Transplant Recipients Research Articles

Immunogenicity and Reactogenicity of High- or Standard-Dose Influenza Vaccine in a Second Consecutive Influenza Season.

Pediatric hematopoietic cell transplant (HCT) recipients are at high risk for morbidity from influenza virus infection. We demonstrated in a primary phase 2 randomized controlled trial that 2 post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given 4 weeks apart were more immunogenic than 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present the immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. A subcohort of study participants reenrolled and had hemagglutinin inhibition titers measured at baseline and 4 weeks after each vaccine dose in year 2. We estimated geometric mean fold rise in hemagglutinin inhibition titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (comparing HD-TIV vs SD-QIV) for each antigen at each time point. We described systemic and injection site reactions. A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Postvaccine geometric mean fold rise and adjusted geometric mean ratio estimates were higher for both groups following a single influenza vaccine dose in year 2 as compared with 2 doses of the same formulation in year 1. Both groups had similar frequencies of injection site and systemic reactions. A single dose of HD-TIV or SD-QIV was more immunogenic in year 2 than 2 doses of the same formulation in year 1. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a 2-dose schedule in the prior year post-HCT. NCT02860039 (ClinicalTrials.gov).

Single lung transplantation is safe when the other lung is declined.

Single lung transplant (SLT) is an acceptable treatment modality for certain patients with end stage lung disease. SLT occurs when two appropriate donor lungs are split between recipients ("split singles") or when one donor lung is adequate for transplant and the other lung is declined ("isolated single"). There is a paucity of literature investigating the outcomes in patients who received an isolated SLT. This study analyzes the characteristics and survival outcomes of isolated SLT recipients. The transplant database at our institution was queried for all lung transplants between 2010 and 2021. The primary outcome of survival was assessed using Kaplan-Meier curves and Cox regression modeling. Secondary outcomes were assessed using Cox regression and Fisher's exact test. Of 759 lung transplant recipients, 164 patients underwent a split SLT and 271 patients underwent an isolated SLT. There was no significant difference when comparing most demographic characteristics between isolated SLT and split SLT patients. Isolated SLT recipients had similar overall mortality when compared to split SLT recipients (HR 0.97, CI 0.72-1.33, p = 0.87). There was no difference in post-operative need for extracorporeal membrane oxygenation (p = 0.209), duration of postoperative ventilation (p = 0.408) and length of hospitalization (p = 0.443). Our analysis demonstrating similar overall survival between recipients of isolated SLT and split SLT shows that a well-selected isolated donor lung can be used safely in the appropriate recipient population. This practice allows expansion of a known scarce donor lung pool and reduction of the waitlist mortality in lung transplant candidates.

Incidence of cancer after paediatric solid organ transplant recipients: A Scoping Review

Background: To investigate the incidence of post-transplant malignancies in paediatric recipients of solid organ transplants. Materials and Methods: We searched MEDLINE, Scopus and Web of Science up to January 2025 for observational studies reporting on cancer incidence in children who underwent solid organ transplantation (SOT). Data extraction and quality assessment were performed by two independent reviewers. Data on incidence rates, types of malignancies, and patient demographics were extracted and analysed. Results: Sixteen studies with a total of 26,310 paediatric transplant recipients were included. The cumulative incidence of cancer after kidney transplantation ranged from 10.2% at 15 years to 27% at 25 years. For liver transplantation, the incidence was 22% at 25 years, with a range from 3.4% to 7.1% incidence of post-transplant lymphoproliferative disorders (PTLD). Following heart transplantation, the incidence was 30.5% at 10 years. Conclusions: Paediatric solid organ transplant recipients face a significant risk of developing cancer, particularly PTLD. Regular monitoring and early intervention are essential for improving long-term outcomes.

Delayed Drug-Drug Interaction Between Antiviral Drugs and Tacrolimus in a Pancreatic Islet Transplant Recipient with SARS-CoV-2 Pneumonia-A Case Study.

PAXLOVID (nirmatrelvir and ritonavir) and VEKLURY (remdesivir) are the first- and second-line antivirals administered to adult patients at risk of severe forms of SARS-CoV-2 infection (COVID-19), such as transplant recipients. As this specific population requires lifelong immunosuppressive treatments, the administration of antivirals with cytochrome P450-modulating properties exposes patients to a high risk of drug-drug interactions (DDI). A 72-year-old male patient who underwent a pancreatic islet transplant experienced DDI between antiviral treatment and tacrolimus during the management of SARS-CoV-2 pneumonia. The patient received a single dose of nirmatelvir/ritonavir followed by a single dose of remdesivir. Tacrolimus treatment was interrupted for the duration of the antiviral treatment, and the concentration of tacrolimus was within the target range for this patient. Once antiviral treatment was stopped, tacrolimus was reintroduced at the initial dose. On day 6, the patient presented with clinical and biological parameters consistent with a tacrolimus overdose. A trough concentration 18 times higher than the therapeutic target was found, prompting tacrolimus to be discontinued for 9 days and reintroduced at a lower dose, followed by a gradual increase based on therapeutic drug monitoring to the initial dose. Clinical and biological parameters gradually returned to baseline levels. Management of DDI between tacrolimus and anti-SARS-CoV-2 drugs requires a substantial therapeutic intervention and close therapeutic drug monitoring during and for several days after antiviral treatment.

Developing clinical prognostic models to predict graft survival after renal transplantation: comparison of statistical and machine learning models

IntroductionRenal transplantation is a critical treatment for end-stage renal disease, but graft failure remains a significant concern. Accurate prediction of graft survival is crucial to identify high-risk patients. This study aimed to develop prognostic models for predicting renal graft survival and compare the performance of statistical and machine learning models.MethodologyThe study utilized data from 278 renal transplant recipients at the Ethiopian National Kidney Transplantation Center between September 2015 and February 2022. To address the class imbalance of the data, SMOTE resampling was applied. Various models were evaluated, including Standard and penalized Cox models, Random Survival Forest, and Stochastic Gradient Boosting. Prognostic predictors were selected based on statistical significance and variable importance.ResultsThe median graft survival time was 33 months, and the mean hazard of graft failure was 0.0755. The 3-month, 1-year, and 3-year graft survival rates were found to be 0.979, 0.953, and 0.911, respectively. The Stochastic Gradient Boosting (SGB) model demonstrated the best discrimination and calibration performance, with a C-index of 0.943 and a Brier score of 0.000351. The Ridge-based Cox model closely followed the SGB model’s prediction performance with better interpretability. The key prognostic predictors of graft survival included an episode of acute and chronic rejections, post-transplant urological complications, post-transplant nonadherence, blood urea nitrogen level, post-transplant regular exercise, and marital status.ConclusionsThe Stochastic Gradient Boosting model demonstrated the highest predictive performance, while the Ridge-Cox model offered better interpretability with a comparable performance. Clinicians should consider the trade-off between prediction accuracy and interpretability when selecting a model. Incorporating these findings into the clinical practice can improve risk stratification and personalized management strategies for kidney transplant recipients.

Aortic Root Dilatation in Children With End-Stage Kidney Disease on Regular Hemodialysis and After Kidney Transplantation.

Cardiovascular disease (CVD) is the major cause of mortality in end-stage kidney disease (ESKD) patients. Aortic root dilatation (ARD) was recently recognized as a cardiovascular (CV) sequela in these patients. This study aims to evaluate the prevalence, risk factors, and progression of ARD in children with ESKD on regular hemodialysis (HD) and after kidney transplantation (KT). Seventy children in HD (HD group) and 80 pediatric kidney transplant recipients (KTR) (KT group) were included. The echocardiographic assessment was done twice at intervals of more than 6 months (6-14 months) except for 3 patients who died before the second assessment. ARD's overall prevalence was higher in HD than in KT groups (71.4% and 40%). ARD was more prominent in patients with increased duration of ESKD, EDW, normalized IDWG%, and normalized UF vol%. In the KTR group, underweight was more prevalent among the ARD group than the non-ARD group. Patients with ARD had higher BP than patients without ARD. Most of the patients with ARD were on classic triple immunosuppressive therapy. ARD patients of both groups had lower HB, higher PLTS, Ph, Ca × Ph levels, and lower e-GFR than non-ARD patients. ARD is prevalent among ESKD children, with furthermore prevalence in HD than in KT patients. Younger age, lower BMI Z-scores, hypertension (HTN), and increased Ca × Ph are risk factors for ARD. Aortic root measures and ARD frequency decrease on ≥ 6-month follow-up of patients.

Long-Term Survival in Children Following Heart Transplantation.

Short-term outcomes following heart transplantation in children have improved, but comparable improvements in long-term survival continues to have barriers. We sought to investigate long-term outcomes following heart transplantation and to identify protective and risk factors associated with long-term survival in children. The Pediatric Heart Transplant Society (PHTS) database was queried for heart transplant recipients from 1993 to 2010 who were ≤ 10 years of age at time of transplant. Patients with conditional graft survival > 3 years and at ≥ 10 years were analyzed. Survival and time-to-event were compared using the Kaplan-Meier method with a log-rank test for significance. Factors associated with graft loss were identified using Cox proportional hazard modeling. There were 1610 patients ≤ 10 year of age who were transplanted between 1993 and 2010 with conditional survival to 3 years post-transplant. Of those patients, there were 1170 with conditional survival to 10 years post-transplant. Patients < 1 year at transplant had improved survival compared to other age groups. Risk factors for graft loss after 3 years post-transplant were malignancy, rejection, cardiac allograft vasculopathy (CAV), age, congenital heart disease, female sex, and Black race (p value for all < 0.05). Heart transplantation remains an effective therapy in children with a growing number of long-term survivors. Risk factors for mortality in patients ≤ 10 years of age at transplant with conditional survival to 3 years post-transplant include CAV, rejection, malignancy, female sex, and Black race. Further studies are needed to understand the social and biologic causes of racial and sex disparities in pediatric transplant patients.

Risk Factors and Outcomes of Invasive Candida Infections in Heart Transplant Recipients: A Case-Control Study.

Invasive Candida infections (ICI) are the most common invasive fungal infections in solid organ transplant recipients. There are limited contemporary data on the risk factors for infection in heart transplant (HT) recipients especially since the expansion of temporary mechanical circulatory support (MCS) use. This was a case-control study conducted at a tertiary care academic hospital of HT recipients from January 2022 to January 2024. All patients who developed ICI by the detection of Candida species from a normally sterile site were included as cases. Four controls who underwent HT, two before the case and two after the case, were selected. ​Fisher's exact or Mann-U-Whitney tests were used for the analysis. There were 12 cases and 48 controls out of a total of 117 transplants during the study period​. The proportion of ICI was 10.6%. The median time to ICI from transplant was 16 days (IQR 10, 83). The most common organisms isolated were Candida parapsilosis and Candida albicans. The majority of infections were mediastinitis. Risk factors for ICI included receipt of antibiotics for more than 7 days within 1 month prior to transplant (58.3%vs. 22.9%, p = 0.03), tracheostomy (41.7%vs. 10.4%, p = 0.02), prolonged chest tube placement (13vs. 9 days, p = 0.02), and temporary MCS (p = 0.042). Patients who developed ICI had increased 90-day all-cause mortality compared to controls (33.3% vs. 4.2%, p = 0.01). This study identified several risk factors for ICI following HT. Further research is essential to develop interventions that mitigate these risk factors in this patient population.

Limited utility of Epstein-Barr virus (EBV) surveillance for predicting post-transplant lymphoproliferative disorders in adult EBV seropositive lung transplant recipients.

EBV DNAemia surveillance, with reduction of immunosuppression at certain viral load (VL) thresholds, is a common practice for mitigating progression from EBV DNAemia to post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTRs). The utility of EBV surveillance in adult EBV seropositive LTRs is unknown. We performed a retrospective cohort study of EBV seropositive adult LTRs who underwent lung transplant between 1/1/19 and 12/31/20 and received whole blood (WB) EBV PCR surveillance. We compared peak WB EBV VLs among 3 groups: 1) asymptomatic LTRs who developed PTLD, before PTLD was clinically suspected, 2) LTRs who developed PTLD, after PTLD was clinically suspected, and 3) LTRs who did not develop PTLD. We calculated the positive predictive value (PPV) of moderate-grade DNAemia (2840 to 11,360 IU/mL) and high-grade DNAemia (≥ 11,360 IU/mL) for identifying active or future PTLD. Six (2.6 %) of 229 LTRs developed PTLD. Among LTRs who developed PTLD, median peak EBV VL was significantly higher after PTLD was suspected than before clinical signs of PTLD were present (16,004 IU/mL vs. ≤568 IU/mL, p = 0.016). Median peak EBV VLs were similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD (median peak EBV VL ≤568 IU/mL vs. ≤568 IU/mL, p = 0.62). The PPVs for moderate- and high-grade DNAemia were 14.7 % and 33.3 %, respectively. EBV surveillance did not accurately identify EBV seropositive LTRs at risk for progressing to PTLD. EBV PCR testing in asymptomatic EBV seropositive transplant recipients may represent an opportunity for diagnostic stewardship.

Prevention of Infections Among Pediatric Solid Organ Transplant Recipients With Asplenia or Hyposplenism.

Pediatric solid organ transplant (SOT) recipients with splenic dysfunction are at increased risk for infections, and tailored guidance on the management of asplenia/hyposplenism among SOT recipients is often lacking. The purpose of this article is to provide practice recommendations via a frequently asked questions (FAQs) format that focuses on three main domains: the identification of asplenia/hyposplenism among SOT recipients/candidates, prophylactic strategies for mitigating the risk of invasive disease associated with splenic dysfunction in the context of transplantation, and the provision of appropriate patient counseling on the risks associated with asplenia/hyposplenism. Answers to the FAQs are based on international expert opinion informed by practices for managing splenic dysfunction and associated data in other populations with asplenia. Gaps in the existing literature and relevant research aims are emphasized.

Impact of text message reminders on immunosuppressive medication adherence among kidney transplant recipients: A randomized controlled study.

One of the most common problems encountered in transplant patients is nonadherence with immunosuppressive drugs, one of the most important reasons for graft rejection. The study aimed to assess the impact of text message reminders on medication adherence among kidney transplant recipients. A randomized controlled trial. The study was conducted from January to October 2021. This study included a total of 100 patients receiving a kidney transplant, 50 in the intervention group and 50 in the control group. Patients in the intervention group were sent text message reminders four times a day during the 6th-9th months after transplantation. Control patients received no such intervention. Tacrolimus concentrations in the bloodstream were monitored for all participants through measurements taken at Months 7, 8 and 9. Data collection tools included Sociodemographic Form and Immunosuppressive Medication Adherence Scale. Patients were homogeneously distributed among the groups. Sending daily text message reminders to transplant recipients caused an independent positive effect on medication adherence scale scores at the end of the study. Mean pretest medication adherence score of all patients was 45.18 ± 4.22 and posttest score was 47.4 ± 3.6. The intervention group exhibited a significantly higher mean posttest adherence score compared to controls, with values of 48.68 ± 2.58 and 45.62 ± 4.42, respectively (p < 0.001). Findings demonstrated a substantial improvement in the final medication adherence scores of transplant patients when they received daily Short Message Service reminders, acting as an independent factor (β = 0.356, p < 0.001). Sending text message reminders to kidney transplant recipients is a statistically and clinically effective intervention to improve immunosuppressive medication adherence.

Macrophage Dvl2 Deficiency Promotes NOD1-Driven Pyroptosis and Exacerbates Inflammatory Liver Injury

Dishevelled 2 (Dvl2) is a key mediator of the Wingless/Wnt signaling pathway that regulates cell proliferation, migration, and immune function. However, little is known about the role of macrophage Dvl2 in modulating NOD1-mediated pyroptosis and hepatocyte death in oxidative stress-induced inflammatory liver injury. In a mouse model of oxidative stress-induced liver inflammation, mice with myeloid-specific Dvl2 knockout (Dvl2M-KO) displayed exacerbated ischemia/reperfusion (IR) stress-induced hepatocellular damage with increased serum ALT levels, oxidative stress, and proinflammatory mediators. Unlike in Dvl2FL/FL controls, Dvl2M-KO enhanced NOD1, caspase-1, GSDMD, and NF-κB activation in liver macrophages after IR. Interestingly, IR stress enhanced YAP colocalized with HSF1 in Dvl2FL/FL macrophages, while macrophage Dvl2 deficiency reduced YAP and HSF1 colocalization in the nucleus under inflammatory conditions. Importantly, Dvl2 deletion diminished nuclear YAP interacted with HSF1 and augmented NOD1/caspase-1 and GSDMD activation in response to inflammatory stimulation. However, Dvl2 activation increased YAP interaction with HSF1 and activated HSF1 target gene eEF2, inhibiting NOD1/caspase-1, GSDMD, and NF-κB activity. Moreover, macrophage eEF2 deletion increased the NOD1-caspase-1 interaction, GSDMD activation, HMGB1 release, and hepatocyte LDH release after macrophage/hepatocyte co-culture. Adoptive transfer of eEF2-expressing macrophages in Dvl2M-KO mice alleviated IR-triggered liver inflammation and hepatocellular damage. Therefore, macrophage Dvl2 deficiency promotes NOD1-mediated pyroptosis and exacerbates IR-induced hepatocellular death by disrupting the YAP-HSF1 axis. eEF2 is crucial for modulating NOD1-driven pyroptosis, inflammatory response, and hepatocyte death. Our findings underscore a novel role of macrophage Dvl2 in modulating liver inflammatory injury and imply the therapeutic potential in organ IRI and transplant recipients.

Optimizing hepatitis B virus seroprotection in thoracic organ transplantation: The role of HepB-CpG (Heplisav-B) vaccination schedule.

Heplisav-B, a CpG-adjuvanted recombinant hepatitis B virus (HBV) vaccine, has a higher seroprotection rate and immunogenicity than the conventional HBV vaccine. This study aimed to identify the predictors of HBV seroprotection post-transplantation in thoracic organ transplant recipients who received Heplisav-B. We conducted a retrospective study of adult thoracic organ (heart and lung) transplant recipients at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2020 and August 2023. Patients who completed Heplisav-B series were classified into three strategies: strategy A (completed 2 doses of Heplisav-B pre-transplantation with achieved seroprotection pre-transplantation), strategy B (received first dose of Heplisav-B pre-transplantation and second dose of Heplisav-B post-transplantation), and strategy C (completed 2 doses of Heplisav-B post-transplantation). HBV seroprotection was defined as HBsAb ≥10IU/L. A total of 154 thoracic organ transplant recipients completed Heplisav-B vaccine series. Post-transplant seroprotection was highest in strategy A, followed by strategy B and strategy C (54/76 [71%] vs. 18/39 [46%] vs. 14/39 [36%]; p<0.001). Multivariate logistic regression analysis identified two independent factors predicting lack of HBV seroprotection post-transplantation; both were related to Heplisav-B schedule: strategy B (adjusted odds ratio [aOR], 2.482; 95% confidence interval [CI] 1.085 5.679; p=0.031), and strategy C (aOR 4.963; 95% CI 2.106 11.697; p<0.001). The vaccine schedule significantly predicts HBV seroprotection in adult thoracic organ transplant recipients. Our data supports the recommendation that pre-transplantation Heplisav-B to achieve HBsAb ≥10IU/L is the optimal vaccination schedule to maintain an HBsAb level of ≥10IU/L post-transplantation. Further studies are needed to determine whether this observation can be replicated in non-thoracic organ transplant recipients or pediatric populations.

A Second Look: Retrospective Identification of Thrombotic Microangiopathy in Pediatric Stem Cell Transplant Patients With Veno-Occlusive Disease.

Veno-occlusive disease (VOD) and transplant-associated thrombotic microangiopathy (TA-TMA) remain a diagnostic and therapeutic challenge for patients undergoing hematopoietic stem cell transplant (HSCT). Both VOD and TA-TMA share an underlying etiology of microvascular endothelial damage. Potential under-recognition of TA-TMA in the context of VOD leaves HSCT recipients vulnerable to additional endothelial damage, and risk of end-organ failure. A cohort of 44 pediatric HSCT recipients diagnosed with VOD between 2010and 2019 were retrospectively evaluated for the development of TA-TMA within 1 week before and 2 months after VOD diagnosis. Patients were classified into three categories: sole diagnosis of VOD (VOD), concurrent clinical diagnosis of TA-TMA during the VOD course (VOD+TA-TMA), and patients with VOD who on retrospective review satisfied criteria for diagnosis of TA-TMA (VOD+rTA-TMA). A total of 42 patients were evaluated and 50% of the patients were diagnosed clinically with TA-TMA (5) or where retrospectively identified to have TA-TMA (16). There was no difference in the severity of the course of VOD between the three groups based on need for intubation, dialysis, and pediatric intensive care unit (PICU) care. Patients in the VOD only group had the highest survival at 1 year (66.7%, n = 14) compared with patients in the VOD+TA-TMA group (60%, n = 3) and VOD+rTA-TMA group (62.5%, n = 10), p = 0.9582. Better understanding of the association between these two endotheliopathies is essential to improve diagnosis, treatment, and prevention of potentially fatal adverse outcomes in transplant recipients.

Interferon-gamma rescues dendritic cell calcineurin-dependent responses to Aspergillus fumigatus via Stat3 to Stat1 switching.

Invasive pulmonary aspergillosis is a lethal opportunistic fungal infection in transplant recipients receiving calcineurin inhibitors. We previously identified a role for the calcineurin pathway in innate immune responses to A.fumigatus and have used exogenous interferon-gamma successfully to treat aspergillosis in this setting. Here we show that calcineurin inhibitors block dendritic cell maturation in response to A.fumigatus, impairing the Th1 polarization of CD4 cells. Interferon gamma, an immunotherapeutic option for invasive aspergillosis, restored maturation and promoted Th1 polarization via a dendritic cell dependent effect that was co-dependent on Tcell interaction. We find that interferon gamma activates alternative transcriptional pathways to calcineurin-NFAT for the augmentation of pathogen handling. Histone modification ChIP-Seq analysis revealed dominant control by an interferon gamma induced regulatory switch from STAT3 to STAT1 transcription factor binding underpinning these observations. These findings provide key insight into the mechanisms of immunotherapy in organ transplant recipients with invasive fungal diseases.

Living Donor Liver Transplantation for Young Biliary Atresia Recipients Is Associated With Improved Outcomes in the Modern Era.

Biliary atresia (BA) is the most common indication for liver transplantation (LT) in children. We aimed to identify risk factors associated with survival in young patients with BA in the modern era. We performed a retrospective analysis of BA patients aged < 2 years who received their first isolated LT with available data from the United Network for Organ Sharing database (01/2013-12/2022). Factors included in the multivariable Cox regression were graft type, race/ethnicity, insurance status, laboratory pediatric end-stage liver disease (PELD) score, history of portal vein thrombosis, and intensive care unit (ICU) status. 1226 BA LT recipients aged < 2 years were included, of whom 501 (40.9%) received deceased donor whole grafts (DDWG), 425 (34.7%) received deceased donor technical variants (DDTV), and 300 (24.5%) received living donor LT (LDLT). LDLT recipients were more likely to be white (p = 0.008) and have private insurance (p < 0.001). Multivariable analysis demonstrated that ICU status (hazard ratio [HR] = 3.23, 95% confidence interval [95% CI]: 1.72-6.08, p < 0.001) and DDTV graft vs. LDLT (HR = 3.03, 95% CI: 1.14-8.04, p = 0.03) were associated with an increased risk of patient mortality. Factors associated with an increased risk of graft loss included ICU status (HR = 1.89, 95% CI: 1.19-3.00, p = 0.007) and both DDWG (HR = 3.37, 95% CI: 1.65-6.87, p = 0.001) and DDTV (HR = 3.47, 95% CI: 1.69-7.14, p = 0.001) grafts vs. LDLT. LDLT is associated with improved survival in patients with BA aged < 2 years; however, socioeconomic differences exist between LDLT and non-LDLT recipients. Efforts to promote early equitable referral to centers offering LDLT are essential for improving outcomes in young children with BA.

CMV Reactivation Following Allogeneic Transplantation in Children From a High-Seroprevalence Population: A Single-Center Experience in Colombia.

Cytomegalovirus (CMV) infection is a frequent complication among hematopoietic stem cell transplant (HSCT) recipients. Data regarding CMV reactivation in children in underdeveloped countries is scarce. This is especially notable considering the increasing utilization of haploidentical-related HSCT with the post-transplant cyclophosphamide platform. This study aimed to describe the incidence, clinical characteristics, and evolution of children with CMV reactivation after HSCT and the possible impact of unmanipulated stem cells with PTCy for GvHD prophylaxis. Retrospective cohort study of children undergoing hematopoietic stem cell transplantation from January 2012 to June 2022. Baseline characteristics and the clinical course were described. Duration of treatment, initial viral load, and time to clearance of DNAemia by type of transplant were compared using the Kruskal-Wallis test. Survival analysis was performed with the Kaplan-Meier method and log-rank test. All statistical analysis was performed using SPSS software, version 20.0. One hundred sixty-six children were included. Among them, 87% of recipients and 88% of donors were CMV positive. The cumulative incidence of cytomegalovirus DNAemia was 28% at 100 days post-transplantation. There were no differences between different donor types. Overall survival at 1 year was 60%, and non-relapse mortality was observed in 28%. CMV reactivation did not appear to negatively impact 1-year overall survival (OS). Our study found no differences in CMV reactivation rates, treatment duration, viral clearance times, co-infections, or 1-year overall survival across different HSCT donor types. Studies are needed to establish more precise criteria for monitoring recipients, particularly in regions where unmanipulated stem cells with PTCy for GvHD prophylaxis are increasing.

How We Diagnose and Manage Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infection After Hematopoietic Cell Transplantation.

Herpes simplex virus (HSV) infection is a clinically significant complication in hematopoietic cell transplant (HCT) recipients. Refractory and resistant (R/R) HSV infections may occur in this patient population, particularly after prolonged exposure to anti-HSV agents. To provide a comprehensive review of the diagnostic approach and the treatment options for R/R HSV mucocutaneous infections in HCT recipients and to highlight future treatment strategies. We searched the PubMed Central Database and Embase to identify published studies on R/R HSV infections in HCT recipients. We used the search terms "herpes simplex virus," "resistant*," OR "refractory," "immunocompromised," "immunosuppress*," and "immunodeficien*," and screened the results for articles reporting R/R HSV infections among HCT recipients. We chose an HCT recipient with a complicated refractory HSV infection as a representative clinical case. A clear clinical definition of refractory HSV infection is currently not available, which can lead to delays in diagnosis and treatment, negatively impacting patient care. Apart from two small randomized controlled trials in the 1990s that looked at treatment with systemic foscarnet and topical cidofovir in patients living with human immunodeficiency virus, all treatment recommendations for R/R HSV infections are based on observational studies and case reports. The use of alternative treatment options often comes with serious side effects, such as kidney toxicity. This underscores the urgent need for safer and effective treatment options. Pritelivir, a new oral antiviral medication, is currently being studied in a phase 3 trial for R/R HSV infections in immunocompromised patients. Limited data from the Early Access Program, which allows compassionate use, suggests that pritelivir holds promise as a treatment option for HCT recipients with R/R HSV infections. The proposed R/R HSV mucocutaneous infection diagnostic and treatment algorithm guides the appropriate management of these difficult-to-treat infections, potentially improving patient outcomes.

Donor pulmonary hemodynamics does not impact recipient outcomes in adult heart transplantation.

PurposeThe impact of donor pulmonary hemodynamics as assessed by mean pulmonary artery pressure (mPAP) and transpulmonary gradients (TPG) on the clinical outcome of heart transplant (HT) recipients is unknown. We compared outcomes of adult HT recipients as stratified by donor pulmonary hemodynamics in the contemporary era in the United States. MethodsWe reviewed adult donor hearts (age ≥ 18 years) which were offered for transplantation between January 2010 and March 2023 in the UNOS database with available right heart catheterization (RHC) data. Adjusted Cox regression was performed to evaluate the relationship between 30-day and 1-year mortality after HT and donor mPAP, TPG, and mean arterial pressure (MAP). Each hemodynamic parameter was modeled as a quadratic polynomial to not assume a linear relationship with mortality. Results2038 HT recipients with complete donor RHC were included: 58 % were on inotrope support. Elevated mPAP (≥25 mmHg), TPG (≥15), and PVR (≥1.5) were present in 416 (20.4 %), 179 (8.8 %), and 2038 (100 %), respectively. No significant association was found between donor mean PAP (HR 1.47, 95 % CI 0.80–2.67), donor TPG (HR 0.47, 95 % CI 0.20–1.08), and donor PVR (HR 1.69, 95 % CI 0.77–3.72) and 30-day mortality. Similarly, no significant association was found between donor mPAP (HR 1.33, 95 % CI 0.90–1.95), donor TPG (HR 0.65, 95 % CI 0.37–1.12), and donor PVR (HR 1.38, 95 % CI 0.83–2.32) and 1-year mortality. ConclusionsDonor pulmonary pressures did not impact post-heart transplant survival in adult recipients. Donors with abnormal pulmonary hemodynamics remain viable donor hearts for transplantation.

Delirium Among Liver Transplant Recipients: ANational Analysis Using MarketScan.

Delirium is a common issue following liver transplantation (LT), but research has mainly focused on single-center cohorts. We studied delirium in a national cohort of adult LT recipients transplanted October, 2015-December, 2020 using the MarketScan database. Claims data were used to identify LT recipients with delirium. Characteristics and outcomes of LT recipients with and without delirium were compared using descriptive statistics. Among 2051 LT recipients, only 32 (1.6%) had a delirium claim. Recipients with versus without delirium were more likely to have a history of encephalopathy (21.9% versus 8.2%, P=0.006) but were of similar age and sex. Recipients with versus without delirium were more likely to be discharged to skilled care or rehabilitation facilities (37.5% versus 14.3%, P=0.003) and had longer median hospital stays (24 versus 14ds, P=0.03). Delirium claims were not associated with median hospitalization costs (P=0.15) or 30-d (P=0.32) and 60-d (P=0.99) readmission. Overall, only 1.6% of adult LT recipients had delirium claims, despite prevalence estimates of up to 47% in single-center studies. This underreporting-which is likely limited to the most severe cases-limits our ability to assess associated outcomes and highlights the need for better delirium recognition and reporting.