The Comparative Effectiveness of Perioperative Antibiotic Regimens to Prevent Surgical Site Infections in Pediatric Liver Transplant Recipients.

INTRODUCTION: Surgical site infections (SSIs) are a common complication in liver transplant(LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients under 18 years using a merged dataset that included data from PHIS and UNOS between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT; with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category relative to category 1 in preventing SSI. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. SSI rate was higher (16.2%) in the younger sub-cohort compared to older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger sub-cohort, the adjusted risk was increased in all categories compared to the reference, most notably in category 3 (OR 2.58; 0.69-9.59) and category 6 (OR 2.76; 0.66-11.56). In the older sub-cohort, estimated ORs were also increased for each category, most notably in category 4 (2.49; 0.99-6.27). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E value assessment suggests it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSION: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either sub-cohort, suggesting that narrower regimens may be adequate.

Association of the social disorganization index with time to first septic shock event in children with acute myeloid leukemia.

BACKGROUND: Pediatric acute myeloid leukemia (AML) chemotherapy increases the risk of life-threatening complications, including septic shock (SS). An area-based measure of social determinants of health, the social disorganization index (SDI), was hypothesized to be associated with SS and SS-associated death (SS-death). METHODS: Children treated for de novo AML on two Children's Oncology Group trials at institutions contributing to the Pediatric Health Information System (PHIS) database were included. The SDI was calculated via residential zip code data from the US Census Bureau. SS was identified via PHIS resource utilization codes. SS-death was defined as death within 2 weeks of an antecedent SS event. Patients were followed from 7 days after the start of chemotherapy until the first of end of front-line therapy, death, relapse, or removal from study. Multivariable-adjusted Cox regressions estimated hazard ratios (HRs) comparing time to first SS by SDI group. RESULTS: The assembled cohort included 700 patients, with 207 (29.6%) sustaining at least one SS event. There were 233 (33%) in the SDI-5 group (highest disorganization). Adjusted time to incident SS did not statistically significantly differ by SDI (reference, SDI-1; SDI-2: HR, 0.84 [95% confidence interval (CI), 0.51-1.41]; SDI-3: HR, 0.70 [95% CI, 0.42-1.16]; SDI-4: HR, 0.97 [95% CI, 0.61-1.53]; SDI-5: HR, 0.72 [95% CI, 0.45-1.14]). Nine patients (4.4%) with SS experienced SS-death; seven of these patients (78%) were in SDI-4 or SDI-5. CONCLUSIONS: In a large, nationally representative cohort of trial-enrolled pediatric patients with AML, there was no significant association between the SDI and time to SS.

Applying machine learning to identify pediatric patients with newly diagnosed acute lymphoblastic leukemia using administrative data.

Case identification in administrative databases is challenging as diagnosis codes alone are not adequate for case ascertainment. We utilized machine learning (ML) to efficiently identify pediatric patients with newly diagnosed acute lymphoblastic leukemia. We tested nine ML models and validated the best model internally and externally. The optimal model had 97% positive predictive value (PPV) and 99% sensitivity in internal validation; 94% PPV and 82% sensitivity in external validation. Our ML model identified a large cohort of 21,044 patients, demonstrating an efficient approach for cohort assembly and enhancing the usability of administrative data.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

Clinical practice guideline-inconsistent management of fever and neutropenia in pediatric oncology: A Children's Oncology Group study.

BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations. RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed. CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.

Effect of cytomegalovirus infection on post-transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach.

BACKGROUND: Cytomegalovirus (CMV) commonly reactivates after allogeneic hematopoietic cell transplant (HCT), potentially leading to CMV disease and significant morbidity and mortality. To reduce morbidity and mortality, many centers conduct weekly CMV blood polymerase chain reaction (PCR) surveillance testing with subsequent initiation of antiviral therapy upon CMV DNAemia detection. However, the impact of CMV DNAemia on subsequent hospitalization risk has not been assessed using models accounting for the time-varying nature of the exposure, outcome, and confounders. METHODS: All allogeneic HCTs at the Children's Hospital of Philadelphia from January 2004-April 2017 were considered for inclusion. Patients were monitored with CMV surveillance via PCR testing for up to 105 days after HCT receipt. We estimated the association between CMV DNAemia and rate of hospitalization using marginal structural models (MSM). RESULTS: There were 343 allogeneic HCT episodes in 330 with CMV surveillance; median age was 9.0 (range: 0.1-26.2) and 46.5% were female. And 24.1% of HCT patients had at least one positive CMV blood PCR during the follow-up period. Median time to CMV DNAemia detection was 19 days (range: 4-97). The MSM estimated the incidence rate ratios for an association of CMV DNAemia with hospitalization to be 1.24, (95% confidence interval: 1.04-1.47). CONCLUSIONS: CMV DNAemia was associated with an increased hospitalization in the post-HCT period. The MSM accounted for time-varying nature of the outcome, exposure and confounders. The findings support prevention of CMV DNAemia in this population. We recommend further investigation into the effectiveness and safety of prophylaxis versus pre-emptive CMV prevention approaches.

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Leveraging machine learning to identify acute myeloid leukemia patients and their chemotherapy regimens in an administrative database.

BACKGROUND: Administrative datasets are useful for identifying rare disease cohorts such as pediatric acute myeloid leukemia (AML). Previously, cohorts were assembled using labor-intensive, manual reviews of patients' longitudinal chemotherapy data. METHODS: We utilized a two-step machine learning (ML) method to (i) identify pediatric patients with newly diagnosed AML, and (ii) among the identified AML patients, their chemotherapy courses, in an administrative/billing database. Using 2558 patients previously manually reviewed, multiple ML algorithms were derived from 75% of the study sample, and the selected model was tested in the remaining hold-out sample. The selected model was also applied to assemble a new pediatric AML cohort and further assessed in an external validation, using a standalone cohort established by manual chart abstraction. RESULTS: For patient identification, the selected Support Vector Machine model yielded a sensitivity of 0.97 and a positive predictive value (PPV) of 0.97 in the hold-out test sample. For course-specific chemotherapy regimen and start date identification, the selected Random Forest model yielded overall PPV greater than or equal to 0.88 and sensitivity greater than or equal to 0.86 across all courses in the test sample. When applied to new cohort assembly, ML identified 3016 AML patients with 10,588 treatment courses. In the external validation subset, PPV was greater than or equal to 0.75 and sensitivity was greater than or equal to 0.82 for patient identification, and PPV was greater than or equal to 0.93 and sensitivity was greater than or equal to 0.94 for regimen identifications. CONCLUSION: A carefully designed ML model can accurately identify pediatric AML patients and their chemotherapy courses from administrative databases. This approach may be generalizable to other diseases and databases.

Children's Oncology Group's 2023 blueprint for research: Cancer control and supportive care.

The objective of the Cancer Control and Supportive Care (CCL) Committee in the Children's Oncology Group (COG) is to reduce the overall morbidity and mortality of therapy-related toxicities in children, adolescents, and young adults with cancer. We have targeted five major domains that cause clinically important toxicity: (i) infections and inflammation; (ii) malnutrition and metabolic dysfunction; (iii) chemotherapy-induced nausea and vomiting; (iv) neuro- and oto-toxicty; and (v) patient-reported outcomes and health-related quality of life. Subcommittees for each domain prioritize randomized controlled trials and biology aims to determine which strategies best mitigate the toxicities. The findings of these trials are impactful, informing clinical practice guidelines (CPGs) and directly leading to changes in the standard of care for oncology practice. With the development of new therapies, there will be new toxicities, and the COG CCL Committee is dedicated to developing interventions to minimize acute and delayed toxicities, lessen morbidity and mortality, and improve quality of life in pediatric and young adult patients with cancer.

Child and family perceptions of satisfaction with neutropenia management in pediatric acute myeloid leukemia.

PURPOSE: Chemotherapy for pediatric acute myeloid leukemia (AML) is very intensive and many, but not all centers, require extended hospitalization until neutrophil recovery. Child and family preferences, beliefs, and experiences around hospitalization have not been systematically assessed. PATIENTS AND METHODS: We recruited children with AML and their parents from nine pediatric cancer centers across the United States for a qualitative interview about their experiences of neutropenia management. Interviews were analyzed using a conventional content analysis approach. RESULTS: Of 116 eligible individuals, 86 (74.1%) agreed to participate. Interviews were conducted with 32 children and 54 parents from 57 families. Of these 57 families, 39 were cared for as inpatients and 18 were managed as outpatients. A very high proportion of respondents in both groups reported satisfaction with the discharge management strategy recommended by the treating institution: 86% (57 individuals) of respondents who experienced inpatient management and 85% (17 individuals) of respondents who experienced outpatient management expressed satisfaction. Respondent perceptions associated with satisfaction related to safety (access to emergency interventions, infection risk, close monitoring) and psychosocial concerns (family separation, low morale, social support). Respondents believed it could not be assumed that all children would have the same experience due to varied life circumstances. CONCLUSION: Children with AML and their parents express a very high degree of satisfaction with the discharge strategy recommended by their treating institution. Respondents saw a nuanced tradeoff between patient safety and psychosocial concerns that was mediated by a child's life circumstances.

Absolute lymphocyte count recovery following initial acute myelogenous leukemia therapy: Implications for adoptive cell therapy.

BACKGROUND: An adequate absolute lymphocyte count (ALC) is an essential first step in autologous chimeric antigen receptor (CAR) T-cell manufacturing. For patients with acute myelogenous leukemia (AML), the intensity of chemotherapy received may affect adequate ALC recovery required for CAR T-cell production. We sought to analyze ALC following each course of upfront therapy as one metric for CAR T-cell manufacturing feasibility in children and young adults with AML. PROCEDURE: ALC data were collected from an observational study of patients with newly diagnosed AML between the ages of 1 month and 21 years who received treatment between the years of 2006 and 2018 at one of three hospitals in the Leukemia Electronic Abstraction of Records Network (LEARN) consortium. RESULTS: Among 193 patients with sufficient ALC data for analysis, the median ALC following induction 1 was 1715 cells/µl (interquartile range: 1166-2388), with successive decreases in ALC with each subsequent course. Similarly, the proportion of patients achieving an ALC >400 cells/µl decreased following each course, ranging from 98.4% (190/193) after course 1 to 66.7% (22/33) for patients who received a fifth course of therapy. CONCLUSIONS: There is a successive decline of ALC recovery with subsequent courses of chemotherapy. Despite this decline, ALC values are likely sufficient to consider apheresis prior to the initiation of each course of upfront therapy for the majority of newly diagnosed pediatric AML patients, thereby providing a window of opportunity for T-cell collection for those patients identified at high risk of relapse or with refractory disease.

Prospective Evaluation of the Fungitell® (1→3) Beta-D-Glucan Assay as a Diagnostic Tool for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report from the Children's Oncology Group.

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period. METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD. RESULTS: A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%-85.3%), and NPV was over 99% (95% CI: 86.8%-99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%-84.2%) and PPV of 0% (95% CI: 0.0%-6.7%). CONCLUSIONS: Fungitell® BDG screening is of limited utility in diagnosing IFD in the post-HCT period, mainly due to high false-positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post-HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low.

Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents.

BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-ß-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard. RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%). CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC. CLINICAL TRIALS REGISTRATION: NCT02220790.

Challenges in the Treatment of Invasive Aspergillosis in Immunocompromised Children.

Invasive aspergillosis (IA) is associated with significant morbidity and mortality. Voriconazole remains the drug of choice for the treatment of IA in children; however, the complex kinetics of voriconazole in children make dosing challenging and therapeutic drug monitoring (TDM) essential for treatment success. The overarching goal of this review is to discuss the role of voriconazole, posaconazole, isavuconazole, liposomal amphotericin B, echinocandins, and combination antifungal therapy for the treatment of IA in children. We also provide a detailed discussion of antifungal TDM in children.

Center Variability in Acute Rejection and Biliary Complications After Pediatric Liver Transplantation.

Transplant center performance and practice variation for pediatric post-liver transplantation (LT) outcomes other than survival are understudied. This was a retrospective cohort study of pediatric LT recipients who received transplants between January 1, 2006, and May 31, 2017, using United Network for Organ Sharing (UNOS) data that were merged with the Pediatric Health Information System database. Center effects for the acute rejection rate at 1 year after LT (AR1) using UNOS coding and the biliary complication rate at 1 year after LT (BC1) using inpatient billing claims data were estimated by center-specific rescaled odds ratios that accounted for potential differences in recipient and donor characteristics. There were 2216 pediatric LT recipients at 24 freestanding children's hospitals in the United States during the study period. The median unadjusted center rate of AR1 was 36.92% (interquartile range [IQR], 22.36%-44.52%), whereas that of BC1 was 32.29% (IQR, 26.14%-40.44%). Accounting for recipient case mix and donor factors, 5/24 centers performed better than expected with regard to AR1, whereas 3/24 centers performed worse than expected. There was less heterogeneity across the center effects for BC1 than for AR1. There was no relationship observed between the center effects for AR1 or BC1 and center volume. Beyond recipient and allograft factors, differences in transplant center management are an important driver of center AR1 performance, and less so of BC1 performance. Further research is needed to identify the sources of variability so as to implement the most effective solutions to broadly enhance outcomes for pediatric LT recipients.

Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia.

BACKGROUND: Fasting hypoglycemia is a recognized occurrence among pediatric patients with acute lymphoblastic leukemia (ALL) during maintenance therapy. Existing publications describing this finding are limited to small studies and case reports. Our objective was to determine the incidence of hypoglycemia during maintenance chemotherapy and to investigate the association of age, as well as other potential risk factors, with this outcome in pediatric patients with ALL. PROCEDURE: This retrospective cohort study included individuals 1 to 21 years of age with ALL treated with antimetabolite-containing maintenance chemotherapy at a large children's hospital between January 2011 and December 2014. The primary endpoint was time to first documented episode of hypoglycemia during maintenance therapy, defined as single measurement of plasma glucose <60 mg/dL. Cox regression was used to evaluate the association with age and identify other potential risk factors. RESULTS: We identified 126 eligible patients, of whom 63% were documented as White, non-Hispanic, 28% as non-White, non-Hispanic, and 9% as Hispanic. Twenty-eight children (22%) had documented hypoglycemia during maintenance therapy. Younger age at the start of maintenance and hepatotoxicity documented during chemotherapy prior to maintenance initiation were associated with hypoglycemia (adjusted HR age = 0.88; 95% CI, 0.78-0.99; adjusted HR prior hepatotoxicity = 3.50; 95% CI, 1.47-8.36). CONCLUSIONS: Nearly one quarter of children in our cohort had hypoglycemia documented during maintenance chemotherapy. Younger age at maintenance initiation and hepatotoxicity during chemotherapy prior to maintenance initiation emerged as risk factors. These findings highlight the importance of counseling about the risk of, and monitoring for, hypoglycemia, particularly in young children.

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation.

BACKGROUND: The contribution of the gastrointestinal tract microbiome to outcomes after allogeneic hematopoietic cell transplantation (HCT) is increasingly recognized. Investigations of larger pediatric cohorts aimed at defining the microbiome state and associated metabolic patterns pretransplant are needed. METHODS: We sought to describe the pretransplant stool microbiome in pediatric allogenic HCT patients at four centers. We performed shotgun metagenomic sequencing and untargeted metabolic profiling on pretransplant stool samples. Samples were compared with normal age-matched controls and by clinical characteristics. We then explored associations between stool microbiome measurements and metabolite concentrations. RESULTS: We profiled stool samples from 88 pediatric allogeneic HCT patients, a median of 4 days before transplant. Pretransplant stool samples differed from healthy controls based on indices of alpha diversity and in the proportional abundance of specific taxa and bacterial genes. Relative to stool from healthy patients, samples from HCT patients had decreased proportion of Bacteroides, Ruminococcaeae, and genes involved in butyrate production, but were enriched for gammaproteobacterial species. No systematic differences in stool microbiome or metabolomic profiles by age, transplant indication, or hospital were noted. Stool metabolites demonstrated strong correlations with microbiome composition. DISCUSSION: Stool samples from pediatric allogeneic HCT patients demonstrate substantial dysbiosis early in the transplant course. As microbiome disruptions associate with adverse transplant outcomes, pediatric-specific analyses examining longitudinal microbiome and metabolome changes are imperative to identify causal associations and to inform rational design of interventions.

Center Variation in Indication and Short-Term Outcomes after Pediatric Heart Transplantation: Analysis of a Merged United Network for Organ Sharing - Pediatric Health Information System Cohort.

The relationship between center-specific variation in indication for pediatric heart transplantation and short-term outcomes after heart transplantation is not well described. We used merged patient- and hospital-level data from the United Network for Organ Sharing and the Pediatric Health Information Systems to analyze outcomes according to transplant indication for a cohort of children (≤ 21 years old) who underwent heart transplantation between 2004 and 2015. Outcomes included 30-day mortality, transplant hospital admission mortality, and hospital length of stay, with multivariable adjustment performed according to patient and center characteristics. The merged cohort reflected 2169 heart transplants at 20 U.S. centers. The median number of transplants annually at each center was 11.6, but ranged from 3.5 to 22.6 transplants/year. Congenital heart disease was the indication in the plurality of cases (49.2%), with cardiomyopathy (46%) and myocarditis (4.8%) accounting for the remainder. There was significant center-to-center variability in congenital heart disease as the principal indication, ranging from 15% to 66% (P < 0.0001). After adjustment, neither center volume nor proportion of indications for transplantation were associated with 30-day or transplant hospital admission mortality. In this large, merged pediatric cohort, variation was observed at center level in annual transplant volume and prevalence of indications for heart transplantation. Despite this variability, center volume and proportion of indications represented at a given center did not appear to impact short-term outcomes.

Human Adenovirus 7-Associated Hemophagocytic Lymphohistiocytosis-like Illness: Clinical and Virological Characteristics in a Cluster of Five Pediatric Cases.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking. METHODS: We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed. RESULTS: All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identified as genomic variant 7d. Adenovirus type 7 DNA was detected in the fifth case. Phylogenetic analysis of genome sequences identified 2 clusters-1 related to strains implicated in 2016-2017 outbreaks in Pennsylvania and New Jersey, the other related to a 2009 Chinese strain. CONCLUSIONS: It can be challenging to determine whether HLH is the result of an infectious pathogen alone or genetic predisposition triggered by an infection. We describe 5 children from the same center presenting with an HLH-like illness after onset of adenovirus type 7 infection. None of the patients were found to have a genetic predisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.

Chlorhexidine gluconate bathing in children with cancer or those undergoing hematopoietic stem cell transplantation: A double-blinded randomized controlled trial from the Children's Oncology Group.

BACKGROUND: To the authors' knowledge, information regarding whether daily bathing with chlorhexidine gluconate (CHG) reduces central line-associated bloodstream infection (CLABSI) in pediatric oncology patients and those undergoing hematopoietic stem cell transplantation (HCT) is limited. METHODS: In the current multicenter, randomized, double-blind, placebo-controlled trial, patients aged ≥2 months and <22 years with cancer or those undergoing allogeneic HCT were randomized 1:1 to once-daily bathing with 2% CHG-impregnated cloths or control cloths for 90 days. The primary outcome was CLABSI. Secondary endpoints included total positive blood cultures, acquisition of resistant organisms, and acquisition of cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration. RESULTS: The study was stopped early because of poor accrual. Among the 177 enrolled patients, 174 were considered as evaluable (88 were randomized to the CHG group and 86 were randomized to the control group). The rate of CLABSI per 1000 central line days in the CHG group was 5.44 versus 3.10 in the control group (risk difference, 2.37; 95% confidence interval, 0.05-4.69 [P = .049]). Post hoc conditional power analysis demonstrated a 0.2% chance that the results would have favored CHG had the study fully enrolled. The rate of total positive blood cultures did not differ between groups (risk difference, 2.37; 95% confidence interval, -0.41 to 5.14 [P = .078]). The number of patients demonstrating the new acquisition of resistant organisms did not differ between groups (P = .54). Patients in the CHG group were found to be more likely to acquire cutaneous staphylococcal isolates with an elevated CHG mean inhibitory concentration (P = .032). CONCLUSIONS: The data from the current study do not support the use of routine CHG bathing in children with cancer or those undergoing allogeneic HCT.