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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. [ABSTRACT FROM AUTHOR]

Tixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration. We retrospectively investigated breakthrough COVID-19 in SOT recipients administered T/C at Kyoto University Hospital, Japan, from November 2022 to March 2023. Patients were monitored for 6 months after T/C administration. SARS-CoV-2 infection was diagnosed using polymerase chain reaction or antigen tests. The monthly incidence rates of SARS-CoV-2 infection were calculated using the person–time method. T/C were administered to 67 SOT recipients (liver, 16; lung, 36; and kidney, 15), of whom five were infected with SARS-CoV-2. All five cases were classified as mild, and none of these patients required admission to the intensive care unit (ICU) or died. All infected individuals tested positive for SARS-CoV-2 after March 2023, when T/C-resistant subvariant strains became predominant. The monthly incidence rate of SARS-CoV-2 infection, calculated using the person–time method, suggested an increasing trend. During the T/C-resistant variant epidemic, SARS-CoV-2 infections were identified even after T/C administration, suggesting that the prophylactic effects of T/C were invalid. Therefore, emerging variants must be carefully monitored and characterized to determine appropriate antiviral strategies, such as the use of suitable neutralizing antibodies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Although acute hepatitis caused by varicella zoster virus mostly develops in immunocompromised patients, hyperacute liver failure is very rare. To our knowledge, there are no previous reports on liver transplant patients. Methods: We report the first case of fatal hyperacute liver failure due to varicella zoster virus immediately after living‐donor liver transplantation without cutaneous lesions and review the literature. Result: The present case exhibited rapid development and progression of acute liver failure from postoperative days 11–13, despite being seropositive for varicella zoster virus but unvaccinated and on immunosuppression before transplantation. Especially in solid organ transplantation, only six cases of severe acute liver failure that included hepatic encephalopathy and/or impaired consciousness and sudden extremely high (> 4000 U/L) serum aspartate aminotransferase levels have been reported in heart, lung, and kidney transplant patients. Conclusions: Early diagnosis of hyperacute liver failure due to varicella zoster virus is challenging because the disease progresses rapidly and skin lesions are absent. [ABSTRACT FROM AUTHOR]

The document discusses the increased risk of skin cancers, specifically basal-cell carcinomas (BCC) and squamous-cell carcinomas (SCC), in solid organ transplant recipients (SOTR) due to immunosuppression. Treatment primarily involves surgical excision, with adjuvant radiotherapy for aggressive SCC. Immune-checkpoint inhibitors (ICI) are used for advanced SCC in non-immunosuppressed patients, but their use in SOTR requires careful consideration due to the risk of allograft rejection. Prevention strategies include treating precancerous lesions and implementing photoprotection measures. Future perspectives include new immunotherapies, HPV vaccination, and local blockade of tacrolimus for tumor rejection. [Extracted from the article]

Eurotransplant is responsible for the international allocation of organs between eight countries in Europe. All HLA laboratories affiliated to Eurotransplant must be EFI or ASHI-accredited and must participate in the Eurotransplant external proficiency testing (EPT) program, organized by the Eurotransplant Reference Laboratory (ETRL). EPT within Eurotransplant has a long tradition, starting in 1978. The current EPT program consists of the following schemes: HLA typing including serology, CDC crossmatching, HLA-specific antibody detection, and identification. Participants enter the results of laboratory tests using a web-based application. Assessed results are visible on the website. An additional component called “patient-based cases” runs since 2016. Results are summarized and published on the EPT website. Furthermore, these results are discussed during the annual extramural tissue typers meeting, which is organized by the ETRL. Thanks to this EPT program, the performance of all HLA laboratories affiliated to Eurotransplant can be monitored and corrected, if necessary. Because all affiliated laboratories are assessed in the same EPT program, where these laboratories show to be consistent in most of their results, Eurotransplant EPT has proven to be an efficient tool to create a more uniform level of quality of histocompatibility testing within Eurotransplant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Patients and Methods Results Conclusion To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty.We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information.The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6–67.2) years and a median (IQR) age at transplantation of 58.6 (52.7–65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate‐specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5–10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow‐up of 5.8 (2.5–10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow‐up of 5.3 (1–8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer.A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression. [ABSTRACT FROM AUTHOR]

Background: While coronavirus disease 2019 (COVID‐19) is no longer a public health emergency, certain patients remain at risk of severe outcomes. To better understand changing risk profiles, we studied the risk factors for patients with and without solid organ transplantation (SOT) through the various waves of the pandemic. Methods: Using the National COVID Cohort Collaborative we studied a cohort of adult patients testing positive for COVID‐19 between January 1, 2020, and May 2, 2022. We separated the data into waves of COVID‐19 as defined by the Centers for Disease Control. In our primary outcome, we used multivariable survival analysis to look at various risk factors for hospitalization in those with and without SOT. Results: A total of 3,570,032 patients were captured. We found an overall risk attenuation of adverse COVID‐19‐associated outcomes over time. In both non‐SOT and SOT populations, diabetes, chronic kidney disease, and congestive heart failure were risk factors for hospitalization. For SOT specifically, longer time periods between transplant and COVID‐19 were protective and age was a risk factor. Notably, asthma was not a risk factor for major adverse renal cardiovascular events, hospitalization, or mortality in either group. Conclusions: Our study provides a longitudinal view of the risks associated with adverse COVID‐related outcomes amongst SOT and non‐SOT patients, and how these risk factors evolved over time. Our work will help inform providers and policymakers to better target high‐risk patients. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. Methods: A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Results: Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Conclusions: Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies. [ABSTRACT FROM AUTHOR]

Vaccination before solid organ transplantation is recommended since post-transplantation immunosuppression is known to impair vaccine responses. However, little is known about post-transplantation seroprotection rates in organ transplant recipients vaccinated pre-transplantation. We aimed to investigate the proportion of transplant recipients vaccinated against hepatitis B virus (HBV) and invasive pneumococcal disease (IPD) pre-transplantation at the time of listing for transplantation with post-transplantation seroprotection. We included 136 solid organ transplant (SOT) recipients vaccinated at the time of listing for transplantation. We investigated post-transplantation antibody concentrations against HBV and IPD. Established antibody thresholds were used to define seroprotection. The proportions of SOT recipients with post-transplantation seroprotection were 27.9% (n = 38) and 42.6% (n = 58) against HBV and IPD, respectively. Compared to completing HBV vaccination pre-transplantation, completing post-transplantation vaccination (adjusted odds ratio (aOR): 7.8, 95% CI: 2.5–24.5, p < 0.001) and incomplete vaccination (aOR: 6.3, 95% CI: 1.2–32.6, p = 0.028) were associated with non-response against HBV, after adjustment for confounders. Importantly, patients with seroprotection at the time of listing had lower odds of non-response against HBV (aOR: 0.04, 95% CI: 0.0–0.1, p < 0.001) and IPD (aOR: 0.3, 95% CI: 0.1–0.7, p = 0.007) compared to those without seroprotection. SOT recipients vaccinated pre-transplantation had low post-transplantation seroprotection rates against HBV and IPD. However, SOT recipients with seroprotection at the time of listing had lower odds of non-response, suggesting early vaccination should be a priority. [ABSTRACT FROM AUTHOR]

Abstract Background Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia. Methods Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life. Discussion This study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy. Trial registration ClinicalTrials.gov NCT05556720. Registered on 23rd August 2022.

Background: Solid organ transplant recipients experience a period of unique vulnerability during adolescence, when normative developmental changes intersect with health‐related variables to influence psychological health. Methods: This article builds on previous reviews of psychological health in solid organ transplant recipients and proposes opportunities for clinical intervention during adolescence. Results: Transplant recipients often experience neurocognitive changes, particularly with respect to executive functions, that impact health management tasks and autonomous care. Recipients should be monitored for the development of anxiety, depression, and posttraumatic stress symptoms during adolescence, which in turn can negatively impact adherence to immunosuppression. Recent research in posttraumatic growth and resiliency factors may represent a promising avenue of intervention, leveraging normative developmental processes during this time period. Conclusions: As pediatric transplant providers, adolescence represents a developmental period for targeted interventions to foster adjustment and adherence and promote a successful transition to adult care. [ABSTRACT FROM AUTHOR]

The International Pediatric Transplant Association convened an expert consensus conference to assess current evidence and develop recommendations for various aspects of care relating to post‐transplant lymphoproliferative disorders (PTLD) after pediatric solid organ transplantation. This report addresses the outcomes of deliberations by the PTLD Management Working Group. A strong recommendation was made for reduction in immunosuppression as the first step in management. Similarly, strong recommendations were made for the use of the anti‐CD20 monoclonal antibody (rituximab) as was the case for chemotherapy in selected scenarios. In some scenarios, there is uncoupling of the strength of the recommendations from the available evidence in situations where such evidence is lacking but collective clinical experiences drive decision‐making. Of note, there are no large, randomized phase III trials of any treatment for PTLD in the pediatric age group. Current gaps and future research priorities are highlighted. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare rates and severity of recurrent acute diverticulitis in patients with and without solid organ transplant. Background: Immunocompromised solid organ transplant recipients have been considered higher risk for both recurrence and severity of acute diverticulitis. Current guidelines recommend an individualized approach for colectomy in these patients, but these are based on singlecenter data. Methods: We identified patients with acute diverticulitis using the Merative MarketScan commercial claims data from 2014 to 2020. Patients were classified by history of solid organ transplant. The primary outcome was recurrence of acute diverticulitis with an associated antibiotic prescription =60 days from the initial episode. Secondary outcomes included hospitalization, colectomy, and ostomy in patients with recurrence. Analyses used inverse probability weighting to adjust for imbalances in covariates. Results: Of 170,697 patients with evidence of acute diverticulitis, 442 (0.2%) had a history of solid organ transplantation. In the weighted cohort, among people who had not been censored at 1 year (n= 515), 112 (22%; 95% CI: 20%-25%) experienced a recurrence within the first year. Solid organ transplantation was not significantly associated with a risk of recurrence (hazard ratio=1.19; 95% CI: 0.94-1.50). There was also no statistically significant difference in the hospitalization rate for recurrent diverticulitis. Restricting the analysis to hospitalized recurrences, there was no statistically significant difference observed in either length of stay or discharge status. Conclusions: In this national analysis of commercially insured patients with acute diverticulitis we found no statistically significant differences in recurrence between those with and without a history of solid organ transplant. We do not support an aggressive colectomy strategy based on concern for increased recurrence rate and severity in a solid organ transplant population. [ABSTRACT FROM AUTHOR]

Purpose: Immunosuppression is a well-established risk factor for primary central nervous system lymphomas (PCNSLs), which present in this context distinct radiological characteristics. Our aim was to describe the radiological evolution of treated PCNSL in immunocompromised patients and suggest adapted MRI response criteria. Methods: We conducted a multicenter retrospective study of patients from the French LOC, K-Virogref and CANCERVIH network databases and enrolled adult immunocompromised patients with newly diagnosed PCNSL. Results: We evaluated the baseline, intermediate, end-of-treatment and follow-up MRI data of 31 patients (9 living with HIV, 16 with solid organ transplantation and 6 with an autoimmune disease under chronic immunosuppressive therapy). At baseline, 23/30 (77%) patients had necrotic lesions with ring enhancement and 28% of the lesions were hemorrhagic. At the end of the first-line treatment, 12/28 (43%) patients could not be classified according to the IPCG criteria. Thirteen of 28 (46%) patients still harbored contrast enhancement, and 11/28 (39%) patients had persistent large necrotic lesions with a median diameter of 15 mm. These aspects were not associated with a pejorative outcome and progressively diminished during follow-up. Six patients relapsed; however, we failed to identify any neuroimaging risk factors on the end-of-treatment MRI. Conclusion: In immunocompromised patients, PCNSLs often harbor alarming features on end-of-treatment MRI, with persistent contrast-enhanced lesions frequently observed. However, these aspects seemed to be related to the necrotic and hemorrhagic nature of the lesions and were not predictive of a pejorative outcome. Specific response criteria for this population are thereby proposed. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplant recipients are at high risk for developing severe zoster-associated neuralgia, and the pharmaceutic therapies of pain management for these patients with limited organ function are challenging. Intravenous lidocaine infusion showed positive analgesic effects and is used for the management of neuropathic pain. This case series reports the safety and effectiveness of intravenous lidocaine infusion in the treatment of intractable zoster-associated neuralgia in solid organ transplant recipients. Case series presentation: Five solid organ transplant recipients suffering from refractory zoster-associated neuralgia (numeric rating scale 8-10, despite using high doses of antiepileptic drugs or combined with opioids) were enrolled. Intravenous lidocaine (5 mg/kg ideal bodyweight) was administered over 1.5 h with the monitoring of vital signs. Pain intensity, patient satisfaction, adverse events, typical liver, and kidney function were evaluated. All subjects reported high satisfaction with their treatment and effective pain relief at the 6-month follow-up. One patient experienced short and mild numbness in the mouth and dizziness after the therapy, but no major adverse reactions were reported. Conclusion: This case series provides evidence that intravenous lidocaine infusion provided effective pain relief as an analgesic treatment option for transplant patients with intractable zoster-associated neuralgia. [ABSTRACT FROM AUTHOR]

In solid organ transplantation (SOT), biologicals such as recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO (blood group) incompatibility, antibody‐mediated rejections and atypical haemolytic uremic syndrome. In this paper, we review the medical evidence available for biologicals used in SOT and the potential for improvement by the application of therapeutic drug monitoring (TDM) and model‐informed precision dosing. Biologicals are used for off‐label indications within the field of SOT, building on the experience from their use on labelled indications. Dosing is currently mostly standard, and experience vs. effect and toxicity is limited. Pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules. Individualization by concentration measurements and modelling has mostly been proof‐of‐concept or feasibility studies that lack the power to provide evidence for improvement in clinical outcome. For some drugs such as alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept, studies have demonstrated significant interindividual variability in pharmacokinetics. Variability in absorption from subcutaneous administration may increase interindividual variability. There is also an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, but trials of adequate size to document the usefulness of TDM and MIPD are scarce. Collaboration within the TDM community seems mandatory to establish studies of sufficient strength to provide evidence for the use of biologicals that are currently used off‐label in SOT and furthermore to identify the settings where TDM may be beneficial. [ABSTRACT FROM AUTHOR]

Background: Immunocompromised hosts (ICH) experience more breakthrough infections and worse clinical outcomes following infection with COVID-19 than immunocompetent people. Prophylactic monoclonal antibody therapies can be challenging to access, and escape variants emerge rapidly. Immunity conferred through vaccination remains a central prevention strategy for COVID-19. COVID-19 vaccines do not elicit optimal immunity in ICH but boosting, through additional doses of vaccine improves humoral and cellular immune responses. This trial aims to assess the immunogenicity and safety of different COVID-19 vaccine booster strategies against SARS-CoV-2 for ICH in Australia. Methods: Bringing optimised COVID-19 vaccine schedules to immunocompromised populations (BOOST-IC) is an adaptive randomised trial of one or two additional doses of COVID-19 vaccines 3 months apart in people living with HIV, solid organ transplant (SOT) recipients, or those who have haematological malignancies (chronic lymphocytic leukaemia, non-Hodgkin lymphoma or multiple myeloma). Key eligibility criteria include having received 3 to 7 doses of Australian Therapeutic Goods Administration (TGA)-approved COVID-19 vaccines at least 3 months earlier, and having not received SARS-CoV-2-specific monoclonal antibodies in the 3 months prior to receiving the study vaccine. The primary outcome is the geometric mean concentration of anti-spike SARS-CoV-2 immunoglobulin G (IgG) 28 days after the final dose of the study vaccine. Key secondary outcomes include anti-spike SARS-CoV-2 IgG titres and the proportion of people seroconverting 6 and 12 months after study vaccines, local and systemic reactions in the 7 days after vaccination, adverse events of special interest, COVID-19 infection, mortality and quality of life. Discussion: This study will enhance the understanding of COVID-19 vaccine responses in ICH, and enable the development of safe, and optimised vaccine schedules in people with HIV, SOT, or haematological malignancy. Trial registration: ClinicalTrials.gov NCT05556720. Registered on 23rd August 2022. [ABSTRACT FROM AUTHOR]

Background: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models. Methods: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients. By utilizing an immunogenic skin transplant model and existing transplantation medicine reagents, we facilitated the clinical translation of our findings. Specifically, antigen-specific Tregs were used. Results: Our study demonstrated that combining the available induction therapies with drug-induced T-cell proliferation due to lymphopenia effectively increased the Treg/T effector ratios. This results in significant Treg accumulation within the graft, leading to long-term tolerance after the transfer of antigen-specific Tregs. Importantly, all the animals achieved operational tolerance, which boosted the presence of adoptively transferred Tregs within the graft. Conclusions: This protocol offers a means to establish tolerance by utilizing antigen-specific Tregs. These results have promising implications for future trials involving adoptive Treg therapy in organ transplantation. [ABSTRACT FROM AUTHOR]

We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes. [ABSTRACT FROM AUTHOR]

Objective: Kidney transplantation is the gold standard therapeutic alternative for patients with end‐stage renal disease; nevertheless, it is not without potential complications leading to considerable morbidity and mortality such as post‐transplant diabetes mellitus (PTDM). This narrative review aims to comprehensively evaluate PTDM in terms of its diagnostic approach, underlying pathophysiological pathways, epidemiological data, and management strategies. Methods: Articles were retrieved from electronic databases using predefined search terms. Inclusion criteria encompassed studies investigating PTDM diagnosis, pathophysiology, epidemiology, and management strategies. Results: PTDM emerges as a significant complication following kidney transplantation, influenced by various pathophysiological factors including peripheral insulin resistance, immunosuppressive medications, infections, and proinflammatory pathways. Despite discrepancies in prevalence estimates, PTDM poses substantial challenges to transplant. Diagnostic approaches, including traditional criteria such as fasting plasma glucose (FPG) and HbA1c, are limited in their ability to capture early PTDM manifestations. Oral glucose tolerance test (OGTT) emerges as a valuable tool, particularly in the early post‐transplant period. Management strategies for PTDM remain unclear, within sufficient evidence from large‐scale randomized clinical trials to guide optimal interventions. Nevertheless, glucose‐lowering agents and life style modifications constitute primary modalities for managing hyperglycemia in transplant recipients. Discussion: The complex interplay between PTDM and the transplant process necessitates individualized diagnostic and management approaches. While early recognition and intervention are paramount, modifications to maintenance immunosuppressive regimens based solely on PTDM risk are not warranted, given the potential adverse consequences such as increased rejection risk. Further research is essential to refine management strategies and enhance outcomes for transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Pretransplant infection screening (IS) of potential organ recipients is essential to optimal outcome of solid organ transplantation (SOT). Methods: A pre‐post study was performed during 2020–2023 to investigate the impact of the STREAM (Solid organ TRansplant stEwArdship and Multidisciplinary approach) intervention to improve IS in SOT. The intervention, performed in 2022, included the implementation of IS through educational meetings, local guidelines, and the availability of a digital screening tool. The objective of the study was the assessment of IS completion, including a list of 17 laboratory tests and the investigation of vaccination status. The reduction of unnecessary tests was also analyzed. The test of proportions and a multilevel multivariate Poisson regression model were used to compare IS completion before and after STREAM. infectious diseases (ID) consultation and urgent evaluation were investigated as predictors of IS completion. Results: A total of 171 patients were enrolled, including liver (44%), heart (32%), and kidney (24%) transplant candidates. Mean age was 56 ± 11 years, and most patients (77%) were males. Ninety‐five (56%) patients were included before the intervention and 76 (44%) after STREAM. IS completion increased after STREAM (IRR 1.41, p < 0.001) with significant improvement recorded for seven (39%) IS items. Unnecessary tests decreased by 43% after the intervention. ID consultation (IRR 1.13, p = 0.02) and urgent evaluation (IRR 0.68, p 〈0.001) were predictors of IS improvement. Conclusions: STREAM was successful in improving IS completion. Further research is needed to investigate the impact of this intervention on posttransplant infections. [ABSTRACT FROM AUTHOR]

Background: The thymus is pivotal for immune system development by facilitating T-cell maturation. Current treatments for congenital athymia typically involve avascular transplantation of allogeneic thymic tissue. However, vascularizing an infant thymus for transplantation could offer improved outcomes, necessitating a detailed understanding of its vascular anatomy. Method: Between June and November 2022, we conducted a feasibility study at our tertiary care university hospital, examining seven thymus glands that were surgically removed and discarded during corrective surgeries for congenital heart disease in patients aged 16 days to 17 months. Results: Angiographic analysis revealed distinct vascular pathways in infant thymic lobes, with arteries averaging 0.5 mm and veins 0.8 mm in diameter, both showing adequate perfusion with Belzer solution. Conclusion: These findings provide critical insights into the vascular anatomy of the infant thymus, underscoring its potential for microvascular revascularization and transplantation.

IntroductionSolid 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.MethodsWe 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.ResultsWe 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.DiscussionOur 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.

Abstract Background The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI). Methods This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded. Results The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5–61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p

Patients with Solid Organ Transplantations (SOTx) face long-term lifestyle adaptations, psychological and social adjustments, and complex self-care regimes to maintain health post-transplant. Self-management (SM) skills represent important aspects of nursing communication with SOTx patients; however, there is potential for SM to be defined narrowly in terms of medication adherence. The study presented here collated the existing definitions in a mixed method review in order to identify SM attributes for this group (including those unique to this population). Secondary analysis of a dataset and bibliographic analysis and an expert panel were used to develop a comprehensive working definition of SOTx patients. The analysis comprised critical interpretation of the evolving definition content, concepts, and contexts of application in current usages and over time. We identified eight definitions and 63 cited definition sources from bibliographic analysis. Findings identified limitations of the existing definitions. Population-specific attributes included optimisation of transplant outcomes, active engagement in healthy behaviours, control, structure, and discipline characteristics, and moderating factors of patient motivation, self-efficacy, and cognitive function. A critical appraisal of definitions indicated inadequately defined aspects such as setting, temporal dimension, concept interaction, interventions, and measurable outcomes. The bibliographic analysis highlighted the influence of broader chronic illness constructions of SM, underpinning the generalisable SM attributes in current definitions. Further research may advance the development of a definition in exploring the relevance of SOTx-specific attributes of the definition.

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%–47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46–2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16–2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03–1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17–1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58–4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42–0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes.

Cytomegalovirus (CMV) infection frequently occurs after solid organ transplantation and is associated with an increased morbidity and mortality. Fortunately, the development of valganciclovir prophylaxis has lowered the incidence of CMV infection and its complications in immunosuppressed solid organ transplant recipients. However, breakthrough infections during valganciclovir prophylaxis and late CMV infection after cessation of valganciclovir prophylaxis still occur with the current prophylactic strategy. Additionally, valganciclovir resistance has emerged among CMV strains, which complicates the treatment of CMV infections. Furthermore, the use of valganciclovir is associated with myelotoxicity, which can lead to the premature withdrawal of prophylaxis. It is important to address these current issues in order to improve the standard care after solid organ transplantation. This paper will therefore discuss the clinical practice of valganciclovir prophylaxis, elaborate on its issues and suggest how to improve the current prophylactic strategy with a possible role for therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Allograft rejection is a critical issue following solid organ transplantation (SOT). Immunosuppressive therapies are crucial in reducing risk of rejection yet are accompanied by several significant side effects, including infection, malignancy, cardiovascular diseases, and nephrotoxicity. There is a current unmet medical need with a lack of effective minimization strategies for these side effects. Extracorporeal photopheresis (ECP) has shown potential as an immunosuppression (IS)-modifying technique in several SOT types, with improvements seen in acute and recurrent rejection, allograft survival, and associated side effects, and could fulfil this unmet need. Through a review of the available literature detailing key areas in which ECP may benefit patients, this review highlights the IS-modifying potential of ECP in the four most common SOT procedures (heart, lung, kidney, and liver transplantation) and highlights existing gaps in data. Current evidence supports the use of ECP for IS modification following SOT, however there is a need for further high-quality research, in particular randomized control trials, in this area. [ABSTRACT FROM AUTHOR]

Background: Adolescent and young adult (AYA) solid organ transplant (SOT) recipients experience increased rates of rejection and graft loss surrounding the time of health care transition, in part due to poor medication adherence. This study aims to examine the impact of a once‐daily formulation of tacrolimus, LCP‐tacrolimus (LCPT), on medication adherence for AYA SOT patients. Methods: A retrospective descriptive analysis was performed for all patients who underwent SOT and were prescribed LCPT after the age of 12 at our single‐center pediatric hospital. Medication adherence was assessed via provider documentation and the medication level variability index (MLVI). Results: Twenty‐nine patients were prescribed LCPT as part of their immunosuppression regimen. Twenty patients were converted to LCPT from immediate‐acting (IR) tacrolimus; six patients were initiated immediately following transplant, and three patients were unable to receive LCPT due to insurance denial. There was a numeric improvement in medication adherence for converted patients when measured by provider assessment (45.0% vs. 68.4%, p =.140) and MLVI (40.0% vs. 71.4%, p =.276), though these did not reach statistical significance. There were no differences in episodes of rejection or adverse effects. LCPT prescription was not associated with decreased medication burden, and two patients transitioned back to IR tacrolimus due to increased cost. Conclusions: LCPT use did not significantly improve patient adherence; however, it resulted in numerically higher perceived and measured adherence rates. LCPT appears to be safe and effective in the management of SOT recipients; however, it may not affect pill burden and may result in a higher financial burden. Use may be considered for a select group of AYA SOT recipients. [ABSTRACT FROM AUTHOR]

Purpose: Lung transplant recipients are at increased risk of severe disease following infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) due to high-dose immunosuppressive drugs and the lung is the main organ affected by Coronavirus disease 2019 (COVID-19). Several studies have confirmed increased SARS-CoV-2-related mortality and morbidity in patients living with lung allografts; however, detailed immunological studies of patients with SARS-CoV-2 infection in the early phase following transplantation remain scarce. Methods: We investigated patients who were infected with SARS-CoV-2 in the early phase (18–103 days) after receiving double-lung allografts (n = 4, LuTx) in comparison to immunocompetent patients who had not received solid organ transplants (n = 88, noTx). We analyzed SARS-CoV-2-specific antibody responses against the SARS-CoV-2 spike and nucleocapsid proteins using enzyme-linked immunosorbent assays (ELISA), chemiluminescence immunoassays (CLIA), and immunoblot assays. T cell responses were investigated using Elispot assays. Results: One LuTx patient suffered from persistent infection with fatal outcome 122 days post-infection despite multiple interventions including remdesivir, convalescent plasma, and the monoclonal antibody bamlanivimab. Two patients experienced clinically mild disease with prolonged viral shedding (47 and 79 days), and one patient remained asymptomatic. Antibody and T cell responses were significantly reduced or undetectable in all LuTx patients compared to noTx patients. Conclusion: Patients in the early phase following lung allograft transplantation are vulnerable to infection with SARS-CoV-2 due to impaired immune responses. This patient population should be vaccinated before LuTx, protected from infection post–LuTx, and in case of infection treated generously with currently available interventions. [ABSTRACT FROM AUTHOR]

Due to an aging population, advances in multiple medical fields, and shifts among indications for surgery, liver and kidney transplantation is increasingly pursued for elderly patients (aged 65 or greater). Elderly patients represent a uniquely vulnerable group, but overall, they appear to have similar outcomes compared to younger patients. As demographics continue to trend to an older median age, physicians and health care systems must be prepared to take care of elderly transplant candidates. [ABSTRACT FROM AUTHOR]

Patients with Solid Organ Transplantations (SOTx) face long-term lifestyle adaptations, psychological and social adjustments, and complex self-care regimes to maintain health post-transplant. Self-management (SM) skills represent important aspects of nursing communication with SOTx patients; however, there is potential for SM to be defined narrowly in terms of medication adherence. The study presented here collated the existing definitions in a mixed method review in order to identify SM attributes for this group (including those unique to this population). Secondary analysis of a dataset and bibliographic analysis and an expert panel were used to develop a comprehensive working definition of SOTx patients. The analysis comprised critical interpretation of the evolving definition content, concepts, and contexts of application in current usages and over time. We identified eight definitions and 63 cited definition sources from bibliographic analysis. Findings identified limitations of the existing definitions. Population-specific attributes included optimisation of transplant outcomes, active engagement in healthy behaviours, control, structure, and discipline characteristics, and moderating factors of patient motivation, self-efficacy, and cognitive function. A critical appraisal of definitions indicated inadequately defined aspects such as setting, temporal dimension, concept interaction, interventions, and measurable outcomes. The bibliographic analysis highlighted the influence of broader chronic illness constructions of SM, underpinning the generalisable SM attributes in current definitions. Further research may advance the development of a definition in exploring the relevance of SOTx-specific attributes of the definition. [ABSTRACT FROM AUTHOR]

Introduction: Workers who undergo solid organ transplantation report frequent conflicts between the unpredictable demands of their health condition and the rigid requirements of their employer and of health services. The present study aimed to describe the self-management strategies adopted by workers while staying at work before transplantation and during sustainable return-to-work posttransplantation. Methods: Fifteen employed kidney, liver, and lung transplant recipients were recruited from 2 large urban university health centers in Montreal, Canada. Three focus groups were held, and thematic analysis was performed. Findings: Seven strategies were identified: responding promptly and consistently to fatigue-related needs, planning ahead with immediate supervisors while remaining strategic about when to disclose transplantation, requesting work accommodations, requesting flexibility in healthcare provision, consulting physicians about work-related issues, informing co-workers about work limitations and immunosuppression and asking not to be treated differently in the workplace. Conclusion: Access to work accommodations, support from physicians and flexibility in treatment and appointment schedules supported workers' ability to manage their health while staying at work before and after undergoing solid organ transplantation. In light of findings, it may be useful for healthcare professionals to address workers' concerns about work limitations and work accommodation implementation, especially when the illness-management burden increases before transplantation and during posttransplantation sick leave. Future studies could describe the strategies used by other important stakeholders when attempting to provide support to workers. [ABSTRACT FROM AUTHOR]

Background: The recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI). Methods: This retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded. Results: The 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5–61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8–795.4 vs. 1049.6, IQR 338.6–2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86–0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01–1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597–0.848, p = 0.0005. Conclusions: PIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully. [ABSTRACT FROM AUTHOR]

Due to its intrinsic complexity and the principle of collective solidarity that governs it, solid organ transplantation (SOT) seems to have been spared from the increase in litigation related to medical activity. Litigation relating to solid organ transplantation that took place in the 29 units of the Assistance Publique-Hôpitaux de Paris and was the subject of a judicial decision between 2015 and 2022 was studied. A total of 52 cases of SOT were recorded, all in adults, representing 1.1% of all cases and increasing from 0.71% to 1.5% over 7 years. The organs transplanted were 25 kidneys (48%), 19 livers (37%), 5 hearts (9%) and 3 lungs (6%). For kidney transplants, 11 complaints (44%) were related to living donor procedures and 6 to donors. The main causes of complaints were early post-operative complications in 31 cases (60%) and late complications in 13 cases (25%). The verdicts were in favour of the institution in 41 cases (79%). Solid organ transplants are increasingly the subject of litigation. Although the medical institution was not held liable in almost 80% of cases, this study makes a strong case for patients, living donors and their relatives to be better informed about SOT. [ABSTRACT FROM AUTHOR]

Introduction: Exercise training post-transplant has been shown to improve physical function and quality of life in solid organ transplant (SOT) recipients. Online resources in the form of websites and videos are commonly used to provide education and instruction on exercise and physical activity in SOT; however, the content and quality of these online resources has not been evaluated. Methods: The first 200 websites and videos identified on Google and YouTube using the English search term "exercise and physical activity in solid organ transplantation" were analyzed. Website and video content was evaluated based on 25 key components of exercise and physical activity in SOT as described in established exercise program recommendations. Website and video quality was determined using DISCERN, Global Quality Scale (GQS), and Patient Education Materials and Assessment Tool (PEMAT; threshold for which material is deemed understandable or actionable is >70%). Parametric and non-parametric tests were used to assess website and video characteristics, content, and quality metrics. Results: Forty-nine unique SOT websites (n = 15) and videos (n = 34) were identified, with the two most common categories being foundation/advocacy organizations and scientific resources. The average reading grade level of websites was 13 ± 3. Website and video content scores varied significantly (websites 11.3 ± 6.4; videos 8.4 ± 5.3). DISCERN total score and GQS score were low (median range for DISCERN 2.5-3.0; median for GQS 2.0 for both websites and videos, out of 5). PEMAT understandability and actionability scores were also low across websites and videos (mean range 57%-67% and 47%-65%, respectively). Foundation/advocacy websites had higher content and quality scores compared to scientific organizations and news/media articles. Conclusions: To our knowledge, this is the first comprehensive assessment of online content and quality of website and video resources on physical activity and exercise in adult SOT recipients. There were a limited number of online English patient-directed resources related to physical activity in SOT, most of which only partly captured items outlined in consensus exercise program recommendations and were of low quality and understandability and actionability. This work provides important insight to the English-speaking transplant community on the current state of online exercise health information and provides future direction for resource development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Türkiye. MATERIAL AND METHODS: Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. RESULTS: TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n = 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. CONCLUSION: We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines. [ABSTRACT FROM AUTHOR]

• ETI is safe in most liver transplanted patients with CF. • Close monitoring of liver function and tacrolimus level is warranted. • An improvement in lung function after ETI is found also in liver transplanted patients. Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation. A systematic review was conducted through MEDLINE/Pubmed and EMBASE databases. English-written articles reporting clinical data on liver transplanted CF patients treated with ETI were included. Article quality was evaluated using the Critical Appraisal Checklist for Case Reports. Twenty cases were retrieved from 6 reports. Temporary discontinuation and/or dose reduction due to elevated transaminases was required in 5 cases. ETI restarted on a reduced dose was tolerated in 3 out of 5 patients, 1 patient tolerated full dose. Tacrolimus dose change was required in 14 cases, in 1 case ETI was discontinued due to tacrolimus toxicity. Improvement in percentage predicted FEV1 was noted in 15/19 patients (median +17 %, range 8 %–38 %). In the majority of liver transplanted patients ETI is well tolerated, although adverse events and liver function abnormalities may occur. Close monitoring of liver function and tacrolimus level is warranted. Significant improvement in lung function after ETI initiation is confirmed, highlighting the importance of accessing this medication for this group of patients. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplantation (SOT) is a lifesaving treatment for end‐stage organ failure. Although many factors affect the success of organ transplantation, recipient and donor sex are important biological factors influencing transplant outcome. However, the impact of the four possible recipient and donor sex combinations (RDSC) on transplant outcome remains largely unclear. Methods: A scoping review was carried out focusing on studies examining the association between RDSC and outcomes (mortality, graft rejection, and infection) after heart, lung, liver, and kidney transplantation. All studies up to February 2023 were included. Results: Multiple studies published between 1998 and 2022 show that RDSC is an important factor affecting the outcome after organ transplantation. Male recipients of SOT have a higher risk of mortality and graft failure than female recipients. Differences regarding the causes of death are observed. Female recipients on the other hand are more susceptible to infections after SOT. Conclusion: Differences in underlying illnesses as well as age, immunosuppressive therapy and underlying biological mechanisms among male and female SOT recipients affect the post‐transplant outcome. However, the precise mechanisms influencing the interaction between RDSC and post‐transplant outcome remain largely unclear. A better understanding of how to identify and modulate these factors may improve outcome, which is particularly important in light of the worldwide organ shortage. An analysis for differences of etiology and causes of graft loss or mortality, respectively, is warranted across the RDSC groups. Practitioner points: Recipient and donor sex combinations affect outcome after solid organ transplantation.While female recipients are more susceptible to infections after solid organ transplantation, they have higher overall survival following SOT, with causes of death differing from male recipients.Sex‐differences should be taken into account in the post‐transplant management. [ABSTRACT FROM AUTHOR]

Solid organ transplant (SOT) recipients with COVID-19 have a higher risk of mortality than those without COVID-19. However, it is unclear how SOT patient outcomes compare to the general population without SOT who contract COVID-19. We used the National Inpatient Sample from January to December 2020 to investigate inpatient outcomes seen in SOT recipients after contracting COVID-19 compared to nontransplant patients. We identified our study sample using ICD-10 CM and excluded those <18 years of age and those with dual organ transplants. Inpatient outcomes were compared in SOT and non-SOT COVID cohorts, and we further evaluated predictors of mortality in the SOT with COVID population. Out of the 1,416,445 COVID-19 admissions included in the study, 8315 (0.59%) were single SOT recipients. Our analysis that adjusted for multiple baseline characteristics and comorbidities demonstrated that COVID-19 in SOT patients was associated with higher rates of acute kidney injury (adjusted odds ratio [aOR] 2.34, 95% confidence interval [CI] 1.81–3.02, P < 0.01), lower rates of acute respiratory distress syndrome (aOR 0.68, 95% CI 0.54–0.85, P < 0.01), and similar rates of cardiac arrest, pulmonary embolism, circulatory shock, cerebrovascular events, and in-hospital mortality. Age >65 was associated with mortality in SOT patients. In this nationally representative sample, SOT patients presenting with COVID-19 experienced similar rates of mortality compared to those without SOT. SOT patients were more likely to develop acute kidney injury. Further research is needed to understand the complex relationship between transplant patient outcomes and COVID-19. [ABSTRACT FROM AUTHOR]

Infectious complications, including widespread human cytomegalovirus (CMV) disease, frequently occur after hematopoietic stem cell and solid organ transplantation due to immunosuppressive treatment causing impairment of T-cell immunity. Therefore, in-depth analysis of the impact of immunosuppressants on antiviral T cells is needed.We analyzed the impact of mTOR inhibitors sirolimus (SIR/S) and everolimus (EVR/E), calcineurin inhibitor tacrolimus (TAC/T), purine synthesis inhibitor mycophenolic acid (MPA/M), glucocorticoid prednisolone (PRE/P) and common double (T+S/E/M/P) and triple (T+S/E/M+P) combinations on antiviral T-cell functionality. T-cell activation and effector molecule production upon antigenic stimulation was impaired in presence of T+P and triple combinations. SIR, EVR and MPA exclusively inhibited T-cell proliferation, TAC inhibited activation and cytokine production and PRE inhibited various aspects of T-cell functionality including cytotoxicity. This was reflected in an in vitro infection model, where elimination of CMV-infected human fibroblasts by CMV-specific T cells was reduced in presence of PRE and all triple combinations. CMV-specific memory T cells were inhibited by TAC and PRE, which was also reflectedwith double (T+P) and triple combinations. EBV- and SARS-CoV-2-specific T cells were similarly affected. These results highlight the need to optimize immune monitoring to identify patients whomay benefit fromindividually tailored immunosuppression. [ABSTRACT FROM AUTHOR]

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare inflammatory disorder with a high mortality rate and a wide range of symptoms. Solid organ transplantation, which provides patients with a unique immunosuppressive state, is a less common predisposing factor for HLH. HLH after solid organ transplantation (HLH-SOT) is very rare and fatal. It is hard to diagnose and treat and extremely understudied. The use of immunosuppressants makes the situation of HLH-SOT more complex. This review summarizes the existing literature on HLH after solid organ transplantation and describes its triggers and symptoms, focusing on its diagnosis and treatment. We performed a literature search of case reports, case series, letters to the editor, and clinical quizzes describing patients with HLH after solid organ transplantation (HLH-SOT). We provide recommendations on the diagnosis protocol and treatment strategy based on the existing evidence. [ABSTRACT FROM AUTHOR]

Objective: Solid organ transplant (SOT) recipients have a poorer SARS‐CoV‐2 vaccine response and higher risk for COVID‐19‐associated complications. However, there is no consensus on the current management of COVID‐19 and data on persistent COVID‐19 rates in SOT recipients are lacking. Methods: An electronic survey concerning the management of COVID‐19 in SOT recipients was distributed among all members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) and of the European Society for Organ Transplantation (ESOT). Four major sections were covered: prevention, early COVID‐19, late COVID‐19, and persistent COVID‐19. We developed a structured questionnaire including eight multiple‐choice questions with branching logic in case of positive answers and three open‐ended questions related to clinical practice. Questions were asked separately for lung and non‐lung transplantation. Results: Thirty‐two physicians from 24 different centers participated. Most answers (n = 30) were provided by European physicians. Thirty of 32 (93.75%) physicians managed non‐lung transplant recipients and 12 of 32 (33.3%) lung transplant recipients. There was a huge variability in practice regarding the treatment of COVID‐19, and particularly noticeable when considering lung and non‐lung transplant recipients. Main discordances included the use of nirmatrelvir alone or in combination therapy for early COVID‐19, the use of immunomodulatory drugs other than steroids for late COVID‐19, and the need for treating asymptomatic viral shedding in persistent COVID‐19. There was more similarity in terms of prophylaxis recommendations. Conclusion: Despite a low number of respondents, this survey shows that there are many differences on how experts manage SARS‐CoV‐2 infections in SOT recipients. [ABSTRACT FROM AUTHOR]

Background: Valganciclovir (VGCV) prophylaxis is associated with an increased risk of hematologic side effects. We analyzed the impact of VGCV prophylaxis on leukopenia and neutropenia rates and explored risk factors for its occurrence. Methods: Retrospective cohort study of adult cytomegalovirus (CMV)‐seronegative solid organ transplantation (SOT) recipients of either CMV‐seropositive (CMV D+/R‐) or CMV‐seronegative (CMV D‐/R‐) donors between July 2005 and March 2019. CMV D+/R‐ SOT recipients received 3–12 months of VGCV prophylaxis whereas CMV D‐/R‐ SOT recipients received no VGCV prophylaxis. Competing risk regression was used to calculate risk factors for significant neutropenia (neutrophil count < 1000/μL). Results: A total of 430 CMV‐seronegative SOT recipients (median age of 52.1 years, 76.5% males) were included, of which 203 (47.2%) were CMV D+/R‐ and 227 (52.8%) CMV D‐/R‐. The unadjusted incidence rate ratio of significant neutropenia attributable to VGCV exposure in the first year post‐transplant was 13.50 (95% confidence interval 7.36–27.11). Acute rejection occurred more frequently in neutropenic patients at 32.5% compared to 19.1% in those without neutropenia (p =.033). On multivariate analysis, VGCV prophylaxis for 1–90 days and 91–180 days versus no VGCV were the strongest risk factors for significant neutropenia with a sub‐distribution hazard ratio of 39.6 (95% CI, 8.57–182.6) and 13.2 (95% CI, 5.46–32.0), respectively. Conclusions: VGCV prophylaxis is limited by high rates of neutropenia. Future prospective studies are needed to assess alternative CMV prophylactic strategies in SOT recipients. [ABSTRACT FROM AUTHOR]

Immune cell metabolism plays a pivotal role in shaping and modulating immune responses. The metabolic state of immune cells influences their development, activation, differentiation, and overall function, impacting both innate and adaptive immunity. While glycolysis is crucial for activation and effector function of CD8 T cells, regulatory T cells mainly use oxidative phosphorylation and fatty acid oxidation, highlighting how different metabolic programs shape immune cells. Modification of cell metabolism may provide new therapeutic approaches to prevent rejection and avoid immunosuppressive toxicities. In particular, the distinct metabolic patterns of effector and suppressive cell subsets offer promising opportunities to target metabolic pathways that influence immune responses and graft outcomes. Herein, we review the main metabolic pathways used by immune cells, the techniques available to assay immune metabolism, and evidence supporting the possibility of shifting the immune response towards a tolerogenic profile by modifying energetic metabolism. [ABSTRACT FROM AUTHOR]

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%–47 % and I2 = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46–2.41 and I2 = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16–2.54 and I2 = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03–1.99 and I2 = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17–1.53 and I2 = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58–4.04 and I2 = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42–0.89 and I2 = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes. [ABSTRACT FROM AUTHOR]

Eurotransplant is responsible for the international allocation of organs between eight countries in Europe. All HLA laboratories affiliated to Eurotransplant must be EFI or ASHI-accredited and must participate in the Eurotransplant external proficiency testing (EPT) program, organized by the Eurotransplant Reference Laboratory (ETRL). EPT within Eurotransplant has a long tradition, starting in 1978. The current EPT program consists of the following schemes: HLA typing including serology, CDC crossmatching, HLA-specific antibody detection, and identification. Participants enter the results of laboratory tests using a web-based application. Assessed results are visible on the website. An additional component called “patient-based cases” runs since 2016. Results are summarized and published on the EPT website. Furthermore, these results are discussed during the annual extramural tissue typers meeting, which is organized by the ETRL. Thanks to this EPT program, the performance of all HLA laboratories affiliated to Eurotransplant can be monitored and corrected, if necessary. Because all affiliated laboratories are assessed in the same EPT program, where these laboratories show to be consistent in most of their results, Eurotransplant EPT has proven to be an efficient tool to create a more uniform level of quality of histocompatibility testing within Eurotransplant.