Pediatric Patients Research Articles

Abstract B012: M-PACT: Methylation-based predictive algorithm for CNS tumor liquid biopsies

Abstract Background: DNA methylation-based classification has been transformative in the molecular diagnostics of pediatric central nervous system (CNS) tumors. Current diagnostic pipelines integrate histopathology and molecular tools in accordance with the WHO classification of CNS tumors which rely on the availability of tissue specimens. However, some tumors are not amenable to neurosurgical resection due to their high-risk locations and tissue collection is not routinely performed at relapse. In addition, molecular biomarkers are largely lacking for longitudinal disease monitoring in pediatric neuro-oncology. Liquid biopsies (LBs) have emerged as a minimally invasive, longitudinal source of tumor-derived cell-free DNA (cfDNA) ideally suited for detecting minimal residual disease (MRD). In addition, LBs provide a sensitive means of studying tumor evolution at high temporal resolution. Success rates of LB analyses in neuro-oncology have varied drastically between studies, warranting the deployment of more robust and reproducible assays. Methods: We applied a novel cfDNA methylation-based workflow to a large cohort of cerebrospinal fluid (CSF) samples collected from pediatric brain tumor patients (n>200 patients). Enzymatic methylation sequencing (EM-seq) was adapted for CSF-derived cfDNA inputs in the picogram range, enabling the acquisition of genome-wide cfDNA methylation profiles across the cohort. Utilizing non-oncological cfDNA profiles and CNS tumor DNA methylation datasets as a reference, we developed an innovative computational pipeline that incorporates DNA methylation imputation and deep learning of a neural network. In addition, deconvolution of cfDNA profiles facilitated classification of low tumor burden samples, including those with balanced genomes that would have been missed using previous generation assays. Results: Our CSF-based classifier, M-PACT (Methylation-based Predictive Algorithm for CNS Tumors), yielded accurate tumor detection and entity prediction (AUC=0.9) in our benchmarking cohort (n>100 CSF samples). Proof-of-concept studies showed the potential of this methodology to track tumor evolution in serial CSF samples at both the genetic and epigenetic level, illuminating potential mechanisms driving treatment resistance and recurrence. Conclusions: Collectively, this study provides the framework for robust methylation- based tumor detection and classification of CSF LBs. M-PACT can be applied to aid in tumor diagnostics and to detect MRD during follow-up, warranting prospective validation of its broad applicability and clinical utility in future trials. Citation Format: Tom T. Fischer, Kyle S. Smith, Katie Han, Anna Kostecka, Hong Lin, Daniel Senfter, Tatjana Wedig, Nathalie Schwarz, Natalia Stepien, Sibylle Madlener, Christine Haberler, Esther Hulleman, Sandeep K. Dhanda, Stefan M. Pfister, Santhosh Upadhyaya, Amar Gajjar, Giles W. Robinson, Joonas Haapasalo, Hannu Haapasalo, Kristiina Nordfors, Johannes Gojo, Kendra K. Maass, Kristian W. Pajtler, Paul A. Northcott. M-PACT: Methylation-based predictive algorithm for CNS tumor liquid biopsies [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B012.

Creating a Risk Score for Prolonged Length of Stay Following Pediatric Lung Transplants.

Pediatric lung transplant (LT) outcomes correlate with prolonged length of stay (pLOS), yet a paucity of research exists predicting pLOS in this population. We aim to identify factors associated with pLOS following pediatric LT, and to create a risk score identifying individual patients at increased risk of pLOS. Using the OPTN database, we analyzed 733 pediatric patients who received an LT between January 2000-July 2022. We used LASSO regularization to identify factors predicting pLOS. A risk score was calculated using odds ratios for each variable in the model. LASSO was run on 51 factors and identified 13 to be included in the model. The variables with the highest negative impact on LOS were recipient ethnicity (Asian, Native American, Pacific Islanders, or Mixed Race) (OR = 3.187), recipient requiring life support (OR = 2.354), and recipient age 2-10 years old (OR = 2.203). In contrast, low cold ischemia time (OR = 0.562), time on waitlist 21-60 days (OR = 0.284), and diagnosis of primary pulmonary hypertension (OR = 0.307) had protective effects on LOS. Using the risk score, we stratified patients into three equal groups: low (mean LOS = 20.60 days), medium (mean LOS = 22.53 days), and high risk (mean LOS = 36.72 days) of pLOS. The c-statistic for the model was 0.7931 and 0.7757 for the risk score. Using this model and risk score, physicians and healthcare systems could identify patients at risk of pLOS and could intervene on preventable variables before transplantation.

BN SO15 - Post Cholecystectomy Syndrome: Definition, Aetiology, Investigation & Management – A Systematic Review

Abstract Background Post-cholecystectomy syndrome (PCS) is a term commonly used to refer to the persistence of abdominal symptoms following cholecystectomy, or de-novo symptoms that develop post operatively. Despite the common use of the term, there is no widely agreed upon consensus definition. PCS is reported to affect between 5-40% of patients that undergo cholecystectomy representing a large populational burden. Despite this, there are no guidelines or protocols in place for the routine investigation and management of this large heterogenous patient group. In this study we systematically review the literature describing definition, aetiology, investigation and up-to-date management of PCS. Method An updated systematic search of the Medline, EMBASE and Cochrane databases was undertaken to identify studies where patients underwent cholecystectomy and subsequently were diagnosed with PCS. Included papers were published between 2016-2024, had a minimum of 10 cases of PCS following laparoscopic or open cholecystectomy. Excluded studies were case reports, narrative and systematic reviews, paediatric patient population or papers unavailable in the English language. Paper characteristics were extracted and where present, the definition of PCS, aetiology, investigations and management of these patients was both extracted and analysed. Results 145 papers were identified of which 13 were included after title, abstract and full text screening. Definition of PCS, where present, was highly heterogenous between papers. Aetiology was often divided into biliary and non-biliary causes, with some papers claiming early-PCS and late-PCS as distinct clinical phenomena. In such papers, early-PCS was most commonly attributed to gastro-oesophageal pathologies and late-PCS to biliary pathologies. Investigation strategy is sparingly reported and without guideline or protocol. Most frequently used tests include LFTs, USS, MRCP, CT, ERCP and OGD. Some studies also used 99m Tc-Mebrofenin Hepatobiliary Scintigraphy, sphincter manometry and colonoscopy. Conclusion PCS has a widely reported prevalence in the published literature. This is potentially due to the heterogeneity of definitions used to cover the syndrome. The effective management of such patients depends on both the accurate diagnosis of the underlying cause, as well as exclusion of procedure related complications. There are currently no guidelines or protocols available for the investigation and management of patients presenting with symptoms post cholecystectomy despite the large populational burden. Further studies should aim to provide a consensus definition of PCS, and work towards guidelines for the investigation and management of this patient group.

A Novel Pediatric Clinical Skills Curriculum to Prepare Medical Students for Pediatrics Clerkship

Abstract Introduction Medical students feel poorly prepared to examine pediatric patients during clerkship. Our institution’s introduction to clinical skills course lacked practice with pediatrics physical examination skills. We developed a novel clinical skills curriculum to increase students’ confidence in examining pediatric patients. Methods Ericsson’s deliberate practice conceptual framework guided curriculum design. We utilized a flipped-classroom model to teach the newborn examination. Students watched a video, then practiced with manikins and patients. For the child examination, students attended a lecture and practiced with hospitalized children and facilitators. Students then participated in a Home, Education, Eating/Exercise, Activities/Employment, Drugs, Suicidality, Sexuality, Safety (HEEADSSS) didactic and role play activity. Before and after participation, students completed REDCap surveys ranking confidence in performing pediatric examinations and identifying normal examination findings on a Likert scale (1 = “Not at all confident,” 4 = “Extremely confident”). We analyzed data using Wilcoxon rank sum tests. Results A total of 97 students participated in the curriculum. Respectively, 56 (58%) and 32 (30%) students completed pre- and post-participation surveys. Post-participation, students reported increased confidence in identifying normal infant (median [interquartile range]; (2 [2,2] vs 4 [3,4]; p < 0.001) and child (2 [2,2] vs 3 [3,4]; p < 0.001) examination findings as well as HEEADSSS assessment components (2 [1.5,2] vs 4 [3,4]; p < 0.001), and had significantly higher scores on confidence performing infant (2 [2,2.5] vs 4 [3,4]; p < 0.001), child (2 [2,2] vs 3 [3,4]; p < 0.001), and HEEADSSS assessment (2 [2,3] vs 4 [3,4]; p < 0.001). Discussion This multi-modal curriculum emphasizing pediatric examination skills improved students’ confidence in pediatric-specific knowledge and skills prior to clerkship.

The effect of interhospital transfer on pediatric burn injury mortality in a resource-limited setting.

The World Health Organization's burn mortality estimate is 180,000 annually. Ninety-five percent of all mortality caused by fire-related burns worldwide occurs in low- and middle-income countries (LMICs). Prior studies have shown that transfer status (direct transfer from an injury scene to a trauma center vs. indirect transfer from another health facility) affects patient outcomes. We evaluated the effect of interhospital transfer on burn mortality. We analyzed a burn database of pediatric patients admitted to the Kamuzu Central Hospital (KCH) burn unit in Lilongwe, Malawi. We performed a bivariate analysis based on their transfer status and mortality and a logistic regression analysis to determine the effect of transfer status on mortality after burn injury. A total of 2301 patients were analyzed, with 1095 (47.6%) being in the transfer cohort from referring hospitals. The median age was 3years (IQR 1-4). The transfer cohort had more patients presenting to the hospital more than 48h after injury. Upon multivariate logistic regression, controlling for pertinent variables, including time to presentation, burn-injured patients in the transfer cohort had increased odds of mortality (OR 2.26, 95% CI 1.22-4.19, and p=0.01) compared to patients who were not transferred. The predictive probabilities of burn mortality by TBSA showed significant differences in mortality based on transfer status at TBSA between 20% and 80%. Ensuring district hospitals and other primary health care centers in resource-limited settings are sufficiently equipped to provide initial burn resuscitation and care may decrease mortality rates associated with transferred patients.

An advantageous practical modification in mini-laparoscopic pyeloplasty for prepubertal children: Extracorporeal ureteral spatulation, suturing and stenting - EUSSS technique.

Ureteral spatulation, the first ureteral suture, and double-J stenting may be challenging and time-consuming in laparoscopic pyeloplasty, especially in small children. We aimed to present our comparative results of the extracorporeal ureteral spatulation, suturing, and stenting (EUSSS) technique in mini-laparoscopic pyeloplasty (MLP) and the conventional intracorporeal technique in prepubertal children. The data of 46 prepubertal pediatric patients (< 12 years) who underwent laparoscopic pyeloplasty by a single surgeon between January 2021 and October 2023 were retrospectively reviewed. The patients were divided into two groups: who underwent EUSSS-MLP (Group-1, n = 26) and who underwent conventional intracorporeal pyeloplasty (Group-2, n = 20). The mean age of all patients was 5.3 years (4.8 ± 2.8 years in Group-1 and 6.0 ± 2.1 years in Group-2 p = 0.126). The mean duration of ureteral preparation plus double-J stenting was 5.7 ± 1.6min in Group-1 and 19.2 ± 4.1min in Group-2 (p < 0.0001). The mean duration of surgery was statistically significantly higher in Group-2 (p = 0.034). There was no significant difference in terms of postoperative complications (p = 0.482). Laparoscopic pyeloplasty was successful in 42 (91.3%) patients, with no statistically significant difference between the two groups (Group-1: 24 (92.3%), Group-2:18 (90%), p = 0.783). Extracorporeal ureteral preparation and double-J stenting can be safely and effectively preferred in MLP for prepubertal children.

Next-generation sequencing in diagnosis of monogenic cholestatic liver disorders: A single-center experience

Introduction Cholestasis in childhood is a rare clinical condition, yet a definitive diagnosis is crucial for initiating treatment of these curable diseases and preventing related morbidity and mortality. The most common cause of infant cholestasis is biliary atresia (25-40%), followed by monogenic cholestatic diseases (25%), metabolic diseases (20%), and cryptogenic cholestasis. This study focuses on assessing the clinical utility of next-generation sequencing (NGS) panels, including clinical exome sequencing and whole exome sequencing, in diagnosing cholestatic diseases when the etiology cannot be elucidated through conventional methods. Materials and Methods We conducted a retrospective examination of pediatric patients who sought care at a single-center pediatric gastroenterology department between August 2020 and March 2022, and were diagnosed with cholestasis. A total of 36 patients underwent a thorough investigation to rule out infectious, toxic, metabolic, structural, chromosomal, and endocrine causes. Patients whose diagnoses were established through traditional investigations were excluded from the study. The remaining 14 patients underwent either whole exome sequencing or targeted next-generation sequencing methods. Results A definitive diagnosis was achieved for 12 patients, while two patients remained undiagnosed despite comprehensive genetic examinations. The most commonly encountered diseases in this cohort were progressive familial intrahepatic cholestasis, linked to mutations in the ABCB11, ATP8B1, and TJP2 genes, as well as Dubin-Johnson syndrome associated with ABCC2 mutations. Next-generation sequencing demonstrated a diagnostic accuracy of 85.7% in patients for whom a diagnosis could not be established through extensive traditional workup. Conclusion Next-generation sequencing emerges as a valuable diagnostic tool in cases of cholestasis where traditional methods fall short in providing a definitive diagnosis. Moreover, our study unveiled three previously undocumented variants in the ABCB11 [c.1165G&gt;C; p.(Ala389Pro) and c.783+1G&gt;A] and ABCC2 [c.4246_4247del; p.(Lys1416ValfsTer46)] genes.

Noonan Syndrome: Relation of Genotype to Cardiovascular Phenotype—A Multi-Center Retrospective Study

Background: Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. Methods: We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. Results: The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in PTPN11 were most commonly associated with pulmonary valve stenosis (PVS), while RAF1 mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development (p = 0.755), even though the likelihood ratio showed significance in that regard (p = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. Conclusions: The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype–phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies.

An 18-Month Case of Langerhans Cell Histiocytosis : Diagnostic Challenges and Treatment Outcome

Background: Langerhans Cell Histiocytosis (LCH) is a rare disorder characterized by the abnormal proliferation of Langerhans cells, which can affect various tissues and organs, often mimicking malignancies. It primarily affects children and can present with a wide range of symptoms, making diagnosis challenging. The etiology of LCH remains uncertain, though recent studies suggest it involves the aberrant growth of Langerhans cells triggering an immune response. Case Presentation: This was a case of an 18-month-old boy who came with fever of unknown origin in the Department of Paediatrics at BBMH who later on diagnosed as Histiocytosis. Conclusion: This case highlights the importance of considering LCH in the differential diagnosis of paediatric patients presenting with systemic symptoms such as fever, organomegaly and anaemia. Early recognition and appropriate treatment, including chemotherapy and corticosteroids are crucial for favourable outcomes. Continuous follow-up is necessary to monitor therapeutic response and manage potential complications. This report contributes to the understanding of LCH and underscores the need for further research into its etiology and treatment protocols. IAHS Medical Journal Vol 7(1), June 2024; 102-104

Abstract 4131424: Exercise Stress Perfusion Cardiac MRI in Pediatric Patients with Coronary Anomalies

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) can result in sudden cardiac death in the young and risk stratification is challenging. Though dobutamine stress cardiac MRI (DS-CMR) is feasible in pediatric patients, exercise stress CMR (ES-CMR) has lower rates of adverse events, higher diagnostic accuracy, and the ability to better reflect the physiologic changes occurring with exercise. No studies have evaluated ES-CMR in the pediatric population. We aim to describe our institution’s experience with ES-CMR using supine bicycle ergometry in patients with AAOCA. Methods: We retrospectively reviewed the medical records of AAOCA patients who underwent ES-CMR at our institution between 2011 and 2024 for demographic, clinical presentation, cardiopulmonary exercise test (CPET) and ES-CMR data. The exercise-based portion of the CMR consisted of supine cycle ergometry utilizing a ramp protocol, immediately after which perfusion imaging was performed. We used descriptive statistics for data analysis. Results: Of 38 patients who underwent ES-CMR, the median age was 16 years (range 13-24) and 68% were male. Diagnoses included anomalous right coronary artery (N=28), anomalous left coronary artery (N=8), and single coronary artery (N=1 single right, N=1 single left). Median maximal heart rate (HR) during ES-CMR was 160 bpm (range 130-190, median 80% predicted) with a median maximal HR during patients’ most recent CPET of 187 bpm (range 160-203, median 97% predicted). No patients had perfusion defects at rest or with exercise stress, or evidence of myocardial scarring. There were no adverse events. Discussion: We demonstrate for the first time the use of ES-CMR in a cohort of pediatric and young adult patients with AAOCA. ES-CMR can provide a unique modality to assess for ischemia at rest and stress as a means of risk stratification and simulate physiologic changes occurring with exercise stress in a single study. Although maximum heart rates during supine cycle ergometry are lower than those reached during CPET, they are similar to those reached during DS-CMR. ES-CMR can be a helpful and safe diagnostic tool in patients with AAOCA.

Open-label, controlled, phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of INM004 in pediatric patients with Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome.

Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS. Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other kidney and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms. Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm. INM004 showed an adequate safety profile. Efficacy non-statistically significant trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a phase 3 study of INM004 in pediatric patients with STEC-HUS.

Abstract 4134590: Procedural Related Major Adverse Events of Cardiac Catheterization in Pediatric Patients with Cardiomyopathy: Insights from IMPACT Registry

Background: Despite the role of cardiac catheterization for hemodynamic assessment and endomyocardial biopsy (EMB) in children with cardiomyopathy, data on procedure-related major adverse events (MAE) in this population is lacking. We aim to describe the rate of MAE in children with cardiomyopathy undergoing cardiac catheterization. Our secondary objective is to compare the rate of MAE among patient subsets within this population. Hypothesis: We hypothesize that the rate of MAE will vary among cardiomyopathy types and that EMB will be associated with an increased rate of MAE. Methods: We included patients with cardiomyopathy from the National Cardiovascular Data Registry Improving Pediatric and Adult Congenital Treatment (IMPACT) who were 18 years or younger and had cardiac catheterization from April 2016 to June 2023. We collected demographic, pre-procedural, procedural, and outcome-related variables. We performed univariate and multivariate analyses to identify variables independently associated with MAE. Results: A total of 15,656 procedures were evaluated, with a median age of 11 years; 50.3% were females. Dilated cardiomyopathy (DCM) was the most prevalent cardiomyopathy in 68%, followed by restrictive cardiomyopathy (RCM) in 14% and hypertrophic cardiomyopathy (HCM) in 9%. MAE was present in 1.6%. The most common MAE was arrhythmia, representing 46% of MAE, followed by cardiac arrest and bleeding each 20%. EMB was associated with a lower rate of MAE in univariate analysis p&lt;0.001. The association between a lower rate of MAE and EMB persisted in the multivariate model when those with heart transplant who had EMB were compared to those without heart transplant who did not have EMB p=0.001. The multivariate analysis also revealed that age less than a year, HCM compared to DCM, history of heart failure, pre-procedural inotropic support, and non-elective procedure were associated with increased rate of MAE. The overall mortality rate was 1.66%. The leading cause of mortality was heart failure in 51% of deceased patients. MAE was associated with an increased mortality rate of 11% p&lt;0.001. Conclusion: Cardiac catheterization is a safe procedure in pediatric patients with cardiomyopathy, with an overall MAE rate of 1.6%. Age of less than a year, HCM, history of heart failure, and prior inotropic support are associated with an increased rate of MAE. EMB was not associated with a higher rate of MAE. MAE occurrence is associated with a sevenfold increase in mortality rate.

Clinical and demographic factors linked to low-value emergency department visits in pediatric patients with spina bifida.

Identifying factors associated with emergency visits that could be delivered at lower-cost sites may help guide population health strategies for pediatric patients with spina bifida. Emergency department encounters (2016-2023) by patients with spina bifida (< 18-years-old) in Pediatric Health Information System were identified. Absence of clinical and imaging charges was defined as low-value emergency visit. We utilized a control population of patients (<18-years-old) with obstructive/reflux uropathy who presented for emergency department encounters (2016-2023). Mixed effects (with repeated individual measurements as random effect) logistic regression was fitted to model odds of low-value emergency visit. In total, we included 22,672 emergency visits by patients with spina bifida. 20.7% of these emergency visits were low-value versus 17.7% in controls (p<0.001). Costs related to low-value emergency visits account for 3.8% of all costs for emergency visit-related encounters in patients with spina bifida. Low-value emergency visits were associated with younger age [OR 1.05 (1.04 - 1.06) per year younger], Hispanic/Latino [OR 1.21 (1.06 - 1.39) compared to non-Hispanics], black [OR 1.35 (1.16 - 1.58) compared to white], public insurance [OR 1.14 (1.01 - 1.29) compared to private insurance], and genitourinary encounter diagnosis [OR 1.16 (1.04 - 1.30)]. Using a standard patient, we found that the odds of low-value emergency visit across hospitals ranged from 0.31 to 5.36. Younger age, Hispanic/Latino ethnicity, black and other race, public insurance, and genitourinary encounter diagnosis were associated with higher odds for low-value emergency visits in pediatric patients with spina bifida. There was wide variation across hospitals that warrants further investigation to elucidate best practices.

Anesthetic Management of Laparoscopic Surgery on a Pediatric Patient: Case Report

Inguinal hernia is an opening on myofascial oblique muscle and transversal muscle or the failure of Nuck canal or processus vaginalis during the gestation week which allows herniation of intra-abdominal or extraperitoneal organ. A 5-year-old child was diagnosed with a left lateral inguinal hernia. The results of the inguinal ultrasound showed movement and movement of the intestines in the left inguinal area through a defect measuring approximately 2.96 centimeters. The patient was planned to undergo laparoscopic high ligation hernia. Laparoscopic technique in adult commonly applied with special consideration. However, the practice in pediatric patient could be more challenging for anesthesiologist. Although laparoscopic surgery is less invasive it could cause more stress due to the pressure of the intra-abdominal pneumoperitoneum by CO2 that is done during the procedure, which then causes hypercapnea due to the absorption of CO2, the decrease of tidal volume, and the decrease of end-tidal volume. Considering pediatric’s different physiology compared to adult and the risks of laparoscopic surgery, special anesthesia management should be conducted.

Automated lung segmentation on chest MRI in children with cystic fibrosis

IntroductionSegmentation of lung structures in medical imaging is crucial for the application of automated post-processing steps on lung diseases like cystic fibrosis (CF). Recently, machine learning methods, particularly neural networks, have demonstrated remarkable improvements, often outperforming conventional segmentation methods. Nonetheless, challenges still remain when attempting to segment various imaging modalities and diseases, especially when the visual characteristics of pathologic findings significantly deviate from healthy tissue.MethodsOur study focuses on imaging of pediatric CF patients [mean age, standard deviation (7.50 ± 4.6)], utilizing deep learning-based methods for automated lung segmentation from chest magnetic resonance imaging (MRI). A total of 165 standardized annual surveillance MRI scans from 84 patients with CF were segmented using the nnU-Net framework. Patient cases represented a range of disease severities and ages. The nnU-Net was trained and evaluated on three MRI sequences (BLADE, VIBE, and HASTE), which are highly relevant for the evaluation of CF induced lung changes. We utilized 40 cases for training per sequence, and tested with 15 cases per sequence, using the Sørensen-Dice-Score, Pearson’s correlation coefficient (r), a segmentation questionnaire, and slice-based analysis.ResultsThe results demonstrated a high level of segmentation performance across all sequences, with only minor differences observed in the mean Dice coefficient: BLADE (0.96 ± 0.05), VIBE (0.96 ± 0.04), and HASTE (0.95 ± 0.05). Additionally, the segmentation quality was consistent across different disease severities, patient ages, and sizes. Manual evaluation identified specific challenges, such as incomplete segmentations near the diaphragm and dorsal regions. Validation on a separate, external dataset of nine toddlers (2–24 months) demonstrated generalizability of the trained model achieving a Dice coefficient of 0.85 ± 0.03.Discussion and conclusionOverall, our study demonstrates the feasibility and effectiveness of using nnU-Net for automated segmentation of lung halves in pediatric CF patients, showing promising directions for advanced image analysis techniques to assist in clinical decision-making and monitoring of CF lung disease progression. Despite these achievements, further improvements are needed to address specific segmentation challenges and enhance generalizability.

Ethanol sclerotherapy in pediatric rectal prolapse: efficacy, complications, and influencing factors.

Rectal prolapse is prevalent in children and the elderly, impacting quality of life significantly. Traditional surgical interventions carry risks, especially in pediatric patients. Ethanol sclerotherapy offers a less invasive alternative, inducing fibrosis and thickening of the rectal wall. Despite its potential benefits, procedural complications are possible, emphasizing the need for careful patient selection and procedural expertise. This study aims to evaluate the safety and efficacy of sclerotherapy in treating rectal prolapse in a tertiary referral center in southern Iran. Patient records from Nemazee Hospital covering January 2014 to December 2023 were retrospectively analyzed. Pediatric patients undergoing ethanol sclerotherapy for rectal prolapse were included. Data on demographics, presentation, procedures, and outcomes were collected. Ethical approval was obtained, and specific inclusion/exclusion criteria were applied. Statistical analyses were conducted using SPSS version 26. One hundred thirtypatients were evaluated, with a mean age of 10.74 ± 5.320years. Most patients experienced constipation (56.9%). 74.2% responded well to sclerotherapy, with 12.9% needing a second injection. Complications were minimal, with bleeding being the most common (4.6%). Recurrence occurred in 18.6% of cases. Male patients showed a higher total complication rate (P = 0.010). Diarrhea-dominant patients had no recurrences post-sclerotherapy. Age significantly influenced treatment response and recurrence (P = 0.017, P = 0.035). Male predominance contradicted global pediatric rectal prolapse ratios, possibly influenced by cultural factors. Sclerotherapy remains effective, though response rates vary. Older age correlated with lower response rates and higher recurrence. Constipation-dominant prolapse was associated with increased recurrence risk. Male patients had a higher complication rate, highlighting the need for tailored management strategies.

Abstract 4122024: Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in pediatric patients. This represents a vulnerable population who often require heart transplantation. Here, we examine the transcriptome in ventricular tissue to identify underlying cellular processes unique to pediatric HCM (pHCM). Methods: We performed single-nucleus RNA sequencing on explanted hearts at transplant in female patients with end-stage pHCM (n=3) and compared findings to pediatric control (n=2) and adult HCM (n=5; Figure 1A-1B). Results: We generated 91,682 single-cell transcriptomes from 8 tissue samples. Principal component analysis exhibited the largest source of transcriptional variation separated pHCM and controls (Figure 1C). We identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells in pHCM. pHCM was enriched in cardiomyocytes with stressed signatures and pathways associated with hypertrophy (Figure 1D); we noted depletion of tissue-resident macrophages (Figure 1D) and increased vascular remodeling in endothelial cells in pHCM. Fibroblasts exhibited activation signatures and compared to adult HCM, showed heightened fibrotic processes and a unique pro-fibrotic cluster with increased metabolic stress, mitochondrial turnover, and anti-apoptotic properties (Figure 2). In cell-to-cell communication, the differential number and weight of interactions were higher in pHCM compared to controls and fibroblasts had the highest strength of outgoing interactions. Conclusions: Our analysis provides the first single-nuclei analysis focused on pHCM. Fibroblast-mediated cellular processes contributed most to the disrupted micro-tissue environment; they had more downstream processes associated with fibrosis and may respond to metabolic stress differently compared to adult HCM. This advances our understanding of the early presentation of pHCM, providing a crucial steppingstone toward improved patient outcomes.

Abstract 4137534: Troponin Can Predict Late Gadolinium Enhancement on Cardiac MRI in COVID-19 Vaccine-Associated Myocarditis

Background/Aim: We previously reported that late gadolinium enhancement (LGE) on cardiac MRI (CMR) was as high as 82% in pediatric patients with COVID-19 vaccine-associated myocarditis (C-VAM) despite mild clinical symptoms and normal left ventricular function. As LGE can be a harbinger for future adverse events including arrhythmias, heart failure or sudden cardiac death, we sought to identify predictors for LGE in C-VAM, specifically assessing troponin as a screening marker for C-VAM patients at risk for myocardial scarring who could then be referred for a confirmatory CMR with LGE. Methods: In this longitudinal multicenter retrospective observational study across 38 U.S. member institutions of the M yocarditis A fter C OVID V accination (MACiV) study network, 333 patients with C-VAM based on CDC criteria were included from April 2021 to November 2022. Data collected included demographics, laboratory values, clinical and cardiac imaging characteristics and outcomes. Using logistic regression, troponin levels at presentation were assessed as a log transformed continuous variable and categorized into tertiles. Results: The C-VAM patients were predominantly white (67%) adolescent males (91%, 15.7± 2.8 years). There were 216/333 (65%) patients who had both a reported troponin value and had a CMR. On univariate analysis, elevated troponin increased the probability of having LGE (OR=1.29, 95% CI: 1.06, 1.58, p=0.012). Even after controlling for age, race, sex, number of vaccine doses and left ventricular ejection fraction (OR=1.32, 95% CI: 1.06, 1.65, p=0.013). Patients &gt;15 years compared to those ≤15 years of age were 2.94 (95% CI: 1.28, 6.75, p=0.011) times more likely to have LGE at presentation. Patients with troponin levels in the highest tertile compared to lowest tertile were 2.66 times (95% CI: 1.04, 6.83, p=0.042) more likely to have LGE along with a greater involvement &gt; 4 AHA myocardial segments with LGE (p=0.004) Conclusions: Higher troponin values are associated with presence of late gadolinium enhancement on cardiac MRI in patients with COVID-19 vaccine-associated myocarditis. Troponin levels at presentation may facilitate risk stratification and function as a screening tool to identify those C-VAM patients with the greatest likelihood of myocardial scarring, who may benefit from undergoing CMR for tissue characterization.

Characterization of Disease Patterns in Children with Intracranial Abscesses for Enhanced Clinical Decision-Making

Background: Intracranial suppurative infections in pediatric patients, while rare, pose a significant risk to patient mortality. Early recognition and fast initiation of diagnosis and treatment are crucial to prevent fatal outcomes. Between December 2022 and May 2023, a significant cluster of nine cases emerged, each necessitating neurosurgical intervention. This series highlights an important trend in clinical outcomes and raises questions about underlying factors contributing to this pattern. The need for surgical procedures in all instances suggests a commonality in severity, warranting further investigation into potential causes and preventative measures. This retrospective monocentric study aims to explore the clinical features associated with these cases to identify specific disease patterns that can expedite management in clinical practice. Methods: Cramer’s V effect size was employed to evaluate combinations of clinical features, followed by Fisher’s exact test applied to a constructed contingency table. A p-value was assessed for significance analysis, with combinations achieving a Cramer’s V value of 0.7 or higher being classified as exhibiting very strong correlations. Results: The analysis revealed distinct patterns of clinical features among children diagnosed with intracranial abscesses. Significant associations were identified, including correlations between sinusitis and Streptococcus pyogenes, and fever accompanied by affected temporal, frontal, and frontobasal lobe regions. Conclusions: Despite the generally limited statistical analysis of pediatric intracranial abscesses in the existing literature, this study provides meaningful significant associations between clinical features, delineating specific disease patterns for children with intracranial abscesses. By addressing this gap, the findings contribute valuable insights and offer a framework that could enhance clinical decision-making and support timely disease management in pediatric cases.

Differential diagnosis of visceral leishmaniasis in children: a five-year retrospective study at a pediatric referral hospital.

Visceral leishmaniasis (VL) is a zoonotic disease caused by protozoa of the genus Leishmania and is transmitted by sandflies of the genus Lutzomyia. Children under 15 years are disproportionately affected. In pediatric patients, the clinical and laboratory features of VL often overlap with those of other infectious and hematology-oncology diseases, making differential diagnosis challenging. Rapid and accurate identification of VL is critical for effective treatment. This study aimed to evaluate the epidemiological, clinical, and laboratory characteristics of pediatric patients initially suspected of having VL and to compare their final diagnoses upon discharge from a referral hospital. We retrospectively analyzed medical records of children with suspected VL, admitted between July 2014 and June 2019. Infectious diseases were confirmed in 61% of cases (86 patients), with VL confirmed in 55 cases. Hematology-oncology diseases were the second most common diagnosis, affecting 22.7% of patients (32 cases). Comparisons between the VL-confirmed group and those with other diagnoses revealed no significant age difference (p = 0.690). However, female sex, spleen size, and leukopenia were identified as significant predictors of VL. Female sex, spleen size, and leukopenia were key predictors for differentiating VL from other pediatric diseases in a referral center in the Northeast Region of Brazil.