethylene propylene (FEP), ethylenetetrafluoroethylene (ETFE), or polyethersulfone (PES), and result in a lower fibrotic response. Allo-presensitized mice are equally protected from allorejection with 0.4 μm pore PTFE-HP transplant devices as non-presensitized mice. Our layered membrane macroencapsulation device is as effective as a single planar device in inhibiting allorejection. Nylon and, secondly, hydrophilic PTFE macroencapsulation transplant devices with 0.4 μm pores robustly prevent allotransplant rejection compared with all membranes tested and induce the least fibrosis. Future studies with nylon membranes are warranted. A multilayered device is described that reduces the skin surface requirement and increases potential islet load. A transplant model using MIN-6 cells is feasible for studying such devices to prevent allorejection.
Aseptic femoral shaft nonunion represents a biologically compromised state in which impaired osteogenesis, insufficient vascularity, and inadequate mechanical stability prevent healing. Although mechanical revision is essential, achieving union often requires effective autologous bone tissue transplantation and biologic stimulation. This study evaluated a multimodal revision strategy integrating structural and cancellous autografts with mechanical reconstruction to restore both biological viability and stability at the nonunion site. Fifty-four patients with aseptic femoral shaft nonunion were retrospectively reviewed. Revision procedures included exchange nailing, augmentation plating with retained nail, plate replacement, or dynamization. All biologic strategies were based on autologous bone transplantation, including iliac crest cancellous bone grafting, cortical onlay strut grafts harvested from the iliac crest, and Judet osteoperiosteal decortication to enhance local vascularity. Union was assessed based on clinical and radiographic criteria during follow-up. The overall union rate was 96.3% (52/54). Hypertrophic and oligotrophic nonunions achieved 100% union, whereas atrophic nonunions achieved 83.3%. Both exchange nailing and augmentation plating resulted in 100% healing. The most favorable outcomes were observed in patients receiving combined autologous bone grafting (cancellous autograft ± cortical strut graft) together with Judet decortication, underscoring the importance of restoring osteogenic potential and biological activity in addition to mechanical rigidity. Multimodal revision combining stable fixation with autologous bone graft transplantation and biologic enhancement provides an effective treatment option for aseptic femoral shaft nonunion. These findings reinforce the principle that addressing biological insufficiency—through cancellous autografting, cortical strut transplantation, and decortication—is essential to achieving successful bone regeneration, particularly in atrophic nonunion.
To address the pressing shortage of donor lungs, Donation after Circulatory Death (DCD) transplantation has become a vital strategy for expanding the donor pool. Minimizing warm ischemic injury is crucial for optimizing organ viability and function. This review synthesizes current evidence on Normothermic Regional Perfusion (NRP) and Ex-Vivo Lung Perfusion (EVLP) in DCD lung transplantation. Analysis reveals their growing efficacy in minimizing ischemic damage, facilitating organ assessment, and expanding the transplantable organ pool. Studies indicate comparable or improved recipient outcomes, including reduce primary graft dysfunction (PGD) and improved survival. However, challenges persist regarding protocol standardization, ethical considerations and long term outcome validation.
The increasing demand for organ transplantation has necessitated innovative strategies to maximize donor organ utilization, especially in donation after circulatory death (DCD) contexts. This article explores the integration of direct lung recovery with abdominal normothermic regional perfusion (A-NRP) to optimize organ preservation and expand the donor pool. A-NRP effectively mitigates warm ischemic injury, supporting the viability of both abdominal and thoracic organs. Our approach emphasizes meticulous surgical planning, efficient bleeding control, and seamless multidisciplinary collaboration to ensure procedure success. By combining A-NRP with state-of-the-art techniques for lung assessment and preservation, we highlight a promising pathway for enhancing graft quality and outcomes. The article discusses key logistical and ethical considerations, emphasizing the need for standardization and cooperative frameworks across transplant centers. This integrated methodology not only addresses current challenges but also sets the stage for future advancements in DCD organ transplantation, ultimately aiming to increase success rates and save more lives.
The editors of OBM Transplantation would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2025. We greatly appreciate the contribution of expert reviewers, which is crucial to the journal's editorial process. We aim to recognize reviewer contributions through several mechanisms, of which the annual publication of reviewer names is one. Reviewers can download a certificate of recognition directly from our submission system. Additionally, reviewers can sign up to the Web of Science Reviewer Recognition Service (formerly Publons) (https://webofscience.com/wos/) to receive recognition. Of course, in these initiatives we are careful not to compromise reviewer confidentiality. Many reviewers see their work as a voluntary and often unseen part of their role as researchers. We are grateful for the time reviewers donate to our journals and the contribution they make.
Antibody mediated rejection (AMR) is a considerable cause of late allograft failure in solid organ transplantation. Conventional approaches, using plasmapheresis, intravenous immunoglobulin, rituximab, bortezomib, and eculizumab have been unsuccessful in improving graft survival. This review aims to assess emerging therapies for AMR treatment across all organs. Using a PubMed search, literature published up to July 20, 2025 regarding tocilizumab, clazakizumab, carfilzomib, daratumumab, imlifidase, felzartamab, and obinutuzumab were reviewed. Articles were included if available in English, full-text, and reported clinical efficacy outcomes, and excluded if they discussed non-AMR indications or were review articles, single case reports, opinion pieces, protocols, animal studies, or in vitro studies. A total of 28 studies were included, and grouped by drug, organ, and indication. Quality was rated with the Newcastle-Ottawa Scale. The majority of evidence was with single-center retrospective studies and kidney transplantation. Tocilizumab demonstrated the most promise for stabilizing graft function in kidney chronic active AMR (cAMR). Clazakizumab failed to meet its primary efficacy outcome in its cAMR phase III study despite encouraging findings in earlier trials. Carfilzomib may be considered in acute AMR when toxicities preclude use of bortezomib, but comes with risks of nephrotoxicity. Evidence to support daratumumab’s utility in acute AMR is limited to highly heterogenous case series. Imlifidase, felzartamab, and obinutuzumab are not widely studied but may be potential therapies in the future. Studies comparing these therapies to standard of care are needed to establish the place in therapy of these agents. Additionally, there is a need to identify patient characteristics most predictive of clinical success.
Dietary guidelines and Nutrient Reference Intakes are important tools for maintaining optimal health in the general population. Similar guidelines have also been developed by specific organ health associations to help their patient populations recover from disorders or prevent/delay clinical events and subsequent complications. However, there are no specific national and international guidelines to provide dietary and nutrient intake recommendations peri-transplantation. The complex nature of transplantation and insufficient high-quality data are among the factors limiting the establishment of such dietary and nutritional guidelines. Therefore, individualized nutritional care seems to be the best strategy peri-transplantation. In this regard, strong cooperation of involved partners, including the patients and their family members/caregivers plus their healthcare providers, along with nutrition knowledge, plays a crucial role. The ultimate goal is to take advantage of the provision of adequate high-quality nutrients to facilitate a faster wound healing process and recovery from surgical procedures, prevent acute infection post-transplantation, reduce the length of hospitalization, and prevent/postpone the onset of post-transplantation metabolic morbidities. Altogether, an optimal nutritional status will help to reduce the complications associated with transplantation and relevant therapies, enhancing survival rates of donor organs. Special considerations should be given to possible interactions between dietary agents and drugs to ensure minimal damages to the “gift-of-life” and maximal rates of a long-term survival.
Bone grafting remains a cornerstone technique in orthopedic and reconstructive surgery, yet achieving successful graft integration continues to pose significant challenges, particularly in conditions such as osteoporosis, diabetes mellitus, and large bone defects. Traditional graft materials such as autografts, allografts, xenografts, and synthetics, often encounter limitations including immune rejection, poor vascularization, and insufficient osteogenic support. Emerging pharmacological strategies have shown promise in enhancing graft integration by modulating bone-healing pathways, promoting angiogenesis, and regulating inflammatory responses. This review comprehensively explores the biological mechanisms underlying bone repair, including the roles of key molecular pathways such as Wnt/β-catenin, BMP signaling, VEGF-mediated angiogenesis, and the RANK/RANKL/OPG axis. It further examines the therapeutic application of osteoinductive agents (e.g., BMPs, PTH analogs), anti-resorptive drugs (e.g., bisphosphonates, Denosumab), angiogenic modulators (e.g., VEGF, PDGF), and biologics targeting inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β). Innovative approaches such as nanotechnology-based drug delivery, scaffold-based release systems, and gene therapy are also discussed for their potential to achieve localized, controlled, and sustained enhancement of graft performance. While several FDA-approved agents, such as rhBMP-2 and PDGF-BB, have advanced clinical practice, persistent challenges including variability in patient healing, delivery limitations, adverse effects, and regulatory hurdles, highlight the need for continued research. Future directions emphasize the development of multifunctional, personalized therapeutics that actively guide bone regeneration, supported by rigorous translational studies to ensure clinical efficacy and safety.
Donation after circulatory death (DCD) offers a vital strategy to expand the donor lung pool; however, DCD lungs are uniquely susceptible to warm ischemic injury during procurement. This chapter reviews evidence-based and emerging donor management strategies aimed at mitigating ischemic damage and optimizing the suitability of DCD lungs for transplantation, encompassing hemodynamic and ventilatory optimization, bronchoscopic clearance, targeted pharmacological interventions, and strategies to minimize transfusion requirements. Remote monitoring holds promise for further improving lung quality. Optimizing donor management strategies is critical to maximizing the utilization of DCD lungs, and future research should focus on refining existing protocols, evaluating new technologies, and addressing ethical considerations to ensure equitable access to lung transplant.
Graft rejection, early allograft dysfunction (EAD), and poor diagnostic accuracy are some of the challenges that still need to be addressed, even though liver transplantation (LT) has the potential to help patients with end-stage liver disease (ESLD) significantly. Traditional procedures, such as liver biopsies and liver function tests (LFTs), often fail to identify abnormalities early and with accuracy. Genomic RNA sequencing (RNA-Seq) has recently emerged as a powerful approach for identifying molecular markers of immune activity and graft healing. This study provides a comprehensive review of the current achievements in RNA-Seq applications for liver transplantation by comparing biomarker profiles of liver biopsies and peripheral blood mononuclear cells (PBMCs). We highlight the success and challenges of integrating RNA-seq into clinical processes by critically examining its consistency, diagnostic importance, and translational potential. Furthermore, we evaluated the possibility of novel diagnostic algorithms and multi-omics techniques for improving early diagnosis, risk profiling, and personalized immunosuppression. This study highlights the gaps in cross-cohort repeatability, clinical validation, and standardization to improve long-term transplant outcomes. This highlights the need for integrated multicenter approaches driven by biomarkers and provides recommendations for further studies.
Lung transplantation (LTx) is the gold standard for the surgical treatment of end-stage lung disease. Ongoing discussions persist whether single lung transplantation (SLT) or bilateral lung transplantation (BLT) lead to better patient outcomes and quality of life. This study analyzed 58 peer-reviewed articles from 1990 to 2024, comparing SLT and BLT across several parameters, including indications for transplantation, overall survival, pulmonary hypertension, complications, chronic rejection, functional status, and quality of life outcomes. The review also addressed native lung complications, the future of lung transplantation, and the outcomes of non-transplanted lungs in SLT cases. Bilateral lung transplantation (BLT) may offer a more definitive solution for bilateral lung disease. However, the choice between single lung transplantation (SLT) and BLT should be personalized according to each patient's unique requirements. Further research is needed to elucidate each approach's specific advantages and limitations, enhance patient outcomes, and refine lung transplantation practices.
Provided that cell-mediated immunity (CMI) is known to be vital in managing CMV infection post-transplant along with improving methods to predict the development of cytomegalovirus (CMV) following transplant, CMV-specific-cell-mediated immunoassays have been developed, commercially and research based, to be used in conjunction with pre-transplant CMV serological testing and prophylaxis to help tailor an individual care plan post-transplant. In this review, we assess the status of CMV CMI assays, and their potential uses in solid organ transplant recipients, including benefits and limitations.
Liver and lung transplantation remain among the most intricate and resource-intensive arenas in modern medicine, challenged by organ scarcity, immunological complexities, and the persistent threat of rejection. According to recent WHO and UNOS reports, approximately 100,000 patients globally await liver transplants annually, with only 30-40% receiving transplants, resulting in waitlist mortality rates of 15-20%. Similarly, lung transplant demand exceeds supply by a factor of 4:1, with 5-year survival rates remaining at 60-65%. This article outlines the evolving landscape of liver and lung transplantation, with a focus on the intersection of immunological science, regenerative medicine, and computational advances. It aims to synthesize current challenges and emerging therapeutic strategies, emphasizing the transformative potential of precision medicine and advanced immunomodulation techniques. Recent decades have witnessed a paradigm shift from standardized immunosuppression toward individualized, data-driven care. Advances in molecular immunology have revealed complex cellular interactions and rejection pathways, informing targeted therapies such as extracorporeal photopheresis (ECP), immune checkpoint modulation, and the engineering of regulatory T cells. Regenerative medicine, including mesenchymal stem cells, iPSC-derived tissues, and gene editing, offers new avenues for organ repair and tolerance induction. Meanwhile, artificial intelligence and digital health platforms enable predictive modeling, risk stratification, and real-time monitoring, optimizing patient selection and management. Nanotechnology and advanced diagnostics, such as liquid biopsy and single-cell sequencing, further refine graft surveillance and intervention. These developments are situated within an ethical, regulatory, and economic context, underscoring the need for global collaboration and equitable access. The future of liver and lung transplantation lies in the convergence of precision immunology, regenerative strategies, and computational innovation. Interdisciplinary, personalized approaches promise to enhance graft survival, patient outcomes, and the sustainable integration of cutting-edge therapies into global healthcare systems.
Antibody-mediated rejection (ABMR) remains a major barrier to long-term graft survival in kidney transplantation. Defined by the presence of donor-specific antibodies (DSAs) and characteristic histological changes, such as C4d deposition in peritubular capillaries, ABMR can present acutely, chronically, or subclinically, often manifesting as graft dysfunction. Recent advances in genomic profiling and diagnostic assays have improved our understanding of its pathophysiology, yet therapeutic strategies remain limited. Early detection through routine monitoring and timely intervention, particularly in subclinical ABMR, may improve outcomes. In this review, we provide an in-depth analysis of ABMR in kidney transplantation, with a particular emphasis on recent insights into its immunopathogenesis—emphasizing the dynamic crosstalk between innate and adaptive immunity and its implications for allograft injury. We also discuss how this evolving understanding is reshaping current diagnostic approaches and informing the development of innovative therapeutic strategies. Key findings from recent literature underscore the need for a more integrated approach that bridges mechanistic insight with clinical application, aiming to improve diagnostic precision and long-term graft outcomes.
To date, all large-scale randomized controlled trials for COVID-19 vaccines have excluded solid organ transplant recipients; therefore, the effectiveness and safety of COVID-19 vaccines in preventing coronavirus infection using COVID-19 vaccines in patients with heart transplants have not been sufficiently studied. This paper presents the characteristics of humoral and cellular immunity in heart transplant recipients following vaccination against coronavirus infection. The study group consisted of 40 patients who underwent orthotopic heart transplantation between 2019 and 2014. They were vaccinated twice with the Vero Cell vaccine (China) or received a 3-dose vaccination with Gam-COVID-Vac (Sputnik V, Russia) booster. 63% of vaccinated individuals with no previous COVID-19 history and 85% of patients with a history of COVID-19 were to develop humoral post-vaccination immunity. The humoral response in patients who seroconverted before vaccination showed high level of virus-specific IgG antibodies to SARS-CoV-2 S protein during the post-vaccination period, with a statistically increase observed 9-12 months after the booster. The specific cellular response to the SARS-CoV-2 S and N proteins remained low throughout the entire follow-up period, and was recorded in 5-40% of heart transplant recipients. A significantly increased number of S- and N-specific T cells was observed 4-6 months after the secondary immunization. Starting from 21-28 days after the primary vaccination and continuing for a year after the booster, increased plasmablasts (CD27highCD38high B cells) were observed, correlating with neutralizing and spike-specific antibodies. In heart transplant recipients, vaccination against coronavirus infection does not result in increased serum autoantibodies (RF-IgG and IgA-RF, anti-SSR, cardiolipin IgG, β2-glycoprotein IgG, ANA, ANCA-Pro, anti-SLA/LP, anti-GD-IgA). In our study, vaccinated heart transplant recipients with a history of coronavirus infection showed an increased level of anti-IFN-α antibodies for 9-12 months after the basic vaccination. This finding, when associated with HLA alleles, must be taken into account for identifying patients at a potential risk of a severe disease.
Though the role of clinical histocompatibility testing is fundamental to successful transplant, systematic risk assessment and mitigation strategies remain underutilised in this domain. This review addresses risk identification, analysis, and control measures across the pre-analytical, analytical, and post-analytical phases of clinical histocompatibility testing, in line with international standards such as ISO 15189:2022. A structured, risk-based quality management system (QMS) is imperative for ensuring accurate testing, timely reporting, and subsequently optimal transplant outcomes. Future directions include leveraging digital tools and fostering a culture of continuous improvement in histocompatibility laboratories.
Home-based hematopoietic stem cell transplantation (HCT) is an innovative care model with growing interest, but its impact on the gut microbiome remains unexplored in a randomized setting. We present interim results from the first randomized controlled trials (RCT) evaluating the effect of HCT location-home versus hospital-on gut microbial diversity and antimicrobial resistance (AMR) gene carriage. We hypothesize that patients randomized to undergo home HCT would have higher gut taxonomic diversity and lower AMR gene abundance compared to those undergoing standard hospital HCT. We analyzed stool samples from the first 28 patients enrolled in ongoing Phase II RCTs comparing home (n = 16) and hospital (n = 12) HCT at Duke University using shotgun metagenomic sequencing to compare taxa and AMR gene composition between groups. We also performed a secondary analysis comparing patients who received transplants at outpatient infusion clinics versus inpatient standard HCT to evaluate the influence of hospitalization duration. In the primary RCT analysis, taxonomic and AMR gene α- and β-diversity were comparable between home and hospital groups, reflecting similar durations of hospitalization despite group allocation. In contrast, secondary analyses demonstrated that patients transplanted in outpatient infusion clinics who experienced significantly reduced hospitalization had higher gut taxonomic α-diversity and differential β-diversity, although AMR gene diversity remained unchanged. In summary, randomization by transplant location did not impact the gut microbiota to the same extent as the duration of hospitalization, although secondary analyses were heavily confounded. Even when taxonomic differences were observed, AMR genes were similar between groups. This RCT represents a novel investigation into how care setting influences the gut microbiome during HCT. Our findings suggest that hospital duration, rather than randomization allocation alone, is the primary driver of microbial disruption. These results underscore the potential for reducing hospital duration to mitigate microbiome injury, thereby informing future interventions to reduce infection risk and improve patient outcomes.
Primary mediastinal large B-cell lymphoma (PMLBCL) is an aggressive B-cell malignancy that may exhibit resistance to standard chemoimmunotherapy. Novel immunotherapeutic strategies, including checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapy, are being explored in cases that are refractory to treatment. We report the case of a 29-year-old patient with refractory PMLBCL who was treated with pembrolizumab as a bridging therapy followed by axicabtagene ciloleucel (CAR-T) after failing R-CHOP and R-DHAP regimens. Initial disease progression following pembrolizumab was consistent with an immune-related flare phenomenon. Subsequent CAR-T infusion led to a complete metabolic response. Immunologic monitoring revealed expansion of CD3+ and CD56+ lymphocyte subsets, suggesting immune activation. Notably, the patient maintained normal endocrine function and conceived spontaneously three years post-treatment, delivering a healthy infant at term. This case highlights the potential synergy between checkpoint inhibition and CAR-T cell therapy in refractory PMLBCL, providing rare evidence of preserved fertility following intensive immunotherapy. Early recognition of immune flare and multidisciplinary management are critical in optimizing outcomes for young patients receiving novel immunotherapeutic approaches.
While heart transplantation is increasingly performed in the United States for elderly patients, survival outcomes have primarily been analyzed in single-center studies. The few existing long-term studies have indicated no difference in HTx outcomes between patients ≥70 years and 60-69 years age, but these studies only assessed to 5-years post-transplant and included data from the 1980-90s, introducing significant variance due to poorer outcomes in that era. We analyzed the UNOS database from 1987-2020, stratified by timeframe at 2000, to derive a more representative comparison of modern HTx survival outcomes. All UNOS HTx recipients over 18 years of age (n = 66,186) were divided into 3 cohorts: 18-59, 60-69 and ≥70 years old. Demographic data as well as perioperative factors were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve and cox regressions with log-rank tests were used to assess 5 through 10 years survival outcomes. 45,748 were 18-59 years old, 19,129 were 60-69 years old and 1,309 were ≥70 years old. The distribution of most demographic and perioperative factors significantly differed between cohorts. Pairwise survival analysis involving the 18-59 cohort always indicated significance. While there was no significance between the two older cohorts in the earlier timeframe, there was significance in the later timeframe from 6-10 years post-HTx (p < 0.05). Cox regressions confirmed results. The results indicate that since 2000, recipients 60-69 years of age have better 6 through 10-year post-transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.
