Cohort Of Pediatric Patients Research Articles

Somatic mitochondrial DNA mutations are a source of heterogeneity among primary leukemic cells.

Somatic mitochondrial DNA (mtDNA) mutations are prevalent in tumors, yet defining their biological significance remains challenging due to the intricate interplay between selective pressure, heteroplasmy, and cell state. Utilizing bulk whole-genome sequencing data from matched tumor and normal samples from two cohorts of pediatric cancer patients, we uncover differences in the accumulation of synonymous and nonsynonymous mtDNA mutations in pediatric leukemias, indicating distinct selective pressures. By integrating single-cell sequencing (SCS) with mathematical modeling and network-based systems biology approaches, we identify a correlation between the extent of cell-state changes associated with tumor-enriched mtDNA mutations and the selective pressures shaping their distribution among individual leukemic cells. Our findings also reveal an association between specific heteroplasmic mtDNA mutations and cellular responses that may contribute to functional heterogeneity among leukemic cells and influence their fitness. This study highlights the potential of SCS strategies for distinguishing between pathogenic and passenger somatic mtDNA mutations in cancer.

Pediatric Inflammatory Bowel Disease Type Unclassified: A Nationwide Cohort Study in Scotland With up to 20 Years Follow-up Shows Reclassification in the Majority and Mild Course in Those Whose Diagnosis Is Unchanged.

Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up. We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up. Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02). In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course.

Abstract A051: Association of residential economic and racial segregation with pediatric cancer survival

Abstract Purpose: Studies have linked residential segregation to inferior outcomes in adult-onset cancers. However, its association with pediatric cancer outcomes remains poorly understood. Racial and ethnic disparities in pediatric cancer outcomes are well-documented, and residential segregation may contribute, at least in part, to these disparities. This study examines the association between residential economic and racial segregation and survival in a statewide, population-based cohort of pediatric oncology patients. Methods: We studied a cohort of children diagnosed with their initial cancer between 2009 and 2016 at age 21 or younger, who were treated at Children’s Healthcare of Atlanta. The Index of Concentration at the Extremes (ICE) was mapped to the ZIP Codes of patient residence at diagnosis to measure economic and racial segregation. ICE was calculated by the difference between the number of non-Hispanic White people with &amp;gt;80th percentile household income and non-Hispanic Black people with &amp;lt;20th percentile household income, divided by the total number of people in the ZIP Code. ICE tertiles were categorized from the most deprived/segregated (tertile 1) to the most privileged/least segregated (tertile 3). We used the Cox proportional hazards model to estimate 5-, 3-, and 1-year overall survival from diagnosis by ICE tertiles, or by ICE tertiles and patient race. All models adjusted for sociodemographic (age at diagnosis, sex, health insurance, rurality) and clinical factors (cancer type, year of diagnosis). Results: Of our cohort (N=2,790), a higher proportion of non-Hispanic Black patients (50.8% vs. 13.4%) and publicly insured patients (62.3% vs. 30.8%) was found in tertile 1 compared to tertile 3. Patients living in tertile 1 consistently exhibited a higher risk of death at 5 years (adjusted hazard ratio [aHR]=1.32, 95% confidence interval [CI]=1.03-1.69, p=0.026), 3 years (aHR=1.35, 95% CI=1.04-1.75, p=0.026), and 1 year (aHR=1.38, 95% CI=0.94-2.03, p=0.099) post diagnosis, compared to those in tertile 3. In addition, compared to non-Hispanic White patients living in ICE tertiles 2-3 (more privileged areas), no survival difference was found among non-Hispanic Black children living in the same tertiles, while non- Hispanic Black children living in ICE tertile 1 had a significantly higher risk of death at 5 years (aHR=1.46, 95% CI=1.11-1.90, p=0.006), 3 years (aHR=1.56, 95% CI=1.17-2.07, p=0.002), and 1 year (aHR=1.65, 95% CI=1.11-2.45, p=0.014) post diagnosis. Conclusion: Our data indicate that residence in more racially segregated and economically deprived neighborhoods is associated with poorer overall survival among children diagnosed with cancer. Further research should explore the mediation and moderation effects of residential segregation on racial disparities in pediatric cancer-specific survival. Citation Format: Xu Ji, Lu Zhang, Xuesong Han, Heeju Sohn, Kinsey Meggett, Rebecca Williamson Lewis, Sharon M Castellino. Association of residential economic and racial segregation with pediatric cancer survival [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A051.

Abstract B135: Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors

Abstract Background: Disparities in pediatric cancer outcomes by race and ethnicity may be influenced by neighborhood characteristics, particularly residential economic and racial segregation. Prior to a new cancer diagnosis, pediatric patients are vulnerable to structural barriers embedded in their neighborhoods. In particular, residential economic and racial segregation may impede access to initial care for early cancer detection, increasing the likelihood of presenting with distant metastatic disease at diagnosis that can translate to excess morbidity and mortality. This study assesses the association of residential economic and racial segregation as measured by the Index of Concentration at the Extremes (ICE) with the likelihood of presenting with distant metastatic disease (as compared to local or locoregional disease) among children newly diagnosed with cancer. Methods: We studied a cohort of pediatric patients diagnosed with solid tumors at Children’s Healthcare of Atlanta between 2010 and 2016. Patients’ ZIP codes were linked to the ICE, which was constructed at the ZIP code level using American Community Survey 2012-2016 five-year estimates. The ICE was categorized into tertile 1 (most deprived) through tertile 3 (most privileged). Multivariable logistic regression models were used to assess the association between residential economic and racial segregation, defined by tertiles of the ICE, and the likelihood of presenting with distant metastatic disease, as determined by initial cancer staging. All models adjusted for patient- and disease-level covariates, including age, sex at birth, health insurance type, and cancer type. Results: Among 829 patients identified in our analytic sample, 27.6% had distant metastatic disease at diagnosis. Living in the most deprived (ICE tertile 1) versus the most privileged (ICE tertiles 2/3) neighborhoods was significantly associated with a higher likelihood of presenting with distant metastatic disease at diagnosis (adjusted odds ratio [OR] = 1.46; 95% confidence interval [CI] = 1.03 to 2.07; p=0.03). Additionally, non-Hispanic Black patients living in the most deprived neighborhoods were more likely to have distant metastatic disease at diagnosis compared to non-Hispanic White patients living in the most privileged neighborhoods (adjusted OR = 1.83; 95% CI = 1.15 to 2.92; p=0.002). Conclusion: This study provides new insights into how residential economic and racial segregation is associated with metastatic disease at diagnosis among children presenting with a new solid tumor. Our findings highlight the need for geographically targeted interventions to improve community care, resource allocation and investment, and public policies aimed at supporting this vulnerable patient population. Citation Format: Alexandra Cathcart, Sharon M. Castellino, Lu Zhang, Karen Wasilewski-Masker, Andrew L. Hong, Heeju Sohn, Xu Ji. Association of residential economic and racial segregation with metastatic disease at diagnosis in pediatric patients with solid tumors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B135.

Optimizing β-lactam-containing antibiotic combination therapy for the treatment of Buruli ulcer.

The current treatment for Buruli ulcer is based on empirical evidence of efficacy. However, there is an opportunity for shortening its duration and improving response rates. Evolving understanding of the pharmacokinetic-pharmacodynamic relationships provides the basis for a stronger dose rationale for antibiotics. In conjunction with modelling and simulation, it is possible to identify dosing regimens with the highest probability of target attainment (PTA). This investigation aims to: (i) assess the dose rationale for a new combination therapy including amoxicillin/clavulanic acid (AMX/CLV) currently in clinical trials; and (ii) compare its performance with alternative dosing regimens including rifampicin, clarithromycin and AMX/CLV. In vitro estimates of the minimum inhibitory (MIC) concentration were selected as a measure of the antibacterial activity of different drug combinations. Clinical trial simulations were used to characterize the concentration vs. time profiles of rifampicin, clarithromycin and amoxicillin in a virtual cohort of adult and paediatric patients, considering the effect of baseline covariates on disposition parameters and interindividual variability in exposure. The PTA of each regimen was then assessed using different thresholds of the time above MIC. A weight-banded dosing regimen including 150-600 mg rifampicin once daily, 250-1000 mg clarithromycin and AMX/CLV 22.5mg/kg /1000 mg twice daily ensures higher PTA than the standard of care with AMX/CLV 45 mg/kg/2000 mg once daily. The higher PTA values support the proposed 4-drug combination (rifampicin, clarithromycin, AMX/CLV) currently under clinical investigation. Our findings also suggest that higher rifampicin doses might contribute to enhanced treatment efficacy.

Derivation of a clinical decision rule for termination of resuscitation in non-traumatic pediatric out-of-hospital cardiac arrest

AimPrehospital termination of resuscitation (ToR) rules are used to predict medical futility in adult out-of-hospital cardiac arrest (OHCA), however, the available evidence for pediatric patients is limited. The primary aim of this study is to derive a Pediatric Termination of Resuscitation (PToR) prediction rule for use in pediatric non-traumatic OHCA patients. MethodsWe analyzed a retrospective cohort of pediatric OHCA patients within the CARES database over a 10-year period (2013–2022). We split the dataset into training and test datasets and fit logistic regressions with Least Absolute Shrinkage and Selection Operator (LASSO) to select predictor variables and estimate predictive test characteristics for the primary outcome of death and a secondary composite outcome of death or survival to hospital discharge with unfavorable neurologic status. ResultsWe analyzed a sample of 21,240 children where 2,326 (11.0%) survived to hospital discharge, and 1,894 (8.9%) survived to hospital discharge with favorable neurologic status. We derived a PToR rule for death demonstrating a specificity of 99.1% and a positive predictive value (PPV) of 99.8% and a PToR rule for death or survival with poor neurologic status with a specificity of 99.7% and PPV of 99.9% within the test dataset. ConclusionWe derived a clinical prediction rule with high specificity and positive predictive value in prehospital settings utilizing Advanced Life Support (ALS) providers which may inform termination of resuscitation considerations in pediatric patients. Further prospective and validation studies will be necessary to define the appropriateness and applicability of these PToR criteria for routine use.

Pediatric Long COVID Subphenotypes: An EHR-based study from the RECOVER program.

Pediatric Long COVID has been associated with a wide variety of symptoms, conditions, and organ systems, but distinct clinical presentations, or subphenotypes, are still being elucidated. In this exploratory analysis, we identified a cohort of pediatric (age <21) patients with evidence of Long COVID and no pre-existing complex chronic conditions using electronic health record data from 38 institutions and used an unsupervised machine learning-based approach to identify subphenotypes. Our method, an extension of the Phe2Vec algorithm, uses tens of thousands of clinical concepts from multiple domains to represent patients' clinical histories to then identify groups of patients with similar presentations. The results indicate that cardiorespiratory presentations are most common (present in 54% of patients) followed by subphenotypes marked (in decreasing order of frequency) by musculoskeletal pain, neuropsychiatric conditions, gastrointestinal symptoms, headache, and fatigue.

The Impact of Diet on Body Composition in a Cohort of Pediatric and Adult Patients with Maple Syrup Urine Disease.

The treatment for Maple Syrup Urine Disease (MSUD) consists of a hypoproteic diet with integration therapy to limit leucine intake, ensuring adequate energy, macronutrients, and micronutrients to prevent catabolism and promote anabolism. We conducted a retrospective cross-sectional study at the Metabolic Rare Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. Patients with MSUD who were over 3 years old, not treated with liver transplantation, and who provided written consent, were included. The study aimed to describe the dietary treatment of patients with MSUD, evaluate growth data, and analyze the effect of a low-protein and semi-synthetic diet on body composition. Data on height, weight, BMI, waist circumference, food intake, physical activity, and DEXA scans were collected. Thirteen subjects (11 classic MSUD, 2 intermediate MSUD) were included, of which 5 < 18 years old. Results indicated that patients with MSUD follow a balanced diet and have body compositions like healthy subjects in terms of fat and lean mass. A high incidence of osteopenia was observed from a young age, with a positive correlation between protein intake and lean mass and a negative correlation between BCAA-free mixture consumption and bone mineral density z-score. The study highlights the positive effects and potential consequences of the semi-synthetic diet on the body composition of patients with MSUD. A similar study involving all Italian metabolic centers treating MSUD is recommended.

Pharmacokinetics, Safety and Tolerability of Single-dose or Multiple-dose Cefiderocol in Hospitalized Pediatric Patients Three Months to Less Than Eighteen Years Old With Infections Treated With Standard-of-care Antibiotics in the PEDI-CEFI Phase 2 Study.

Multidrug-resistant Gram-negative bacterial infections are increasing globally in neonates, infants and children; antibiotic options are limited. This international, multicenter, open-label phase 2 study, investigated the pharmacokinetics, safety and tolerability of single-dose and multiple-dose cefiderocol [as a 3-hour infusion (every 8 hours) dosed at 2000 mg for body weight ≥34 kg and at 60 mg/kg for body weight <34 kg], over a range of renal function, in hospitalized pediatric patients with aerobic Gram-negative bacterial infection; multiple-dose patients required standard-of-care systemic antibiotics for 5-14 days. Four cohorts of pediatric patients were enrolled (cohort 1: 12 to <18 years, cohort 2: 6 to <12 years, cohort 3: 2 to <6 years and cohort 4: 3 months to <2 years). A total of 53 patients (median age: 73.5 months) were enrolled. Plasma concentration profiles were similar with single-dose (n = 24) and multiple-dose (n = 29) cefiderocol, irrespective of age and body weight in those with normal renal function or mild renal impairment. Geometric mean concentrations at the end of infusion ranged between 72.7 and 97.1 μg/mL for single-dose cefiderocol and between 88.8 and 106.0 μg/mL after multiple doses. At 8 hours, corresponding trough concentrations ranged from 7.86 to 10.8 μg/mL with single-dose cefiderocol and from 9.64 to 18.1 μg/mL with multiple doses. There were no deaths, no cefiderocol-related serious adverse events, significant related laboratory abnormalities or discontinuations. Multiple-dose cefiderocol, administered for 5-14 days and according to body weight, achieved steady-state plasma concentrations that remained above the susceptibility breakpoints of Gram-negative bacteria throughout the dosing period. Cefiderocol was well tolerated.

Phenotype-Genotype Correlation of a Cohort of Patients with Congenital Myopathy: A Single Centre Experience from India.

Congenital myopathies (CMs) are a diverse group of inherited muscle disorders with broad genotypic and phenotypic heterogeneity. While the literature on CM is available from European countries, comprehensive data from the Indian subcontinent is lacking. This study aims to describe the clinical and histopathological characteristics of a cohort of genetically confirmed CMs from India and attempts to do phenotype-genotype correlation. A retrospective chart review of genetically confirmed CMs was evaluated between January 2016 and December 2020 at the neuromuscular clinic. The clinical, genetic, and follow-up data were recorded in a pre-structured proforma as per the medical records, and the data was analyzed. A total of 31(M: F = 14 : 17) unrelated patients were included. The median age at onset and duration of illness are 2.0(IQR:1-8) years and 6.0(IQR:3-10) years respectively. Clinical features observed were proximodistal weakness (54.8%), facial weakness (64.5%), and myopathic facies (54.8%), followed by ptosis (33.3%), and ophthalmoplegia (19.4%). Muscle histopathology was available in 38.7% of patients, and centronuclear myopathy was the most common histopathology finding. The pathogenic genetic variants were identified in RYR1 (29.0%), DNM2 (19.4%), SELENON (12.9%), KBTBD13 (9.7%), NEB (6.5%), and MYPN (6.5%) genes. Novel mutations were observed in 30.3% of the cohort. Follow-up details were available in 77.4% of children, and the median duration of follow-up and age at last follow-up was 4.5 (Range 0.5-11) years and 13 (Range 3-35) years, respectively. The majority were ambulant with minimal assistance at the last follow-up. Mortality was noted in 8.3% due to respiratory failure in Centronuclear myopathy 1 and congenital myopathy 3 with rigid spines (SELENON). This study highlights the various phenotypes and patterns of genetic mutations in a cohort of pediatric patients with congenital myopathy from India. Centronuclear myopathy was the most common histological classification and the mutations in RYR1 followed by DNM2 gene were the common pathogenic variants identified. The majority were independent in their activities of daily living during the last follow-up, highlighting the fact that the disease has slow progression irrespective of the genotype.

Predicting cerebellar mutism syndrome in children using lesion map combined with clinical features.

This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

Genotype–Phenotype Correlations in 83 Korean X-linked Retinoschisis Patients: Impact of Retinoschisin 1 Secretion Profiles on Clinical Phenotypes

To assess the correlation between genotype and phenotype severity in X-linked juvenile retinoschisis (XLRS) by examining clinical and genetic features of a cohort of Korean XLRS patients. Retrospective, observational study. Data from 83 consecutive male patients with molecularly confirmed XLRS were collected retrospectively. Clinical evaluation included best-corrected visual acuity (BCVA), fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography (ERG). The phenotypic characteristics of a cohort of pediatric Korean XLRS patients, based on mutation types (truncating versus missense) and secretory profile (secretion versus non-secretion), were assessed. One hundred sixty-six eyes of 83 patients were included. The mean age at diagnosis was 6.1 ± 8.8 years (range, 0.5-20.7 years), with a mean follow-up time of 9.2 ± 7.0 years (range, 0.6-24.3 years). The BCVA at first and last examination ranged from light perception to 0.1 logarithm of the minimum angle of resolution (mean ± SD, 0.75 ± 0.59 and 0.82 ± 0.65, respectively). There were no significant differences in the first and last BCVA measurements between the truncating (0.71 ± 0.51 and 0.75 ± 0.44) and missense (0.77 ± 0.59 and 0.84 ± 0.66) variants (P = 0.678 and 0.551, respectively). Additionally, there were no differences in clinical parameters from fundus photography, SD-OCT, and full-field ERG. However, the BCVA at the first and last measurement were better for patients in the secretion group (0.51 ± 0.24 and 0.61 ± 0.30) compared to patients in the non-secretion group (0.65 ± 0.71 and 0.87 ± 0.81). The last BCVA showed a statistically significant difference between the two groups (P = 0.021). In OCT findings, the frequency of ellipsoid zone disruption was higher in patients with non-secretion variants than those with secretion variants (P = 0.030), with no significant differences in other parameters. The secretion profile of RS1 could influence the severity of XLRS phenotypes. Patients with RS1-secreted mutants, particularly with intact octamerization, exhibit more homogeneous phenotypes and better visual acuity than the RS1-non-secreted group. This data provides insights for studying genotype and phenotype correlations in both clinical and research fields.

CAT Study: Pediatric Catheter-Associated Thrombosis: A Retrospective Electronic Record Review

Highlights CAT is a significant problem in pediatric patients with CVCs and other risk factors. CAT was found in 4% of the sample with estimated 0.23 events per 1,000 CVC days. Incidence of CAT was lower than anticipated but consistent with published evidence. Median LOS was substantial in the CAT group suggesting increased disease burden. Specific clinical modifiers and CVC factors were more common in the CAT group. Findings provide valuable foundation for future CAT research and risk models. Clinicians and researchers should collaborate to reduce CAT incidence. Abstract Background: Catheter-associated thrombosis (CAT) is a serious condition, especially among pediatric surgical patients. This study describes the CAT incidence rate and clinical, demographic, and central venous catheter (CVC)-specific risk factors that may be associated with CAT, for a cohort of pediatric surgical patients. Methods: An electronic record review of 124 pediatric surgical patients with indwelling CVCs receiving parenteral nutrition (PN) cared for in a single pediatric hospital between 2016 and 2018 was performed. Results: Of the 297 CVCs, 4% of patients (n = 5) developed CAT, resulting in an estimated incidence rate of 0.23 events per 1,000 CVC days (95% confidence interval 0.15–0.31). Patients diagnosed with CAT had a higher burden of anemia, blood product administration, chronic lung disease, congenital heart disease, sepsis, prolonged mechanical ventilation, extracorporeal membrane oxygenation use, increased surgical complexity, and longer hospital stays. They also had a higher frequency of peripherally inserted central catheters, small caliber size CVCs, double lumen CVCs, extended PN and lipid course, lack of ethanol prophylaxis, higher rates of intravenous antibiotics, lower rates of treatment-dose heparin, and prolonged CVC duration. Conclusion: The incidence of CAT in this study was consistent with published rates for hospitalized pediatric patients with CVCs. The study provides additional foundational evidence about clinical, demographic, and CVC-specific risk factors associated with CAT in pediatric surgical patients with CVCs. It can help guide future research and collaborative efforts to develop risk assessment and other preventative strategies to reduce CAT incidence and improve patient care outcomes.

Association between Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the susceptibility to psoriasis and oxidative stress (OS) in a cohort of pediatric psoriatic patients in Sri Lanka: A cross sectional study.

Pediatric psoriasis accounts for nearly one-third of the global psoriasis burden. Multiple lines of evidence have shown the relationship between Angiotensin-converting enzyme (ACE) Insertion (I)/deletion(D) polymorphism with psoriasis susceptibility, and oxidative stress (OS) in psoriatic patients. However, such studies, particularly on pediatric psoriasis, are scarce in the local setting. Our study investigated the prevalence of ACE I/D polymorphism and its associations with oxidative stress in pediatric psoriasis patients in Sri Lanka. Thirty patients were recruited for this study after obtaining ethical clearance. The polymerase chain reaction was used to explore the ACE I/D polymorphism. Serum Nitric Oxide (NO) levels and the Total Antioxidant Capacity (TAC) were measured using the Griess assay and the FRAP assay. Clinical details were obtained from the clinic reports. Female predominance (76.67%) in pediatric psoriasis was reported, while Plaque psoriasis (66.67%) was found to be the most prevalent form. I/D was reported as the predominant genotype (66.67%) while I/I and D/D genotypes were recorded in 23.33% and 10% of patients, respectively. Significantly higher NO levels were observed in I/D patients than in I/I patients but not among other groups. No differences in TAC among ACE genotypes were reported. This pilot study revealed female gender and I/D genotype with increased NO levels as risk factors for pediatric psoriasis in Sri Lanka. However, it is prudent to increase the sample size to further validate the results.

Age as a predictor of reoperations and complications in surgically managed pediatric Chiari malformation type I

OBJECTIVE Chiari malformation type I (CM-I) is defined by the herniation of the cerebellar tonsils into the spinal canal. When symptomatic, surgical decompression is recommended. Reported CM-I reoperation rates have ranged from 3% to 30%. However, the relationship between patient age at first surgical intervention and the likelihood of reoperation and postoperative complications remains poorly characterized. Therefore, this study aimed to determine whether patient age was associated with reoperation and complication rates. METHODS Patients 0–21 years old with a diagnosis of CM-I and surgical decompression were queried from the 2007–2021 MarketScan databases. Patient sex, age at time of first procedure, comorbidities, 90-day postoperative complications, and reoperations were identified. Bootstrap-augmented binary classifiers were constructed to determine the optimal timing of first surgical decompression with respect to all-cause 90-day postoperative complications and reoperation. Multivariate logistic regression models were built to assess the relationship between age, sex, and comorbidities and the likelihood of reoperation and complications following surgical decompression. RESULTS A total of 2675 patients were included for analysis of 90-day postoperative complications, and 1157 were included in the reoperation analysis cohort. A total of 524 patients (19.6%) experienced a complication within 90 days of surgical decompression, and 84 patients (7.3%) had reoperations. On multivariate regression, increased age was an independent predictor of a reduced likelihood of both reoperations (OR 0.94, 95% CI 0.90–0.98; p &lt; 0.01) and 90-day postoperative complications (OR 0.96, 95% CI 0.94–0.98; p &lt; 0.01). The optimal age cutoff to predict both complications and reoperations was 4 years. For patients ages 4 years and older, both the reoperation rate (5.5% vs 13.2%, p &lt; 0.01) and 90-day postoperative complication rates (18.4% vs 27.7%; p &lt; 0.01) were significantly less than those for children 3 years and younger. CONCLUSIONS In a national cohort of pediatric patients undergoing surgically managed CM-I, there was a significantly increased likelihood of reoperation and complications in patients ages 3 years and younger. Although CM-I decompression should not be postponed in the face of progressive neurological deficits, the authors’ findings suggest that delaying surgery until after the age of 3 years, when medically feasible, may help mitigate adverse events.

External lumbar drainage for the management of refractory intracranial hypertension in pediatric severe traumatic brain injury: a retrospective single-center case series

OBJECTIVE Guidelines for the management of pediatric severe traumatic brain injury (TBI) recommend external ventricular drainage for CSF drainage as a first-tier treatment in the intracranial pressure (ICP) pathway. However, ventriculostomy in children can sometimes be challenging because of the small size of the lateral ventricles. External lumbar drainage (ELD) may be a useful alternative; therefore, the authors analyzed the outcome of a cohort of pediatric patients who underwent ELD to manage intracranial hypertension (ICH). METHODS This study retrospectively enrolled pediatric patients with ICH following severe TBI who underwent ELD. Radiological and clinical severity scores (Marshall classification, Rotterdam score, Injury Severity Score, and Pediatric Trauma Score) were noted. ICP and cerebral perfusion pressure (CPP) curves were analyzed 12 hours before and after the procedure. Any change in medical therapy was recorded, as well as the total volume and duration of drainage. Cerebellar tonsillar position according to the McRae line was noted before and after ELD. Glasgow Outcome Scale-Extended score at follow-up was also noted. RESULTS Thirty patients were included, with a mean age of 8 ± 4.4 years, and a median admission Glasgow Coma Scale score of 7 ± 4 (range 3–13). ELD was performed after a median delay of 1 day (range 0–7 days), mean drainage volume/day was 296 ± 129 ml, and median duration of drainage was 7 ± 5 (range 2–12) days. Forty-three percent of the patients underwent ELD as a part of the first-tier therapy. ICP decreased after ELD (mean difference 13.4 ± 6.2 mm Hg, p &lt; 0.001), whereas CPP increased (mean difference 10.6 ± 6.4 mm Hg, p &lt; 0.001). Fifty-three percent of the cohort did not need any further second-tier therapy after ELD. The study found 1 case of drain revision and 3 cases of cerebellar tonsil herniation. CONCLUSIONS These preliminary data suggest ELD is a valuable option to treat ICH in severely head-injured children, limiting the use of second-tier treatments. This pilot study should lay the foundation for a multicenter prospective trial.

Genetic variants in canonical Wnt signaling pathway associated with pediatric immune thrombocytopenia

AbstractThrough the use of genetic sequencing, molecular variants driving autoimmunity are increasingly identified in patients with chronic and refractory immune cytopenias. With the goal of discovering genetic variants that predispose to pediatric immune thrombocytopenia (ITP) or increase risk for chronic disease, we conducted a genome-wide association study in a large multi-institutional cohort of pediatric patients with ITP. A total of 591 patients were genotyped using an Illumina Global Screening Array BeadChip. Six variants met genome-wide significance in comparison between children with ITP and a cohort of healthy children. One variant in NAV2 was inversely associated with ITP (adjusted odds ratio [aOR], 0.52; P = 3.2 × 10−11). Two other variants in close proximity to NKD1 were also inversely associated with ITP (aOR, 0.43; P = 8.86 × 10−15; aOR, 0.48; P = 1.84 × 10−16). These genes have been linked to the canonical Wnt signaling pathway. No variants met genome-wide significance in comparison of those with ITP that self-resolved in <1 year versus those who developed chronic ITP. This study identifies genetic variants that may contribute to ITP risk and raises a novel pathway with a potential role in ITP pathogenesis.

The Prevalence of Cancer Predisposition Syndromes (CPSs) in Children with a Neoplasm: A Cohort Study in a Central and Eastern European Population.

The etiology of pediatric cancers is often unclear; however, advancements in genetics have identified significant roles for genetic disorders in their development. Over time, the number of cancer predisposition syndromes (CPSs) and awareness of them have increased, providing the possibility of cancer prevention and early detection. In this study, we present data concerning the number and type of oncological cases and their correlation with CPS occurrence in a cohort of Central and Eastern European pediatric patients. The data were collected between 2000 and 2019 at the Karol Jonscher Clinical Hospital of Poznan University of Medical Sciences, resulting in a cohort of 2190 cases in total, of which 193 children (8.81%) were confirmed to have a CPS. CPSs occurred most frequently in infancy (22.90% of all children suffering from any diagnosed cancer during the first year of life; p < 0.0001), accounting for more than one-quarter of all CPS cases in our cohort. CPSs were least likely to be observed in patients aged 14 and 15 years (2.17% and 2.44% of children diagnosed with any of the listed cancers at the exact age, respectively; p < 0.05). Among CPSs, the most common were neurofibromatosis type I (NF1), Li-Fraumeni syndrome (LFS), and Down syndrome (DS). To conclude, it is important to emphasize the need for personalized treatment for each patient affected by both CPSs and subsequent cancer in order to reduce the toxicity of therapy and improve quality of life by reducing the risk of side effects.

EHR-based Case Identification of Pediatric Long COVID: A Report from the RECOVER EHR Cohort.

Long COVID, marked by persistent, recurring, or new symptoms post-COVID-19 infection, impacts children's well-being yet lacks a unified clinical definition. This study evaluates the performance of an empirically derived Long COVID case identification algorithm, or computable phenotype, with manual chart review in a pediatric sample. This approach aims to facilitate large-scale research efforts to understand this condition better. The algorithm, composed of diagnostic codes empirically associated with Long COVID, was applied to a cohort of pediatric patients with SARS-CoV-2 infection in the RECOVER PCORnet EHR database. The algorithm classified 31,781 patients with conclusive, probable, or possible Long COVID and 307,686 patients without evidence of Long COVID. A chart review was performed on a subset of patients (n=651) to determine the overlap between the two methods. Instances of discordance were reviewed to understand the reasons for differences. The sample comprised 651 pediatric patients (339 females, M age = 10.10 years) across 16 hospital systems. Results showed moderate overlap between phenotype and chart review Long COVID identification (accuracy = 0.62, PPV = 0.49, NPV = 0.75); however, there were also numerous cases of disagreement. No notable differences were found when the analyses were stratified by age at infection or era of infection. Further examination of the discordant cases revealed that the most common cause of disagreement was the clinician reviewers' tendency to attribute Long COVID-like symptoms to prior medical conditions. The performance of the phenotype improved when prior medical conditions were considered (accuracy = 0.71, PPV = 0.65, NPV = 0.74). Although there was moderate overlap between the two methods, the discrepancies between the two sources are likely attributed to the lack of consensus on a Long COVID clinical definition. It is essential to consider the strengths and limitations of each method when developing Long COVID classification algorithms.

Predictive factors of persistent disease in a large cohort of pediatric patients with differentiated thyroid carcinoma

Predictive factors of persistent disease in a large cohort of pediatric patients with differentiated thyroid carcinoma