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In solid organ transplant recipients (SOTRs), the oncogenic virus human herpesvirus-8 (HHV-8) also named Kaposi sarcoma herpesvirus (KSHV) causes four clinical diseases: Kaposi Sarcoma, Primary Effusion Lymphoma, Multicentric Castleman Disease (MCD), and KSHV inflammatory cytokine syndrome (KICS). This review outlines these clinical scenarios and discusses their management. Although HHV8-related disease in SOTR was first described more than three decades ago, there is a lack of data on treatment so much of the guidance is based on evidence in other immunodeficient patients, particularly people living with HIV. Whilst reduction of immunosuppression and switch from calcineurin inhibitors to mTOR inhibitors may be sufficient in early-stage post-transplant KS, systemic chemotherapy is necessary for advanced-stage KS and in KSHV-related lymphomas. For MCD and KICS, which usually follow primary HHV-8 infection, rituximab-based immunochemotherapy regimens are the cornerstone of treatment for these potentially lethal diseases. Although HHV-8 infection in SOTR is well recognized, it remains under-reported and greater awareness of the different clinical presentations of HHV-8 in this context is fundamental to improve outcomes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest that could have influenced this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

The growing number of organ donors in the United States, from 14,011 in 2012 to 21,374 in 2022, highlights progress in addressing the critical issue of organ shortages. However, the demand remains high, with 17 patients dying daily while on the waiting list. As of August 2023, over 103,544 individuals are awaiting transplants, predominantly for kidneys (85.7%). To expand the donor pool, the inclusion of elderly donors, including those with a history of malignancies, is increasingly considered. In 2022, 7% of all donors were aged 65 and above, despite the complexities their medical histories may introduce, particularly the risk of donor-transmitted cancer (DTC). This review examines the challenges and potential benefits of using donors with known malignancy histories, balancing the risks of DTC against the urgency for transplants. A critical analysis is presented on current knowledge and the decision-making processes that consider cancer types, stages, and patient survival outcomes. The goal is to identify missed opportunities and improve strategies for safe and effective organ transplantation from this donor demographic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Turra, Manzi, Rombach, Zaragoza, Ferreira, Guerra, Conzen, Nydam, Livingstone, Vianna and Abreu.)

BACKGROUND Infection is a cause of morbidity and mortality in solid-organ transplantation (SOT). We evaluated a new score that is applied during the first month after transplantation. The score comprises biomarkers of innate and acquired immunity to predict infections in SOT. MATERIAL AND METHODS Prospectively collected blood samples from 377 heart, liver, or kidney recipients were analyzed at 2 centers in Madrid (Spain) and Lima (Peru). Biomarkers were tested before transplantation and at days 7 and 30 after transplantation. During the first 6 months after transplantation, 183 (48.5%) patients developed severe infections (bacterial infections and/or CMV disease). Risk for severe infection was assessed using logistic regression analysis. We designed a score, the routine immunity score (RIS2020), which is based on the sum of the hazard ratios (HRs) of each biomarker. RESULTS The risk factors for severe infection were as follows: Moderate IgG hypogammaglobulinemia (IgG <600 mg/dL at days 7 or 30, HR 2.07, 95% CI 1.37-3.12, p=0.0005, 2 points), CD4 <400 cells/uL at day 30 (HR 1.76, 95% CI 1.03-3.04, p=0.039, 2 points), C3 <80 mg/dL at day 30 (HR 2.18, 95%CI 1.16-4.06, p=0.014, 2 points), and CRP >3 mg/dL at day 30 (HR 2.11, 95% CI 1.12-3.97, p=0.02, 2 points). In patients with ≥4 points, the HR for infection was 5.18 (95% CI 3.06-8.75; p<0.001). RIS2020 was an independent predictor of severe infection in multivariate models. CONCLUSIONS An immunological score combining moderate IgG hypogammaglobulinemia and other parameters of innate and acquired immunity could better identify the risk for severe infection in SOT.

Introduction: Organ transplant recipients face a substantial risk of developing posttransplant lymphoproliferative disorders (PTLD). In over 90% of cases with B-cell PTLD following solid organ transplantation, the Epstein-Barr virus (EBV) genome is promptly identified, usually within the initial year. A continuing discussion revolves around the efficacy of antiviral prophylaxis in mitigating the incidence of PTLD in solid organ transplant (SOT) patients. This study aimed to conduct a systematic review and meta-analysis to investigate this issue., Method: A comprehensive search was conducted up to December 31, 2023, in databases including PubMed, Embase, and the Cochrane Library for retrospective and prospective studies comparing antiviral prophylaxis effects on EVB viremia and PTLD incidence in SOT recipients. Fixed or random effect models were applied based on the heterogeneity assessed via the I 2 statistic, using Stata 16.0 software for data analysis., Results: In total, 22 eligible studies involving 13,498 patients were analyzed. Antiviral prophylaxis was associated with a significant reduction in EBV viremia incidence in SOT recipients, as demonstrated in 10 studies (relative risk (RR) 0.69, 95% CI 0.54 to 0.88). The rate of PTLD was significantly lower among those who received antiviral prophylaxis compared to those who did not, as reported in 18 studies (RR 0.77, 95% CI 0.63 to 0.94). No significant difference was observed in the subgroup of high-risk recipients based on EBV serology (RR 1.13, 95% CI 0.72 to 1.78). Additionally, a notable reduction in PTLD incidence was seen in the pediatric subgroup (RR 0.58, 95% CI 0.43 to 0.79) using antiviral prophylaxis, while no significant differences were observed in the subgroup of adults (RR 0.88, 95% CI 0.64 to 1.21). Administration of antiviral prophylaxis can significantly reduce the incidence of PTLD among kidney (RR 0.63, 95% CI 0.46 to 0.87) and heart transplant patients (RR 0.61, 95% CI 0.39 to 0.96). PTLD incidence was significantly reduced among recipients of T-cell depletion or steroid-based immunosuppression using antiviral prophylaxis (RR 0.54, 95% CI 0.39-0.74 and RR 0.55, 95% CI 0.41-0.73, respectively)., Conclusion: This meta-analysis revealed that administering antiviral prophylaxis to patients after solid organ transplantation reduces PTLD and EBV viremia occurrences, especially among pediatric recipients, individuals undergoing kidney or heart transplantation, and those receiving high-intensity immunosuppression regimens. Post-transplant lymphoproliferative disorders (PTLD) and other EBV syndromes are among the most serious complications following solid organ transplantation (SOT), primarily due to the necessity for prolonged immunosuppressive therapy. Among the strategies for preventing EBV-related complications, the use of antiviral prophylaxis is a subject of ongoing debate. This systematic review and meta-analysis found that antiviral prophylaxis significantly reduced EBV viremia incidence (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.54 to 0.88) compared to those without prophylaxis. In the sub-analysis related to high-risk EBV serologically mismatched SOT recipients (EBV D+/R-), the result did not show a significant difference in terms of PTLD incidence (RR 1.13, 95% CI 0.72 to 1.78). Antiviral prophylaxis significantly impacted the occurrence of PTLD events among pediatric SOT patients (RR 0.58, 95% CI 0.43 to 0.79), but not among adult patients (RR 0.88, 95% CI 0.64 to 1.21). Antiviral prophylaxis significantly impacted the occurrence of PTLD events among kidney/simultaneous pancreas and kidney (RR 0.63, 95% CI 0.46 to 0.87) and heart (RR 0.61, 95% CI 0.39 to 0.96) transplant patients but not liver  (RR 0.5, 95% CI 0.23 to 1.08) transplant recipients., Competing Interests: Declarations. Declarations: Ethical approval and consent to participate. Not applicable. Consent for publication: This article is authors’ own work and does not need consent for publication from third party. All authors agree with its publication. Competing interest: All authors declare no competing interest., (© 2025. The Author(s).)

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels. In addition, transplant recipients exhibit decreased plasmablasts and transitional B cells, and increased senescent T cells. Blood and nasal transcriptional profiling demonstrate unexpected upregulation of innate immune signaling pathways and increased levels of several proinflammatory serum chemokines. Severe disease in transplant recipients, however, is characterized by a less robust induction of pro-inflammatory genes and chemokines. Together, our study reveals distinct immune features and altered viral dynamics in solid organ transplant recipients., Competing Interests: Competing interests: F.K. has the following financial interests: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines, and influenza virus therapeutics which list Florian Krammer as co-inventor (Patent title and number: Influenza Virus Vaccines and Uses Thereof (Chimeric HA 2) 9,371,366; Influenza Virus Vaccines and Uses Thereof (Chimeric HA 1) 10,131,695; Influenza Virus Vaccines and Uses Thereof (Chimeric HA 2) 2934581; Influenza Virus Vaccines and Uses Thereof (Chimeric HA 2) 9,968,670; Influenza Virus Vaccines and Uses Thereof (Chimeric HA 2) 10,137,189, Influenza Virus Vaccines and Uses Thereof (Chimeric HA 2) 10,583,188; Influenza Virus Vaccines and Uses Thereof (Chimeric HA 1) EP2758075; Influenza Virus Vaccination Regimens (Neuraminidase) 10,736,956; Anti-Influenza B Virus Neuraminidase Antibodies and Uses Thereof 11254733; Influenza Virus Hemagluttinin Proteins and Uses Thereof (Mosaic) 7237344). Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. F.K. is a co-founder and scientific advisory board member of Castlevax. F.K. has consulted for Merck, Curevac, Seqirus, and Pfizer and is currently consulting for 3rd Rock Ventures, GSK, Gritstone, and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development. R.R.M. has a Leadership Councilor role 2018-2021 for the Society of Leukocyte Biology. O.L. has received support as a speaker for presentation regarding the Coronavirus pandemic from Midsized Bank Coalition of Americ (MBCA) and Moody’s Analytics. N.G.R. has research grants from Pfizer, Merck, Sanofi, Quidel, Immorna, Vaccine Company, and Lilly, serves on safety committees for ICON and EMMES and the advisory boards of Moderna, Seqirus, Pfizer, and Sanofi, and is a paid safety consultant for ICON, CyanVac and EMMES. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore, it is of substantial clinical significance to develop immunosuppressants that possess both immunosuppressive and anti-tumor properties. For instance, mTOR inhibitors demonstrate anti-tumor effects among antimetabolite immunosuppressive drugs, and recent studies indicate that capecitabine, an antimetabolite chemotherapeutic, may also exhibit immunosuppressive activity in the clinic for liver transplants suffering from hepatocellular carcinoma. This review systematically explores potential immunosuppressants with dual anti-tumor and immunosuppressive effects to support the management of transplant patients at elevated risk of tumor occurrence or recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Kong, Duan, Chen, Wang, Ren, Lu, Chen, Song, Wu, Chang, Yin, Shen and Zheng.)

Objectives: Solid-organ transplant recipients are prone to infections due to intensive immunosuppression treatments after transplant. Incidence of viral infections is gradually increasing. During the COVID-19 pandemic, transplant patients were shown to be at increased risk of infections. We investigated viral infections in transplant patients before and during the pandemic to guide patient follow-up., Materials and Methods: We collected data of solid-organ transplant recipients ≥18 years old who experienced viral infections during 2019-2023. We analyzed demographic data, transplant types, and clinical outcomes with SPSS software (version 25.0); P < .05 was statistically significant., Results: We analyzed 238 patients (mean age 43.9 ± 14.9 years; 69.7% male) diagnosed with viral infections: 79.8% received kidney transplants, 16.4% liver, and 3.8% heart. The most prevalent virus was SARS-CoV-2 (64.7%), followed by influenza (18.1%) and cytomegalovirus (7.6%). Mean age for heart transplant was lower than among other transplant types (P = .015). Fever, cough, and sputum production were common in influenza infections (P = .012, P = .041, and P = .009, respectively); myalgia and dyspnea were common with SARS-CoV-2 (P = .029 and P = .013, respectively). Rates of bacteremia and intensive care unit admission were high for cytomegalovirus infections (P = .002, P = .031). Thrombocytopenia and bacteremia were detected more frequently for liver transplants (P = .004 and P = .013, respectively). Empirical antibiotic treatment was started in 17.2% of patients. Twenty-nine patients were monitored in the intensive care unit, and 12.1% died. Mortality was significantly higher in patients >65 years old and in the presence of bacteremia (P = .001)., Conclusions: Vaccination, early detection, and preventive strategies play pivotal roles to manage viral infections in solid-organ transplant recipients. Future research should focus on optimized prophylaxis and individualized care plans.

Objectives: Diabetes constitutes a prevalent condition posttransplant, imposing a substantial burden on solid organ transplant recipients, including increased risk of graft loss and reduced overall survival. Consequently, the implementation of effective glycemic control strategies is vital. Tirzepatide, the first dual glucosedependent insulinotropic polypeptide/glucagon-like peptide-1 receptor coagonist, represents a novel therapeutic option in the general population; however, further data are needed to support its use in solid-organ transplant recipients., Materials and Methods: In this retrospective chart review, we examined a cohort of 41 heterogenous patients who were undergoing tirzepatide therapy after solid-organ transplant in Abu Dhabi, United Arab Emirates, from January 2017 to January 2024., Results: Within our study cohort, the median time elapsed from transplant to tirzepatide therapy commencement was 2.91 years (range, 1.04-4.38 y), with use that lasted for a median follow-up duration of 11 months (range, 7-13 mo) until date of data collection. Tirzepatide facilitated optimal glycemic control, elicited significant weight reductions, and improved renal function without adversely affecting graft function or patient survival, showing an adverse effect profile similar to that of the general population, as shown in the literature., Conclusions: Tirzepatide represents a promising therapeutic avenue for management of posttransplant diabetes mellitus and type 2 diabetes mellitus in solidorgan transplant recipients.

Backgruound: Limited data are available on the adverse effects of new-onset diabetes after transplantation (NODAT) in solid organ transplantation (TPL) other than kidney. This study aimed to identify the risk of complications associated with NODAT in recipients of kidney, liver, or heart TPL., Methods: Using the Korean National Health Insurance Service database, recipients of kidney, liver, or heart TPL between 2009 and 2015 were identified. The incidence of coronary artery disease (CAD), cerebrovascular accident (CVA), and malignancy was compared across groups with NODAT, pretransplant diabetes mellitus (DM), and without DM using Cox regression analysis., Results: A total of 9,632 kidney, liver, or heart TPL recipients were included. During the median follow-up of 5.9 years, NODAT independently increased the incidence of CAD (hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.39 to 4.30) and overall mortality (HR, 1.48; 95% CI, 1.14 to 1.95) compared to the reference group even after adjustment for confounders; this was more prominent in kidney TPL than in liver TPL. The risk of CVA was significantly increased by pretransplant DM but not by NODAT in both kidney and liver TPL (HR, 2.47; 95% CI, 1.68 to 3.65; and HR, 3.18; 95% CI, 1.07 to 9.48, respectively). NODAT increased the risk of malignancy in the crude model, which lost its statistical significance after confounder adjustment., Conclusion: NODAT independently increases the risk of CAD and mortality after TPL, which is more evident in kidney recipients. There was no additional increased risk of CVA or malignancy with NODAT in solid organ TPL.

Introduction: Coronavirus disease 2019 (COVID-19) is a life-threatening disease that was declared a pandemic in March 2020. Organ transplant recipients are vulnerable to infection and complications from COVID-19. The objective of this study was to investigate the rates of infection, mortality, and case-fatality ratios (CFR) in solid organ transplant recipients and patients on the waiting list for organ allocation in the period prior to the availability of specific vaccines., Methodology: This was an observational study of official sources that are used to report information on COVID-19. Quantitative variables were described with arithmetic means and categorical variables with proportions. Percentages of positivity to infection, number of deaths, CFR, and all-cause mortality were calculated for each group and subgroup., Results: There were 2,551 eligible subjects; 602 (26.2%) were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There were 265 (10.4%) deaths from all causes during the follow-up period; 119 (44.9%) of them were associated with COVID-19, which indicated a COVID-19-related mortality rate of 4.7 %. CFRs were 21.4% and 17.1% in transplant recipients and waitlisted patients, respectively. CFR was significantly higher in transplant recipients (23.8%) than in patients waitlisted for kidney (16.5%; p = 0.044) Among SARS-CoV-2-positive patients, the probability of dying from COVID-19 was higher in the first group (87.3% and 73%, respectively; p = 0.034)., Conclusions: COVID-19 had a significant impact on the deaths of transplant patients and patients on the solid organ waiting list during the first year of the pandemic in Colombia, before the availability of vaccines., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Yazmin R Arias-Murillo, Maria A Salinas-Nova, Miguel Á Castro-Jiménez, Camilo Montero, Jorge A Cortes.)

Objective: This study aims to assess the efficacy of pharmacological interventions in mitigating graft injury in transplant patients with antibody-mediated rejection (AMR) through a network meta-analysis (NMA)., Methods: A search was conducted on databases such as Cochrane Library, PubMed, EmBase, and Web of Science for randomized controlled trials (RCTs) on pharmacological interventions for alleviating graft injury following AMR. The search was performed for publications up to April 12, 2024. Two reviewers conducted independent reviews of the literature, extracted data, and assessed the risk of bias (ROB) in the included studies using the ROB assessment tool recommended by the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. A Bayesian NMA was conducted using R 4.4.0, RStudio software, and the GeMTC package to assess the outcomes in estimated glomerular filtration rate (eGFR), mean fluorescence intensity (MFI), g-score, and infection under pharmacological treatments., Results: A total of 8 RCTs involving 215 patients and 6 different pharmacological treatments were included in this NMA. The results indicated that the increase in eGFR by eculizumab (SUCRA score: 81) appeared to be more promising. The decrease in MFI by bortezomib (SUCRA score: 72.3), rituximab (SUCRA score: 68.2), and clazakizumab (SUCRA score: 67.1) demonstrated better efficacy. The decrease in g-score by eculizumab (SUCRA score: 74.3), clazakizumab (SUCRA score: 72.2), and C1INH (SUCRA score: 63.6) appeared to have more likelihood. For infection reduction, clazakizumab (SUCRA score: 83.5) and bortezomib (SUCRA score: 66.8) might be better choices., Conclusion: The results of this study indicate that eculizumab has the potential to enhance eGFR and reduce g-score. Bortezomib demonstrates superior efficacy in reducing MFI. Clazakizumab appears to be more effective in reducing infections., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024546483., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Yu, Huang, Zhang, Zhu, He, Li and Sun.)

Intestinal microsporidiosis caused by Enterocytozoon bieneusi is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication. We aimed to describe therapeutic management of E. bieneusi infections in this context. We conducted a French nationwide observational retrospective study on reported cases of E. bieneusi infections in SOT recipients. We identified 154 cases: 64 (41.6%) were managed by simply modifying the immunosuppressive regimen, 54 (35.1%) were given fumagillin, and 36 (23.4%) were given nitazoxanide. Clinical remission rate ranged from 77.8% to 90.7% and was not significantly different between therapeutic strategies but tended to be lower with nitazoxanide. Stool negativization rate was highest with fumagillin (91.7%) and lowest with nitazoxanide (28.6%). Relapses occurred in 6.9% of cases and were more frequent with nitazoxanide (14.3%). This study shows that tapering immunosuppression can result in a satisfactory remission rate but is sometimes accompanied by relapses. Nitazoxanide had limited effectiveness, whereas fumagillin had good results that provide a solid rationale for bringing fumagillin back to market., Trial Registration Number: ClinicalTrials.gov ID: NCT05417815., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Garrouste, Poirier, Uro-Coste, Iriart, Kamar, Bonhomme, Calvar, Le Gal, Lanfranco, Autier, Rakoff, Durieux, Danthu, Morio, Deltombe, Moreno-Sabater, Ouali, Costa, Bertrand, Chesnay, Gatault, Rabodonirina, Morelon, Dumortier, Sitterlé, Scemla, Hamane, Cachera, Damiani, Poulain, L’Ollivier, Moal, Delhaes, Kaminski, Cateau, Ecotière, Brunet, Caillard, Valot, Tinel, Argy, Raimbourg, Robert, Noble, Boignard, Botterel, Matignon, Bellanger, Crépin, Leroy, Lionet, Debourgogne, Nicolas, Claudéon, Moniot, Lambert and Nourrisson.)

Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection. This was a single-center retrospective study of clinical outcomes of patients who received MBV compared to a control group who received FOS for an episode of CMV infection. Each cohort consisted of 27 episodes of CMV infection. Twenty patients in the MBV cohort and from the FOS cohort cleared the infection, with five and three patients developing MBV or FOS resistance, respectively. There were no statistically significant differences in failure of therapy as evidenced by persistent DNAemia ( p = 0.56) or development of antiviral resistance ( p = 0.24). In conclusion, MBV was as effective as FOS for the treatment of R/R CMV infection and was better tolerated without increased risk of antiviral resistance.

Organ transplantation is a vital intervention for end-stage organ failure; however, ischemia-reperfusion injury is a complication of transplantation, affecting the prognosis and survival of transplant recipients. As a complex ecosystem, recent research has highlighted the role of the intestinal microecology in transplantation, revealing its significant interplay with ischemia-reperfusion injury. This review explores the interaction between ischemia-reperfusion injury and intestinal microecology, with a special focus on how ischemia-reperfusion injury affects intestinal microecology and how these microecological changes contribute to complications after organ transplantation, such as infection and rejection. Based on a comprehensive analysis of current research advances, this study proposes potential strategies to improve transplant outcomes, offering guidance for future research and clinical practice., Competing Interests: The authors declare that this study was conducted in the absence of any commercial or financial relationship that could be interpreted as a potential conflict of interest., (Copyright © 2024 Lian, Li, Guo, Tao, Liu, Liang and Zhu.)

Though antimicrobial stewardship programs (ASPs) are required for hospitals, the involvement of transplant recipients in programmatic interventions, protocols, and metrics has historically been limited. Though there is a growing interest in studying stewardship practices in transplant patients, optimal practices have not been clearly established. A component of ASPs, antiviral stewardship (AVS), specifically targeting cytomegalovirus (CMV), has been more recently described. Understanding AVS opportunities and interventions is particularly important for transplant recipients, given the morbidity and mortality associated with viral infections, challenging clinical syndromes, ultrasensitive molecular diagnostic assays, antiviral resistance, and costs of viral disease and medications, as well as antiviral drug toxicities. This review highlights opportunities for AVS for CMV, EBV, HSV, VZV, SARS-CoV-2, respiratory syncytial virus, and BK polyomavirus in transplant patients.

Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C. The median age was 61.0 (51-69) years, 330 (67.6%) and 158 (32.4%) were men and women, respectively, 415 (85%) had pneumonia, and 161 (33%) had SpO 2  < 95% at admission. All-cause mortality occurred in 105 (21.5%) cases. It was higher in nonvaccinated versus vaccinated SOTR (23.4% vs 13.8%, P = 0.04). Patients in the entire cohort were classified into phenotypes A (n = 149, 30.5%), B (n = 187, 38.3%), and C (n = 152, 31.1%), with mortality rates of 8.7%, 16.6%, and 40.1%, respectively, which were similar to those of nonvaccinated SOTR (9.5%, 16.7%, and 52.0%) and lower in vaccinated SOTR (4.4%, 15.8%, and 17.3%, respectively), with difference between nonvaccinated and vaccinated in the phenotype C (P < 0.001). In conclusion, COVID-19 clinical phenotypes are useful in SOTR, and all-cause mortality decreases in vaccinated patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Statement: The views expressed in this publication are the sole responsibility of the authors and the Commission is not responsible for any use that may be made of the information it contains., (© 2024. The Author(s).)

De novo food allergy is a common phenomenon among pediatric solid organ recipients (8.5%-57%) when compared with the general population (0.45%-10%). Other associated disorders include non-IgE-mediated immune reactions and clinical predisposition to asthma and alterations in the oral mucosa. Originally, passive mechanisms (passive transfer of IgE and immune cells) were thought to be responsible for acute, transient cases of food allergies with a previous history of sensitization for a specific allergen in the donor. Recently proposed pathophysiological mechanisms to explain de novo allergies include TH2/B-cell imbalance, regulatory T-cell (Treg) disruption, gastrointestinal immaturity, and altered gastrointestinal permeability. Recent studies also suggest that immunosuppressive drugs, especially tacrolimus, promote naïve T-cell differentiation into TH2 cells, IgE-promoting cytokine production, decreased IL-5 and IL-10 levels, increased IgA levels, and Treg disruption. Such immunological interactions, in conjunction with altered intestinal permeability, intestinal immaturity in children, history of viral infection, and a personal history of allergies or eczema, are thought to explain most clinical cases of pediatric de novo food allergy after solid organ transplantation reported in the literature. A better understanding of the immunological mechanisms underpinning organ donors and recipients may unveil some of the caveats concerning therapeutic management and improve the quality of life of affected individuals.

The number of older adults undergoing organ transplantation, and waiting lists are increasing. The epidemiological data on infections in older transplant patients are scarce. The objective of the study was to investigate the incidence and distribution of infectious complications in older patients according to post-transplant periods. This retrospective study was conducted in a university hospital between 1 January 2018 and 31 March 2023. All infectious episodes were analyzed over three post-transplant periods. Forty-four patients were enrolled. The median age was 67 years (min: 65 and max: 87 years). Patients experienced a total of 98 infectious episodes. The median number of infectious events per patient was 1.0 (min: 0 and max: 8). The overall incidence rate of infectious events was 2.18 infectious episodes per 1000 transplant days. Of the patients at risk, 18.2% had 12 (12.4% of all infections) infections in the first month (9.09 episodes per 1000 transplant days), 56.8% had 52 (53.1%) infections between 1 and 6 months (7.88 episodes per 1000 transplant days), and 40.9% had 34 (35%) infections >6-12 months post-transplant (0.92 episodes per 1000 transplant days) The most prevalent type of infection was bacterial (79.6%, n = 78) followed by viral (18.4%, n = 18) and fungal (2.0%, n = 2) infections. The overall mortality rate of the 44 patients was 13.6%. The bacterial infections were more prevalent, and the incidence of infection was high during all post-transplant periods. These results may guide infection management in older transplant patients.

Background and Purpose: Tremor is a frequent complaint of solid organ transplant recipients. We report on the largest population investigated with clinical neurophysiological methods. Our aim is to objectively establish the tremor prevalence and syndrome in the largest population of solid organ transplant recipients., Methods: Tremor was measured in heart, kidney, liver, and lung recipients, using accelerometers during rest, postural, and weight-loaded conditions. The 95th percentile of healthy kidney donors' tremor amplitude was used as the cutoff to determine the presence of tremor in transplant recipients. Tremor frequency, frequency variability, and effect of loading were used to investigate enhanced physiological tremor as the likely tremor syndrome. Impact on activities of daily life was assessed, and correlations with tacrolimus blood levels were investigated., Results: Tremor was present in 52% of 246 transplant recipients, typically in postural positions. Mean tremor frequency was 6.1 (±2.0) Hz; mean tremor variability was 2.6 (±1.8) Hz. A frequency decrease upon loading was found in 83% of patients with tremor. Sixty-five percent of patients met formal clinical neurophysiological criteria for enhanced physiological tremor. Tremor-related impairment was present in 55% and correlated with tremor amplitude (ρ = 0.23, p ≤ 0.001). In a binominal regression analysis, tacrolimus blood levels were independently associated with tremor prevalence (p = 0.009)., Conclusions: More than half of solid organ transplant recipients experience a tremor that best fits the syndrome of enhanced physiological tremor. This is the first objective study on tremor that has established a better understanding of the neurophysiological mechanisms of tremor in a large population of solid organ transplant recipients., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: Respiratory tract infections are commonly seen and compose a great burden on health care. The causing pathogens might be either bacteria or viruses. Because treatment is different for each, prompt diagnosis and early treatment are crucial, especially in immunocompromised patients like solid-organ transplant recipients who often present with obscure findings. The aim of this study was to compare the respiratory multiplex polymerase chain reaction results of solid-organ transplant recipients with results of other hospitalized patients (control group) and to analyze whether results played a role in morbidity and mortality prediction., Materials and Methods: The study was approved by the ethical committee of Başkent University (KA23/233) and included all patients who were hospitalized from January 1, 2023, to December 31, 2023, and who underwent multiplex polymerase chain reaction for diagnosis of respiratory tract infection., Results: Among analyses of 192 polymerase chain reaction samples performed in 177 patients (45 solid-organ transplant patients and 132 controls), no differences in frequency or pathogen type were shown between the groups. A positive result was associated with increased mortality in transplant patients but not in controls. Kaplan-Meier survival analysis showed no difference for survival time within 6 months of follow-up between the groups. Logistic regression analysis showed an increase of 4.28-fold in mortality for transplant patients if a positive polymerase chain reaction result was present., Conclusions: Respiratory multiplex polymerase chain reaction is a tool for fast diagnosis and prompt initiation of the right treatment. A positive result in transplant patients was associated with increased mortality.

Objective: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients., Methods: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis., Results: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p = .001) were factors independently associated with recurrence., Conclusions: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: GT received honoraria for educational meetings by Shionogi and participated to scientific board for MSD. MF received unconditional grants from MSD, Gilead and speaker honoraria from Shionogi, Pfizer, Menarini, MSD, Gilead, GSK, MundiPharma and TermoFisher. Declared conflicts of interest are outside the submitted work and did not affect the scientific objectivity of this study. The other authors have none to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients., Methods: This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023., Results: A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization., Conclusion: Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

Introduction: In solid-organ transplant (SOT) recipients, while survival rates have improved with immunosuppressive therapies, the risk of opportunistic infections has also increased. This study aimed to evaluate the frequency of pneumonia, identify microbiological factors, investigate diagnostic methods, and analyse prognosis., Materials and Methods: A retrospective study was conducted to identify adult SOT recipients referred to the pulmonary diseases department with a preliminary pneumonia diagnosis between 2011 and 2019. Data on demographics, clinical and transplantation characteristics, pneumonia frequency, microbiological sampling methods, pathogens, radiological findings, and prognosis were collected. Confirmed pneumonia was defined as symptoms consistent with pneumonia alongside microbiological confirmation., Result: We conducted 426 pulmonary consultations involving 168 patients (86 kidney; 82 liver transplant recipients) with a preliminary pneumonia diagnosis. Pneumonia was diagnosed in 87% of the cases, with common findings including multiple symptoms, glucocorticoid use, focal or multilobar infiltrations, and diffuse ground-glass nodules. Pneumonia frequency was higher during the first, sixth, and twelfth months for liver transplants and after twelve months for kidney transplants. Diagnostic sampling was conducted for 128 patients, with a success rate of 63.3%. Of 476 respiratory samples, 32.6% yielded diagnoses, with bacterial growth detected in 42.9%, predominantly Pseudomonas aeruginosa. Microbiological agents were isolated by 18.4% using non-invasive methods, 15.5% using invasive methods. Non-invasive methods primarily isolated gram-positive and gram-negative bacteria, Acinetobacter spp., Klebsiella spp., Haemophilus spp., whereas invasive methods were more effective for Candida spp. Acinetobacter spp. was more prevalent in liver transplant patients and fungal species in kidney transplant patients. Intensive care unit admission occurred in 36.3% of the patients, 19% died., Conclusions: : While pneumonia was common among SOT recipients, the associated mortality rate was relatively low. Over half the patients were diagnosed through microbiological sampling. Invasive sampling is valuable for non-bacterial agents. Due to high gramnegative bacteria frequency and early post-transplant pneumonia, increased attention is needed for hospital-acquired agents.

Louseborne Bartonella quintana infections in the United States occur almost exclusively among persons experiencing homelessness because of inadequate access to hygiene resources. Homelessness is increasing, and persons experiencing homelessness can be organ donors, despite barriers to receiving donated organs themselves. Recent reports have documented B. quintana transmission via organs transplanted from donors who had recently experienced homelessness. Those reports demonstrate the threat of severe bartonellosis in immunosuppressed organ transplant recipients after donor-derived B. quintana infection. Addressing the root causes of B. quintana transmission could improve the quality of life for persons experiencing homelessness and simultaneously mitigate risk for donor-derived B. quintana transmission. Interventions include improved access to housing, consistent access to hot water for showers and laundry, early treatment of body lice infestation and B. quintana infection, and B. quintana testing and prophylactic treatment of recipients of organs from donors who have experienced risk factors for B. quintana, including homelessness.

Infection and rejection are major complications that impact transplant longevity and recipient survival. Balancing their risks is a significant challenge for clinicians. Current strategies aimed at interrogating the degree of immune deficiency or activation and their attendant risks of infection and rejection are imprecise. These include immune (cell counts, function and subsets, immunoglobulin levels) and non-immune (drug levels, viral loads) markers. The shared risk factors between infection and rejection and the bidirectional and intricate relationship between both entities further complicate transplant recipient care and decision-making. Understanding the dynamic changes in the underlying net state of immunity and the overall risk of both complications in parallel is key to optimizing outcomes. The allograft biopsy is the current gold standard for the diagnosis of rejection but is associated with inherent risks that warrant careful consideration. Several biomarkers, in particular, donor derived cell-free-DNA and urinary chemokines (CXCL9 and CXCL10), show significant promise in improving subclinical and clinical rejection risk prediction, which may reduce the need for allograft biopsies in some situations. Integrating conventional and emerging risk assessment tools can help stratify the individual's short- and longer-term infection and rejection risks in parallel. Individuals identified as having a low risk of rejection may tolerate immunosuppression wean to reduce medication-related toxicity. Serial monitoring following immunosuppression reduction or escalation with minimally invasive tools can help mitigate infection and rejection risks and allow for timely diagnosis and treatment of these complications, ultimately improving allograft and patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tharmaraj, Mulley and Dendle.)

Background: Keratinocyte carcinomas such as basal cell carcinomas and squamous cell carcinomas are a major burden affecting morbidity and mortality in solid organ transplant recipients (SOTRs). Best treatment includes frequent skin checks for early detection and surgery for high incidence of skin cancers. Sirolimus is an immunosuppressive drug which may reduce the burden of skin cancer but may be poorly tolerated when given orally. Topical sirolimus has been proven effective at reducing the burden of skin cancers in animal models, and its safety has long been established in children with tuberous sclerosis. A recent 12-week phase II trial of topical sirolimus suggested it was safe and effective at reducing the early signs of skin cancer in the absence of major side effects. The aim of the SiroSkin trial is to determine whether topical sirolimus can fill a major gap in current therapies by reducing the onset and number of new skin cancers thus reducing burden of disease and cost-effectiveness., Methods: Protocol for a multi-centred phase III, participant- and clinician assessor-blinded, placebo-controlled randomised trial in SOTRs. A minimum 146 participants randomised 1:1 will be treated with 1% topical sirolimus versus placebo applied to the face on a regular basis for 24 weeks. Participation is 24 months in total-24 weeks of treatment and 18 months of follow-up. Outcomes include the number of keratinocyte carcinomas at 24 weeks of treatment compared to placebo and then at 12 and 24 months after initiation of treatment. Analysis will be as per protocol and intention to treat., Discussion: The results of this trial will inform management strategies for skin cancers in SOTRs and provide evidence for cost-effectiveness., Trial Registration: Clinicaltrials.gov NCT05860881. Registered on June 15, 2023, and on anzctr.org.au (registration number NCT05860881)., Competing Interests: Declarations. Ethics approval and consent to participate {24}: The study was approved by Metro South Human Research Ethics Committee on 18 April 2023 (HREC/2023/QMS/95325). All participants will have to provide written informed consent before participation. Consent for publication {32}: This is not applicable. No identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. The participant information materials and informed consent form are available from the corresponding author on request. All authors listed above meet the authorship criteria according to the latest guidelines of the International Committee of Medical Journal Editors, and all authors agree with the manuscript. Competing interests {28}: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: The pathogenesis and outcome of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) reflects the interplay between viral replication and CMV-specific immunity. Despite advances in its diagnosis and treatment, CMV continues to cause significant morbidity after SOT. Since CMV is an opportunistic pathogen that occurs as a result of impaired pathogen-specific immunity, laboratory assays that measure CMV-specific immune responses may be useful in assisting clinicians in its management., Methods and Results: The author summarizes the evolving and emerging data on the clinical utility of assays that quantify cell-mediated immune responses to CMV in SOT recipients. The majority of publications are observational studies that demonstrate that a lack or deficiency in CMV-specific cell-mediated immunity is correlated with a heightened risk of primary, reactivation, or recurrent CMV after transplantation. A few prospective interventional studies have utilized CMV-specific cell-mediated immune assays in guiding the duration of antiviral prophylaxis among CMV-seropositive SOT recipients. Likewise, CMV-specific cell-mediated immunity assays have been suggested to inform the need for secondary antiviral prophylaxis and immunologic optimization to prevent CMV relapse after treatment., Conclusions: CMV-specific cell-mediated immune assays are emerging to assist transplant clinicians in predicting a patient's risk of CMV after transplantation, and these assays have been utilized to individualize the approach to CMV prevention and treatment. The author suggests the conduct of more interventional studies to further solidify the role of CMV-specific cell-mediated immune assays in routine clinical practice.

The incidence of arbovirus infections has increased in recent decades. Other than dengue, chikungunya, and West Nile viruses, the data on arbovirus in solid organ transplant (SOT) are limited to case reports, and infections in renal transplant recipients account for most of the reported cases. Dengue and West Nile infections seem to be more severe with higher mortality in SOT patients than in the general population. Acute kidney injury is more frequent in patients with dengue and chikungunya although persistent arthralgia with the latter is less frequent. There is no clear relationship between arboviral infection and acute cellular rejection. Pre-transplant screening of donors should be implemented during increased arboviral activity but, despite donor screening and negative donor nucleic acid amplification test (NAT), donor derived infection can occur. NAT may be transiently positive. IgM tests lack specificity, and neutralizing antibody assays are more specific but not readily available. Other tests, such as immunohistochemistry, antigen tests, PCR, metagenomic assays, and viral culture, can also be performed. There are a few vaccines available against some arboviruses, but live vaccines should be avoided. Treatment is largely supportive. More data on arboviral infection in SOT are needed to understand its epidemiology and clinical course.

Purpose: The Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections in solid organ transplant (SOT) recipients and allogenic haematopoietic stem-cell transplant (HSCT) recipients and 2) advance research in the field of transplantation by collecting data from a multitude of sources., Participants: All SOT and HSCT recipients at Copenhagen University Hospital, Rigshospitalet, are followed in MATCH. By February 2021, a total of 1192 HSCT recipients and 2039 SOT recipients have been included. Participants are followed life long. An automated electronic data capture system retrieves prospective data from nationwide registries. Data from the years prior to transplantation are also collected., Findings to Date: Data entries before and after transplantation include the following: biochemistry: 13 995 222 and 26 127 817; microbiology, cultures: 242 023 and 410 558; other microbiological analyses: 265 007 and 566 402; and pathology: 170 884 and 200 394. There are genomic data on 2431 transplant recipients, whole blood biobank samples from 1003 transplant recipients and faeces biobank samples from 207 HSCT recipients. Clinical data collected in MATCH have contributed to 50 scientific papers published in peer-reviewed journals and have demonstrated success in reducing cytomegalovirus disease in SOT recipients. The programme has established international collaborations with the Swiss Transplant Cohort Study and the lung transplant cohort at Toronto General Hospital., Future Plans: Enrolment into MATCH is ongoing with no planned end date for enrolment or follow-up. MATCH will continue to provide high-quality data on transplant recipients and expand and strengthen international collaborations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Immunocompromised persons are at high risk of persistent Human Papilloma Virus (HPV) infection and associated diseases. Few studies evaluated HPV vaccines in immunocompromised persons. This study aimed to evaluate the quadrivalent HPV vaccine (4vHPV) immunogenicity and safety in solid organ transplant (SOT) recipients, in comparison to immunocompetent women (IC)., Methods: Open-label clinical trial that enrolled SOT recipients and immunocompetent women aged 18 to 45 years. All participants received three doses of 4vHPV vaccine. Blood samples were drawn for evaluation of immune responses at baseline and one month after the third vaccination. Seroconversion rates and antibody geometric mean concentration (GMC) against HPV 6, 11, 16, 18, 31, 35, 52 and 58 were measured with in-house multiplexed serology assay (xMAP technology). Follow-up for the local and systemic adverse events (AEs) continued for seven days after each vaccination. Severe AEs were evaluated throughout the study., Results: 125 SOT and 132 immunocompetent women were enrolled; 105 (84%) SOT and 119 (90%) immunocompetent women completed the study. At baseline, HPV seropositivity was not significantly different between groups. Seroconversion rates were significantly lower in SOT (HPV18, 57%; HPV6 and 16, 69%; and HPV11, 72%) than in immunocompetent women (100% seroconversion to all vaccine types) ( p <0.001). Antibody GMCs of all four HPV vaccine types were also significantly lower in SOT ( p <0.001). Pain in the injection site and headache were the most frequent adverse event in both groups. Local pain was more frequent in immunocompetent women than in SOT recipients. Rates of other AEs were comparable in both groups., Conclusion: 4vHPV vaccine was well-tolerated by SOT recipients. We found strong evidence of lower humoral immune responses to 4vHPV vaccine in SOT compared to immunocompetent women, which strengthen recommendation of routine cervical cancer screening in SOT recipients regardless of HPV vaccination status., Competing Interests: Since June 2020, VI is an employee of Instituto Butantan and since March 2021, KM is an employee of Instituto Butantan producer of 4vHPV vaccine in Brazil, through a technology transfer agreement. CR is an employee of Instituto Butantan since April 2023. AL, AS and CP received grant from Instituto Butantan in 2021-2022, to conduct studies on COVID vaccines. Data collection for this study and analysis were performed before that. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miyaji, Infante, Picone, Dillner, Kann, Eklund, Levi, de Oliveira, Lara, Kawakami, Tacla, Castanheira, Mayaud and Sartori.)

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05-1.83)), chronic lung disease (HR 1.71 (95% CI 1.13-2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61-4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66-17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75-7.19)), corticosteroid use (OR 2.93 (95% CI 1.03-2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65-17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type., (© 2024. The Author(s).)

Introduction: Tacrolimus is an immunosuppressant commonly administered in transplant recipients. Given its narrow therapeutic range and susceptibility to various influencing variables, determining its optimal dosage is challenging. This systematic review seeks to identify effective analytical modelling techniques and methods for optimal tacrolimus dose prediction in solid transplant recipients., Methods and Analysis: This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The study will review the literature published from database inception to 11 March 2024, that assesses predictive models of tacrolimus dosing through analytical modelling techniques. We will include both randomised and non-randomised, as well as cross-sectional, qualitative and before-and-after studies and will perform our searches in four main databases-Ovid/MEDLINE, PubMed/MEDLINE, Scopus, Embase and Web of Science, and search engines including Centers for Disease Control (CDC) and Google Scholar. Papers that are not published in English or French are excluded from this study. A narrative synthesis and meta-analysis will be done if the extracted information permits such analysis. Conference abstracts will be ignored unless they are recent (published within 2 years of the search date)., Ethics and Dissemination: Ethics clearance is not required for this study as no primary data will be collected. The completed manuscript will be published, and the results of the study will be presented at conferences., Study Registration: International Prospective Register of Systematic Reviews (PROSPERO), CRD42024537212., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tacrolimus, a calcineurin inhibitor, is a highly effective immunosuppressant used in solid organ transplantation (SOT). However, it is characterized by a narrow therapeutic range and high inter-patient variability in pharmacokinetics. Standard weight-based dosing followed by empiric dose titration is suboptimal in controlling drug concentrations, increasing risk of rejection or toxicity, particularly in the initial months post transplantation. This review explores the potential of combined pre-transplant genotyping and pharmacokinetic (PK) modelling to improve tacrolimus dosing in paediatric SOT recipients. A systematic search of Medline, Embase and Cochrane databases identified studies published between March 2013 and March 2023 that investigated genotype- and PK model-informed tacrolimus dosing in children post-SOT. The Newcastle-Ottawa Scale assessed study quality. Seven studies encompassing paediatric kidney, heart, liver and lung transplants reported using genotype and model-informed dosing. A combination of clinical and genetic factors significantly impacts tacrolimus clearance and thus initial dose recommendation. Body size, transplant organ and co-medications were consistently important, while either time post-transplant or haematocrit emerged in some studies. Several models were identified, however, with limitations evident in some and with absence of evidence for their effectiveness in optimizing initial and subsequent dosing. This review highlights the development of PK models in paediatric SOT that integrate genotype and clinical covariates to personalize early tacrolimus dosing. While promising, prospective studies are needed to validate and confirm their effectiveness in improving time to therapeutic concentrations and reducing under- or overexposure. This approach has the potential to optimize tacrolimus therapy in paediatric SOT, thereby improving outcomes., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Access to solid organ transplantation in patients with intellectual disability is associated with health inequities due to concerns about treatment adherence, survival rates, and post-transplant quality of life. This systematic literature review aims to compare outcomes after organ transplantation in patients with intellectual disability compared to patients without intellectual disability. Embase, Medline Ovid, PsycINFO, Web of Science, Cochrane Central Register of Trials, and Google Scholar databases were systematically searched for studies concerning pediatric or adult solid organ transplantation in recipients with a diagnosis of intellectual disability prior to transplantation. Primary outcomes were patient and graft survival rates. Secondary outcomes were acute rejection rate, adherence rates, and quality of life. Nine studies were included, describing kidney (n = 6), heart (n = 4) and liver (n = 1) transplantation. Reported graft survival rates were non-inferior or better compared to patients without intellectual disability, while patient survival was reportedly slightly lower in two studies reporting on kidney transplantation. Although current evidence has a potential selection bias based on including patients with a sufficient support network, intellectual disability alone should not be regarded a relative or absolute contra-indication for solid organ transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Rover, Orlandini, Darwish Murad, Polak, Hartley, Sharif, Sneiders and Hartog.)

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear., Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination., Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion., Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Donadeu, Gomez-Olles, Casanova, Torija, Lopez-Meseguer, Boada-Pérez, Kervella, Crespo, Carrera-Muñoz, Campos-Varela, Castells, Cortese, Esperalba, Fernández-Naval, Quintero, Muñoz, Agüero, Gonzalez-Costello, Lladó, Favà, Cañas, del Mar de la Hoz-Caballero, Meneghini, Torres, Juvé, Hafkamp, Vila, Robles, Buzón, Toapanta, Zúñiga, Monforte, Saez-Giménez, Len, Arcos, Miret, Ariceta, Pardo, Martínez, Moreso and Bestard.)

Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Grossi, Wolfe and Peghin.)

Objectives: Despite increased rates of survival, pediatric organ transplant is characterized by clinical complexities and psychosocial challenges. Understanding and addressing the psychosocial issues inherent in this population are crucial for optimizing their overall well-being and transplant outcomes. In this systematic review, we thus aimed to provide a comprehensive analysis of the psychosocial issues encountered by pediatric patients undergoing or awaiting organ transplant., Materials and Methods: This systematic review was conducted by retrospectively searching PubMed, Scopus, ScienceDirect, and Cochrane electronic databases using the keywords "pediatric kidney transplantation" or "pediatric liver transplantation" or "pediatric heart transplantation" and "psychosocial problems" or "psychosocial issues" or "psychosocial outcomes" or "psychosocial needs." The literature review resulted in 3746 initial studies, with 6 studies included in this systematic review., Results: Examination of psychosocial problems experienced by pediatric organ transplant recipients in included studies showed factors such as depression, anxiety, quality of life, medication adherence, psychological distress, children's psychosocial characteristics, healthy behaviors, mental and somatic well-being, fear of rejection, fear of recurrence, fear of secondary diseases, sleep problems, sadness, and exhaustion., Conclusions: Pediatric organ transplant intertwines complex medical procedures with intricate psychosocial dynamics, placing nurses at the forefront of care delivery for pediatric transplant recipients and their families. In embracing a holistic approach to care, nurses advocate for the integration of psychosocial support into standard practice protocols, recognizing that optimal health outcomes extend beyond physiological parameters.

Objectives: This systematic review delves into the intricate relationship between pediatric organ transplantation and posttraumatic stress disorder, shedding light on interventions crucial for addressing the psychosocial well-being of young transplant recipients. This review of the multifaceted nature of posttraumatic stress disorder in the context of pediatric transplantation examined the effects of transplant on the mental health of recipients. We aimed to review studies on posttraumatic stress disorder among pediatric patients who have had or were waiting for organ transplant and to systematically analyze the results of these studies., Materials and Methods: This systematic review was conducted by retrospectively searching PubMed, Scopus, ScienceDirect, Web of Science, and Cochrane electronic databases using the keywords "pediatric kidney transplantation," or "pediatric liver transplantation," or "pediatric heart transplantation," and "posttraumatic stress disorders." Descriptive studies were included if they met the association between posttraumatic stress disorder and pediatric organ transplant recipients., Results: From 267 articles, 5 articles were included in the systematic review. Posttraumatic stress disorder was shown to be more common in pediatric transplant recipients. Rate of low-level posttraumatic stress disorder ranged from 9.2% to 85.2%, whereas rate of high-level posttraumatic stress disorder ranged from 13.1% to 22.6%., Conclusions: This review highlighted the imperative need to recognize and address the psychosocial effects of pediatric organ transplantation, with a specific focus on posttraumatic stress disorder. By incorporating comprehensive mental health care into the transplant journey, psychiatric nurses can contribute to the overall well-being of young recipients and their families, ensuring that the transformative power of organ transplant extends beyond mere physical survival to encompass psychological resilience and recovery. By acknowledging and addressing the emotional dimensions of the transplant journey, nurses can contribute to the well-being of recipients, ensuring a more holistic and resilient recovery.

Objectives: Organ transplant is a vital treatment for pediatric patients. Kidney, liver, heart, and other organ transplants can significantly improve the quality of life for children with various chronic diseases and can improve long-term survival rates. However, the effects of transplant on cognitive and educational aspects should be considered, including the effects of pre- and posttransplant treatment protocols, medications, psychosocial stress, and surgical interventions. Learning disabilities can negatively affect the child's educational life, social relationships, and overall quality of life. We aimed to examine the prevalence of learning difficulties after organ transplant, the influencing factors, and the interventions aimed at solving these problems by conducting a systematic review of existing research on learning difficulties associated with pediatric organ transplant., Materials and Methods: For this systematic review, We searched PubMed, Cochrane, Web of Science, Science Direct, and Scopus databases to examine studies conducted during the past decade. We used the key words organ transplantation, pediatrics, and learning disabilities for our search. We included English language, full-text articles in the study; meta-analyses, systematic reviews, and case reports for which the full text was not available in English were excluded from the study., Results: Among an initial search result of 174 articles, 4 met the inclusion criteria. Across all studies, a consistent observation emerged that indicated a decline in neurocognitive functions among children who had undergone organ transplant. Specific areas affected included verbal intelligence, memory, reading/spelling skills, mathematical ability, motor skills, attention, and memory, collectively contributing to learning difficulties., Conclusions: In light of the findings, minimizing learning difficulties in children after organ transplant necessitates strategies such as reducing transplant waiting times, seamlessly integrating children into the posttransplant school environment, and implementing specialized programs within educational institutions.

Importance: Cytomegalovirus (CMV) is associated with significant morbidity and mortality in solid organ transplant (SOT) recipients. The risk factors for CMV seropositivity in SOT recipients, including area-level social deprivation in the US, have not been fully characterized., Objective: To (1) evaluate CMV seroprevalence, (2) assess the recipient characteristics associated with CMV seropositivity, and (3) assess the association of area-level social deprivation index (SDI) scores with pretransplant CMV serostatus., Design, Setting, and Participants: This retrospective cross-sectional analysis of the Scientific Registry of Transplant Recipients database included all adult (aged ≥18 years) SOT recipients from January 1, 2008, to May 31, 2022. Data were analyzed from April 10 to October 25, 2023., Exposure: Recipient characteristics and area-level SDI., Main Outcomes and Measures: Multivariable generalized linear models were used to evaluate the association between (1) patient characteristics and CMV and (2) social deprivation (measured by SDI scores, which were assessed in quintiles, from lowest to highest) and CMV seropositivity. In addition, differences based on patient demographics and the transplanted organ(s) were evaluated., Results: Among the 389 288 SOT recipients included in the analysis, mean (SD) age was 53.3 (13.0) years; 63.0% were male, 21.4% were Black, 15.2% were Hispanic White, 56.2% were non-Hispanic White, and 62.7% were CMV seropositive. The mean (SD) age was higher among CMV seropositive (54.0 [12.7] years) compared with CMV seronegative (52.0 [13.5] years) patients. Seropositivity for CMV was higher among women (69.9%) than men (58.5%) and among Black (74.8%) and Hispanic White (80.2%) patients compared with non-Hispanic White patients (50.4%). Seropositivity for CMV was highest among kidney (64.5%), liver (63.6%), and kidney and liver (66.2%) recipients. Greater SDI scores were associated with greater CMV seropositivity, ranging from 51.7% for the least deprived to 75.5% for the most deprived quintiles (P < .001), independent of age, sex, or race., Conclusions and Relevance: In this cross-sectional study, an association between SDI and CMV seropositivity was observed among SOT recipients, independent of age, sex, or race and ethnicity. To optimize posttransplant outcomes in CMV seropositive recipients, efforts targeting prevention of CMV reactivation need to be prioritized in these higher-risk populations.

Background: Whether solid organ transplant (SOT) can be safely performed in recipients with ongoing SARS-CoV-2 infection is still a debated question., Methods: A systematic review of the literature on recipients with ongoing SARS-CoV-2 infection at the time of surgery and the associated outcomes., Results: From 29 studies, we identified 54 recipients; their median age was 47.5 years, and over half (23/54, 54.85%) were affected by fewer than two comorbidities. Kidney was the most common transplanted organ (24/54, 44.4%). SOT was performed without knowing the ongoing infection in 11.1% (6/54) of patients. On average, 16.1 (SD 23.2) days elapsed between SARS-CoV-2 infection and SOT, with a mean Ct value at diagnosis and transplantation of 29 and 31.9, respectively. Most patients (25/39,64.1%) had received previous COVID-19 vaccinations. Twenty-four patients (45.3%) received an anti-SARS-CoV-2 therapy. Ten patients (18.5%) required oxygen support, while seven (13.7%) were admitted to the intensive care unit. There were two reported cases (3.7%) of all-cause death, while there were no cases of COVID-19-related death., Conclusions: Deliberate SOT of recipients with ongoing SARS-CoV-2 is performed worldwide in candidates of nonlung transplant who are fit, immunized against the virus, and displaying a nonsevere disease course. No COVID-19-related deaths were recorded., Competing Interests: Declarations of competing interest All the authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Monitoring the status of grafts and the occurrence of postoperative complications, such as rejection, is crucial for ensuring the success and long-term survival of organ transplants. Traditional histopathological examination, though effective, is an invasive procedure and poses risks of complications, making frequent use impractical. In recent years, graft-derived cell-free DNA (gd-cfDNA) has emerged as a promising non-invasive biomarker. It not only provides early warnings of rejection and other types of graft injury but also offers important information about the effectiveness of immunosuppressive therapy and prognosis. gd-cfDNA shows potential in the monitoring of organ transplants. The early, real-time information on graft injury provided by gd-cfDNA facilitates timely individualized treatment and improves patient outcomes. However, the progress of research on gd-cfDNA varies across different organs. Therefore, this article will comprehensively review the application and findings of gd-cfDNA in monitoring various solid organs, discussing the advantages, limitations, and some future research directions to aid in its clinical application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Liu, Jia, Wang, Cao, Wu, Ye and Gao.)

Background: Organ transplantation in children is a vital procedure for those with end-stage organ failure, but it has been linked to the development of post-transplant allergies, especially food allergies. This phenomenon, known as transplant-acquired food allergy (TAFA), is becoming increasingly recognized, though its mechanisms remain under investigation. Pediatric transplant recipients often require lifelong immunosuppressive therapy to prevent graft rejection, which can alter immune function and heighten the risk of allergic reactions. Our review aimed to gather the latest evidence on TAFA., Methods: We conducted a PubMed search from 25 June to 5 July 2024, using specific search terms, identifying 143 articles. After screening, 36 studies were included: 24 retrospective studies, 1 prospective study, 2 cross-sectional researches, and 9 case reports/series., Results: Most studies focused on liver transplants in children. The prevalence of food allergies ranged from 3.3% to 54.3%. Tacrolimus, alongside corticosteroids, was the most commonly used immunosuppressive therapy. In addition to food allergies, some patients developed atopic dermatitis, asthma, and rhinitis. Allergic symptoms typically emerged within a year post-transplant, with common allergens including milk, eggs, fish, nuts, soy, wheat, and shellfish. Both IgE-mediated and non-IgE-mediated reactions were observed, with treatment often involving the removal of offending foods and the use of adrenaline when necessary., Conclusions: Consistent immunological monitoring, such as skin prick tests and IgE level assessments, is essential for early detection and management of allergies in these patients. Understanding the link between transplantation and allergy development is crucial for improving long-term outcomes for pediatric transplant recipients.

Purpose: The significance of dental status and oral hygiene on a range of medical conditions is well-recognised. However, the correlation between periodontitis, oral bacterial dysbiosis and visceral surgical outcomes is less well established. To this end, we study sought to determine the influence of dental health and oral hygiene on the rates of postoperative complications following major visceral and transplant surgery in an exploratory, single-center, retrospective, non-interventional study., Methods: Our retrospective non-interventional study was conducted at the Department of General, Visceral, and Transplant Surgery, University Hospital Heidelberg, Germany. Patients operated on between January 2018 and December 2019 were retrospectively enrolled in the study based on inclusion (minimum age of 18 years, surgery at our Department, intensive care / IMC treatment after major surgery, availability of patient-specific preoperative dental status assessment, documentation of postoperative complications) and exclusion criteria (minor patients or legally incapacitated patients, lack of intensive care or intermediate care (IMC) monitoring, incomplete documentation of preoperative dental status, intestinal surgery with potential intraoperative contamination of the site by intestinal microbes, pre-existing preoperative infection, absence of data regarding the primary endpoints of the study). The primary study endpoint was the incidence of postoperative complications. Secondary study endpoints were: 30-day mortality, length of hospital stay, duration of intensive care stay, Incidence of infectious complications, the microbial spectrum of infectious complication. A bacteriology examination was added whenever possible (if and only if the examination was safe for the patient)for infectious complications., Results: The final patient cohort consisted of 417 patients. While dental status did not show an influence (p = 0.73) on postoperative complications, BMI (p = 0.035), age (p = 0.049) and quick (p = 0.033) were shown to be significant prognostic factors. There was significant association between oral health and the rate of infectious complications for all surgical procedures (p = 0.034), excluding transplant surgery. However, this did not result in increased 30-day mortality rates, prolonged intensive care unit treatment or an increase in the length of hospital stay (LOS) for the cohort as a whole. In contrast there was a significant correlation between the presence of oral pathogens and postoperative complications for a group as a whole (p < 0.001) and the visceral surgery subgroup (p < 0.001). Whilst this was not the case in the cohort who underwent transplant surgery, there was a correlation between oral health and LOS in this subgroup (p = 0.040). Bacterial swabs supports the link between poor oral health and infectious morbidity., Conclusions: Dental status was a significant predictor of postoperative infectious complications in this visceral surgery cohort. This study highlights the importance preoperative dental assessment and treatment prior to major surgery, particularly in the case of elective surgical procedures. Further research is required to determine the effect of oral health on surgical outcomes in order to inform future practice., Trial Registration: Trial registered under the ethics-number S-082/2022 (Ethic Committee of the University Heidelberg)., (© 2024. The Author(s).)

Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the non-immunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients ( p -values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28-1.61 for mortality; aHR 1.31-1.47 for MACE; aHR 1.72-1.90 for MARCE; aHR 1.75-2.07 for AKI; and aOR 1.53-1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2024 Vinson, Anzalone, Schissel, Dai, Agarwal, Lee, Olex and Mannon.)

Cytomegalovirus (CMV) infection is arguably the most important infectious complication that negatively affects the outcome of solid organ transplantation. For decades, CMV management after transplantation has relied on antiviral drugs that inhibit viral DNA polymerase (ganciclovir, foscarnet, and cidofovir). However, their use has been complicated by myelosuppression, nephrotoxicity, and selection of drug-resistant viruses. During the past few years, the therapeutic armamentarium for the management of CMV in solid organ transplant recipients has expanded with the approval of letermovir for CMV prophylaxis in high-risk CMV D+/R- kidney recipients, and maribavir for the treatment of refractory and resistant CMV infection. Both drugs offer significant improvement when compared to standard anti-CMV therapies; letermovir was as efficacious for CMV prevention, whereas maribavir was more effective in treating refractory and resistant CMV infections. Both letermovir and maribavir have favorable safety profiles compared to CMV DNA polymerase inhibitors, without the risk of neutropenia and leukopenia associated with ganciclovir and renal toxicities associated with foscarnet and cidofovir. Moreover, letermovir and maribavir are orally bioavailable, which allows convenient outpatient treatment. However, letermovir and maribavir have a significant drug interaction potential in solid organ transplant recipients, resulting in higher levels of calcineurin inhibitors (cyclosporine and tacrolimus) and mTOR inhibitors (sirolimus and everolimus). Both letermovir and maribavir are CMV-specific and do not have clinical efficacy against other herpes viruses. Thus, there is a need for additional antiviral drugs to prevent herpes simplex and other herpes viruses when clinically indicated. This article provides a comprehensive review of the clinical data supporting the use of letermovir and maribavir in clinical practice. The author provides perspectives on the role of these newly approved drugs in the current management landscape of CMV infection in solid organ transplantation., Competing Interests: Dr Raymund Razonable reports grants from Gilead, grants from Roche, grants from Regeneron, personal fees from Allovir, personal fees from Novartis, outside the submitted work. The author reports no other conflicts of interest in this work., (© 2024 Razonable.)

Context.—: Posttransplant lymphoproliferative disorder (PTLD) remains a significant complication in pediatric patients undergoing solid organ transplant (SOT). The majority involve Epstein-Barr virus (EBV)-driven CD20+ B-cell proliferations, which respond to reduction of immunosuppression and anti-CD20-directed immunotherapy. Owing to the low overall incidence, prospective studies of pediatric PTLD are scarce, leading to a lack of comprehensive understanding of this disorder in pediatric populations. This review aims to bridge this knowledge gap by providing a comprehensive analysis of the clinical, morphologic, and molecular genetic features of PTLD in children, adolescents, and young adults after SOT., Objective.—: To examine the clinical features, pathogenesis, and classification of pediatric PTLDs after SOT., Data Sources.—: Personal experiences and published works in PubMed., Conclusions.—: PTLD includes a broad and heterogeneous spectrum of disorders, ranging from nonmalignant lymphoproliferations to lymphomas. While most pediatric PTLDs are EBV+, an increasing number of EBV- PTLDs have been recognized. The pathologic classification of PTLDs has evolved in recent decades, reflecting advancements in understanding the underlying pathobiology. Nevertheless, there remains a great need for further research to elucidate the biology, identify patients at higher risk for aggressive disease, and establish optimal treatment strategies for relapsed/refractory disease., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

For patients with intestinal failure, small bowel transplantation remains one of the most effective treatments despite continuous advancements in parenteral nutrition techniques. Long-term use of parenteral nutrition can result in serious complications that lead to metabolic dysfunction and organ failure. However, the small intestine is a highly immunogenic organ with a large amount of mucosa-associated lymphoid tissue and histocompatibility antigens; therefore, the small intestine is highly susceptible to severe immune rejection. This article discusses the mechanisms underlying immune rejection after small bowel transplantation and presents various options for prevention and treatment. Our findings offer new insights into the development of small bowel transplantation., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.