Search Results (610)

Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients. Full article

Malaria is one of the most severe parasitic diseases worldwide and presents unique challenges in solid organ transplantation (SOT). Donor-derived malaria, although rare, can cause severe morbidity and mortality due to diagnostic delays and the altered immunity of transplant recipients. This manuscript synthesizes available evidence on transmission routes, diagnostic timing, clinical manifestations, geographic variability, and cyclosporin’s mechanistic antimalarial properties, and integrates recommendations from major transplant associations. The findings highlight that global travel and migration have increased donor-derived malaria risk, Polymerase Chain Reaction (PCR) is the most sensitive screening tool, and cyclosporin shows potent in vitro antiplasmodial activity without documented clinical protection. International guidelines consistently emphasize epidemiologic donor screening, risk-based laboratory testing, post-transplant surveillance, and pre-travel prophylaxis. Full article

Introduction: Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, with a subset progressing to locally advanced (laSCC) or metastatic (mSCC) stages. The introduction of anti-PD1 immunotherapy has transformed treatment, but real-world data remain limited, particularly in immunosuppressed patients. Methods: This single-centre, retrospective study included 189 patients with advanced cSCC treated between 2012 and 2022. Demographic, clinical, and treatment data were analyzed to assess clinical management and outcomes before and after the introduction of anti-PD1. Results: Among the 189 patients, 72.5% were male, with a median age of 79 years. Overall, 86 patients presented with laSCC and 103 with mSCC. In 100 patients, a preceding primary cSCC was documented, and its complete resection (R0) was associated with significantly better overall survival (OS) after diagnosis of advanced disease (p < 0.001). Immunosuppressed patients, including organ transplant recipients and those with chronic lymphocytic leukemia (CLL), had significantly reduced OS (p = 0.017 and p = 0.0059, respectively). First-line treatment prior to 2018 predominantly involved surgery and radiotherapy. Following the introduction of anti-PD1 therapy, its use increased rapidly in both first- and second-line settings. From 2018 onward, the number of advanced cSCC cases discussed at the multidisciplinary tumorboard increased approximately threefold. Median OS was significantly longer for mSCC patients treated in the post-2018 era (p = 0.025), while the survival disadvantage of CLL patients compared to non-CLL patients widened, suggesting limited benefit from advances in systemic therapy in this subgroup. Best overall response to first-line anti-PD1 correlated significantly with OS, with complete responders achieving a 1-year progression-free survival of 83.3%. Conclusions: The introduction of anti-PD1 has demonstrated improved survival outcomes in advanced cSCC, though significant challenges remain for immunosuppressed patients, particularly those with CLL and solid organ transplant recipients. Future research should focus on optimizing treatment for these high-risk groups, therapeutic sequencing, and the role of perioperative (neoadjuvant and adjuvant) immunotherapy strategies. Full article

Background/Objectives: Prostate cancer is one of the most common non-skin solid malignancies among male solid organ transplant recipients (SOTRs), in whom radical prostatectomy is technically demanding. We report the first use of indocyanine green (ICG) fluorescence for simultaneous transplanted-ureter identification and renal graft vascular mapping during robot-assisted radical prostatectomy (RARP), and the first use of the CMR Versius^® platform in a SOTR. Methods: Retrospective case series of four consecutive male SOTRs (two renal [RTRs], two hepatic) undergoing RARP. In both RTRs, a dual-route ICG protocol was used on the da Vinci Xi with Firefly^® imaging: pre-docking intraureteral ICG via a ureteral catheter for ureter identification, plus an intravenous ICG bolus for graft vascular mapping and cortical perfusion. One hepatic recipient was operated with the CMR Versius^® system using an infra-umbilical port configuration to avoid the chevron transplant scar. Results: All four procedures were completed robotically without conversion. Median operative time was 176 min and median estimated blood loss 350 mL. Surgical margins were negative (R0) in all four; final pathology was pT3aN0 in three and pT2N0 in one, although in the renal recipients nodal staging reflected a contralateral-only dissection. PSA was undetectable at three months in all patients. One hepatic recipient later developed biochemical recurrence, managed with salvage radiotherapy and androgen deprivation therapy, with subsequent undetectable PSA. One hepatic recipient had a Clavien–Dindo IIIa complication. No graft dysfunction occurred. Conclusions: ICG-guided RARP and the CMR Versius^® platform appear technically feasible in carefully selected solid organ transplant recipients treated at an experienced multidisciplinary centre, with no graft-related complications observed in this small initial series. These preliminary findings require validation in larger, multicenter studies before general safety and oncological efficacy can be established. Full article

(1) Background: Hepatitis E remains a major public health challenge in India. (2) Methods: In August 2025, the recombinant HEV 239 vaccine was approved in India for adults aged 18 to 65 years. To establish clinical guidelines tailored to the Indian setting, an expert panel consensus was conducted using a modified Delphi process in accordance with the ACCORD reporting guidelines. (3) Results: A steering committee put forth 18 statements covering vaccine safety, efficacy, and clinical indications, which were independently evaluated by 33 senior Indian hepatologists and epidemiologists. Consensus was assessed using the GRADE framework for level of evidence, balance of benefits and harms, and strength of recommendations. Of the 18 statements, 12 reached the 70% consensus threshold. The panel concluded that the vaccine, which is administered on a standard three-dose schedule, is safe and highly effective in healthy adults, providing protection for up to 10 years. Targeted vaccination was recommended for five high-risk populations: outbreak-affected groups, hyperendemic pockets, women of childbearing age, patients with CLD, and solid organ transplant recipients. Although derived from HEV genotype 1, the vaccine demonstrated cross-protective efficacy against HEV genotype 4. (4) Conclusions: This consensus report provides a framework for deploying the HEV vaccine to mitigate disease burden in India while emphasizing the need for real-world effectiveness and safety data from India. Full article

The Omicron variant of SARS-CoV-2 is associated with milder symptoms and lower hospitalization and mortality rates than Delta variants, although the impact of Omicron on immunocompromised patients, especially solid organ transplant (SOT) recipients, is still unclear. This study compares the hospitalization rate and outcomes between immunocompromised, immunocompetent, and SOT patients during the Delta and Omicron periods. We included adult patients who tested positive for SARS-CoV-2 on PCR or nasopharyngeal antigen test between 26 June 2021 to 8 September 2022, at our institution. A total of 12,401 COVID-19 patients were included, of which 11,055 were immunocompetent, and 1346 were immunocompromised (375 SOT recipients). Throughout the Delta and Omicron outbreaks, immunocompromised patients exhibited higher comorbidities and 30-day hospitalizations, but rates of mechanical ventilation and ICU-level care were like immunocompetent patients. During the Omicron wave, immunocompromised patients had higher unadjusted relative risk estimates (RR = 2.37, 95% CI 1.96–2.87, p < 0.05) than Delta (RR = 1.58, 95% CI 1.24–2.01, p < 0.05), with higher adjusted relative risk for hospitalization in Omicron (RR = 1.50, 95% CI 1.10–2.03, p = 0.01). Analyses show increased hospitalization risk in immunocompromised during the Omicron wave compared to the Delta wave, with no significant difference in hospitalization outcomes. The relative risk of hospitalization for SOT patients was higher in both waves. Full article

The quality and productivity of tomato (Solanum lycopersicum L.) crops largely depend on the quality of the seedlings used for cultivation. Several factors, including cultivation strategy, fertilization practices, and abiotic and biotic stressors during early plant development, influence seedling quality. Recently, anaerobic digestate has attracted attention as a potential organic fertilizer and substrate component; however, information about its effects on tomato seedling quality remains limited, particularly when comparing different seedling establishment methods such as direct sowing and transplanting. Therefore, this study aimed to evaluate the effects of different concentrations of solid grain waste digestate (further digestate) in the peat substrate on the growth and physiological characteristics of tomato seedlings grown by means of direct sowing and transplanting. The experiment was conducted at the Institute of Horticulture of the Lithuanian Research Centre for Agriculture and Forestry in unheated greenhouses covered with double polymer film. Two cultivation strategies were applied (factor A): transplanting and direct sowing into pots. To evaluate the influence of digestate (factor B), different substrate compositions were used: peat (control) and peat mixed with 10%, 20%, 30%, 40%, and 50% digestate. The strong decline in growth parameters with increasing digestate concentration indicates that higher proportions of digestate created unfavorable conditions for seedling development in both cultivation stategies. A 10% digestate addition improved certain plant characteristics, while 20% improved some physiological indices but was associated with reduced growth. However, higher digestate concentrations (≥30%) negatively affected plant growth and physiological activity. Seedlings grown in substrates with higher digestate levels exhibited reduced transpiration rates and lower gas exchange indices, suggesting impaired water relations and stomatal regulation. These effects were more pronounced in transplanted plants compared with direct-sown seedlings, indicating greater sensitivity to changes in substrate composition after transplanting. Overall, the results demonstrate that digestate can be used as a substrate component for tomato seedling production. Still, its concentration must be carefully optimized to avoid negative effects on plant growth and physiological performance. Full article

Background: Kidney transplantation is the preferred treatment for end-stage kidney disease (ESKD), but long-term outcomes remain limited by chronic allograft injury, infections, metabolic complications, and cardiovascular risk. Gut microbiota alterations and microbiota-derived metabolites may influence immune regulation, inflammation, drug metabolism, and graft outcomes through the gut–kidney axis. This review summarizes evidence on the gut microbiota in kidney transplantation, emphasizing immune tolerance, complications, cardiovascular risk, graft function, and perspectives. Methods: A structured search was conducted in PubMed, Scopus, and Web of Science to May 2026. Eligible publications included studies involving kidney transplant recipients (KTR), kidney disease or solid organ transplant populations, and mechanistic models. Evidence was synthesized narratively. Results: Gut microbiota alterations in KTR reflect pre-transplant dysbiosis and post-transplant exposures, including antibiotics, immunosuppression, infection, diet, hospitalization, and graft function. Dietary factors and nutrient-derived substrates may modulate microbial composition and production of relevant metabolites, including short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), tryptophan-derived compounds, bile acid derivatives, and uremic toxins. Microbiota-related pathways may involve barrier dysfunction, microbial translocation, innate immune activation, altered regulatory T cell/T helper 17 (Treg/Th17) balance, metabolite signaling, uremic toxin generation, and endothelial stress. Clinical studies associate dysbiosis and microbial metabolites with diarrhea, infections, delayed graft function (DGF), rejection-related shifts, tacrolimus variability, cardiovascular risk, graft dysfunction, graft failure, and mortality. Most findings need validation. Conclusions: Gut microbiota signatures and microbial metabolites are promising markers of transplant-related risk, but not established causal determinants or therapeutic targets. Clinical translation requires standardized methods, multi-omics integration, and prospective patient- and graft-centered trials. Full article

Cytomegalovirus (CMV) is a major determinant of post-transplant morbidity in solid organ transplant recipients, not only through direct viral disease but also through a broad spectrum of indirect effects that may adversely influence graft and patient outcomes. This review summarizes current clinical and mechanistic evidence regarding the mechanisms of CMV-associated indirect injury in transplantation, drawing on human observational studies together with supporting in vitro and animal-model data. CMV establishes lifelong latency with intermittent reactivation and exerts sustained immunomodulatory effects on both innate and adaptive immunity, which may persist even during low-level viral replication. The mechanisms discussed include monocyte reprogramming, altered antigen presentation, T-cell and natural killer cell dysregulation, endothelial activation and dysfunction, chronic inflammatory signaling, impaired antimicrobial defense, and disturbances in metabolic regulation. The review considers how these mechanisms have been proposed to translate into major post-transplant complications, including acute rejection, chronic allograft dysfunction, cardiovascular and thrombotic disease, post-transplant diabetes, and increased susceptibility to secondary bacterial, fungal, and viral infections. It also addresses current preventive strategies, although evidence regarding their effectiveness in reducing indirect clinical outcomes remains limited and largely observational. Much of the supporting evidence is associative, and the contribution of CMV is often difficult to separate from that of the overall immunosuppressive burden and the comorbidities of transplant recipients. With these considerations, the available evidence supports regarding CMV not merely as an opportunistic pathogen, but as a persistent immunobiological driver of long-term transplant injury. Improved understanding of these indirect effects may enhance risk stratification, support biomarker-guided prevention, and inform future strategies aimed at reducing long-term graft dysfunction and patient morbidity after transplantation. Full article

Background/Objectives: There is limited data on treatment outcomes under immune checkpoint inhibitor (ICI) administration in solid organ transplant recipients (sOTRs). This study aims to evaluate cancer outcome and allograft rejection risk in sOTRs receiving ICI. Methods: This is a retrospective multicenter study. The data had been collected within the Swiss Transplant Cohort Study (STCS) database. We searched for matching individuals from May 2008 up to the end of 2024. The primary outcomes were treatment response and survival; the secondary outcome was allograft rejection. Additional analyses included associated factors such as tumor, transplant, and treatment characteristics. Results: We identified ten patients, six of whom received a kidney allograft, while the remaining four received a liver, lung, pancreas, or combined kidney–pancreas transplant. Treatment response was achieved in half of the sOTRs, with a complete response (CR) in three and prolonged stable disease (SD) in two patients. CR was achieved in all three patients after only a few infusions. At the time of data analysis, four out of ten patients were still alive. Graft rejection occurred in six out of ten cases, five of which occurred after the first cycle of ICI administration. Conclusions: Data is limited and definitive conclusions from this study cannot be drawn given the limited sample size. However, ICI displays promising effects on cancer outcomes in sOTRs with advanced malignancies. The study’s findings demonstrate an overall response in half of sOTRs, but with graft rejection occurring in a similar number of patients. We propose initiating immunotherapy as early as possible, given the promising results, particularly in patients with kidney transplants. We further suggest that in sOTRs, a few ICI infusions could potentially be a cautious option, pending further evidence. Full article

Heart transplantation remains a vital therapy for patients with end-stage heart failure, yet organ scarcity and evolving allocation policies necessitate robust risk prediction models to optimize outcomes and equity. This narrative review explores the current landscape of risk assessment in heart transplantation, contextualized within the broader framework of solid organ allocation and the emerging continuous distribution (CD) model. While kidney, liver, and lung transplantation have integrated validated risk scores into allocation systems, heart transplantation continues to rely on therapy-based criteria without a unified, benefit-based approach. We examine existing pre- and post-transplant predictive models and highlight their strengths and limitations. Additionally, we discuss the multidimensional factors influencing transplant success, ranging from donor and recipient characteristics to psychosocial and system-level variables. As CD expands across organ types, the development and integration of validated heart-specific risk scores will be essential to ensure equitable and effective organ allocation. Full article

Post-transplant lymphoproliferative disorder (PTLD) involving the central nervous system (CNS) is a rare but serious life-threatening complication seen in recipients of solid organ transplant. Primary CNS encompasses 5–15% of all types of PTLD diagnoses, and heart transplant recipients represent 3–5% of those reported cases. Diagnosis is often delayed due to the highly variable presentation, with some cases remaining undiagnosed for years. Multidisciplinary collaboration is crucial for early diagnosis and management. A 53-year-old woman patient presented with altered mental status. MRI revealed nodular ventriculitis and bilateral periventricular hyperdense infiltrates. CSF studies demonstrated lymphocytic pleocytosis, elevated protein, and EBV-PCR-positive results. A stereotactic brain needle biopsy confirmed the presence of EBV-positive diffuse large B-cell lymphoma, consistent with primary CNS PTLD, 14 months after her heart transplant. Despite appropriate management, the patient experienced progressive neurological decline and ultimately suffered a fatal intracerebral hemorrhage. We demonstrate the importance of the early diagnosis and variable presentation of post-heart-transplant PTLD. The importance of surveillance regardless of EBV status and close monitoring of disease progression due to potential life-threatening complications, such as fatal hemorrhages. Therefore, primary CNS-PTLD remains a challenging disease and is being increasingly recognized with improved transplant recipient survival and prolonged exposure to chronic immunosuppression. Full article

Adoptive cell therapies, and more specifically, regulatory T cell (Treg) therapies, have shown significant therapeutic promise across multiple immune-mediated diseases including graft-versus-host disease (GvHD), solid organ transplant (SOT) rejection, and autoimmune diseases. One key challenge is the lack of insight into the biodistribution and fate of adoptively transferred T cells and Tregs in living organisms. These uncertainties delay progress on establishing optimal dosage(s), infusion timing and route, as well as investigations into off-target effects. Magnetic resonance imaging (MRI) cell tracking is particularly beneficial in this setting because it enables real-time, deep-tissue coverage without ionizing radiation. In this review, we compare existing MRI T cell tracking strategies using iron oxide particles and fluorinated agents. We describe preclinical and clinical applications of MRI for cell therapy tracking and provide a perspective on the potential impact on the field. Full article

Background: Immunosuppressive drugs (ISDs) are essential for preventing organ rejection but have been reported to increase cancer risk with prolonged use. This study compares cancer risk between ISDs used for long-term maintenance after transplantation (T-ISDs) and those prescribed for non-transplant chronic conditions including cell-mediated (C-ISDs) and receptor-mediated (R-ISDs) ISDs. We hypothesized that cancer risk would differ between T-ISDs and both C-ISD and R-ISD groups. Methods: Using the TriNetX database, solid organ transplant recipients treated with tacrolimus (TAC), cyclosporine (CY), rapamycin (RAPA), or mycophenolate (MMF) were compared to propensity-matched R-ISDs (adalimumab, infliximab, etc.) or C-ISDs (methotrexate, azathioprine, etc.) for at least 24 encounters to determine risk of malignancy. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to assess the three-year cancer risk. Results: After matching, T-ISDs were associated with higher malignancy risk compared to both R-ISDs (n = 29,748; HR 2.616, 95% CI 2.427–2.820) and C-ISDs (n = 31,704; HR 1.271, 95% CI 1.195–1.351). Each individual immunosuppressant in the T-ISD cohort was associated with increased cancer risk compared to R-ISDs, while only TAC and CY showed higher risk than C-ISDs (TAC: n = 9846, HR 1.354, 95% CI 1.228–1.492; CY: n = 1801, HR 1.234, 95% CI 1.007–1.512). Organ-specific analyses showed consistent patterns across systems. Conclusions: Overall, T-ISDs are associated with increased malignancy risk compared to R-ISDs and modestly compared to C-ISDs. TAC and CY confer the greatest risk, while MMF demonstrates relatively lower relative risk. These findings underscore the need to individualize ISD regimens to minimize long-term cancer risk. Full article

Background Cytomegalovirus (CMV) infection is a major contributor to morbidity and mortality in recipients of hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), and chimeric antigen receptor T-cell (CAR-T) therapy. While antiviral agents remain the cornerstone of treatment, CMV-specific immunoglobulins (CMVIG) have been utilized as adjunct therapy with variable outcomes. This study aims to evaluate the virological response and tolerability of CMVIG in cases of severe or refractory CMV viremia, with or without CMV disease. Methods: We conducted a single-center retrospective case series of adult recipients of SOT, allogeneic HSCT, and/or CAR-T cell therapy who developed CMV viremia or disease and received at least one dose of CMVIG between May 2017 and May 2023 at our center. Virological improvement within 14 days of starting CMVIG and tolerability of CMVIG are the primary outcome of this study. Results: A total of 33 patients were included. Of these, 29 underwent transplantation [SOT: 48.2%, HSCT: 51.7%], and five underwent CAR-T cell therapy (one post-HSCT). High-risk CMV serostatus was present in 12%. CMV viremia was documented in 32 patients (97%), and tissue-invasive disease was present in 11 patients (33.3%). Virological response, was observed in 65.6% of the cohort. The median time to undetectable CMV viral load following CMVIG initiation was 28 days. CMVIG was well-tolerated. All-cause mortality at 90 days remained high (57%). Conclusion: In this case series, CMVIG demonstrated a virological response rate of 65.6% in patients with severe or refractory CMV infection. While CMVIG was well-tolerated with minimal adverse events, the high mortality rate despite virological response suggests that CMVIG may be insufficient for this critically ill population. Our findings should be interpreted as observational data from a small case series, and prospective controlled trials are needed to establish the true benefit of CMVIG in combination with standard antiviral therapy. Full article