Profile Of Pediatric Patients Research Articles

Onychomycosis in the US Pediatric Population-AnEmphasis on Fusarium Onychomycosis.

Onychomycosis is a common nail disease that is often difficult to treat with a high risk of recurrence. To update our current understanding of the etiologic profile in pediatric patients with onychomycosis utilizing molecular diagnosis by polymerase chain reaction (PCR) combined with histopathologic examination. Records of 19,770 unique pediatric patients were retrieved from a single diagnostic laboratory in the United States spanning over a 9-year period (March 2015 to April 2024). This cohort represents patients clinically suspected of onychomycosis seen by dermatologists and podiatrists. Dermatophytes, nondermatophyte molds (NDMs), and yeasts were identified by multiplex real-time PCR corroborated by the demonstration of fungal invasion on histopathology. An average of 37.0% of all patients sampled were mycology-confirmed to have onychomycosis. Most patients were between ages 11 and 16 years, and the rate of mycologically confirmed onychomycosis was significantly higher among the 6- to 8-year (47.2%) and 9- to 11-year (42.7%) age groups compared to the 0- to 5-year (33.1%), 12- to 14-year (33.2%), and 15- to 17-year (36.7%) age groups. The majority of infections were caused dermatophytes (74.7%) followed by NDMs (17.4%). The Trichophyton rubrum complex represents the dominant pathogen with higher detection rates in the 6- to 11-year-olds. Fusarium was the most commonly isolated NDM with an increasing prevalence with age. Elementary school-aged children have a higher risk of contracting onychomycosis which may be attributed to the onset of hyperhidrosis at puberty, use of occlusive footwear, nail unit trauma, and walking barefoot. Fusarium onychomycosis may be more prevalent than expected, and this may merit consideration of management strategies.

Cytokine profile of cerebrospinal fluid in pediatric patients with metastatic medulloblastoma

BackgroundMedulloblastoma (MB) is a malignant pediatric central nervous system tumor that is prone to leptomeningeal metastasis. Currently, apart from magnetic resonance imaging and cerebrospinal fluid (CSF) cytology, there are no reliable biomarkers for MB progression. Cytokines are key proteins in signaling pathways in the tumor microenvironment and are closely related to tumor recurrence and progression. This study aimed to investigate the CSF cytokine profile in pediatric patients with MB to identify biomarkers of tumor progression and metastasis. MethodsIn total, 10 patients were recruited for this study. Five patients had nonmetastatic MB and five had metastatic MB. A cytokine antibody array was used to detect the expression of 120 cytokines in the CSF, and differentially expressed cytokines were screened by integrated bioinformatics analysis. ResultsTwenty-seven cytokines were upregulated in patients with MB compared to control individuals. Of these, eight were upregulated by >1.5-fold (CCL2, BMP-4, beta-NGF, FGF-7, IL-12p40, eotaxin-2, M-CSF, and NT-4). Twelve cytokines were differentially expressed between patients with metastatic MB and nonmetastatic (nine cytokines were upregulated and three were downregulated). Among them, NAP-2, MIP-1α, MIP-1β, IGFBP-1, IGFBP-2 and IGFBP-3 were upregulated by more than two-fold. Gene Ontology analysis revealed that the upregulated cytokines were enriched mainly in “epithelial cell proliferation” and “chemotaxis,” and the Kyoto Encyclopedia of Genes and Genomes analysis indicated the enrichment of the “MAPK,” “PI3K-Akt,” and “Ras” signaling pathways. ConclusionsThe present study investigated cytokine profiles in the CSF of pediatric patients with MB. Our results suggest that these differentially expressed cytokines may serve as novel markers for detecting MB, especially for assessing the risk of progression and metastasis.

Effect of Omega-3 Fatty Acids Supplementation in Pediatric Patients with Type 1 Diabetes Mellitus

Abstract Background Omega-3 fatty acids (O3FAs) are polyunsaturated fatty acids derived from fish oil. Beneficial effects of O3FA supplementation in a wide range of disease condition have been well studied. However; the role of O3FA in management of type 1 diabetes mellitus (T1DM) remains unclear and controversial. Objectives Therefore, we performed a randomized-controlled trial to assess the effect of oral O3FAssupplementation on glycemic control and lipid profile in pediatric patients with T1DM. Methods This study included 70 children and adolescents with T1DM. Patients were randomly assigned into two groups; intervention group and received oral O3FAs capsules (1 gram daily). The other group did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c and fasting lipids. Results Supplementation with O3FAs was safe and well-tolerated. After 6 months, O3FAs adjuvant therapy for the intervention group resulted in a significant decrease of systolic blood pressure, insulin dose, FBG, HbA1c, triglycerides, total cholesterol and LDL-cholesterol compared with baseline levels and compared with the control group (p < 0.05). On the other hand, T1DM patients without O3FAs adjuvant therapy (control group) had higher blood glucose levels and HbA1c at study end compared with baseline levels (p < 0.001). Conclusions O3FAs as an adjuvant therapy to insulin improved blood glucose levels, glycemic control and dyslipidemia leading to reduction in insulin dose in pediatric patients with T1DM.

Efficacy and Safety of Resveratrol in Patients with Type 1 Diabetes Mellitus

Abstract Background Resveratrol is a food component found in grapes, peanuts, cranberries.. It has a wide range of effects including antimicrobial, anti-inflammatory and anti-apoptotic effects. Resveratrol could ameliorate diabetes in diabetic animals and it showed beneficial effects in adults with type 1 diabetes mellitus (T1DM). Objectives This randomized-controlled trial assessed the efficacy and safety of oral resveratrol supplementation on glycemic control and lipid profile in pediatric patients with T1DM. Methods This study included 60 children and adolescents with T1DM. Enrolled patients aged 12- 18 years with disease duration > 5 years. Patients were randomly assigned into two groups; intervention group who received oral resveratrol tablets 250 mg twice daily. The other group (did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c% and fasting lipid profile. Results After 6 months, resveratrol therapy resulted in a significant decrease of FBG, HbA1c, triglycerides and total cholesterol compared with baseline levels and compared with the control group (p < 0.001). No significant difference was found between Patients with T1DM without resveratrol adjuvant therapy at baseline and at 6 months as regards any of the studied variables except for triglycerides and total cholesterol which were significantly increased at study end. Conclusions Resveratrol as an adjuvant therapy to insulin improved blood glucose levels, glycemic control and dyslipidemia without adverse effects in pediatric patients with T1DM.

HGG-02. LONG-TERM EFFICACY AND SAFETY OF LAROTRECTINIB IN PEDIATRIC PATIENTS WITH TRK FUSION PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS: AN UPDATED ANALYSIS

Abstract BACKGROUND Larotrectinib is the first-in-class, highly selective TRK inhibitor approved for tumor-agnostic use in patients with TRK fusion cancer. We report data on larotrectinib-treated pediatric patients with TRK fusion primary CNS tumors. METHODS Patients aged <18 years with TRK fusion primary CNS tumors enrolled in two clinical trials (NCT02637687, NCT02576431) were included. Responses were independent review committee (IRC)-assessed per RANO. Patients were permitted to stop larotrectinib in the absence of on-treatment progression (wait-and-see) and remain on trial. RESULTS As of July 2023, 38 patients were eligible for efficacy analyses by IRC, including 11 patients with only non-measurable disease at baseline. Median age at enrollment was 7 years (range 0–17). Tumor histologic groups included: high-grade glioma (HGG; n=18), low-grade glioma (LGG; n=12), and other (n=8). Eleven (29%) patients had received ≥2 prior systemic therapies. Overall response rate was 37% (95% CI 22–54): three complete response, 11 partial response, 17 stable disease, five progressive disease, and two not evaluable. The 24-week disease control rate was 74% (95% CI 57–87). Medians for duration of response, progression-free survival, and overall survival (OS) were 17.2 months (95% CI 5.7–not estimable [NE]), 19.8 months (95% CI 11.1–50.8), and not reached (95% CI 32.7–NE), respectively. The 48-month OS rate was 60%. At data cutoff, one patient with HGG and four with LGG entered wait-and-see; median duration of the first wait-and-see period was 20.2 months (range 4–29). One patient with LGG resumed treatment following wait-and-see. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. No patients discontinued treatment due to TRAEs. CONCLUSION Larotrectinib demonstrated rapid, durable responses and a manageable safety profile in pediatric patients with TRK fusion primary CNS tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing pediatric patients with CNS tumors.

Utilization of Indocyanine Green (ICG) Fluorescence in Patients with Pediatric Colorectal Diseases: The Current Applications and Reported Outcomes.

In pediatric colorectal surgery, achieving and visualizing adequate perfusion during complex reconstructive procedures are paramount to ensure postoperative success. However, intraoperative identification of proper perfusion remains a challeng. This review synthesizes findings from the literature spanning from January 2010 to March 2024, sourced from Medline/PubMed, EMBASE, and other databases, to evaluate the role of indocyanine green (ICG) fluorescence imaging in enhancing surgical outcomes. Specifically, it explores the use of ICG in surgeries related to Hirschsprung disease, anorectal malformations, cloacal reconstructions, vaginal agenesis, bladder augmentation, and the construction of antegrade continence channels. Preliminary evidence suggests that ICG fluorescence significantly aids in intraoperative decision-making by improving the visualization of vascular networks and assessing tissue perfusion. Despite the limited number of studies, initial findings indicate that ICG may offer advantages over traditional clinical assessments for intestinal perfusion. Its application has demonstrated a promising safety profile in pediatric patients, underscoring the need for larger, prospective studies to validate these observations, quantify benefits, and further assess its impact on clinical outcomes. The potential of ICG to enhance pediatric colorectal surgery by providing real-time, accurate perfusion data could significantly improve surgical precision and patient recovery.

PCA-pump for analgesia following pediatric scoliosis surgery: bolus administration with/without basal infusion.

The aim of this study is to compare the use of two different opioid delivery systems (bolus PCA with/without basal infusion) to control postoperative pain and evaluate the side effect profile in pediatric patients undergoing scoliosis surgery. 38 patients who underwent posterior spinal fusion for adolescent idiopathic scoliosis were included in the study. Patients were randomly divided into 2 groups by the computer. Patients who received only bolus PCA were named Group 1, and patients who received bolus PCA with basal infusion were named Group 2.Morphine consumption, postoperative pain assessmentduring rest, movement and coughing with numeric rating scale (NRS) and the Wong -Baker pain scale, heart rate and average blood pressure, sedation levels withRamsey sedation scale and side effects such as nausea, vomiting, itching, desaturation, and urinary retention were recorded. Total mean morphine consumption (mg) was 32.7 ± 9.7 in Group 1 and 43.4 ± 9.1 in Group 2. The mean morphine consumption (mg) at 12-24hours and 0-48hours in Group 1 was statistically lower than Group 2 (p = 0.001). There was no significant difference between the groups in terms of median NRS scores (p = 0.55). There was no statistically significant difference in the evaluation of the groups in terms of Wong-Baker pain scale. Wong-Baker pain scale is p:0.66 at the 2nd hour, p:0.951 at the 12th hour and p:0.467 at the 24th hour.There was no statistically significant difference in Ramsay Sedation Scale evaluation between groups during each follow-up time (p > 0.05). The Ramsay Sedation Scale was p: 0.94 at the 2nd hour, p:1.0 at the 12th hour, and p:1.0 at the 24th hour. The duration of vomiting between 0-2h, 2-24h and 0-48h was higher in Group 2 (p = 0.001, p = 0.024, p = 0.001). The two administration settings of morphine sulphate by PCA pump have shown to be equally effective in the treatment of postoperative pain following PSF. In addition, PCA with basal infusion administration causes more opioid consumption and more systemic side effects. Therefore, the use of only bolus PCA in pediatric scoliosis surgery should be encouraged. LevelII, Randomized Controlled Trial.

Postoperative Analgetic Profile in Pediatric Patients at Dr. Kariadi Hospital

Background: Pain management is pivotal for pediatric patients post-surgery due to its common occurrence and significant impact on well-being. Effective management involves considerations such as surgical type, analgesic selection, and proper pain assessment.Objective: Knowing the profile of postoperative analgesia in pediatric patients at Dr. Kariadi Hospital using pain assessment instruments based on age classification.Method: Employing an observational descriptive approach with a prospective cohort design, the study sampled 172 pediatric patients across varying pain severity levels. Utilizing total sampling, patients were assessed using age-specific pain instruments. Descriptive statistics were utilized to describe patients' characteristics, as well as the attributes of analgesic effectiveness concerning age, surgery type, and drugs administered. Texts and tables were employed to present the results.Results: Sampling on 172 patients with grouping based on the type of surgery that causes mild, moderate, and severe pain. Pain scales and analgesics were recorded at 4 moments: (1) when entering the recovery room; (2) leaving the recovery room; (3) 8 hours and (4) 24 hours postoperative. The results showed that the highest use of analgesics was paracetamol alone (59.9%); analgesic effectiveness in the mild pain surgery 97.2-98.6%; moderate pain 92.2-98.9%, and severe pain 90.9-100%.Conclusion: Postoperative analgesic utilization in pediatric patients at Dr. Kariadi Hospital is generally adequate, predominantly relying on paracetamol. However, enhancements are needed to optimize pain management, particularly for moderate-to- severe pain cases. Strategies to improve analgesic effectiveness should be pursued to ensure comprehensive pain relief for pediatric surgical patients.

Abstract 1323: Anti-B7-H3 chimeric antigen receptor NK cells suppress the growth of atypical teratoid/rhabdoid tumor orthotopic xenografts

Abstract Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are the most common malignant CNS tumor in infants. AT/RT patients have a 5-year overall survival rate of ~35% and high rates of relapse, emphasizing a dire need for new safe and effective therapies. These therapy-resistant tumors frequently overexpress the immune checkpoint cell surface molecule B7-H3 (CD276). CAR-T cell studies have an established safety profile in pediatric patients. We developed B7-H3 targeted chimeric antigen receptor (CAR) natural killer (NK) cells as a tumor-specific cell therapy for aggressive pediatric brain tumors. CAR-NK cells have several advantages over CAR-T cells. NK cells can be obtained from healthy donors and produced as an “off-the-shelf” product. NK cells also have a lower risk of inflammatory toxicity and graft-versus-host disease compared to T-cells when transferred across the HLA barrier from healthy donors to patients. Methods: We have designed a library of variable affinity B7-H3-targeted CARs, produced replication incompetent γ-retroviral vector, and used this for generation of B7-H3 CAR-NK cells. We verified B7-H3 expression in a panel of AT/RT cell lines, and further engineered firefly luciferase expressing AT/RT (CHLA06.ffLuc, BT12.ffLuc, BT37.ffLuc) as well as a CHLA06-derived B7-H3 knockout. We developed an orthotopic CHLA06.ffLuc xenograft model. We tested CAR-NK cell functionality using in vitro co-culture and cytotoxicity assays. In vivo study was performed in our xenograft with intratumoral delivery of CAR-NK cells. Results: B7-H3 targeted CAR-NK cells demonstrate target-specific cytotoxicity when compared to untransduced NK cells (36.8±12.5% vs. 72.4±24.2% at effector:target ratio of 1:1, n=3). CRISPR/Cas9 mediated knockout of B7-H3 in target cells abolished the difference in CAR vs. no-CAR NK-mediated target killing. When delivered intracranially to CHLA-06 orthotopic xenograft bearing mice, B7-H3 CAR NK cells eliminate tumor cells and prolong survival, whereas unmodified NK cells did not (log-ranked median survival = 20 vs. 84 days, p<0.0001). We are currently testing intracranial delivery of our B7-H3 CAR NK against other AT/RT orthotopic xenografts. Conclusions: Targeting pediatric brain tumors with an anti-B7-H3 CAR-NK cell therapy may provide a safe and effective treatment for patients who have extremely limited therapeutic options. Direct intracranial injections of cell therapies into pediatric patients is currently being explored in clinical trials. As B7-H3 is a tumor associated antigen found to be overexpressed in a large variety of tumor types, this strategy may also be useful for treatment of other B7-H3 expressing cancers. Citation Format: Jun Choe, Sachiv Chakravarti, Natalie Holl, Ruyan Rahnama, Megan Zinsky, Danielle G. Jones, Stamatia Vorri, Arjun Modi, Eric H. Raabe, Challice L. Bonifant. Anti-B7-H3 chimeric antigen receptor NK cells suppress the growth of atypical teratoid/rhabdoid tumor orthotopic xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1323.

Pediatric Extrapolation Approach for U.S. Food and Drug Administration Approval of Brexpiprazole in Patients Aged 13 to 17 Years with Schizophrenia.

A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13-17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020, the US Food and Drug Administration issued a general advice letter to sponsors highlighting the acceptance of efficacy extrapolation of certain atypical antipsychotics from adult patients to pediatric patients considering the similarity in disease and exposure-response relationships. Brexpiprazole is the first atypical antipsychotic approved in pediatrics using this approach. The PK data available from pediatric patients aged 13-17 years have shown high variability due to the limited number of PK evaluable subjects, which limits a robust estimation of differences between adult and pediatric patients. The PK model-based approach was thus utilized to evaluate the appropriateness of the dosing regimen by comparing PK exposures in pediatric patients aged 13-17 years with exposures achieved in adults at the approved doses. In addition to exposure matching, safety data from a long-term open-label clinical study in pediatric patients informed the safety profile in pediatric patients. This report illustrates the potential of leveraging previously collected efficacy, safety, and PK data in adult patients to make a regulatory decision in pediatric patients for the indication of schizophrenia.

Nivolumab Plus 5-Azacitidine in Pediatric Relapsed/Refractory Acute Myeloid Leukemia (AML): Phase I/II Trial Results from the Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3–4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.

Pediatric palliative care and childhood neurosurgery: reflections based on a quantitative analysis of a survey data

INTRODUCTION: In recent years, the profile of pediatric patients has changed, with the need for assistance for children living with chronic and life-threatening diseases becoming increasingly frequent. In this scenario, Pediatric Palliative Care (PPC) emerges as an integral and respectful form of assistance for these patients and their families. Understanding that neurosurgery is an extremely important area within Pediatric Palliative Care, as there are many intersections between the two areas, this research aimed to reflect on how this interaction is being carried out in practice. MATERIAL AND METHODS: It is an observational, descriptive, cross-sectional study, of survey type, in which the study population was composed of a convenience sample, using the snowball strategy. Analyses were performed with the aid of the statistical program Stata version 13.0 (Stata Corp, L. C.). Results are presented as frequencies and 95% confidence intervals, graph, and table. RESULTS: The sample represented 90 PPC services, almost all of which have physicians (97.90%). Among the medical specialties, none of the services reported having a neurosurgeon on the team. DISCUSSION: Several themes required by the National Medical Residency Commission for the training of neurosurgeons cover Pediatric Palliative Care, such as pain, bioethics, communicating difficult news and others. Therefore, the real rapprochement of the two areas is extremely important to ensure comprehensive care for the patient. CONCLUSIONS: There are important gaps between Pediatric Palliative Care and Pediatric Neurosurgery, reinforcing the importance of including the topic for neurosurgery residents and continuing education for those already trained.

Everolimus in combination with vandetanib in children, adolescents, and young adults: a phase I study

Combined use of inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF-2) receptors is a potential strategy to overcome resistance to either class of drugs when used alone. We designed a phase 1 trial to test the drug combination of a multikinase VEGF receptor 2 inhibitor, vandetanib, and an mTOR inhibitor, everolimus, in a pediatric and young adult patient cohort with advanced cancers. Exceptional responders were probed for tumor mutational profile to explore possible molecular mechanisms of response. Among 21 enrolled patients, clinical benefit was observed in 38% (one patient with partial response and eight patients with stable disease) with a median progression-free survival of 3.3 months. The most common treatment-related adverse event was rash (n= 13). Other treatment-related toxicities included diarrhea, fatigue, hypertension, QT prolongation, hypertriglyceridemia/hypercholesterolemia, transaminitis, thrombocytopenia, and weight loss. None of the patients experienced dose-limiting toxicities. Three exceptional responders were analyzed and were found to harbor genetic alterations including kinase insert domain receptor (KDR) Q472H mutation, EWSR1-CREB3L1, CDKN2A/B loss, and ASPL/ASPSCR1-TFE3 fusion. The combination of vandetanib and everolimus showed early activity and tolerable toxicity profile in pediatric patients with advanced cancers.

Health-Related Quality-of-Life Profile of Pediatric Patients with β Thalassemia after Hematopoietic Stem Cell Transplantation.

Matched hematopoietic stem cell transplantation (HSCT) is a feasible and curative treatment in pediatric patients with beta thalassemia major (β-TM). However, little data are available regarding patients and their parents' health-related quality of life (HRQoL) after the procedure. As such, we investigated the HRQoL of pediatric patients with β-TM after HSCT compared to that of patients treated with blood transfusions and iron chelation. The health-related quality of life of 43 β-TM pediatric patients and 43 parents were evaluated using the Pediatric Quality of Life Inventory (PedsQL). A total of 25 patients underwent HSCT: 15 from a sibling and 10 from an HLA-matched donor. The median follow-up time from HSCT was 5 years (range 1-13 years). The mean ages at the survey were 10.1 years (range 5-15) and 9.6 years (range 5-15) for transfused and transplanted patients, respectively. A significant reduction in HRQoL was reported in the group of transfused patients compared with that of patients transplanted in the following PedsQL domains: children's and parents' physical functions, Δ = -15.4, p = 0.009 and Δ = -11.3, p = 0.002, respectively; children's and parents' emotional functioning, Δ = -15.2, p = 0.026 and Δ = -15.2, p = 0.045, respectively; child's and parents' school functioning, Δ = -25, p = 0.005 and Δ = -22.5, p = 0.011, respectively; total child and parents scores, Δ = -14.5, p = 0.004 and Δ = -13.2, p = 0.005, respectively. The results of a multivariable analysis showed that the HSCT procedure was significantly associated with a higher total child PedsQL score (adjusted mean difference = 15.3, p = 0.001) and a higher total parent PedsQL score (adjusted mean difference = 14.1, p = 0.006). We found no significant difference in the HRQoL measured after sibling or unrelated human leukocyte antigen (HLA)-matched HSCT. Finally, a significant positive correlation across all the PedsQL domains was found between the scores reported by the children and those reported by their parents. In conclusion, our study shows that HSCT in pediatric patients with β-TM is associated with a good overall HRQoL profile. This information further supports physicians when counseling patients and their parents before the HSCT procedure.

42456 Characterizing the Cutaneous Side Effect Profile in Pediatric Patients Receiving Mitogen- Activated Kinase Inhibitor Therapy

42456 Characterizing the Cutaneous Side Effect Profile in Pediatric Patients Receiving Mitogen- Activated Kinase Inhibitor Therapy

Cognitive-Behavioral Profile in Pediatric Patients with Syndrome 5p-; Genotype-Phenotype Correlationships.

(1) Background: 5p minus Syndrome (S5p-) is a neurodevelopmental disorder caused by a deletion in the short arm of chromosome 5. Among the phenotypic characteristics of S5p-, the most characteristic and representative element is a monochromatic cry with a high-pitched tone reminiscent of a cat's meow. Individuals may also show great phenotypic heterogeneity and great genetic variability. Regarding cognitive-behavioral aspects of the syndrome, the studies are scarce and do not establish a general profile of the main cognitive-behavioral particularities that this syndrome presents. The main objective of this work was to describe the development profile of a cohort of 45 children with 5p minus Syndrome, concerning the biomedical, genetic, cognitive, and behavioral aspects. Establishing putative genotype-phenotype (cognitive-behavioral profiles) relationships in our cohort, from an interdisciplinary approach. (2) Methods: A selection of instruments of measures was selected for neuropsychological assessment (3) Results: In general, children with S5p- have a higher cognitive level than a communicative and motor level. Language difficulties, especially expressive ones, influence the frequency and severity of the most frequent behavioral problems in S5p. The most significant problem behavior of children with S5p-, especially girls, is self-harm. Compulsive behavior, limited preferences, and interest in monotony are significantly more frequent in subjects with better cognitive levels. We also find a significant correlation between the size of the loss of genetic material on 5p and the cognitive level of the subjects. (4) Conclusions: We described for the first time, the cognitive-behavioral profile of a cohort of minors with S5p-. Remarkably, it was found that language, especially of an expressive nature, modulates the most frequent behavioral aspects in subjects with lower cognitive levels, so it is essential to develop verbal or alternative communication strategies adjusted to these individuals.

A Cross - Sectional Study of Renal Profile in Pediatric Patients with Sickle Cell Disease

A Cross - Sectional Study of Renal Profile in Pediatric Patients with Sickle Cell Disease

Profile of Pediatric Patients at Emergency DepartementRSIA Puri Bunda Denpasar in July- December 2021

Background. Emergency is a clinical condition that requires immediate medical action to save lives and prevent. Emergency treatment in children is different from adults. The emergency room is place where responsible for admission, triage, initial assessment, stabilization, management of children with acute conditions, injuries and referrals for continuing care. In Indonesia itself there is still no definite data that describes the number of visits by pediatric patients in Indonesia. Objective. Knowing the description of pediatric patient visits in the emergency department of RSIA Puri Bunda Denpasar in July-December 2021 according to age, sex, triage, working diagnosis and waiting time. Methods. A descriptive observational study research. Number of sample 3003 patients. Research variables consist of age, sex, triage, working diagnosis and waiting time. Results. The results of this study showed that male patients more than female patients, the most common age of patients is in the toddler age group, more cases of false emergencies than emergency cases, the most common working diagnosis is fever, pediatric patients are treated more in less than 30 minutes. Conclusion out of 3003 patients, there were many male patients, toddler age group, more false emergencies, most working diagnoses were febrile and patients were treated in less than 30 minutes.

727: LONGITUDINAL STUDY OF THYROID PROFILE IN CHILDREN DURING SEPTIC SHOCK AND ITS IMPACT ON OUTCOMES

Introduction: Non-thyroidal illness syndrome (NTIS) is common in septic shock. Data on thyroid profile in pediatric patients from low- and middle-income countries (LMICs) are scarce, where undernutrition is common. Longitudinal behaviour of thyroid hormones during initial 7 days of septic shock and its association with clinical outcome in children from LMICs was studied. Methods: This prospective observational study was conducted in pediatric emergency room and pediatric intensive care unit in a tertiary care centre of a low-middle income country. Sixty-two patients (age, 6mo-12yrs) with fluid refractory septic shock at admission or developing it within 24hrs of admission were enrolled. Exclusions were history of CPR, chronic illness, endocrine disorders, and recent radio-contrast study. Serum levels of Thyroid Stimulating Hormone (TSH), T4 and T3 were measured on Day 1, 3 and 7. Correlation between thyroid hormones and severity of organ dysfunctions, outcomes and nutritional status were analysed. Results: TSH was low in 20% patients, which remained unaltered during 7 days. T4 and T3 levels were low in the majority (Day 1: 84% and 72%; Day 7: 68% and 59% respectively). Non-Survivors (n=24) have significantly lower TSH and T4 levels during 7 days compared to survivors (n=38) (p=0.045 and p=0.004 respectively). Non-survivors had significantly lower T3 on day 1 (p< 0.001), however it increased significantly over 7 days (p=0.05) to become similar to that among survivors. TSH, T4 and T3 levels were negatively correlated with admission pSOFA, maximum pSOFA and PRISM-III scores (p< 0.05). Children with VIS >40 had significantly lower T3 levels on day 1 and 3 (p=0.008 and p=0.034 respectively). Time to shock reversal was negatively correlated with T3 levels on day 3 (rho=-0.43, p=0.008). Children requiring ventilation had lower thyroid hormones on day 1 and 3. Their levels were positively correlated with ventilator-free days and acute care area free days. Nutritional status did not affect thyroid profile. Conclusions: Children with more severe disease had lower levels of all thyroid hormones on day 1 and 3. Non-survivors had significantly lower thyroid hormones on day 1, which mostly failed to increase during initial 7 days as compare to survivors. Nutritional status did not affect thyroid profile.

Mutational Profile of Children with Myeloproliferative Neoplasms

Introduction Myeloproliferative neoplasms (MPNs) are clonal bone marrow disorders of over proliferation driven largely by mutations in the JAK2, CALR, and MPL genes. Mutational profiles including driver and secondary mutations in adult subjects with MPNs have been well studied and recent work has determined that driver mutations occur as early as in utero. There is little described about mutational profiles in pediatric patients with MPNs. Given the importance of clonal evolution and the relevance of MPN-associated mutations for risk assessment, clinical features, and outcomes, it is important to develop an understanding of the mutational spectrum in young subjects. Therefore, we sought to evaluate a pediatric MPN cohort for potential MPN-associated mutations. Methods We isolated mononuclear cells from the blood and/or bone marrow of 29 pediatric patients (median age 10 years, range 2-21) with MPNs. DNA was extracted and sequenced on the HEMEPACT platform, a gene panel including almost 600 genes focused on myeloid malignancies. Variants were called using a combination of variant callers. For single-nucleotide variants (SNV), we used CaVEMan, Mutect, and Strelka, and for small insertions and deletions also used Pindel. VAF was uniformly reported across all called variants using a realignment procedure. Likely artifact variants were filtered out based on: (i) The number of callers calling a given variant and the combination of filters from the triple callers. (ii) Variants with VAF <2% in all samples or less than 3 mutant supporting reads were excluded. Results In this cohort, 18 subjects had essential thrombocytosis (ET), 8 subjects had polycythemia vera (PV), 2 had pre-fibrotic myelofibrosis, and 1 had myelofibrosis. Clinical sequencing identified 9 subjects with ET with a JAK2V617F mutation, 3 ET subjects with CALR mutations, and 6 ET subjects who were "triple negative" (TN) for driver mutations. Six subjects with PV were found to have a JAK2V617F mutation, while 2 had JAK2 exon 12 mutations. Both subjects with pre-fibrotic myelofibrosis had CALR mutations, and the subject with myelofibrosis had a MPL mutation. HEMEPACT identified mutations in 10 additional cancer-associated genes (Figure 1A). After JAK2 and CALR, the most frequently mutated genes were TET2 and SETBP1. Two subjects had TET2 mutations that co-occurred with JAK2V617F (Figure 1B), and both had very low TET2 variant allele frequencies (VAFs). Two subjects had SETBP1 mutations, one co-occurring with JAK2V617F, and 1 with CALR mutation (Figure 1B), both of whom had high SETBP1 VAFs, possibly implying a germline mutation. No mutations in ASXL1, EZH2, or DNMT3A were identified. Of the 6 TN subjects, 3 had mutations detected on HEMEPACT (in CHEK2, CUX1, and RB1). Eight of the 29 subjects (28%) had more than 1 mutation detected, and the average number of mutations was 1.2 per subject. In contrast, in a small cohort of adult (median age 41 years, range 21-82) subjects with ET (n=2) and PV (n=7), 6 of 9 subjects (67%) had more than 1 mutation identified, and the average number of mutations per subject was 2. JAK2V617F variant allele frequency of the adult cohort was 4-times higher than in the pediatric cohort (median=0.16 vs. median=0.04). Conclusion This is one of the largest analyses to date of the mutational spectrum of pediatric MPNs. TET2 and SETBP1 mutations co-occurred with driver mutations, and no DNMT3A or ASXL1 mutations were seen in these young patients. While fewer pediatric than adult subjects had multiple mutations, there were some young patients who had already developed multiple mutations in childhood and it is important to better understand the role clonal hematopoiesis may play in pediatric MPNs. Buccal samples in our pediatric patients showed evidence of contamination and identifying the best way to sample the germline from children with these disorders is crucial for the study of MPNs in young patients. There is much to learn about the mutational spectrum of pediatric MPNs, including the role of germline mutations in disease pathogenesis, drivers of MPN development in triple-negative MPNs, mutation acquisition over time, and role of various mutations in MPN progression and outcomes. With this initial evaluation we have begun the process of answering some of these questions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal