Solid Organ Transplant Recipients Research Articles

Use of biologics for psoriasis in solid organ transplant recipients.

Biologics have significantly advanced the treatment of inflammatory disorders, including psoriasis. However, their use in immunosuppressed patients, such as those with solid-organ transplants, is less understood. These patients often face dermatological issues, but inflammatory skin diseases are rare due to their immunosuppressive treatments. Our study aims to assess biologics' effectiveness in such immunocompromised patients. We report a case from our institution of a 29-year-old man with a history of psoriasis, who underwent a kidney transplant and later developed erythroderma. He did not respond to traditional treatments and was successfully treated with adalimumab, leading to the discontinuation of MMF. We also reviewed literature in solid organ transplant patients with psoriasis. Our findings, based on 10 articles, indicate a cautious approach to using biologics in this group, with further research needed for efficacy and safety.

A Multiplex Fluorescence of Loop Primer Upon Self-Dequenching Loop-Mediated Isothermal Amplification Assay for the Detection of Epstein-Barr Virus and Human Parvovirus B19 in Clinical Transplant Samples.

Viral infections are major causes of mortality in solid-organ and hematopoietic stem cell transplant recipients. Epstein-Barr virus (EBV) and Parvovirus B19 (B19V) are among the common viral infections after transplantation and were recommended for increased screening in relevant guidelines. Therefore, the development of rapid, specific, and cost-effective diagnostic methods for EBV and B19V is of paramount importance. We applied Fluorescence of Loop Primer Upon Self-Dequenching Loop-mediated Isothermal Amplification (FLOS-LAMP) for the first time to develop a novel multiplex assay for the detection of EBV and B19V; the fluorophore attached to the probe are self-quenched in unbound state. After binding to the dumbbell-shaped DNA target, the fluorophore is dequenched, resulting in fluorescence development. The novel multiplex FLOS-LAMP assay was optimized by testing various ratios of primer sets. This novel assay, with great specificity, did not cross-react with the common virus. For the detection of EBV and B19V, the limits of detection could reach 969 and 798 copies/μL, respectively, and the assay could be completed within 25 min. Applying this novel assay to detect 200 clinical transplant individuals indicated that the novel assay had high specificity and good sensitivity. We developed multiplex FLOS-LAMP assay for the detection of EBV and B19V, which has the potential to become an important tool for clinical transplant patient screening.

Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center

Invasive mold infections (IMD) are an emerging concern due to the growing prevalence of patients at risk, encompassing but not limited to allogeneic hematopoietic stem cell transplant recipients, hematological malignancies patients, solid organ transplant recipients and intensive care unit patients. In contrast with invasive aspergillosis and mucormycosis, other hyalohyphomycoses and phaeohyphomycoses remain poorly known. We conducted a retrospective analysis of the clinical, biological, microbiological and evolutive features of 92 IMD having occurred in patients in our tertiary-care center over more than 25 years. A quarter of these infections were due to multiple molds. Molds involved were Fusarium spp. (36.2% of IMD with a single agent, 43.5% of IMD with multiple agents), followed by Scedosporium spp. (respectively 14.5% and 26.1%) and Alternaria spp. (respectively 13.0% and 8.7%). Mortality at day 84 was higher for Fusarium spp., Scedosporium spp. or multiple pathogens IMD compared with Alternaria or other pathogens (51.7% vs. 17.6%, p < 0.05). Mortality at day 84 was also influenced by host factor: higher among hematology and alloHSCT patients than in other patients (30.6% vs. 20.9% at day 42 and 50.0% vs. 27.9% at day 84, p = 0.041). Better awareness, understanding and treatments are awaited to improve patient prognosis.

Monocentric, Retrospective Study on Infectious Complications within One Year after Solid-Organ Transplantation at a Belgian University Hospital

The epidemiology, diagnostic methods and management of infectious complications after solid-organ transplantation (SOT) are evolving. The aim of our study is to describe current infectious complications in the year following SOT and risk factors for their development and outcome. We conducted a retrospective study in adult SOT recipients in a Belgian university hospital between 2018 and 2019. We gathered demographic characteristics, comorbidities leading to transplantation, clinical, microbiological, surgery-specific and therapeutic data concerning infectious episodes, and survival status up to one year post-transplantation. Two-hundred-and-thirty-one SOT recipients were included (90 kidneys, 79 livers, 35 lungs, 19 hearts and 8 multiple organs). We observed 381 infections in 143 (62%) patients, due to bacteria (235 (62%)), viruses (67 (18%)), and fungi (32 (8%)). Patients presented a median of two (1–5) infections, and the first infection occurred during the first six months. Nineteen (8%) patients died, eleven (58%) due to infectious causes. Protective factors identified against developing infection were obesity [OR [IC]: 0.41 [0.19–0.89]; p = 0.025] and liver transplantation [OR [IC]: 0.21 [0.07–0.66]; p = 0.007]. Risk factors identified for developing an infection were lung transplantation [OR [IC]: 6.80 [1.17–39.36]; p = 0.032], CMV mismatch [OR [IC]: 3.53 [1.45–8.64]; p = 0.006] and neutropenia [OR [IC]: 2.87 [1.27–6.47]; p = 0.011]. Risk factors identified for death were inadequate cytomegalovirus prophylaxis, infection severity and absence of pneumococcal vaccination. Post-transplant infections were common. Addressing modifiable risk factors is crucial, such as pneumococcal vaccination.

Bridging the gap: assessing CMV DNAemia in kidney transplant recipients with previous solid organ transplants

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7–5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5–8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.

Abstract CT003: Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS)

Abstract Background: Skin cancers are common post-transplant malignancies in solid organ transplant (SOT) recipients. The use of immune checkpoint inhibitors has improved outcomes in the general patient (pt) population but is associated with a high risk of allograft rejection in transplant recipients. RP1 is an oncolytic immunotherapy that expresses a fusogenic glycoprotein (GALV-GP-R−) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The purpose of this study is to assess the safety and efficacy of single-agent RP1 in SOT recipients with skin cancer (NCT04349436). Methods: The trial will enroll up to 65 transplant recipients with histologically confirmed advanced cutaneous squamous cell carcinoma (CSCC) and up to 10 pts with advanced non-CSCC skin cancer in 2 parts. Part A (completed) enrolled kidney and liver transplant recipients until safety was established, and Part B is enrolling kidney, liver, heart, and lung transplant recipients. Pts must have stable allograft function and ECOG performance status ≤1. Pts with visceral metastases are excluded. Pts receive an initial RP1 dose at 1 × 106 plaque-forming units (PFU)/mL followed by 1 × 107 PFU/mL after 2 weeks and continuing every 2 weeks until prespecified study endpoints are met. Tumor biopsies are collected for biomarker analyses and HSV-1 serostatus is monitored. Results: At the data cutoff (Sept 18, 2023), 27 transplant recipients were enrolled (kidney, n = 22; liver, n = 4; lung, n = 1) with a median (range) age of 68 (48-86) years; 24 pts had CSCC and 3 had Merkel cell carcinoma. Nearly half of pts (44%) had metastatic disease at study baseline. The investigator-assessed objective response rate (ORR) for efficacy-evaluable pts was 35% (8/23); 22% of pts (5/23) had complete response (CR). Most responses were ongoing. The most common (>20%) treatment-emergent adverse events were fatigue (33%), chills (26%), and pyrexia (26%). There was no evidence of allograft rejection. Eight deaths were reported; none were related to RP1. Immunohistochemistry from tumor biopsies indicated influx of CD8+ T cells and upregulation of PD-L1 expression after RP1 treatment. Additional biomarker data from gene expression analysis will be presented. Conclusions: This is the first trial assessing single-agent RP1 activity in solid organ transplant recipients with advanced cutaneous malignancies. RP1 monotherapy showed compelling antitumor activity (ORR 35%; 22% CR) in evaluable pts. Additionally, RP1 monotherapy was well tolerated, and the safety profile was similar to non-immunocompromised pts with advanced skin cancers (IGNYTE study). Citation Format: Michael R. Migden, Wanxing Chai-Ho, Gregory A. Daniels, Theresa Medina, Trisha M. Wise-Draper, Meenal Kheterpal, Jennifer C. Tang, Sherrif F. Ibrahim, Diana Bolotin, Claire Verschraegen, Nathalie C. Zeitouni, Katy K. Tsai, Laxminarasimha Donthireddy, Praveen K. Bommareddy, Jeannie W. Hou, Walter Hong, Diwakar Davar. Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT003.

COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children

Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.

Incidence, causative organisms, and risk factors of bloodstream infections in pediatric liver transplant patients: a systematic review.

Bacterial bloodstream infections (BSI) are the leading cause of mortality and morbidity in pediatric solid organ transplant recipients. This systematic review aimed to pool global data from leading transplant institutions and identify the overall incidence, risk factors, and causative organisms of BSI in pediatric liver transplant recipients. A systematic review of the PubMed and OVID databases was conducted from 2000 to 2022. The initial search yielded 252 unique articles, which were independently reviewed by 2 authors. Articles that reported pediatric-specific data on BSI in isolated liver transplant patients were included, including the incidence of BSI, isolated organisms, and involved risk factors involved. This systematic review was registered with PROSPERO (ID: CRD42023403206). Fourteen articles from the United States, France, Iran, Japan, Korea, South Africa, Thailand, and Turkey were included. A total of 4,812 liver transplants were included in the final analysis. The mean patient age was 25 months (age range, 0-18 years), and 50.9% were male. The overall incidence of BSI was 23.5% (range, 14.7%-55%). The most commonly reported organisms were Staphylococcus epidermidis, Enterococcus, Klebsiella spp., and Escherichia coli. Among the risk factors studied, postoperative biliary complications, a medical history of biliary atresia, and younger age were the risk factors most commonly associated with BSI. Bacterial BSI after pediatric liver transplantation occur at a high incidence, with a unique organism profile notable for a higher percentage of gram-negative organisms. Further studies are required to determine the most appropriate prophylactic and empirical antibiotic management strategies for this population.

Solid organ transplant-related central nervous system infections.

Central nervous system (CNS) infections in solid organ transplant (SOT) recipients may present atypical or nonspecific symptoms. Due to a wider range of infectious agents compared with immunocompetent hosts, diagnosis is challenging. This review categorizes CNS infections in SOT recipients by cause. New studies have reported new data on the epidemiology and the risk factors associated with each specific pathogen described in this review. Additionally, we included the treatment recommendations. The latest findings give us an insight into the different pathogens causing infectious neurologic complications in SOT recipients.

Cardiovascular outcomes in solid organ transplant recipients undergoing cardiac surgery: A matched pair analysis.

This study aimed to compare postoperative outcomes after cardiac surgery in solid-organ transplant recipients and nontransplant patients. We performed a retrospective analysis of 78 consecutive transplant recipients who underwent cardiac surgery at Asan Medical Center between 2000 and 2022 and were matched with 312 nontransplant patients who underwent cardiac surgery at a 1:4 ratio. The outcomes included 30-day mortality, all-cause death, cardiac death, readmission, and cardiac readmission. There was no significant difference in baseline characteristics between the two groups. The most common type of cardiac surgery performed in solid organ transplant recipients was isolated valve surgery, followed by isolated CABG. The 30-day mortality was not significantly different between transplant recipients and nontransplant patients (3.9%vs. 3.5%; P>.99). Solid organ transplant recipients showed a higher all-cause mortality compared to nontransplant patients (29.1%vs. 14.3% at 5 years; P=.001); however, there was no significant difference in cardiac death between the two groups (2.6%vs. 3.2% at 5 years; P=.80). In addition, the readmission and cardiac readmission rates showed comparable findings to that of mortality. Cardiac surgery can be performed safely in solid organ transplant recipients, with postoperative cardiovascular outcomes comparable to those observed in nontransplant patients.

Personal Resources and Expectations and Health Behaviors Among Solid Organ Transplant Recipients—A Multicenter Study

BackgroundThe long-term success of organ transplantation (Tx) depends on the transplant recipient's ability to self-manage symptoms, treatment, lifestyle changes, and psychosocial consequences. Health behavior (HB) determinants include personality traits such as optimism, self-efficacy, and health locus of control. PurposeAssessing the relationship between personal resources and expectations and health behaviors of organ transplant recipients. Material and methodsThe study was conducted between 01/04/2018 and 30/10/2019 at 3 transplant centers in Poland. The study group consisted of 243 Tx recipients of kidney, heart, liver, and lung. The Health Behavior Inventory, Multidimensional Health Locus of Control Scale (MHLC), General Self-Efficacy Scale, Dispositional Optimism Scale, and Hospital Anxiety and Depression Scale were used to collect data. FindingsThe study group had medium levels of dispositional optimism (mean 15) and high levels of self-efficacy (mean 30.18). The MHLC scale was dominated by a belief in the influence of others and an internal locus of control over one's health. The respondents presented a high level of HB (mean 92.09). A positive relationship was found between personal resources (self-efficacy and optimism), MHLC and HB. The presence of depression and anxiety negatively affected personal resources and internal locus of health control and HB in terms of a positive mental attitude. Type of Tx differentiated internal locus of health control and HB. Predictors of HB were dispositional optimism, self-efficacy, influence of others with health locus of control, symptoms of depression, age and time since transplantation-explaining between 6.1% and 14.5% of health behavior categories. ConclusionsTo improve health practices among organ recipients, strengthening their personal resources is recommended. It is necessary to form an internal locus of control for adherence to positive HB.

Absence of maribavir penetration into the central nervous system: confirmation by multiple cerebrospinal fluid dosages in a solid organ transplant recipient.

Absence of maribavir penetration into the central nervous system: confirmation by multiple cerebrospinal fluid dosages in a solid organ transplant recipient.

Daratumumab treatment in six highly sensitised solid organ transplant recipients: A case series and literature review.

We report data on six kidney or heart recipients who were administered daratumumab to treat or prevent antibody-mediated rejection (ABMR). To date, data are scarce concerning the use of daratumumab in solid organ transplantation and most reports show a decrease in donor-specific antigen (DSA) levels and an improvement in ABMR using a multiple myeloma daratumumab administration scheme, that is, with sequential systematic administration. Here, we report on the efficacy of daratumumab 1/ in reducing the histological signs of ABMR, 2/ in reducing the ability of DSA to bind to donor cells in vitro through negativation of flow cytometry crossmatching, 3/ in preferentially being directed towards antibodies sharing epitopes, suggesting that daratumumab may specifically target activated plasma cells, 4/ and when administered as a single dose. This last point suggests, for the first time, that, as for rituximab in auto-immune diseases, the scheme for daratumumab administration could be different for targeting DSA-producing plasma cells than for tumour cells.

Solid organ transplant recipients exhibit more TET2-mutant clonal hematopoiesis of indeterminate potential not driven by increased transplantation risk.

Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants. We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts. We find individuals with an allograft prior to their biobank enrollment had an increased prevalence of TET2 mutations (OR 1.90; p = 4.0e-4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. Additionally, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR 1.02; p = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure. These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.

Clinical description and outcome of overall varicella-zoster virus-related organ dysfunctions admitted in intensive care units: the VAZOREA cohort study

BackgroundDue to aging population and increasing part of immunocompromised patients, a raise in life-threatening organ damage related to VZV can be expected. Two retrospective studies were already conducted on VZV in ICU but focused on specific organ injury. Patients with high-risk of VZV disease still must be identified. The objective of this study was to report the clinical features and outcome of all life-threatening VZV manifestations requiring intensive care unit (ICU) admission. This retrospective cohort study was conducted in 26 French ICUs and included all adult patients with any life-threatening VZV-related event requiring ICU admission or occurring in ICU between 2010 and 2019.ResultsOne-hundred nineteen patients were included with a median SOFA score of 6. One hundred eight patients (90.8%) were admitted in ICU for VZV disease, leaving 11 (9.2%) with VZV disease occurring in ICU. Sixty-one patients (51.3%) were immunocompromised. Encephalitis was the most prominent organ involvement (55.5%), followed by pneumonia (44.5%) and hepatitis (9.2%). Fifty-four patients (45.4%) received norepinephrine, 72 (60.5% of the total cohort) needed invasive mechanical ventilation, and 31 (26.3%) received renal-replacement therapy. In-hospital mortality was 36.1% and was significantly associated with three independent risk factors by multivariable logistic regression: immunosuppression, VZV disease occurring in ICU and alcohol abuse. Hierarchical clustering on principal components revealed five phenotypically distinct clusters of patients: VZV-related pneumonia, mild encephalitis, severe encephalitis in solid organ transplant recipients, encephalitis in other immunocompromised hosts and VZV disease occurring in ICU. In-hospital mortality was highly different across phenotypes, ranging from zero to 75% (p < 0.001).ConclusionOverall, severe VZV manifestations are associated with high mortality in the ICU, which appears to be driven by immunosuppression status rather than any specific organ involvement. Deciphering the clinical phenotypes may help clinicians identify high-risk patients and assess prognosis.

Post-traumatic growth among pediatric transplant recipients and their caregivers: A scoping review.

Pediatric transplantation can be a stressful process for patients and caregivers. Some individuals may experience post-traumatic stress symptoms (PTSS) and post-traumatic growth (PTG) as a result. Although post-traumatic stress disorder (PTSD) has been well-studied in this population, the purpose of the present scoping review is to provide a first synthesis of the existing literature on PTG in pediatric transplant populations. We conducted a literature search of PsycINFO and Scopus in May 2023. Eligible articles must have included a sample of solid organ transplant (SOT) or stem cell transplant (SCT) recipients under age 18, siblings of recipients, or caregivers; and must have examined PTG. Twenty-three studies were identified, and nine studies met inclusion criteria and were included in the review (n = 5 cross sectional; n = 4 qualitative). Cross-sectional studies examined demographic, mental health, and medical correlates of PTG in children and caregivers. PTG was correlated with PTSS among caregivers. Qualitative studies identified themes along each of the five factors of PTG. Findings overwhelmingly focused on caregiver PTG. Qualitative study findings align with the theoretical model of PTG. Additional research is needed to investigate PTG in siblings of children with a transplant and associations between PTG and medication adherence. This scoping review provides insight into positive change processes following a transplant among children and their caregivers.

Rapid Life-Saving Response to Anti-PD-1 in a Solid Organ Transplant Recipient With Metastatic Cutaneous Squamous Cell Carcinoma: A Case Report and Review.

Anti-programmed cell death protein 1 (PD-1) therapy is considered effective in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma but the use of these agents in solid organ transplant recipients (SOTRs) is often taken with caution. While anti-tumor effects without graft rejection have been reported, studies have shown high rates of fatal graft rejection with immune checkpoint therapy. In this case report, we present an SOTR patient with life-threatening, acute hypoxic respiratory failure due to rapidly progressive metastatic cutaneous squamous cell carcinoma with lung and pleural involvement. Modification of their immunosuppressive regimen and treatment with front-line anti-PD-1 inhibitor, pembrolizumab, led to rapid clinical response with near complete resolution of metastatic pulmonary disease and no long-term evidence of graft rejection. Our case report shows that front-line treatment with PD-1 inhibitors can be safely administered in SOTR patients with rapid metastatic disease control.

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15ng/mL, including three patients exceeding 40ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

Presentation, anagement, and outcomes of norovirus in adult and pediatric solid organ and hematopoietic stem cell transplant recipients: A multicenter, retrospective study.

Norovirus (NoV) can cause chronic relapsing and remitting diarrhea in immunocompromised patients.  Few multicenter studies have described the clinical course, outcomes, and complications of chronic NoV in transplant recipients. A multicenter retrospective study of adult and pediatric SOT and HSCT recipients diagnosed with NoV between November 1, 2017, and February 28, 2021. Data were obtained from electronic medical records (EMR) and entered into a central REDCap database. Descriptive statistics were calculated. A total of 280 NoV+ patients were identified across eight sites. The majority were adults (74.1%) and SOT recipients (91.4%). Initial diagnosis of NoV occurred a median of 36 months post-Tx (IQR [15.0, 90.0]). Most NoV cases had >3 diarrheal episodes daily (66.0%), nausea and vomiting (60.1%). Duration of diarrhea varied greatly (median = 10 days, mean = 85.9 days, range (1, 2100)). 71.3% were hospitalized. Adjustment of immunosuppression, including reduction and discontinuation of mToR inhibitor, CNI, and/or MMF, was the most common management intervention for NoV. Other therapies resulted only in temporary improvement. Four patients died within 30 days and three others died by 180 days postdiagnosis. Clinically significant renal dysfunction was observed in 12.5% by 30 days and 21.4% by 180 days post-NoV diagnosis. In HSCT and SOT patients, NoV frequently resulted in severe symptoms, prolonged diarrhea (30% persistent with diarrhea for >30 days), and clinically significant renal dysfunction (up to 21% of patients). Utilized therapies did not reliably result in the resolution of infection demonstrating the need for more effective treatment.

Challenges Faced by Solid Organ Transplant Recipients During the COVID-19 Pandemic in France: Historical Insights and Key Takeaways.

Challenges Faced by Solid Organ Transplant Recipients During the COVID-19 Pandemic in France: Historical Insights and Key Takeaways.