Adenoviral infections in pediatric liver transplant recipients.
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ABSTRACT:
SUBMITTER: Koneru B
PROVIDER: S-EPMC2964055 | biostudies-other | 1987 Jul 24-31
REPOSITORIES: biostudies-other
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Project description:BackgroundBacterial and fungal bloodstream infections (BSI) are common after pediatric liver and kidney transplantations and associated with morbidity and mortality. However, knowledge about incidence rates, pathogen composition, and resistance patterns is limited. We aimed to describe the pattern of bacterial and fungal BSI in a cohort of pediatric liver and kidney transplant recipients.MethodsA prospective study of 85 pediatric liver and kidney transplant recipients transplanted from 2010 to 2017 with a total of 390 person-years of follow-up. Clinical characteristics and BSI were retrieved from national registries assuring nationwide follow-up for at least 1 year. BSI incidence rates and pathogen composition were investigated and stratified by the time post-transplantation and type of transplanted organ.ResultsA total of 29 BSI were observed within the first 5 years post-transplantation with 16 different pathogens. The overall incidence rate of first BSI was 1.91 per 100 recipients per month (95% CI, 1.1-3.1) in the first year post-transplantation. The most common pathogens were Enterococcus faecium, Candida albicans, Escherichia coli, and Klebsiella pneumoniae. The pathogen composition depended on the transplanted organ with a higher proportion of BSI with Enterobacterales in kidney transplant recipients than in liver transplant recipients (67% vs. 20%, p = 0.03), while multiple pathogens were detected in the liver transplant recipients.ConclusionsBSI were common in pediatric liver and kidney transplant recipients and the pathogen composition differed between liver and kidney transplant recipients. Guidelines for empiric antibiotic therapy should consider the type of transplanted organ as well as the local resistance patterns.
| S-EPMC8188646 | biostudies-literature
Project description:PurposeTo distinguish clinical factors that have time-varying (as opposed to constant) impact upon patient and graft survival among pediatric liver transplant recipients.MethodsUsing national data from 2002 through 2013, we examined potential clinical and demographic covariates using Gray's piecewise constant time-varying coefficients (TVC) models. For both patient and graft survival, we estimated univariable and multivariable Gray's TVC, retaining significant covariates based on backward selection. We then estimated the same specification using traditional Cox proportional hazards (PH) models and compared our findings.ResultsFor patient survival, covariates included recipient diagnosis, age, race/ethnicity, ventilator support, encephalopathy, creatinine levels, use of living donor, and donor age. Only the effects of recipient diagnosis and donor age were constant; effects of other covariates varied over time. We retained identical covariates in the graft survival model but found several differences in their impact.ConclusionThe flexibility afforded by Gray's TVC estimation methods identify several covariates that do not satisfy constant proportionality assumptions of the Cox PH model. Incorporating better survival estimates is critical for improving risk prediction tools used by the transplant community to inform organ allocation decisions.
| S-EPMC5978879 | biostudies-literature
Project description:ObjectiveTo investigate the role of calcineurin inhibitor exposure and states of insulin resistance-obesity and adolescence-in prediabetes after pediatric liver transplant via oral glucose tolerance testing, which previously has not been done systematically in these at-risk youths.Study designThis was a cross-sectional study of 81 pediatric recipients of liver transplant. Prediabetes was defined as impaired glucose tolerance (IGT; glucose ≥140 mg/dL at 2 hours) or impaired fasting glucose (IFG, ≥100 mg/dL). Corrected insulin response (CIR) was calculated as measure of insulin secretion, corrected for glucose (CIR30, CIR60, CIR120).ResultsSubjects were aged 8.1-30.0 years and 1.1-24.7 years post-transplant; 44% had prediabetes-27% IGT, 14% IFG, and 3% both. IGT was characterized by insulin hyposecretion, with lower CIR60 and CIR120 in IGT than subjects with normal glucose tolerance. Subjects with tacrolimus trough >6 µg/mL at study visit had lower CIR120 than those with trough ≤6 µg/mL and those off calcineurin-inhibitors. Mean of tacrolimus troughs preceding the study visit, years since transplant, and rejection episodes were not associated significantly with lower CIR. CIR suppression by tacrolimus was most pronounced >6 years from transplant. Overweight/obese subjects and adolescents who retained normal glucose tolerance had greater CIR than those who were IGT.ConclusionIGT after pediatric liver transplant is driven by inadequate insulin secretion. It is quite common but not detectable with fasting laboratory values-the screening recommended by current guidelines. Calcineurin inhibitors suppress insulin secretion in these patients in a dose-dependent manner. Given the recent focus on long-term outcomes and immunosuppression withdrawal in these children, longitudinal studies are warranted to investigate whether IGT is reversible with calcineurin inhibitor minimization.
| S-EPMC5328850 | biostudies-literature
Project description:Immunosuppression following solid organ transplantation (SOT) has a deleterious effect on cellular immunity leading to frequent and prolonged viral infections. To better understand the relationship between posttransplant immunosuppression and circulating virus-specific T cells, we prospectively monitored the frequency and function of T cells directed to a range of latent (CMV, EBV, HHV6, BK) and lytic (AdV) viruses in 16 children undergoing liver transplantation for up to 1 year posttransplant. Following transplant, there was an immediate decline in circulating virus-specific T cells, which recovered posttransplant, coincident with the introduction and subsequent routine tapering of immunosuppression. Furthermore, 12 of 14 infections/reactivations that occurred posttransplant were successfully controlled with immunosuppression reduction (and/or antiviral use) and in all cases we detected a temporal increase in the circulating frequency of virus-specific T cells directed against the infecting virus, which was absent in 2 cases where infections remained uncontrolled by the end of follow-up. Our study illustrates the dynamic changes in virus-specific T cells that occur in children following liver transplantation, driven both by active viral replication and modulation of immunosuppression.
| S-EPMC6117219 | biostudies-literature
Project description:Invasive mold infections represent an increasing source of morbidity and mortality in solid organ transplant recipients. Whereas there is a large literature regarding invasive molds infections in hematopoietic stem cell transplants, data in solid organ transplants are scarcer. In this comprehensive review, we focused on invasive mold infection in the specific population of solid organ transplant. We highlighted epidemiology and specific risk factors for these infections and we assessed the main clinical and imaging findings by fungi and by type of solid organ transplant. Finally, we attempted to summarize the diagnostic strategy for detection of these fungi and tried to give an overview of the current prophylaxis treatments and outcomes of these infections in solid organ transplant recipients.
| S-EPMC4261198 | biostudies-other
Project description:UnlabelledAlthough some studies have examined the epidemiology of bloodstream infections after liver transplantation, they were based in single centers and did not identify bloodstream infections treated in other hospitals.MethodsWe retrospectively examined a cohort of 7912 adult liver transplant recipients from 24 transplant centers using 2004 to 2012 International Classification of Diseases, Ninth Revision, Clinical Modification billing data from 3 State Inpatient Databases, and identified bloodstream infections, inpatient death, and cumulative 1-year hospital costs. Multilevel Cox regression analyses were used to determine factors associated with bloodstream infections and death.ResultsBloodstream infections were identified in 29% (n = 2326) of liver transplant recipients, with a range of 19% to 40% across transplant centers. Only 63% of bloodstream infections occurring more than 100 days posttransplant were identified at the original transplant center. Bloodstream infections were associated with posttransplant laparotomy (adjusted hazard ratio [aHR], 1.52), prior liver transplant (aHR, 1.42), increasing age (aHR, 1.07/decade), and some comorbidities. Death was associated with bloodstream infections with and without septic shock (aHR, 10.96 and 3.71, respectively), transplant failure or rejection (aHR, 1.41), posttransplant laparotomy (aHR, 1.40), prior solid-organ transplant (aHR, 1.48), increasing age (aHR, 1.15/decade), and hepatitis C cirrhosis (aHR, 1.20). The risk of bloodstream infections and death varied across transplant centers. Median 1-year cumulative hospital costs were higher for patients who developed bloodstream infections within 1 year of transplant compared with patients who were bloodstream infection-free (US $229 806 vs US $111 313; P < 0.001).ConclusionsBloodstream infections are common and costly complications after liver transplantation that are associated with a markedly increased risk of death. The incidence and risk of developing bloodstream infections may vary across transplant centers.
| S-EPMC4946508 | biostudies-literature
Project description:Recipients of solid organ and hematopoietic stem cell transplantation undergo substantial immune suppression, placing them at risk for opportunistic viral infection. Few randomized controlled trials have been dedicated to the treatment of viral infections in children, and current practices are extrapolated from data generated from adult patients. Here we discuss the prevention and treatment of viral infections using available antiviral drugs, as well as novel agents that may provide benefit to pediatric patients in the future.
| S-EPMC8900721 | biostudies-literature
Project description:ObjectiveTo investigate the distribution of health-related quality of life in pediatric liver transplant recipients compared with a normative population.Study designThis cross-sectional, multicenter study was conducted at select centers. Patients between 2 and 18 years of age, surviving liver transplantation by at least 12 months, were eligible. Parent/guardian fluency in English or Spanish was required. Children > or =8 years and parents of all children completed the age-appropriate versions of the PedsQL 4.0 (Mapi Research Institute, Lyon, France). Scores were compared with a sample of healthy children (n = 3911) matched by age group, sex, and race/ethnicity and with a sample of pediatric patients with cancer receiving chemotherapy and/or radiation.ResultsParticipants included 65% (873/1339) of eligible patients. Mean age was 8.17 +/- 4.43 years, and 55% were female. The total and subscale scores of PedsQL 4.0 were lower than in healthy children (P < .001), with effect sizes for self-report ranging from -0.25 for Emotional Functioning to -0.68 for School Functioning. Patients and their parents reported better physical functioning than patients with cancer but similar social and school functioning. Correlations between parent and self-reports were in the moderate agreement range.ConclusionsPediatric liver transplant recipients and their parents report lower health-related quality of life than control subjects with some domains equal to children receiving cancer therapy.
| S-EPMC3736556 | biostudies-literature
Project description:A central pathology or site reading of biopsy slides is used in liver transplant clinical trials to determine rejection. We evaluated interrater reliability of readings of "rejection or not" using digitized slides from the Medication Adherence in Children who had a Liver Transplant (MALT) study. Four masked experienced pathologists read the digitized slides and then reread them after a study-specific histologic endpoint development program. Agreement was expressed throughout as a Kappa or Fleiss Kappa statistic (ҡ). A ҡ > 0.6 was predefined as desirable. Readings were correlated with immunosuppressant adherence (the Medication Level Variability Index, [MLVI]), and maximal liver enzyme levels during the study period. Interrater agreement between site and central review in MALT, and between 4 pathologists later on, was low (ҡ = 0.44, Fleiss ҡ = 0.41, respectively). Following the endpoint development program, agreement improved and became acceptable (ҡ = 0.71). The final reading was better-aligned with maximal gamma-glutamyl transferase levels and MLVI as compared with the original central reading. We found substantial disagreement between experienced pathologists reading the same slides. A unique study-specific procedure improved interrater reliability to the point it was acceptable. Such a procedure may be indicated to increase reliability of histopathologic determinations in future research, and perhaps also clinically.
| S-EPMC7785571 | biostudies-literature
Project description:BackgroundInvasive fungal infections remain a leading cause of morbidity and mortality among liver transplant recipients (LTRs). In this patient population, invasive Candida infections (ICIs) account for the large majority of cases. To date, only small studies and case-series analysing clinical presentation and risk factors for mortality in LTRs with ICIs are available.MethodsWe performed a retrospective multicenter multinational study in 10 centers in Europe and Brazil. All consecutive LTRs developing ICIs during the period January 2011 to December 2013 were included in the study.ResultsA total of 42 LTRs were included. Median age was 52.5 years, and 78.6% of patients were men. Viral hepatitis was the most common cause for liver transplantation (42.9%). Candidemia represented the majority of cases (24, 57.1%), followed by intra-abdominal candidiasis (18, 42.9%). Overall 30-day mortality was 23.8%, with higher mortality in patients with candidemia compared with intra-abdominal candidiasis (37.5% vs 5.6%, P = 0.02). Multivariate analysis showed candidemia to be a risk factor associated with mortality among LTRs presenting ICIs (odds ratio, 11.86; 95% confidence interval, 1.5-280; P = 0.01). Candida albicans represented the most common isolate (59.5%). High rates of antifungal resistances were found, with 16.7% and 4.8% of isolates displaying resistance to azoles and caspofungin, respectively.ConclusionsOur study confirms the occurrence of high mortality rates in LTRs developing ICIs. Mortality rates varied according to the type of infection, with candidemia representing a risk factor for mortality. The high rates of antifungal resistance should be considered in the choice of the empiric antifungal regimen.
| S-EPMC5441987 | biostudies-literature