Search Results (337)

Autologous stem cell transplantation (ASCT) after high-dose chemo-therapy (HDCT) is an option of consolidation therapy in patients with AML, lymphoma, or myeloma. Clonal hematopoiesis (CH) is a premalignant state, associated with an increased risk of hematological cancer. The incidence of CH in patients with AML, myeloma, and lymphoma and its effect on the outcome after HDCT/ASCT remain poorly studied. Here we screened 142 patients treated with HDCT/ASCT between 2002 and 2021 at Bern University Hospital for somatic gene mutations in ASXL1, DNMT3A, JAK2, TET2, and TP53. CH-associated somatic gene mutations were detected in 14/31 AML patients (45%), 13/64 myeloma patients (20%), and 9/47 lymphoma patients (19%). Clinical characteristics, treatment modalities, and responses to treatment were similar in patients with and without CH. Patients with CH-associated gene mutations had higher relapse rates and reduced progression free survival, most evident in lymphoma patients (p = 0.007). Overall survival tended to be shorter in lymphoma patients with CH-associated mutations (p = 0.078), whereas this was not observed in AML and myeloma patients. Survival in lymphoma patients with CH was inferior, which may have an impact on post-transplant surveillance strategies in the future. In contrast, survival outcomes were not associated significantly with CH in AML and myeloma patients in our study. Longer follow-ups and larger cohorts will be needed to validate our observations. Full article

Introduction and Aim: Renal transplant recipients face significant long-term graft and patient loss due to post-transplant malignancies. This study aimed to characterize post-transplant malignancies, determine mortality risk factors, and evaluate patient outcomes. Materials and Methods: This retrospective study included 2052 kidney transplant recipients who underwent transplantation between 1976 and 2019 at our institution, other national centers, or international facilities, and who had at least six months of follow-up. Regardless of the transplant center, all patients were followed exclusively at our nephrology department for post-transplant care. A comprehensive review of patient files was conducted, encompassing demographic data, malignancy type and treatment, mortality rates, tissue compatibility assessments, viral serology results, immunosuppression protocols, acute rejection history, and pre-transplant malignancies. The relationships between these variables and mortality were examined. Results: A total of 167 malignant events were observed in 163 patients out of 2052 renal transplant patients (7.9%). The female patients comprised 34.4% (n = 56) of the participants. Ages at transplantation and malignancy diagnosis had medians of 40.0 (13–72) and 50.0 (23–78) years, respectively. The leading malignancy was skin cancer at 30.0%, with Kaposi sarcoma at 11.3% and post-transplant lymphoproliferative disease at 10.6% following. Of the patients followed up, 58.9% (93 patients) had mortality. In univariate analysis, older age at transplant, older age at malignancy diagnosis, and male sex were associated with mortality; however, no independent predictors were identified in the multivariate model (all p > 0.05), likely due to sample size limitations and inter-variable collinearity. Mortality showed statistically significant associations (p < 0.05) with increased age at transplantation, increased age at malignancy diagnosis, and male gender. Conclusions: Post-transplant malignancies significantly compromise both graft longevity and patient survival. Particularly aggressive skin cancers demand heightened clinical vigilance. Early detection through regular dermatological screening, patient education, and timely biopsies must become integral to long-term transplant care protocols. Full article

Despite improvements in kidney transplantation rates, the shortage of donor kidneys remains a critical issue, exacerbated by non-utilization of recovered kidneys due to quality concerns, necessitating advancements in perfusion methods to enhance graft outcomes and usage. Although static cold storage remains the default standard for kidney preservation, newer methods like hypothermic machine perfusion have shown improved outcomes, including reduced delayed graft function and better survival rates. Hypothermic oxygenated machine perfusion and normothermic machine perfusion offer some potential clinical benefits but studies to date have demonstrated mixed results. In the United States, LifePort and the XVIVO’s Kidney Assist Transport are the most popular hypothermic perfusion devices, with NMP devices mostly in trials. Combining perfusion with biomarkers such as mitochondrial flavin mononucleotide, neutrophil gelatinase-associated lipocalin, and osteopontin shows promise in assessing kidney viability and predicting post-transplant outcomes, though further research is also needed. Emphasis on repair biomarkers, such as uromodulin and osteopontin, aims to better predict graft outcomes and develop new therapies. While notable advancements have been made in the use of machine perfusion and viability testing for liver transplantation, additional research with larger sample sizes is essential to substantiate these results and enhance kidney transplantation outcomes. Full article

Introduction: Tacrolimus is a cornerstone immunosuppressant in kidney transplantation (KT), but its narrow therapeutic index necessitates precise monitoring. Early post-transplant tacrolimus trough concentrations (C0) are critical, as suboptimal levels can increase rejection and infection risks. This study evaluated the impact of C0 levels at discharge on early post-transplant outcomes in a large Korean cohort. Materials and Methods: This retrospective analysis included 5293 KT recipients from the Korean Organ Transplant Registry (KOTRY) who received a kidney transplant between 2014 and 2019. Recipients were categorized into three groups based on C0 levels at discharge: <5.9 ng/mL, 5.9–9.5 ng/mL, and >9.5 ng/mL. Clinical outcomes, including serum creatinine (sCr), biopsy-proven acute rejection (BPAR), and infections requiring hospitalization, were analyzed using the Kruskal–Wallis test and chi-squared test. Results: The BPAR rates were 22.5%, 20.9%, and 21.5% for the low, middle, and high C0 groups, respectively (p = 0.221). However, the incidence of infections requiring hospitalization was significantly higher in the high C0 group (28.1%) compared to the middle (23.9%) and low (21.7%) groups at 1-year follow-up (p < 0.001). In high-risk recipients, lower C0 levels correlated with increased BPAR rates (33.9% vs. 29.1% and 26.4%, p = 0.030). Higher intrapatient variability (IPV) between discharge and 6 months was linked to higher infection risk in all recipients and increased BPAR and infection risk in high-risk patients. Conclusions: Optimal C0 levels at discharge are essential to balance rejection and infection risks in KT. Lower C0 levels and higher IPV increase the risk of adverse outcomes, especially in high-risk sensitized recipients, underscoring the need for careful monitoring and personalized management. Full article

Background: Graft-versus-host disease (GVHD) is a rare but serious complication following solid organ transplantation (SOT), particularly in transplants involving organs with a high volume of passenger donor T-lymphocytes. This case highlights the clinical course and diagnostic challenges of GVHD following simultaneous pancreas and pre-emptive kidney transplantation. Methods: A 51-year-old male with long-standing type 1 diabetes mellitus underwent simultaneous pancreas and kidney transplantation with induction therapy using rabbit anti-thymocyte globulin and methylprednisolone. Three months post-transplant, he presented with a diffuse lichenoid cutaneous eruption. Diagnostic evaluation included an extensive infectious workup, skin punch biopsy, liver and bone marrow biopsies, and microchimerism assay. Results: Skin biopsy revealed interface vacuolar dermatitis consistent with cutaneous GVHD. Subsequent liver and bone marrow biopsies confirmed GVHD involvement, with microchimerism assay showing 43% donor-origin T-cells in the bone marrow. Initial treatment with systemic and topical corticosteroids led to temporary improvement. However, the patient developed bone marrow suppression, recurrent bacteremia, and invasive fungal infection, resulting in a prolonged ICU stay and ultimately death. Conclusions: This case underscores the importance of considering SOT-GVHD in patients receiving organs rich in donor lymphocytes, such as pancreas transplants. Early recognition and multidisciplinary management are critical to improving outcomes in this rare but life-threatening condition. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Background Sex disparity has been highlighted in personalized medicine for various human diseases including acute/chronic liver diseases. In the transplant community, greater graft failure risk in female-to-male liver transplantation (LT) has been repeatedly reported, and a recent study in living donor LT reported that the inferiority of female-to-male LT is shown only when donor age is ≤40 y. We aimed to analyze the United Network for Organ Sharing (UNOS) database to test if the poorer outcome of female-to-male LT changes by donor age of 40 y in deceased donor LT, as shown in living donor LT. Methods In this retrospective cohort study, 11,752 adult patients in the UNOS registry who underwent deceased donor LT between 2000–2023 were analyzed. Multivariable analysis was performed to adjust the effects from transplant years, graft ischemia time, disease severity, and others. The primary outcome was graft failure. Results Within the subgroup of recipients with ≤40 y donors, graft failure risk was significantly greater in female-to-male LT than others (vs. female-to-female, HR = 1.43 [1.16–1.76], p < 0.001; vs. male-to-female, HR = 1.46 [1.18–1.81], p < 0.001; vs. male-to-male, HR = 1.26 [1.16–1.49], p = 0.009). In contrast, within the subgroup of recipients with >40 y donors, the risk was comparable between female-to-male LT and other donor-recipient sex groups (vs. female-to-female, p = 0.907; vs. male-to-female, p = 0.781; vs. male-to-male, p = 0.937). We tested various cutoff donor ages and determined that 40 y is the best cutoff value to define the risk subgroup in female-to-male LT. Conclusions In the current study, we found that the sex disparity shown in living donor LT is also observed in deceased donor LT. That is, post-transplant graft failure risk was greater in female-to-male LT than other donor–recipient sex groups only when donor age was ≤40 y. In contrast, graft failure risk was comparable irrespective of donor-recipient sex combinations when donor age was >40 y. Full article

Background/Objectives: Heart transplantation is a life-saving procedure for patients with end-stage heart failure, yet it involves significant psychological and emotional challenges throughout its various stages. International guidelines recommend a multi-professional approach to the care of these patients and a psycho-social assessment for listing. The recommendations focus on content aspects, but not on the psychometric measure to be administered to patients as part of the assessment. Therefore, the purpose of this study is to provide the preliminary results of administering the protocol used by our center, measuring coping strategies, cognitive functioning, quality of life, and psychological distress in a sample of patients who are candidates for and undergo cardiac transplantation, and to observe any variations after the procedure. Methods: We conducted a comprehensive psychological-clinical assessment involving 40 patients, focusing on psychosocial functioning, cognitive reserves, mental health, and coping strategies. Tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Beck Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), General Anxiety Disorder 7 (GAD-7), and Medical Outcomes Survey Short Form 36 (SF-36) were employed to evaluate readiness for transplantation and post-transplant adaptation. Results: Results showed high levels of clinical anxiety (52.5%) and low perceived physical health (98%) before the transplant, while post-operative evaluations indicated reduced anxiety (13.51%) and depressive symptoms (10.81%), along with improved psychological well-being and reintegration into daily life. Conclusions: These results show improvement in physical and cognitive levels, accompanied by a state of enhanced psychological well-being after transplantation. A longitudinal psychological approach, from pre-transplant screening to post-discharge follow-up, is needed to address distress, improve coping mechanisms, and promote treatment adherence. This integrative strategy is critical to improving the quality of life and long-term outcomes for heart transplant recipients. Full article

Background/Objectives: Pediatric allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicated by iron overload and hypomagnesemia, both contributing to immune dysfunction and post-transplant morbidity. The combined impact of these metabolic disturbances on pediatric allo-HSCT outcomes remains unexplored. This study aims to determine whether hypomagnesemia can serve as a prognostic biomarker for delayed immune reconstitution and explores its interplay with iron overload in predicting post-transplant complications and survival outcomes. Methods: A retrospective analysis was conducted on 163 pediatric allo-HSCT recipients. Serum magnesium levels were measured at defined intervals post-transplant, and outcomes were correlated with CD4+ T cell recovery, time to engraftment, incidence of graft-versus-host disease (GVHD), and survival within 12 months. Iron status, including siderosis severity, was evaluated using imaging and laboratory parameters obtained from clinical records. Results: Patients who died within 12 months post-transplant exhibited significantly lower magnesium levels. Hypomagnesemia was associated with delayed CD4+ T cell recovery, prolonged engraftment, and an increased risk of acute GVHD. A strong inverse correlation was observed between magnesium levels and the severity of siderosis. Iron overload appeared to exacerbate magnesium deficiency. Additionally, the coexistence of hypomagnesemia and siderosis significantly increased the risk of immune dysfunction and early mortality. No significant association was found with chronic GVHD. Conclusions: Hypomagnesemia is a significant, early predictor of poor outcomes in pediatric allo-HSCT, particularly in the context of iron overload, underscoring the need for early intervention, including iron chelation and MRI, to improve outcomes. Full article

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization. Full article

Kidney transplant recipients face a substantial burden of premature mortality and morbidity, primarily due to persistent inflammation, cardiovascular risk, and nutritional deficiencies. Traditional nutritional interventions in this population have either focused on supplementing individual nutrients—often with limited efficacy—or required comprehensive dietary overhauls that compromise patient adherence. In this narrative review, we explore the rationale for dietary nut enrichment as a feasible, multi-nutrient strategy tailored to the needs of kidney transplant recipients. Nuts, including peanuts and tree nuts with no added salt, sugar, or oil, are rich in beneficial fats, proteins, vitamins, minerals, and bioactive compounds. We summarize the multiple post-transplant challenges—including obesity, sarcopenia, dyslipidemia, hypertension, immunological dysfunction, and chronic inflammation—and discuss how nut consumption may mitigate these issues through mechanisms involving improved micro-nutrient intake (e.g., magnesium, potassium, selenium), lipid profile modulation, endothelial function, immune support, and gut microbiota health. Additionally, we highlight the scarcity of randomized controlled trials in high-risk populations such as kidney transplant recipients and make the case for studying this group as a model for investigating the clinical efficacy of nuts as a nutritional intervention. We also consider practical aspects for future clinical trials, including the choice of study population, intervention design, duration, nut type, dosage, and primary outcome measures such as systemic inflammation. Finally, potential risks such as nut allergies and oxalate or mycotoxin exposure are addressed. Altogether, this review proposes dietary nut enrichment as a promising, simple, and sustainable multi-nutrient approach to support cardiometabolic and immune health in kidney transplant recipients, warranting formal investigation in clinical trials. Full article

Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival and quality of life (QoL) advantages compared to dialysis for this demographic. Nevertheless, key determinants such as frailty, physical functionality, and cognitive function have emerged as critical predictors of post-transplant success. Despite their relevance, standardized methodologies for evaluating these parameters in transplantation candidacy remain absent. This systematic review examines the influence of frailty, physical functionality, and cognitive function on outcomes in elderly kidney transplant recipients. Methods: Adhering to PRISMA guidelines, a rigorous literature search was conducted across PubMed, CINAHL, Embase, PsycINFO, and the Web of Science for studies published up to October 31, 2024. Relevant studies focused on elderly transplant candidates and examined correlations between frailty, physical functionality, or cognitive function and post-transplant outcomes. The Newcastle–Ottawa Scale was employed to evaluate studies quality. Results: Seven studies met the inclusion criteria. Five explored physical functionality, demonstrating that better pre-transplant physical performance predicts enhanced survival. Two studies addressed frailty, utilizing the Fried frailty phenotype, and linked frailty to elevated mortality and diminished QoL recovery. Notably, no studies explored cognitive function in elderly kidney transplant candidates or recipients and its association with post-transplant outcomes, exposing a salient gap in the literature. The included studies’ varied methodologies, reliance on single time-point assessments, and exclusive focus on kidney transplant recipients restrict both comparability among studies and the generalizability of findings to the broader end-stage renal disease (ESRD) population. Conclusions: These findings underscore the profound impact of physical functionality and frailty on transplant outcomes in the growing elderly kidney transplant population, illuminating the necessity for standardized assessment protocols and targeted pre-transplant interventions. The critical gap in cognitive function research underscores a vital direction for future investigation. This research received no external funding. This review is registered with PROSPERO under registration ID CRD42025645838. Full article

Background/Objectives: Renal transplantation (RT) represents the optimal treatment for end-stage renal disease (ESRD), offering improved quality of life and restored fertility in women post-transplant. While post-transplant pregnancies are possible, they can lead to complications including pre-eclampsia, graft dysfunction, and other adverse outcomes. This study evaluates existing literature to assess pregnancy’s impact on kidney transplantation outcomes, specifically long-term graft function and survival. Methods: We conducted a systematic review of English-language literature from January 2000 to September 2023 across multiple databases, following PRISMA guidelines. We established inclusion criteria focusing on graft function and adverse events. Two independent reviewers performed data extraction, and we assessed risk of bias using the ROBINS-I tool. Results: From 4917 articles, we included 26 studies encompassing 1202 pregnancies in 902 kidney transplant recipients. Mean maternal age was 30.8 years, with an average interval of 52 months between transplant and pregnancy. Pre-pregnancy hypertension occurred in 54.2% of cases, and pre-eclampsia developed in 25.7%. The live birth rate reached 70.5%, while miscarriage, stillbirth, and neonatal death rates were 11.3%, 2.7%, and 2.5%, respectively. We noticed graft dysfunction during pregnancy in 20.2% of cases. Though kidney function often deteriorated temporarily, most patients recovered post-delivery. Discussion: Post-transplant pregnancies remain viable but high-risk, with elevated rates of obstetric complications. Our findings highlight the need for standardized data collection and reporting to better understand and manage pregnancy’s impact on graft outcomes. Conclusions: With appropriate management, pregnancy in kidney transplant recipients is feasible, though it carries elevated risks of obstetric complications. We recommend further multicenter studies with standardized data collection to improve understanding and outcomes. Full article

Although transplantation remains the gold-standard treatment for patients with end-organ failure, lifelong adherence to immunosuppressant medication is required to prevent rejection, graft failure, and mortality. Given the increase in thoracic organ transplantation, it is crucial to better understand the associated barriers to treatment. Examining sociodemographic, transplant, healthcare access, post-transplant treatment, and patient-related psychosocial factors may help to elucidate treatment barriers that have not been previously considered in the existing literature. This single-site cross-sectional study surveyed 65 thoracic (heart and lung) transplant recipients (mean age: 62 years; 76.2% male; 72.3% White, and 21.5% Black) via phone interviews. Immunosuppressant nonadherence was found in 49.2% of participants (46.9% heart, 51.5% lung). In a four-week period, 20% of participants missed at least one dose, 40% did not take their medications on time, and 1% stopped completely. Significant correlates of nonadherence included poorer diet quality, fewer comorbidities, and maladaptive coping responses to perceived discrimination. This preliminary study highlights the importance of considering the social determinants of health—particularly post-transplant treatment and psychosocial patient-related factors—to inform post-transplant care. Addressing such variables may improve medication adherence and, subsequently, overall health outcomes. Further research with larger samples is needed to better understand the associated correlates and inform effective interventions for enhanced medication adherence. Full article

Protocol biopsies are a fundamental component in the management of kidney transplant recipients, offering critical insights into graft health by detecting subclinical pathological changes undetectable through routine clinical and laboratory assessments. Conducted at predetermined intervals, these biopsies enable early identification of subclinical rejection, chronic allograft nephropathy, drug-induced toxicities, viral infections such as BK polyomavirus nephropathy, and recurrence of primary glomerular diseases. Early detection facilitates timely therapeutic interventions, including immunosuppressive regimen adjustments, which are pivotal in preserving graft function and improving long-term outcomes. While the optimal timing and frequency of protocol biopsies vary, early post-transplant biopsies within the first year are widely advocated. High-risk groups, including ABO- and HLA-incompatible recipients and those with recurrent primary nephropathies, particularly benefit from surveillance biopsies. Despite the invasive nature and associated risks of biopsy procedures, most experts agree that the benefits outweigh the risks in selected populations. However, the role of routine protocol biopsies in low-risk patients remains debated due to unclear long-term outcome improvements and resource considerations. Retrospective observational studies have demonstrated the ability of protocol biopsies to detect subclinical pathological changes such as rejection, drug toxicity, viral infections, and recurrent diseases before clinical or laboratory abnormalities appear. These studies also highlight the impact of biopsy-guided interventions on graft survival and management in high-risk groups (e.g., HLA- and ABO-incompatible recipients, and patients at risk for disease recurrence). Furthermore, randomized controlled trials provide higher-level evidence showing that protocol biopsy-guided interventions improve graft function, reflected by better serum creatinine levels and glomerular filtration rates, compared to indicated biopsies alone. They also emphasize the importance of both early and late surveillance biopsies for predicting long-term outcomes. Expert opinion and consensus acknowledge the benefits of protocol biopsies for early detection and tailored management but also highlight ongoing debates regarding their routine use in low-risk patients due to risks, costs, and resource considerations. Overall, protocol biopsies represent a valuable tool for personalized graft monitoring and management, aiding in early detection of complications, guiding immunosuppressive therapy, and enhancing graft longevity. Further multicenter randomized trials are needed to refine guidelines and optimize their clinical utility. Full article