Search

BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

BACKGROUND: Kidney transplant (KT) candidates with HIV face higher mortality on the waitlist compared with candidates without HIV. Because the HIV Organ Policy Equity (HOPE) Act has expanded the donor pool to allow donors with HIV (D + ), it is crucial to understand whether this has impacted transplant rates for this population. METHODS: Using a linkage between the HOPE in Action trial (NCT03500315) and Scientific Registry of Transplant Recipients, we identified 324 candidates listed for D + kidneys (HOPE) compared with 46 025 candidates not listed for D + kidneys (non-HOPE) at the same centers between April 26, 2018, and May 24, 2022. We characterized KT rate, KT type (D + , false-positive [FP; donor with false-positive HIV testing], D - [donor without HIV], living donor [LD]) and quantified the association between HOPE enrollment and KT rate using multivariable Cox regression with center-level clustering; HOPE was a time-varying exposure. RESULTS: HOPE candidates were more likely male individuals (79% versus 62%), Black (73% versus 35%), and publicly insured (71% versus 52%; P

Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.

BACKGROUND: Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS: This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS: During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS: Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION: NCT02860039.

OBJECTIVES: Patients with pre-transplant metabolic dysfunction-associated steatohepatitis (MASH) are at high risk of metabolic syndrome (MetS) after liver transplant. While many patients are co-managed by a transplant team, most preventative screening and MetS management may occur in the primary care setting. We aimed to evaluate primary care utilization by MASH liver transplant recipients as well as MetS screening and control. METHODS: We conducted a retrospective chart review that included adults who underwent liver transplant for MASH or cryptogenic cirrhosis at a single institution from January 2010 to December 2016, had available primary care data, and at least 36-months of follow-up post-transplant. Measures included primary care utilization, adherence to screening guidelines, and control of MetS. We used Fischers exact test to explore the association of primary care utilization with screening and control. RESULTS: A total of 37 patients met inclusion criteria with 366 visits reviewed. The median time to first visit was 68 days post-transplant and patients had a median of 9 total visits. Few patients met screening guidelines for diabetes (8.1%) or hyperlipidemia (10.8%). The percentage of patients with control of obesity, hypertension, diabetes, and hyperlipidemia decreased over the 36-month follow-up period. Primary care utilization was not associated with adherence to screening recommendations for diabetes (P = .141) or hyperlipidemia (P = .103). Higher primary care utilization was not associated with control of hypertension (P = .107), diabetes (P = .871), or hyperlipidemia (P = .999). CONCLUSION: More research is needed to investigate barriers to screening and management of MetS conditions in this high-risk patient population in the primary care setting as well as to optimize post-transplant care coordination.

Key points The study found a higher incidence of chronic rhinosinusitis (CRS) and recalcitrant CRS in cadaveric organ transplant recipients compared to those receiving living donor transplants. Recipients of cadaveric transplants were 1.32 times more likely to develop CRS and 1.68 times more likely to develop medically recalcitrant CRS. Living kidney transplants significantly reduced the risk of developing CRS (OR = 0.12) and recalcitrant CRS (OR = 0.11), highlighting a potentially protective effect against these conditions. In contrast, cadaveric liver transplants were associated with an increased risk of CRS and medically recalcitrant CRS. Kaplan–Meier survival analysis indicated a significant difference in time to CRS onset between cadaveric and living donor transplants. Median time to CRS onset was longer for living donor recipients (21.1 months) compared to cadaveric recipients (15.6 months). This study underscores the need for transplant teams and otolaryngologist to consider donor type during transplant follow‐up due to differing risks of CRS development. [ABSTRACT FROM AUTHOR]

Purpose: Due to the shortage of lung donors relative to the number of patients waiting for lung transplantation (LTx), more than one-third of patients on the waitlist have died without receiving LTx in Korea. Therefore, the importance of fair and effective allocation policies has been emphasized. This study investigated the characteristics of the current urgency-based allocation system in Korea by simulating the Eurotransplant lung allocation score (ET-LAS) using a nationwide multi-institutional registry for LTx in Korea. Materials and Methods: This study used data from the Korean Organ Transplantation Registry (KOTRY), along with additional retrospective data for ET-LAS calculation. A total of 194 patients were included in this study between January 2015 and December 2019. The Korean urgency definition classifies an LTx candidate as having statuses 0–3 according to urgency. The ET-LAS was analyzed according to the Korean urgency status. Results: In total, 92 patients received lung transplants at status 0, 85 at status 1, and 17 at status 2/3. The ET-LAS showed a bimodal distribution with distinct peaks corresponding to status 0 and non-status 0. There was no significant difference in the ET-LAS among non-status 0 patients. In logistic and decision tree analyses, oxygen supplementation methods, particularly oxygen masks and high-flow nasal cannulas, were significantly associated with a high ET-LAS (≥50) among non-status 0 patients. Conclusion: Simulation of the ET-LAS with KOTRY data showed that the Korean urgency definition may not allocate lungs by urgency, especially for patients in non-status 0; therefore, it needs to be revised. [ABSTRACT FROM AUTHOR]

Background Methicillin-resistant Staphylococcus aureus (MRSA) nares screening has been shown to be a powerful antibiotic stewardship tool for MRSA infections within 7 days of screening across a variety of anatomical locations given the high negative predictive value (NPV). However, the utility outside of 7 days and among transplant recipients and patients with neutropenia is less clear. Methods This was a retrospective cohort study across Veterans Affairs medical centers in the United States from 1 January 2007 to 1 January 2023 of patients tested for MRSA colonization and who had a subsequent positive bacterial culture within 28 days of MRSA sc---reening. Sensitivity, specificity, positive predictive value, and NPV were calculated across different time points and anatomical culture locations. Results The cohort consisted of 686 174 patients, 6 277 437 MRSA nares tests, and 2 446 766 positive bacterial cultures within 28 days of MRSA testing. The NPV of MRSA nares screening for ruling out a MRSA infection within 28 days was 95.8% across all anatomical culture sites. The NPV was 97.9% among patients with neutropenia and 97.5% in solid organ and hemopoietic stem cell transplant recipients. Conclusions MRSA nares screening can reliably be used for de-escalation of anti-MRSA therapy within 28 days of bacterial culture for all patients, including solid organ and hematopoietic transplant recipients and patients with neutropenia. [ABSTRACT FROM AUTHOR]

Despite the significant progress made, CMV infection is one of the most frequent infectious complications in transplant recipients. CMV infections that become refractory or resistant (R/R) to the available antiviral drugs constitute a clinical challenge and are associated with increased morbidity and mortality. Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir. [ABSTRACT FROM AUTHOR]

In the aftermath of the COVID-19 pandemic, the ongoing necessity for preventive measures such as mask-wearing and vaccination remains particularly critical for organ transplant recipients, a group highly susceptible to infections due to immunosuppressive therapy. Given that many individuals nowadays increasingly utilize Artificial Intelligence (AI), understanding AI perspectives is important. Thus, this study utilizes AI, specifically ChatGPT 4.0, to assess its perspectives in offering precise health recommendations for mask-wearing and COVID-19 vaccination tailored to this vulnerable population. Through a series of scenarios reflecting diverse environmental settings and health statuses in December 2023, we evaluated the AI's responses to gauge its precision, adaptability, and potential biases in advising high-risk patient groups. Our findings reveal that ChatGPT 4.0 consistently recommends mask-wearing in crowded and indoor environments for transplant recipients, underscoring their elevated risk. In contrast, for settings with fewer transmission risks, such as outdoor areas where social distancing is possible, the AI suggests that mask-wearing might be less imperative. Regarding vaccination guidance, the AI strongly advocates for the COVID-19 vaccine across most scenarios for kidney transplant recipients. However, it recommends a personalized consultation with healthcare providers in cases where patients express concerns about vaccine-related side effects, demonstrating an ability to adapt recommendations based on individual health considerations. While this study provides valuable insights into the current AI perspective on these important topics, it is crucial to note that the findings do not directly reflect or influence health policy. Nevertheless, given the increasing utilization of AI in various domains, understanding AI's viewpoints on such critical matters is essential for informed decision-making and future research. [ABSTRACT FROM AUTHOR]

Background: Cutaneous squamous cell carcinoma is a significant cause of morbidity for immunosuppressed patients such as organ transplant recipients; however, histological parameters which predict the likelihood of tumor progression are typically based on general population studies in which immunosuppressed patients represent only a small fraction of cases. Objectives: To determine the histological parameters which have independent prognostic value for cutaneous squamous cell carcinoma arising in renal transplant recipients. Methods: Case-control study incorporating a retrospective blinded histological review of 70 archived specimens of cutaneous squamous cell carcinoma diagnosed in renal transplant recipients, comprising 10 cases where the tumor had progressed and 60 controls. Results: Progression was significantly associated with head and neck location, size, depth, poor histological grade, perineural invasion (including small caliber perineural invasion), lymphovascular invasion, and a desmoplastic growth pattern. Limitations: The retrospective nature and the low number of cases compared to controls. Conclusion: In immunosuppressed patients both small caliber perineural invasion and a desmoplastic growth pattern may also have prognostic significance in addition to other histological parameters already recognized in formal staging schemes.

Background Methods Results Conclusions Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America.This 56‐year (1967–2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long‐term incidence of malignant cutaneous neoplasms in Mexican RTRs.Over 56 years, 1642 RTRs (58% male) were studied. Median follow‐up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5–7.9), with an incidence density rate of 6.5 (95% CI: 5.4–7.9) per 1000 person‐years and a median latency of 9.8 years. Incidence increased with longer transplantation‐related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6–9.1) for any skin cancer and 7.5 (95% CI: 3.8–14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer‐related mortality rate of 2.7%. Limitations of the study include its single‐center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure.Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non‐White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs. [ABSTRACT FROM AUTHOR]

Sodium glucose co‐transporter 2 (SGLT2) inhibitors are used for the treatment of diabetes and for their cardiovascular and kidney benefits in patients with or without diabetes. Use in solid organ transplant recipients is controversial because transplant recipients were excluded from the major clinical trials assessing SGLT2 inhibitors. The goal of this review was to assess the available literature regarding the use of SGLT2 inhibitors in solid organ transplant recipients. A PubMed search was conducted for studies published in English through December 31, 2023. Studies were excluded if they were meta‐analyses, review articles, commentaries, single case reports, or in vitro studies, or did not involve the use of SGLT2 inhibitors in solid organ transplant recipients with a diabetic, cardiovascular, or kidney outcome being assessed. In the final review, 20 studies were included: kidney (n = 15), heart (n = 4), and liver/lung/kidney (n = 1) transplant recipients. SGLT2 inhibitors had similar A1c reduction efficacy and were found to be weight neutral with possible weight reduction effects. Cardiovascular and kidney outcomes were not adequately assessed in the available studies. Adverse effects were reported to occur at a similar rate in transplant recipients compared to the general population. SGLT2 inhibitors were initiated ≥1‐year post‐transplant in most transplant recipients included in these studies. The overall safety and antihyperglycemic efficacy of SGLT2 inhibitors in kidney and heart transplant recipients is similar to the general population. Data assessing SGLT2 inhibitors use in solid organ transplant recipients for longer durations are needed. [ABSTRACT FROM AUTHOR]

• Based on the new ARDS definition, approximately 22.6 % of hospitalized SOTRs infected with SARS-CoV-2 developed ARDS. • Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS following COVID-19 infection in SOTRs. • A nomogram prediction model was created utilizing the aforementioned factors to facilitate early prediction of ARDS, exhibiting an AUC of 0.81. Solid organ transplant recipients (SOTRs) are more likely to suffer complications after being infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to describe the clinical features of SOTRs infected with SARS-CoV-2 and to assess independent risk factors associated with the development of acute respiratory distress syndrome (ARDS) following COVID-19 infection in SOTRs based on the new ARDS definition. 358 SOTRs infected with SARS-CoV-2 were recruited and divided into two groups, patients with ARDS (n = 81) and patients without ARDS (n = 277). Demographic data, initial laboratory findings, therapeutic measures, and outcome indicators were compared between the two groups. The association between the onset of ARDS and related factors was analyzed using a logistic regression model. A nomogram was created to estimate the probability of developing ARDS. Approximately 22.6 % (81/358) of hospitalized SOTRs infected with SARS-CoV-2 developed ARDS. In comparison to patients without ARDS, those with ARDS presented with more underlying conditions, decreased lymphocyte counts and serum albumin levels, but increased levels of leukocytes, serum creatinine, nitrogen urea, uric acid, and inflammatory markers. Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS in this population. Furthermore, a nomogram prediction model was created utilizing the aforementioned factors to facilitate early prediction of ARDS, exhibiting an AUC (area under curve) of 0.81. Cerebrovascular disease, leukocyte counts, albumin levels, and IL-6 levels were independent risk factors for the development of ARDS following COVID-19 infection in SOTRs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Much of our knowledge of organ rejection after transplantation is derived from rodent models. METHODS: We used single-nucleus RNA sequencing to investigate the inflammatory myocardial microenvironment in human pediatric cardiac allografts at different stages after transplantation. We distinguished donor- from recipient-derived cells using naturally occurring genetic variants embedded in single-nucleus RNA sequencing data. RESULTS: Donor-derived tissue resident macrophages, which accompany the allograft into the recipient, are lost over time after transplantation. In contrast, monocyte-derived macrophages from the recipient populate the heart within days after transplantation and form 2 macrophage populations: recipient MP1 and recipient MP2. Recipient MP2s have cell signatures similar to donor-derived resident macrophages; however, they lack signatures of pro-reparative phagocytic activity typical of donor-derived resident macrophages and instead express profibrotic genes. In contrast, recipient MP1s express genes consistent with hallmarks of cellular rejection. Our data suggest that recipient MP1s activate a subset of natural killer cells, turning them into a cytotoxic cell population through feed-forward signaling between recipient MP1s and natural killer cells. CONCLUSIONS: Our findings reveal an imbalance of donor-derived and recipient-derived macrophages in the pediatric cardiac allograft that contributes to allograft failure. [ABSTRACT FROM AUTHOR]

Introduction. Numerous studies indicate an increased incidence of skin malignancies among organ transplant recipients. Melanoma pose a significant threat to post-transplant recipients, leading to considerable mortality. This study explores the incidence of melanoma after 17,252 organ transplantations in Poland over the past 13 years. Materials and methods. The data on the occurrence of melanoma in patients after renal, heart, or liver transplantation were obtained from the National Health Fund, encompassing individuals who underwent kidney, heart, or liver transplantation between 2010 and 2022. The analysis focused on skin melanoma (C43). Results. The study examined skin melanoma in renal (12,250 cases), liver (3,584 cases), and heart (1,418 cases) transplant recipients over a period of thirteen years. Melanoma incidence slightly increased in renal recipients (1-year cumulative incidence 0.016% vs. 0.007%, p = 0.024; 5-year cumulative incidence 0.131% vs. 0.040% p < 0.001; the 10-year cumulative incidence 0.213% vs. 0,09, p < 0.001). In liver transplant recipients there is a non-significant difference 1-year after transplantation (cumulative incidence 0.03% vs. 0.01%, p = 0.337) but after 5 and 10 years the difference between the two groups remains statistically significant (5-year cumulative incidence 0.14% vs. 0.04%, p < 0.014; the 10-year cumulative incidence 0.14% vs. 0.09%, p < 0.001). In heart transplant recipients, a paradoxical reduction in incidence was observed compared to the general population (1-year cumulative incidence 0% vs. 0.01%, p = 0.317; 5-year cumulative incidence 0.07% vs. 0.04%, p = 0.049; the 10-year cumulative incidence 0.07% vs. 0.09, p < 0.001). Conclusions. The incidence of melanoma increases in kidney transplant recipients over the first 10 years post-transplant, with a peak between 4 to 7 years. For heart and liver transplant recipients, melanoma cases occur within the initial 5 years post-transplant, and no new cases were recorded afterward. The long-term surviving kidney, heart, and liver transplant recipients show a steady rise in new cases over time. Our study, based on a thorough analysis of data from the National Health Fund, confirms the link between an elevated risk of melanoma in organ transplant recipients. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient‐centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre‐emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant. [ABSTRACT FROM AUTHOR]

Dupilumab is an interleukin‐4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune‐mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon. [ABSTRACT FROM AUTHOR]

Background: BK polyomavirus (BKV) can cause permanent loss of allograft function due to BKV‐associated nephropathy (BKVN) in kidney transplant recipients. Besides immunosuppression reduction, there are no consistently effective interventions for BKV infection. Study purpose was to define natural history of BKV infection, identify risk factors for BKV reactivation and BKVN in kidney transplant recipients, and inform the design/conduct of future clinical trials of BKV‐targeted therapeutics. Methods: We conducted a multicenter prospective observational study of incident kidney transplant recipients at six U.S. transplant centers. Participants were monitored every 4 weeks for BKV reactivation and followed for up to 24 months post‐transplant. We used regression models (logistic, survival, mixed models) to study relationships between BK viremia/BKVN, clinical characteristics, and allograft function. Results: We enrolled 335 participants. Fifty‐eight (17%) developed BK viremia, 6 (2%) developed biopsy‐proven BKVN, and 29 (9%) developed suspected/presumed BKVN (defined as BKV viral load > 10,000 copies/mL without biopsy). Male donor sex was associated with lower odds for BK viremia, whereas recipient Black race was associated with two‐fold increased odds for BK viremia. Recipient female sex was associated with more rapid clearance of BK viremia. Persistent BK viremia/BKVN was associated with poorer allograft function by 24 months post‐transplant. Conclusions: We identified multiple donor and recipient demographic factors associated with risk for BKV infection and poorer allograft function by 24 months post‐transplant. This may help design future clinical trials of therapies to prevent or mitigate the deleterious impact of BKV reactivation on kidney transplant outcomes. [ABSTRACT FROM AUTHOR]

Infections remain the most common cause of hospitalization after kidney transplantation, contributing to significant post-transplant morbidity and mortality. There is a growing body of literature that suggests that immunoglobulins may have a significant protective role against post-transplant infections, although the literature remains sparse, inconsistent, and not well publicized among pediatric nephrologists. Of great concern are data indicating a high prevalence of immunoglobulin abnormalities following transplantation and a possible link between these abnormalities and poorer outcomes. Our educational review focuses on the epidemiology and risk factors for the development of immunoglobulin abnormalities after kidney transplantation, the outcomes in patients with low immunoglobulin levels, and studies evaluating possible interventions to correct these immunoglobulin abnormalities.

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post-transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post-transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty-five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (

BACKGROUND: The Scientific Registry of Transplant Recipients (SRTR) Living Donor Collective (LDC), the first effort to create a lifetime registry for living donor candidates in the United States, requires transplant programs to register donor candidates while the SRTR conducts follow-up. METHODS: To better understand facilitators and barriers to program participation, we conducted a brief electronic survey of U.S. transplant program staff from October 26, 2021 to December 17, 2021. RESULTS: We received 132 responses, with at least one response from 87 living donor programs (46 kidney programs, 33 kidney and liver programs, and eight liver programs alone). We found 86% of program representatives strongly agreed or agreed that funding adequate to cover the cost of data collection would facilitate LDC participation, 92% agreed or strongly agreed with importance of electronic data submission options, and 74% reported that elimination of requirements to submit duplicative pre-operative information to the Organ Procurement and Transplantation Network (OPTN) would be helpful. Other potentially enabling factors include reduction in duration of OPTN postdonation follow-up requirements, ease-of-use, protection from data use for regulation, adequate data security, and equity in data access. CONCLUSION: This survey identifies potential targets to strengthen participation in the effort to create a national living donor registry in the United States. Collaboration and investment to overcome barriers to LDC participation among transplant programs are vital to generate long-term data on living donation for donor candidates, donors, and patients in need of transplant.

Bacteriophage therapy is the use of viruses to kill bacteria for the treatment of antibiotic-resistant infections. Little is known about the human immune response following phage therapy. We report the development of phage-specific CD4 T cells alongside rising phage-specific immunoglobulin G and neutralizing antibodies in response to adjunctive bacteriophage therapy used to treat a multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient. Clinically, treatment was considered a success despite the development phage-specific immune responses.

BackgroundAdditional "booster" doses of mRNA SARS-CoV-2 vaccines have become standard of care for immunosuppressed patients, including kidney transplant recipients (KTR). While these additional doses have been shown to be efficacious in the adult KTR population, there is paucity of data for pediatric and adolescent KTR.MethodsWe conducted a retrospective single-center observational study to determine the proportion of pediatric and adolescent KTR who seroconverted following two- and three-dose regimens of an mRNA SARS-CoV-2 vaccine series.ResultsForty-three pediatric and adolescent KTR at our center received at least two doses of an mRNA SARS-CoV-2 vaccine. Seroconversion was noted in 56% of those who received a 2-dose series and increased to 85% in those who received a third dose. In the 16 patients who did not seroconvert after a two-dose series, 12 (75%) seroconverted following the third dose. No serious adverse effects of immunization were noted.ConclusionsOur results demonstrate that additional SARS-CoV-2 vaccine doses are not only safe and efficacious in pediatric and adolescent KTR, but may be necessary to optimize antibody response. A higher resolution version of the Graphical abstract is available as Supplementary information.

BackgroundAlthough mRNA vaccines have overall efficacy preventing morbidity/mortality from SARS-CoV-2 infection, immunocompromised persons remain at risk. Antibodies mostly prevent early symptomatic infection, but cellular immunity, particularly the virus-specific CD8+ T cell response, is protective against disease. Defects in T cell responses to vaccination have not been well characterized in immunocompromised hosts; persons with lung transplantation are particularly vulnerable to vaccine failure with severe illness.MethodsComparison groups included persons with lung transplantation and no history of COVID-19 (21 and 19 persons after initial mRNA vaccination and a third booster vaccination respectively), 8 lung transplantation participants recovered from COVID-19, and 22 non-immunocompromised healthy control individuals after initial mRNA vaccination (without history of COVID-19). Anti-spike T cell responses were assayed by stimulating peripheral blood mononuclear cells (PBMCs) with pooled small overlapping peptides spanning the SARS-CoV-2 spike protein, followed by intracellular cytokine staining (ICS) and flow cytometry for release of cytokines in response to stimulation, including negative controls (no peptide stimulation) and positive controls (phorbol myristate acetate [PMA] and ionomycin stimulation). To evaluate for low frequency memory responses, PBMCs were cultured in the presence of the mRNA-1273 vaccine for 14 days before this evaluation.ResultsIonophore stimulation of PBMCs revealed a less inflammatory milieu in terms of interleukin (IL)-2, IL-4, and IL-10 profiling in lung transplantation individuals, reflecting the effect of immunosuppressive treatments. Similar to what we previously reported in healthy vaccinees, spike-specific responses in lung transplantation recipients were undetectable (

Objective: Renal transplantation is a challenging process for the recipients. One of the important problems in this process is unwanted weight gain. This study aimed to determine the change in body mass index (BMI) and to evaluate the effect of recipient characteristics on BMI during one-year period after renal transplantation. Methods: The article was conducted in a retrospective design. In the study, files of 170 patients who underwent renal transplantation between 2015 and 2016 were reviewed retrospectively. T-test, ANOVA, and correlation analysis were used in the analysis of data. Results: It was determined that the patients had a tendency to have increased BMI after transplantation, with a higher rate in the first three months. The increase in BMI was higher in singles than in married participants (p=0.01 and p0.05). Conclusion: In the study, it was determined that the increase in BMI was higher especially in the first three months after renal transplantation. For this reason, it is an important requirement to address the counseling and support to patients and their relatives regarding weight management in the early period.

In the aftermath of the COVID-19 pandemic, the ongoing necessity for preventive measures such as mask-wearing and vaccination remains particularly critical for organ transplant recipients, a group highly susceptible to infections due to immunosuppressive therapy. Given that many individuals nowadays increasingly utilize Artificial Intelligence (AI), understanding AI perspectives is important. Thus, this study utilizes AI, specifically ChatGPT 4.0, to assess its perspectives in offering precise health recommendations for mask-wearing and COVID-19 vaccination tailored to this vulnerable population. Through a series of scenarios reflecting diverse environmental settings and health statuses in December 2023, we evaluated the AI’s responses to gauge its precision, adaptability, and potential biases in advising high-risk patient groups. Our findings reveal that ChatGPT 4.0 consistently recommends mask-wearing in crowded and indoor environments for transplant recipients, underscoring their elevated risk. In contrast, for settings with fewer transmission risks, such as outdoor areas where social distancing is possible, the AI suggests that mask-wearing might be less imperative. Regarding vaccination guidance, the AI strongly advocates for the COVID-19 vaccine across most scenarios for kidney transplant recipients. However, it recommends a personalized consultation with healthcare providers in cases where patients express concerns about vaccine-related side effects, demonstrating an ability to adapt recommendations based on individual health considerations. While this study provides valuable insights into the current AI perspective on these important topics, it is crucial to note that the findings do not directly reflect or influence health policy. Nevertheless, given the increasing utilization of AI in various domains, understanding AI’s viewpoints on such critical matters is essential for informed decision-making and future research.

Potential regional variations in effects of COVID-19 on federally mandated, program-specific evaluations by the Scientific Registry of Transplant Recipients (SRTR) have been controversial. SRTR January 2022 program evaluations ended transplant follow-up on March 12, 2020, and excluded transplants performed from March 13, 2020 to June 12, 2020 (the "carve-out"). This study examined the carve-out's impact, and the effect of additionally censoring COVID-19 deaths, on first-year posttransplant outcomes for transplants from July 2018 through December 2020. Program-specific hazard ratios (HRs) for graft failure and death estimated under two alternative scenarios were compared with published HRs: (1) the carve-out was removed; (2) the carve-out was retained, but deaths due to COVID-19 were additionally censored. The HRs estimated by censoring COVID-19 deaths were highly correlated with those estimated with the carve-out alone (r2  = .96). Removal of the carve-out resulted in greater variation in HRs while remaining highly correlated (r2  = .82); however, little geographic impact of the carve-out was observed. The carve-out increased average HR in the Northwest by 0.049; carve-out plus censoring reduced average HR in the Midwest by 0.009. Other regions of the country were not significantly affected. Thus, the current COVID-19 carve-out does not appear to impart substantial bias based on the region of the country.

Background Males have 2–3-fold greater risk of cancer than females at most shared anatomic sites, possibly reflecting enhanced immune surveillance against cancer in females. We examined whether these sex differences remained among immunocompromised adults. Methods Using the Transplant Cancer Match (TCM) study, we estimated the male-to-female incidence rate ratio in TCM (M:F IRRTransplant) for 15 cancer sites diagnosed between 1995 and 2017 using Poisson regression. Male to female IRRs in the general population (M:F IRRGP) were calculated using expected cancer counts from the Surveillance, Epidemiology, and End Results Program, standardized to the transplant population on age, race and ethnicity, and diagnosis year. Male to female IRRs were compared using a chi-square test. Results Among 343 802 solid organ transplants, 211 206 (61.4%) were among men and 132 596 (38.6%) among women. An excess cancer incidence in males was seen in transplant recipients, but the sex difference was attenuated for cancers of the lip (M:F IRRTransplant: 1.81 vs M:F IRRGP: 3.96; P  <  .0001), stomach (1.51 vs 2.09; P  =  .002), colorectum (0.98 vs 1.43; P  <  .0001), liver (2.39 vs 3.44; P  =  .002), kidney (1.67 vs 2.24; P  <  .0001), bladder (2.02 vs 4.19; P  <  .0001), Kaposi sarcoma (1.79 vs 3.26; P  =  .0009), and non-Hodgkin lymphoma (1.34 vs 1.64; P  <  .0001). The M:F IRRTransplant was not statistically different from the M:F IRRGP for other cancer sites. Conclusions Although male solid organ transplant recipients have higher cancer incidence than female recipients, the attenuation in the male to female ratio for many cancers studied relative to the general population might suggest the importance of immunosurveillance, with some loss of advantage in female recipients due to immunosuppression after transplantation. [ABSTRACT FROM AUTHOR]

Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed. [ABSTRACT FROM AUTHOR]

Respiratory viral infections (RVIs) are among the leading cause of morbidity and mortality in pediatric hematopoietic stem cell transplant (HCT) and solid organ transplant (SOT) recipients. Transplant recipients remain at high risk for super imposed bacterial and fungal pneumonia, chronic graft dysfunction, and graft failure as a result of RVIs. Recent multicenter retrospective studies and prospective studies utilizing contemporary molecular diagnostic techniques have better delineated the epidemiology and outcomes of RVIs in pediatric transplant recipients and have advanced the development of preventative vaccines and treatment interventions in this population. In this review, we will define the epidemiology and outcomes of RVIs in SOT and HSCT recipients, describe the available assays for diagnosing a suspected RVI, highlight evolving management and vaccination strategies, review the risk of donor derived RVI in SOT recipients, and discuss considerations for delaying transplantation in the presence of an RVI. [ABSTRACT FROM AUTHOR]

Despite current prophylaxis regimens, cytomegalovirus (CMV) is common in hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) and remains a significant cause of morbidity and mortality. Newer antiviral medications are reshaping the landscape for prevention and treatment of CMV DNAemia, infection, and disease. Letermovir is approved for CMV prevention in adult HCT patients and is attractive due to the absence of marrow suppression seen with ganciclovir/valganciclovir. Letermovir should not be routinely used for CMV treatment due to its low threshold for resistance. Maribavir is approved for the treatment of refractory or resistant CMV disease in HCT and SOT recipients ≥12 years of age, though it has no current role in CMV prevention. More research is needed to fully elucidate the roles, efficacy, and safety of these newer agents in prevention and treatment of CMV in pediatric transplant recipients. [ABSTRACT FROM AUTHOR]

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n  = 8), hyalohyphomycetes (n  = 3), dermatophytes (n  = 1), and mucorale (n  = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up. [ABSTRACT FROM AUTHOR]

Objective: Renal transplantation is a challenging process for the recipients. One of the important problems in this process is unwanted weight gain. This study aimed to determine the change in body mass index (BMI) and to evaluate the effect of recipient characteristics on BMI during one-year period after renal transplantation. Methods: The article was conducted in a retrospective design. In the study, files of 170 patients who underwent renal transplantation between 2015 and 2016 were reviewed retrospectively. T-test, ANOVA, and correlation analysis were used in the analysis of data. Results: It was determined that the patients had a tendency to have increased BMI after transplantation, with a higher rate in the first three months. The increase in BMI was higher in singles than in married participants (p=0.01 and p<0.05), and in men than in women (p=0.01 and p<0.05). It was determined that there was no significant relationship between BMI values and glomerular filtration rate, and creatinine levels of adult renal transplant recipients (p>0.05). Conclusion: In the study, it was determined that the increase in BMI was higher especially in the first three months after renal transplantation. For this reason, it is an important requirement to address the counseling and support to patients and their relatives regarding weight management in the early period. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases are major complications after solid organ transplantation. Heart transplant patients have a high mortality rate after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) vaccines have shown efficacy in generating specific immune response. This study aims to describe the COVID-19 infection before and after vaccination in heart transplant recipients. Methods: This was a single-center cohort study including 95 heart transplant recipients with laboratory radiological confirmed COVID-19. Results: COVID-19 infection was present before vaccination in 33 (35.78%) patients. The most frequent COVID-19 clinical presentations before vaccination were cough in 21 (63.63%) and myalgia in 19 (57.57%) patients; 12 (36.36%) were hospitalized; 17 (51.51%) cases had oxygen depletion and required supplemental oxygen; none of them needed invasive ventilation. Of the entire 33 COVID-19 patients, two patients (6.06%) re-experienced the disease about two months after complete vaccination and both of them were recovered. 63 heart transplant patients had not experienced COVID-19 before vaccination, of which 59 patients received vaccination. After two months, 23 vaccinated patients were infected with COVID-19 again, and 2 of the 3 patients who were not vaccinated were also infected. Five patients passed away in the whole study. Conclusion: Heart transplant patients infected with SARS-CoV-2 are at greater risk of severe infection and death compared with immunocompetent individuals. Thus, COVID-19 vaccination for all HT recipients is of paramount importance. [ABSTRACT FROM AUTHOR]

BackgroundThe COVID-19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities.MethodsWe reviewed outcomes in a cohort of SOT (n = 129) and non-SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID-19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups.ResultsSOT and NSOT patients with COVID-19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p = .013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p = .001) and neurologic condition (OR 2.66, p

Objective To investigate the clinical efficacy of domino liver transplantation (DLT) and to provide a refe-rence for expanding the sources of donor livers. Methods The clinical data of two cases who underwent DLT at our hospital in 2021 were collected, and a literature review was performed. Results Donor 1 was a healthy subject, recipient 1 (DLT donor) was a patient with ornithine transcarbamylase deficiency, and recipient 2 (DLT recipient) was a patient with Cirgler-Najiar syndrome. Donor 2 was a brain-dead donor as per the internationally standardized definitions, recipient 3 (DLT donor) was a patient with familial hypercholesterolemia, and recipient 4 (DLT recipient) was a patient with malignant liver tumor. After transplantation, all patients experienced recovery of their liver function in 1 week, and were discharged from the hospital after 2 to 4 weeks of hospitalization. Recipient 2 developed thrombosis in the left portal vein on day 4 after operation; after emergent thrombolysis and anticoagulant therapy, the blood flow of the portal vein was effectively improved, and no serious outcomes were identified; the bilirubin level of the patient returned to normal at 1 week after operation. Recipient 4 developed hyperlipidemia after operation and was treated with atorvastatin and ezetimibe for lipid regulation; the patient was followed up till now with no additional complications found. Conclusion DLT can effectively expand the sources of donor livers.

Despite the significant progress made, CMV infection is one of the most frequent infectious complications in transplant recipients. CMV infections that become refractory or resistant (R/R) to the available antiviral drugs constitute a clinical challenge and are associated with increased morbidity and mortality. Novel anti-CMV therapies have been recently developed and introduced in clinical practice, which may improve the treatment of these infections. In this review, we summarize the treatment options for R/R CMV infections in adult hematopoietic cell transplant and solid organ transplant recipients, with a special focus on newly available antiviral agents with anti-CMV activity, including maribavir and letermovir.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was

BackgroundKidney transplant patients are at high risk for coronavirus disease 2019 (COVID-19)-related mortality. However, limited data are available on longer-term clinical, functional, and mental health outcomes in patients who survive COVID-19.MethodsWe analyzed data from adult kidney transplant patients in the European Renal Association COVID-19 Database who presented with COVID-19 between February 1, 2020, and January 31, 2021.ResultsWe included 912 patients with a mean age of 56.7 (±13.7) y. 26.4% were not hospitalized, 57.5% were hospitalized without need for intensive care unit (ICU) admission, and 16.1% were hospitalized and admitted to the ICU. At 3 mo follow-up survival was 82.3% overall, and 98.8%, 84.2%, and 49.0%, respectively, in each group. At 3 mo follow-up biopsy-proven acute rejection, need for renal replacement therapy, and graft failure occurred in the overall group in 0.8%, 2.6%, and 1.8% respectively, and in 2.1%, 10.6%, and 10.6% of ICU-admitted patients, respectively. Of the surviving patients, 83.3% and 94.4% reached their pre-COVID-19 physician-reported functional and mental health status, respectively, within 3 mo. Of patients who had not yet reached their prior functional and mental health status, their treating physicians expected that 79.6% and 80.0%, respectively, still would do so within the coming year. ICU admission was independently associated with a low likelihood to reach prior functional and mental health status.ConclusionsIn kidney transplant recipients alive at 3-mo follow-up, clinical, physician-reported functional, and mental health recovery was good for both nonhospitalized and hospitalized patients. Recovery was, however, less favorable for patients who had been admitted to the ICU.

BackgroundTelomere dysfunction is associated with idiopathic pulmonary fibrosis (IPF) and worse outcomes following lung transplantation. Telomere dysfunction may impair immunity by upregulating p53 and arresting proliferation, but its influence on allograft-specific immune responses is unknown. We hypothesized that subjects undergoing lung transplantation for IPF would have impaired T cell proliferation to donor antigens.MethodsWe analyzed peripheral blood mononuclear cells (PBMC) from 14 IPF lung transplant recipients and 12 age-matched non-IPF subjects, before and 2 years after transplantation, as well as PBMC from 9 non-transplant controls. We quantified T cell proliferation and cytokine secretion to donor antigens. Associations between PBMC telomere length, measured by quantitative PCR, and T cell proliferation to alloantigens were evaluated with generalized estimating equation models.ResultsIPF subjects demonstrated impaired CD8+ T cell proliferation to donor antigens pre-transplant (p < 0.05). IL-2, IL-7, and IL-15 cytokine stimulation restored T cell proliferation, while p53 upregulation blocked proliferation. IPF subjects had shorter PBMC telomere lengths than non-IPF subjects (p < 0.001), and short PBMC telomere length was associated with impaired CD8+ T cell proliferation to alloantigens (p = 0.002).ConclusionsIPF as an indication for lung transplant is associated with short PBMC telomere length and impaired T cell responses to donor antigens. However, the rescue of proliferation following cytokine exposure suggests that alloimmune anergy could be overcome. Telomere length may inform immunosuppression strategies for IPF recipients.

For pediatric liver transplant (LT) recipients, an ideal outcome is to survive and thrive into adulthood. However, outcomes reporting for all LT recipients typically rely on much shorter-term outcomes, 1-5 years post-LT. Using Organ Procurement and Transplantation Network (OPTN) registry data from 1990 to 2018, this analysis seeks to determine if long-term follow-up and outcome data are complete for pediatric LT recipients age 0 to 12 years who survive at least 1 year post-LT without graft loss (n = 9309). Of the 7948 pediatric transplant recipients who did not die or require re-LT, 1 in 6 was reported as lost to follow-up by their transplant center during long-term follow-up. Rates of lost to follow-up were highest in those transplanted between 1990 and 1999 and increased in early adulthood for all recipients. Almost 10% of pediatric LT recipients who remained in follow-up required relisting for LT. 8% of children remaining in follow-up had graft failure. Lost to follow-up may bias estimates of long-term outcomes and risk factors for poor outcomes. For those remaining in follow-up, graft failure and death continue to occur in the decades after LT. Continued proactive monitoring, management, and innovations are needed to truly optimize post-LT survival for all children.

BackgroundClinical effectiveness of coronavirus disease 2019 (COVID-19) vaccination in solid organ transplant recipients (SOTRs) is not well documented despite multiple studies demonstrating sub-optimal immunogenicity.MethodsWe reviewed medical records of eligible SOTRs at a single center to assess vaccination status and identify cases of symptomatic COVID-19 from January 1 to August 12, 2021. We developed a Cox proportional hazards model using the date of vaccination and time since transplantation as a time-varying covariate with age and gender as potential time-invariant confounders. Survival curves were created using the parameters estimated from the Cox model.ResultsAmong 1904 SOTRs, 1362 were fully vaccinated (96% received mRNA vaccines) and 542 were either unvaccinated (n = 470) or partially vaccinated (n = 72). There were 115 cases of COVID-19, of which 12 occurred in fully vaccinated individuals. Cox regression with the date of vaccination and time since transplantation as the time-varying co-variates showed that after baseline adjustment for age and sex, being fully vaccinated had a significantly lower hazard for COVID-19, hazard ratio (HR) = 0.29 and 95% confidence interval ([CI] 0.09, 0.91).ConclusionWe found that 2-dose mRNA COVID-19 vaccination was protective of symptomatic COVID-19 in vaccinated versus unvaccinated SOTRs.TweetCOVID-19 vaccination was associated with a significantly lower hazard for symptomatic COVID-19 (HR 0.29; 95% CI 0.09, 0.91) among 1904 SOT recipients at a single center from January 1 to August 12, 2021.

Older kidney transplant recipients demonstrate increased rates of infection, and lower rates of rejection, compared with younger kidney transplant recipients. However, the mechanism behind this observation remains unknown. To develop a multifaceted view of age-associated immune dysfunction, we determined the function and phenotype of T cells predisposing to vulnerability to infection on a molecular level. Overlapping peptide pools representing the dominant CMV antigens were used to stimulate PBMC collected from 51 kidney transplant recipients, using cytokine secretion to determine specificity and intensity of response. Staphylococcal endotoxin B (SEB) was analyzed in parallel. To define immune cell subsets, we used single cell RNA sequencing (scRNAseq) to evaluate cellular surface markers and gene expression. We found increased frequency of SEB- and CMV-specific T cells was associated with freedom from infection, especially in older patients. Spatialized t-SNE analysis revealed decreased frequency of naïve T cells, increased frequency of TEMRA cells, and decreased frequency of IFNγ secreting T cells in patients with infection. Application of scRNAseq analysis revealed increased frequency of terminally differentiated T cells expressing NK-associated receptors and inhibitory markers. These findings offer unique insight into the mechanism behind vulnerability to infection in the kidney transplant recipient, revealing a specific T cell subtype of impaired antigen response and terminal effector phenotype as markers of T cell senescence.

The article concentrates on the perioperative management techniques employed during isolated pancreas and simultaneous pancreas kidney transplantation procedures. It explores aspects concerning pancreas transplantation, perioperative medicine in transplant recipients, and strategies for effectively managing patients undergoing these specific types of transplantation surgeries.

Introduction: Hematopoietic stem cell transplantation (HSCT) is a vital treatment for various hematological disorders. However, HSCT recipients face increased risks of infectious complications due to immunosuppression. Parasitic infections are a significant concern in this vulnerable population and can lead to substantial morbidity and mortality. This review examines parasitic infections in HSCT recipients, focusing on major infections affecting different organ systems, including intestinal parasites (Giardia spp., Entamoeba histolytica, and Cryptosporidium spp.), hematologic parasites (Plasmodium spp. and Babesia spp.), and tissue/visceral parasites (Toxoplasma gondii, Leishmania spp., and Trypanosoma cruzi). Methods: A systematic search of relevant literature was conducted and included studies up to August 2023. Databases included PubMed, Google Scholar, were queried using specific keywords related to parasitic infections in HSCT patients. The epidemiology, risk factors, clinical presentation, diagnostic methods, and treatment approaches for each infection were evaluated. Results and Conclusion: Knowing the epidemiology, risk factors, and clinical presentations are crucial for timely intervention and successful management. By emphasizing early detection, effective therapies, and the unique challenges posed by each of these infections, this review highlights the importance of tailored strategies for HSCT recipients. Future research can further refine management protocols to enhance care and outcomes for these patients. [ABSTRACT FROM AUTHOR]

Introduction: The influence of lung disease on the diaphragm has been poorly studied. The study aimed to evaluate the diaphragm morphology (height and thickness) in single-lung transplantation (SLTx), using computed tomography (CT), by assessing the evolution of the hemidiaphragm of the transplanted and the native side. Methods: Patients who underwent single lung transplantation in our center (Marseille, France) between January 2009 and January 2022 were retrospectively included. Thoracic or abdominal CT scans performed before and the closest to and at least 3 months after the surgery were used to measure the diaphragm crus thickness and the diaphragm dome height. Results: 31 patients mainly transplanted for emphysema or pulmonary fibrosis were included. We demonstrated a significant increase in diaphragm crus thickness on the side of the transplanted lung, with an estimated difference of + 1.25 mm, p = <0.001, at the level of the celiac artery, and + 0.90 mm, p < 0.001, at the level of the L1 vertebra while no significant difference was observed on the side of the native lung. We showed a significant reduction in the diaphragm height after SLTx on the transplanted side (-1.20 cm, p = 0.05), while no change on the native side (+0.02 cm, p = 0.88). Conclusion: After a SLTx, diaphragmatic morphology significantly changed on the transplanted lung, while remaining altered on the native lung. These results highlights that an impaired lung may have a negative impact on its diaphragm. Replacement with a healthy lung can promote the recovery of the diaphragm to its anatomical morphology, reinforcing the close relationship between these two organs. [ABSTRACT FROM AUTHOR]