Pediatric Studies Research Articles

Fluid accumulation in critically ill children: a systematic review and meta-analysis

Fluids are often administered for various purposes, such as resuscitation, replacement, maintenance, nutrition, or drug infusion. However, its use is not without risks. Critically ill patients are highly susceptible to fluid accumulation (FA), which is associated with poor outcomes, including organ dysfunction, prolonged mechanical ventilation, extended hospital stays, and increased mortality. This study aimed to assess the association between FA and poor outcomes in critically ill children. In this systematic review and meta-analysis, we searched PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases from inception to May 2024. Relevant publications were searched using the following terms: child, children, infant, infants, pediatric, pediatrics, critically ill children, critical illness, critical care, intensive care, pediatric intensive care, pediatric intensive care unit, fluid balance, fluid overload, fluid accumulation, fluid therapy, edema, respiratory failure, respiratory insufficiency, pulmonary edema, mechanical ventilation, hemodynamic instability, shock, sepsis, acute renal failure, acute kidney failure, acute kidney injury, renal replacement therapy, dialysis, mortality. Paediatric studies were considered eligible if they assessed the effect of FA on the outcomes of interest. The main outcome was all-cause mortality. Pooled analyses were performed by using random-effects models. This review was registered on PROSPERO (CRD42023432879). A total of 120 studies (44,682 children) were included. Thirty-five FA definitions were identified. In general, FA was significantly associated with increased mortality (odds ratio [OR] 4.36; 95% confidence interval [CI] 3.53-5.38), acute kidney injury (OR 1.98; 95% CI 1.60-2.44), prolonged mechanical ventilation (weighted mean difference [WMD] 38.1h, 95% CI 19.35-56.84), and longer stay in the intensive care unit (WMD 2.29 days; 95% CI 1.19-3.38). The percentage of FA was lower in survivors when compared to non-survivors (WMD-4.95 [95% CI,-6.03 to-3.87]). When considering only studies that controlled for potential confounding variables, the pooled analysis revealed 6% increased odds of mortality associated with each 1% increase in the percentage of FA (adjusted OR=1.06 [95% CI, 1.04-1.09). FA is significantly associated with poorer outcomes in critically ill children. Thus, clinicians should closely monitor fluid balance, especially when new-onset or worsening organ dysfunction occurs in oedematous patients, indicating potential FA syndrome. Future research should explore interventions like restrictive fluid therapy or de-resuscitation methods. Meanwhile, preventive measures should be prioritized to mitigate FA until further evidence is available. None.

Longitudinal Associations of Sugar-Sweetened Beverage Intake With Serum Carbon Isotope Ratio (CIR) in Youth: Findings From Two Independent Pediatric Cohort Studies

Longitudinal Associations of Sugar-Sweetened Beverage Intake With Serum Carbon Isotope Ratio (CIR) in Youth: Findings From Two Independent Pediatric Cohort Studies

Chest X-Ray-Based Telemedicine Platform for Pediatric Tuberculosis Diagnosis in Low-Resource Settings: Development and Validation Study.

Tuberculosis (TB) remains a major cause of morbidity and death worldwide, with a significant impact on children, especially those under the age of 5 years. The complex diagnosis of pediatric TB, compounded by limited access to more accurate diagnostic tests, underscores the need for improved tools to enhance diagnosis and care in resource-limited settings. This study aims to present a telemedicine web platform, BITScreen PTB (Biomedical Image Technologies Screen for Pediatric Tuberculosis), aimed at improving the evaluation of pulmonary TB in children based on digital chest x-ray (CXR) imaging and clinical information in resource-limited settings. The platform was evaluated by 3 independent expert readers through a retrospective assessment of a data set with 218 imaging examinations of children under 3 years of age, selected from a previous study performed in Mozambique. The key aspects assessed were the usability through a standardized questionnaire, the time needed to complete the assessment through the platform, the performance of the readers to identify TB cases based on the CXR, the association between the TB features identified in the CXRs and the initial diagnostic classification, and the interreader agreement of the global assessment and the radiological findings. The platform's usability and user satisfaction were evaluated using a questionnaire, which received an average rating of 4.4 (SD 0.59) out of 5. The average examination completion time ranged from 35 to 110 seconds. In addition, the study on CXR showed low sensitivity (16.3%-28.2%) but high specificity (91.1%-98.2%) in the assessment of the consensus case definition of pediatric TB using the platform. The CXR finding having a stronger association with the initial diagnostic classification was air space opacification (χ21>20.38, P<.001). The study found varying levels of interreader agreement, with moderate/substantial agreement for air space opacification (κ=0.54-0.67) and pleural effusion (κ=0.43-0.72). Our findings support the promising role of telemedicine platforms such as BITScreen PTB in enhancing pediatric TB diagnosis access, particularly in resource-limited settings. Additionally, these platforms could facilitate the multireader and systematic assessment of CXR in pediatric TB clinical studies.

Effect of Short-term Deep Breathing Exercises on Perioperative Anxiety and Pain in Pediatric Orthopedic Patients: A Randomized Controlled Trial

PurposeThere are currently no pediatric studies examining the effects of deep breathing on perioperative pain and anxiety. This study sought to determine the effect of short-term deep breathing exercises on perioperative anxiety and pain in pediatric patients and their parents. DesignA randomized controlled trial was conducted in the Department of Orthopaedic Surgery where pediatric patients about to undergo surgery were allocated to a control group or a deep breathing group. In the intervention group, patients and their main guardian were guided to practice 10 minutes of deep breathing exercises twice a day for 3 to 4 days prior to surgery. Perioperative anxiety and pain were measured for both the children and parents as outcome indicators. MethodsPerioperative anxiety was measured using the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) and state anxiety was measured using the State-Trait Anxiety Inventory (STAI). Patients reported their pain levels daily using the Wong-Baker FACES Pain Rating Scale. The following cutoffs were determined as high levels of anxiety: STAI (adult) > 44, STAI (child) > 36, and mYPAS-SF ≥ 30. FindingsNo significant differences were found in the STAI, mYPAS-SF, and Wong-Baker FACES Pain Rating Scale scores of the patients between the intervention and control group. Overall statistics showed that parents had significantly higher postoperative state anxiety levels toward female children (44.93 ± 9.01) compared to male children (40.18 ± 9.89). Preoperative and postoperative parental state anxiety levels were correlated with the child’s postoperative anxiety. Furthermore, children’s postoperative state anxiety was slightly correlated with postoperative pain. ConclusionsShort-term use of our deep breathing exercises was ineffective in reducing incidences of perioperative pain and anxiety in pediatric orthopedic patients. A longer period of deep breathing administration may be required for the intervention to be effective. Parental anxiety may have an effect on anxiety levels in children, and postoperative parental anxiety may be affected by the gender of the child.

Effect of Ablation Energy Source on Outcomes of Slow Pathway Modification for AVNRT in Children

BackgroundSelection of radiofrequency ablation (RF) or cryoablation (Cryo) for atrioventricular nodal re-entrant tachycardia (AVNRT) in children remains controversial due to a lack of contemporary comparison studies in this population. ObjectivesThis study sought to compare outcomes of RF and Cryo for AVNRT in the pediatric population. MethodsAVNRT ablation outcomes were retrospectively analyzed utilizing the National Cardiovascular Data Registry IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry from April 2016 to March 2019. Data from subjects 1 to 21 years of age undergoing elective first-time slow pathway (SP) modification for AVNRT were included. Exclusion criteria included <1 year of age, congenital heart disease, and >1 ablation target. Cases were analyzed by ablation energy: 1) RF only; 2) Cryo only; 3) radiofrequency ablation switching to cryoablation (RF→Cryo); and 4) cryoablation switching to radiofrequency ablation (Cryo→RF). The primary outcome was acute ablation failure. Secondary outcomes included in-hospital adverse events. ResultsAmong 2,448 patients (mean age 13.6 ± 3.4 years, 60% female), RF only was employed in 43% (n = 1,046), Cryo only in 49% (n = 1,201), RF→Cryo in 6% (n = 135), and Cryo→RF in 66 (3%). Acute ablation failure occurred in 1.3% (n = 33), with no difference by energy source (1% in RF only, 1.5% in Cryo only, 1.5% in RF→Cryo, 3% in Cryo→RF; P = 0.5). Atrioventricular (AV) block requiring permanent pacemaker did not occur in any group; transient AV block occurred in 0.4% of the cohort, with no difference by group. ConclusionsIn this largest pediatric study of AVNRT ablation, RF and Cryo demonstrated comparable high acute success and rare documentation of AV block that did not result in temporary or permanent pacing. Longitudinal data are important for further comparison of these modalities with regard to recurrence risk and late complications.

Nutritional Ketosis as a Therapeutic Approach in Critical Illness: A Systematic Review.

Critical illness encompasses the dysfunction of vital organs, the risk of death, and potential reversibility; it is a major cause of morbidity and mortality globally. The pathophysiology underlying many critical illnesses includes bioenergetic failure, inflammation, and oxidative stress. This systematic review aims to explore the use of nutritional ketosis (ketogenic feeds and exogenous ketone body administration) as a potential therapy, affecting the aforementioned pathways in patients with critical illnesses. This study was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was conducted, systematically using PubMed, PubMed Central (PMC), Google Scholar, and the ScienceDirect databases in February 2024. The inclusion criteria were set to free full-text articles published within the past five years: human and animal studies, literature reviews, systematic reviews, meta-analyses, observational studies, randomized controlled trials, case reports, book chapters, gray literature, studies investigating adult samples, and articles in the English language. Exclusion criteria included pediatric studies as the topic has been studied more extensively in children, and this review aims to explore potential benefits in adult patients. The search was conducted through four databases; after the screening process, the remaining studies were assessed through quality appraisal tools appropriate to each study type. In the end, 11 studies were selected, including eight narrative reviews, one cohort study, one animal study, and one randomized controlled trial. The results of this review demonstrated that nutritional ketosis has potential safe and effective benefits for humans and animals. Nutritional ketosis shows therapeutic benefits for a vast variety of complications commonly associated with critical illness, status epilepticus, sepsis, viral infections, and glycemic control. In the end, both randomized and nonrandomized clinical trials are necessary for more conclusive findings.

A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients.

Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity. We performed a proof-of-concept study (EudraCT 2016-003785-77) to evaluate whether pharmacokinetics after a sub-pharmacological test dose of 1000µg docetaxel (millidose) could be used to predict therapeutic dose exposure. Thirty prostate cancer patients eligible for treatment with docetaxel as part of routine clinical care were included. An intravenous docetaxel millidose was administered 1-7 days prior to therapeutic docetaxel. After both doses plasma docetaxel concentrations were measured by ultra- high performance liquid chromatography-tandem mass spectrometry. The docetaxel clearance was estimated with non-linear mixed effects modeling. Geometric mean docetaxel clearance was 57.9L/h (GCV 78.6%) after admission of a millidose and 40.3L/h (GCV 60.7%) after admission of a therapeutic dose. The millidose and therapeutic dose in a single patient were not significantly correlated (Spearman's rho R = 0.02, P = 0.92). Docetaxel pharmacokinetics at milli- and therapeutic dose level showed insufficient correlation for individual dose optimization. However, the clearance of a docetaxel millidose and full dose are within the same order of magnitude. Therefore, docetaxel millidose pharmacokinetics could potentially facilitate prediction of docetaxel pharmacokinetics at a population level in situations where therapeutic dose levels are impractical, such as pharmacokinetic drug-drug interaction studies or pediatric studies.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients.

Valganciclovir is the only approved antiviral for cytomegalovirus (CMV) prevention in pediatric solid organ transplantation (SOT). Additional approaches may be needed to improve outcomes. A multicenter retrospective study from 2016 to 2019 was conducted of pediatric SOT recipients in whom at least 3 months of valganciclovir prophylaxis was planned. Episodes of CMV DNA in blood (DNAemia), CMV disease, drug-related toxicities, as well as other infections in the first year posttransplant and demographic and clinical data were collected. CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was analyzed by multivariate hazard models. Among the 749 patients enrolled, 131 (17.5%) had CMV DNAemia at any time in the first year; 85 (11.4%) had breakthrough DNAemia, and 46 (6.1%) had DNAemia after prophylaxis. CMV disease occurred in 30 (4%). In a multivariate model, liver transplantation compared to kidney or heart, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity were associated with increased risk of total and/or breakthrough DNAemia. Bacteremia was also associated with increased hazard ratio for CMV DNAemia. In a separate multivariate analysis, rejection occurred more often in those with breakthrough CMV DNAemia (P = .002); liver transplants, specifically, had increased rejection if CMV DNAemia occurred in the first year (P = .004). These associations may be bidirectional as rejection may contribute to infection risk. CMV DNAemia in the first year posttransplantation occurs despite valganciclovir prophylaxis and is associated with medication toxicity, bacteremia, and rejection. Pediatric studies of newer antivirals, especially in higher-risk subpopulations, appear to be warranted.

Metabolic Comorbidities in Pediatric Psoriasis-A Comparative Cross-Sectional Study in South-Asian Children.

There is only limited data on the association between psoriasis and metabolic comorbidities in South-Asian children. To examine metabolic comorbidities among South-Asian children with and without psoriasis. A hospital-based, comparative, cross-sectional study was conducted in children with and without psoriasis over 19 months. Anthropometric, clinical, and metabolic comorbidity details (including disease extent and severity scores, obesity, systemic hypertension, diabetes mellitus, lipid abnormalities, and metabolic syndrome) were obtained in both groups according to standard criteria. Fifty-eight children with psoriasis (25 males/33 females, age 11.3 ± 3.0 years, range 4 to 17 years) and 62 children without psoriasis (37 males/25 females, age 11.0 ± 3.6 years, range 4 to 18 years) were recruited. The prevalence of obesity (31.0% versus 14.5%, P = 0.031, odds ratio 2.65) and metabolic syndrome (18.6% versus 4.6%, P = 0.044, odds ratio 4.68) were higher in children with psoriasis than without. The prevalence of other metabolic comorbidities (systemic hypertension, pre-diabetes, lipid abnormalities, elevated serum alanine aminotransferase, and non-alcoholic fatty liver disease) was not different between children with and without psoriasis and between obese and non-obese children with psoriasis. Among children with psoriasis, those with abdominal obesity had significantly lower disease severity and extent scores than those without. Psoriasis is associated with a significantly higher prevalence of obesity and close to significantly higher prevalence of metabolic syndrome in South-Asian children. Screening for metabolic comorbidities is essential even in non-obese children with psoriasis. Disease extent and severity are less in obese compared to non-obese South-Asian children with psoriasis.

Evaluation of a multiplex-qPCR for paediatric pleural empyema-An observational study in hospitalised children.

Pleural empyema is a serious complication of pneumonia in children. Negative bacterial cultures commonly impede optimal antibiotic therapy. To improve bacterial identification, we developed a molecular assay and evaluated its performance compared with bacterial culture. Our multiplex-quantitative PCR to detect Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Haemophilus influenzae was assessed using bacterial genomic DNA and laboratory-prepared samples (n = 267). To evaluate clinical performance, we conducted the Molecular Assessment of Thoracic Empyema (MATE) observational study, enrolling children hospitalised with empyema. Pleural fluids were tested by bacterial culture and multiplex-qPCR, and performance determined using a study gold standard. We determined clinical sensitivity and time-to-organism-identification to assess the potential of the multiplex-qPCR to reduce the duration of empiric untargeted antibiotic therapy. Using spiked samples, the multiplex-qPCR demonstrated 213/215 (99.1%) sensitivity and 52/52 (100%) specificity for all organisms. During May 2019-March 2023, 100 children were enrolled in the MATE study; median age was 3.9 years (IQR 2-5.6). A bacterial pathogen was identified in 90/100 (90%) specimens by multiplex-qPCR, and 24/100 (24%) by bacterial culture (P <0.001). Multiplex-qPCR identified a bacterial cause in 68/76 (90%) culture-negative specimens. S. pneumoniae was the most common pathogen, identified in 67/100 (67%) specimens. We estimate our multiplex-qPCR would have reduced the duration of untargeted antibiotic therapy in 61% of cases by a median 20 days (IQR 17.5-23, range 1-55). Multiplex-qPCR significantly increased pathogen detection compared with culture and may allow for reducing the duration of untargeted antibiotic therapy.

Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.

Association between language discordance and unplanned hospital readmissions or emergency department revisits: a systematic review and meta-analysis

Background and objectiveStudies conflict about whether language discordance increases rates of hospital readmissions or emergency department (ED) revisits for adult and paediatric patients. The literature was systematically reviewed to investigate...

EPEN-24. 5FU SENSITIVITY IS MEDIATED THROUGH TRISOMY UCK2 EXPRESSION IN 1Q+ PFA EPN

Abstract BACKGROUND Nearly all children with gain of chromosome 1q (1q+) PFA ependymoma (EPN) will die, highlighting the urgent need to develop new treatment strategies for these patients. It has recently been shown that 1q+ creates a p53 mutant-like phenotype through trisomy expression of MDM4, a repressor of p53 signaling. This same study found toxic uracil analogs could reverse trisomy MDM4 effect on p53 and this was mediated through another 1q-trisomy gene UCK2. We and other have previously identified 5-fluorouracil (5FU) as an ependymoma specific inhibitor. In this study, we present the mechanism for 5FU sensitivity. METHODS In this study we utilize 1q+ PFA in vitro models to test the efficacy of combination radiation and 5FU in a preclinical setting. We measured p53 signaling through proteomic array and qRT-PCR for p21, a p53 response gene. RESULTS 5FU enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental down regulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. Though not statistically significant, we did see prolong survival and decreased tumor burden in 1q+ PFA orthotopic patient-derived xenograft models treated with focal 2Gyx5days radiation and 5FU. CONCLUSION These results are the first to identify a 1q+ specific therapy approach in PFA EPN. Existing phase 1 studies in pediatrics have already established safety and dose of 5FU, providing a rapid translation into phase 2 trials for children both up front and at recurrence for 1q+ PFA.

DIPG-40. LONG TERM SURVIVAL OF A 14 YEAR OLD GIRL WITH H3K27M MUTATED DIFFUSE MIDLINE GLIOMA FOLLOWING RADIOTHERAPY AND PROLONGED TUMOR TREATING FIELDS (TTFIELDS) -CASE REPORT

Abstract INTRODUCTION Pediatric diffuse midline H3K27M mutated glioma has a dismal prognosis. Most cases are treated by radiotherapy and oral chemotherapy, with surgical resection having a debatable role in some. Tumor-treating fields (TTFields) is a noninvasive modality in which alternating electrical fields exert biophysical force on charged and polarizable molecules known as dipoles. TTFields has been shown to extend survival for adult patients with newly diagnosed and recurrent GBM, and is FDA approved for these indications. There is sparse data about pediatric patients. CASE REPORT A 14-year-old girl presented with headache and vomiting. A large left thalamic tumor was diagnosed and underwent subtotal resection. Diagnosis was diffuse midline glioma, H3K27M positive, IDH negative. Molecular Panel: Tumor mutation burden low, microsatellite stable. Genomic findings: FGFR1, NF1, H3F3A -K28M, ATRX R666, MAP3K1 She was re-operated due to a fast tumor relapse within a few weeks, prior to radiotherapy, followed with radiotherapy with local field 59Gy. She then received temozolamide (12 months) concomitant with TTfields (Optune, Novocure). TTfields therapy was administered for 5 years without adverse effects and excellent compliance (above 85%). After 5 years, therapy was withheld, and she is now off therapy NED for another 15 months. DISCUSSION Diffuse midline H3K27M glioma harbors a poor prognosis in children. Children refrain from this treatment both for lack of evidence and because of the difficulty in adhering to a regimen that demands carrying a battery of 1.5-2kg all day and shaving all hair every 3 days. Our patient had a high compliance and as she wore a head scarf for religious customs, the device was not visible. To our knowledge this is the first pediatric reported case of long-term survival of H3K27mutatted midline glioma using TTFields. Further pediatric studies are warranted.

METB-08. CIRCULAR EXTRACHROMOSOMAL DNA IS ASSOCIATED WITH POOR SURVIVAL IN CHILDHOOD CANCER TYPES

Abstract BACKGROUND Circular extrachromosomal DNA (ecDNA) is a common form of oncogene amplification in aggressive cancers and a promising target for improved cancer therapy. The frequency and diversity of ecDNA has been described in different types of adult cancers and in selected childhood cancer types such as neuroblastoma and medulloblastoma. However, the frequency of ecDNA and its association with survival has not been comprehensively analyzed across the spectrum of pediatric cancers. METHODS We performed a pediatric pan-cancer study of ecDNA in which we mined large pediatric cancer genomics repositories and reconstructed ecDNA sequence structures from whole genome sequencing data. RESULTS We analyzed a retrospective cohort of 1684 tumor biopsies from 1506 different patients, covering all major childhood cancers, many of which occur exclusively in children, including rare embryonal tumor types. The fraction of patients with ecDNA-positive tumors was 10%, varying significantly by tumor type. Aggressive tumor types had particularly high incidences of ecDNA, including embryonal tumors with multilayered rosettes (n = 6, 67%), osteosarcoma (n = 55, 47%), rhabdomyosarcoma (n = 38, 39%), and neuroblastoma (n = 111, 30%). Survival analysis revealed that ecDNA amplifications are significantly associated with poor outcome. Furthermore, we catalogued known and potentially novel oncogenes that are recurrently amplified on ecDNA in pediatric cancers and showed that ecDNA often evolves during disease progression. CONCLUSIONS These results reveal childhood tumor types in which ecDNA is widely prevalent and highlight patient populations that could potentially benefit from future therapies targeting mechanisms of ecDNA biogenesis and function.

LMIC-01. SURVIVAL AND PROGNOSTIC FACTORS IN CHILDHOOD MEDULLOBLASTOMA SINGLE TERTIARY CENTER EXPERIENCE FROM KING FAHAD MEDICAL CITY KFMC SAUDI ARABIA

Abstract BACKGROUND Medulloblastoma (MB) is the most common childhood malignant brain tumor treated with intensive multimodalities therapy including Surgery, Craniospinal Radiation, and chemotherapy. Our study aims to document the clinical courses, prognostic factors, and survival outcomes in Saudi children above three years with Medulloblastoma treated in King Fahad Medical City KFMC. METHODS Retrospective analysis of MB patients diagnosed between January 2009 to January 2022 All patients received Risk-adapted Radiation therapy followed by maintenance chemotherapy,3 patients progressed and died after surgery and were excluded from analysis. RESULTS We identified 145 MB patients 65.5 % were male. median age at Diagnosis 7.00 years (range3-14 years), Age less than 5 years did not have a worse outcome in our cohort. Classic histology was predominant (80%), 42.1% of patients had metastatic disease at presentation; the Median time to start radiation therapy after surgery was 35 days. 51.7% were treated as High-Risk HR MB and Average Risk AR MB 48.3%. 65 cases having molecular testing for MB molecular subgroups. 6 patients 4.1% developed a second malignancy with a median time of 6 years post diagnosis. Multivariate survival analysis showed that progression-free survival was significantly reduced by the extent of surgical resection (P=0.021) and Metastatic MB at diagnosis(P=0.014). At Median follow-up of 7 years, Progression-free survival PFS and overall survival OS for the whole cohort were 72.4% and 71.7% respectively. PFS for AR MB and HR MB was 81.4% and 64.0% respectively. PFS analysis based on molecular subgroup: WNT subgroup 92.3%, SHH 69.2%, Group 4:57.7%:and group 3: 46.2%. CONCLUSIONS Our study is the largest analysis of childhood MB treatment outcomes in Saudi Arabia Defining the poor prognostic factor for these patients and will form the baseline for future pediatric Neuro-Oncology studies in KFMC, which may help to improve the outcome of childhood MB in Saudi Arabia.

Development and Quality Control of a Population Pharmacokinetic Model Library for Caspofungin.

Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.

Phase II study of vemurafenib in children and young adults with tumors harboring BRAF V600 mutations: NCI-COG pediatric MATCH trial (APEC1621) Arm G.

This is a phase II subprotocol of the NCI-COG Pediatric MATCH study evaluating vemurafenib, a selective oral inhibitor of BRAF V600 mutated kinase, in patients with relapsed or refractory solid tumors harboring BRAF V600 mutations. Patients received vemurafenib at 550 mg/m2 (maximum 960 mg/dose) orally twice daily for 28-day cycles until progression or intolerable toxicity. The primary aim was to determine the objective response rate and secondary objectives included estimating progression-free survival and assessing the tolerability of vemurafenib. Twenty-two patients matched to the subprotocol and 4 patients (18%) enrolled. Primary reasons for non-enrollment were ineligibility due to exclusions of low-grade glioma (n = 7) and prior BRAF inhibitor therapy (n = 7). Enrolled diagnoses were one each of histiocytosis, ameloblastoma, Ewing sarcoma, and high-grade glioma, all with BRAF V600E mutations. Treatment was overall tolerable with mostly expected grade 1/2 adverse events (AE). Grade 3 or 4 AE on treatment were acute kidney injury, hyperglycemia, and maculopapular rash. One patient came off therapy due to AE. One patient (glioma) had an objective partial response and remained on protocol therapy for 15 cycles. There was a low accrual rate on this MATCH subprotocol, with only 18% of those who matched with BRAFV600 mutations enrolling, resulting in early termination, and limiting study results (ClinicalTrials.gov Identifier: NCT03220035).

Digital Gaming and Exercise Among Youth With Type 1 Diabetes: Cross-Sectional Analysis of Data From the Type 1 Diabetes Exercise Initiative Pediatric Study.

Regular physical activity and exercise are fundamental components of a healthy lifestyle for youth living with type 1 diabetes (T1D). Yet, few youth living with T1D achieve the daily minimum recommended levels of physical activity. For all youth, regardless of their disease status, minutes of physical activity compete with other daily activities, including digital gaming. There is an emerging area of research exploring whether digital games could be displacing other physical activities and exercise among youth, though, to date, no studies have examined this question in the context of youth living with T1D. We examined characteristics of digital gaming versus nondigital gaming (other exercise) sessions and whether youth with T1D who play digital games (gamers) engaged in less other exercise than youth who do not (nongamers), using data from the Type 1 Diabetes Exercise Initiative Pediatric study. During a 10-day observation period, youth self-reported exercise sessions, digital gaming sessions, and insulin use. We also collected data from activity wearables, continuous glucose monitors, and insulin pumps (if available). The sample included 251 youths with T1D (age: mean 14, SD 2 y; self-reported glycated hemoglobin A1c level: mean 7.1%, SD 1.3%), of whom 105 (41.8%) were female. Youth logged 123 digital gaming sessions and 3658 other exercise (nondigital gaming) sessions during the 10-day observation period. Digital gaming sessions lasted longer, and youth had less changes in glucose and lower mean heart rates during these sessions than during other exercise sessions. Youth described a greater percentage of digital gaming sessions as low intensity (82/123, 66.7%) when compared to other exercise sessions (1104/3658, 30.2%). We had 31 youths with T1D who reported at least 1 digital gaming session (gamers) and 220 youths who reported no digital gaming (nongamers). Notably, gamers engaged in a mean of 86 (SD 43) minutes of other exercise per day, which was similar to the minutes of other exercise per day reported by nongamers (mean 80, SD 47 min). Digital gaming sessions were longer in duration, and youth had less changes in glucose and lower mean heart rates during these sessions when compared to other exercise sessions. Nevertheless, gamers reported similar levels of other exercise per day as nongamers, suggesting that digital gaming may not fully displace other exercise among youth with T1D.

Micobacterias no tuberculosas: cuando categorizarlas en pediatría

Background: The term "nontuberculous mycobacteria" refers to more than 170 different species of bacteria that are not Mycobacterium tuberculosis or M. leprae. These bacteria can cause a variety of infections in children. Accurate diagnosis is crucial, as they can be confused with other diseases. Treatment can be challenging due to antibiotic resistance in some strains. The literature review focuses on improving the diagnosis and treatment of these infections in the pediatric population. The characterization of these bacteria, through methods such as PCR, is essential for effective treatment. Material and methods: A systematic review was performed to determine the need to categorize nontuberculous mycobacteria in pediatrics. Various databases and Boolean operators were used to search for relevant information. Inclusion and exclusion criteria were applied to select documents. The review covered the period from 2012 to 2023. They focused on pediatric studies on nontuberculous mycobacteria. Results: The article "Idiopathic CD4+ lymphocytopenia and juvenile laryngeal papillomatosis" describes a case of juvenile laryngeal papillomatosis (JLP) that was complicated by idiopathic CD4 lymphocytopenia (ICL). Despite treatments and surgeries, JLP progressed. The patient developed ICL based on the decrease in CD4+ lymphocytes without HIV. After receiving interferon-alpha with partial response, he died. The study "Prevalence and species spectrum of both pulmonary and extrapulmonary nontuberculous mycobacteria isolates" highlights the high prevalence of nontuberculous mycobacteria in India, especially M. abscessus. "Nontuberculous Mycobacteria in Denmark" evaluates the incidence and clinical relevance of NTM in Denmark from 1991 to 2015, finding a stable incidence and differences in age groups and species. These studies enrich the understanding of these medical conditions. Conclusion: The four studies analyzed offer a global vision of the incidence and characteristics of nontuberculous mycobacteria (NTM) in various regions. Although they all address NTM, they reveal geographic variability in their incidence and characteristics. A global increase in the incidence of NTM is observed, raising concerns about its clinical relevance. Furthermore, the study in New York highlights the increase in NTM in densely populated urban environments. Botswana underlines the importance of accurate diagnosis, especially in areas with high prevalence of tuberculosis and HIV. In Denmark, no significant increase in the incidence of NTM is observed, suggesting regional variability. Together, these findings emphasize the need to understand the local epidemiology of NTM and the importance of its prevention and control