Response In Pediatric Patients Research Articles

Hemadsorption with CytoSorb in Infants with Sepsis: Non-Systematic Review of Cases

Sepsis is a severe and potentially life-threatening condition that occurs when the body’s response to an infection damages its own tissues and organs. It can lead to organ failure and death if not treated. Cytosorb is a promising medical device for hemadsorption in pediatric septic patients (under 18 years old). As many studies conclude, Cytosorb results in efficient hemodynamics stabilization. This paper is a nonsystematic review of cases. PubMed-, Google Scholar-, and Scopus-indexed journals were used to collect papers for the research. Overall, 11 pediatric cases (six journal articles) were collected. Reductions in interleukin (IL)-6 and IL-10 levels after hemoperfusion with CytoSorb suggest a potential benefit in modulating the inflammatory response in pediatric patients. Moreover, other septic shock indicators such as C-reactive protein, lactate, procalcitonin, ALT, and AST were also significantly reduced in surviving patients within the first few hours of hemadsorption with CytoSorb. The use of CytoSorb seems to be efficient in managing different sepsis-related conditions, even in neonatal and infant populations, as a valuable supplementary tool. However, overcoming the obstacles associated with the age and weight of pediatric patients might necessitate the creation of CytoSorb devices tailored specifically to their needs.

Long-term cytokine profile in multisystem inflammatory disease among children

BackgroundMultisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. MethodsTwenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1β, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. ResultsIP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6–12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1β, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. ConclusionsOur study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

Impact of Atopic Status on Clinical Presentation and Treatment Response in Pediatric Patients With Eosinophilic Esophagitis

BackgroundNearly 80% of patients with eosinophilic esophagitis have co-existing atopic disease, yet a subset do not. It is unclear if this lack of atopy impacts presentation or response to therapy. ObjectivesTo characterize the presentation and response to therapy in atopic versus non-atopic pediatric patients with EoE MethodsA case-control study of EoE patients, ages 6 months to 18 years (between 2018-2021) was performed. Patients were eligible if they had allergy testing, assessment of atopic history, and at least one endoscopy following initiation of treatment. Patients were considered non-atopic if they had negative allergy testing and no history of significant atopy. Response to therapy was classified as complete (peak eos < 15/hpf), partial (≥ 15 eos/hpf but at least a 50% reduction in peak eos), or non-response. Results168 participants were enrolled. The majority were white (n=141, 84%), male (n=124, 74%), and non-Hispanic (n=158, 95%). Mean age at diagnosis was 9.4 years (SD: ± 4.8). 123 participants (73.2%) were atopic and 45 (26.8%) were non-atopic. There was no significant difference between atopic and non-atopic for most demographics or presenting symptoms. Non-atopic participants presented younger than atopic participants (8.14 vs. 9.8 years, p=0.046). Swallowed topical corticosteroids (STC) and food elimination diets (FED) were utilized at a similar rate. There were no differences in treatment response between atopic/non-atopic participants in regards to STC, FED, or STC+FED. ConclusionAtopic status does not significantly impact presentation or response to treatment in pediatric EoE, but a lack of atopy may be a risk for earlier onset of disease.

Post-discharge follow-up of pediatric COVID-19 patients: insights into serological dynamics.

Limited data are available regarding SARS-CoV-2 serological response dynamics in pediatric patients with COVID-19, contributing to gaps in our understanding of the immune response in this population. This study aimed to investigate SARS-CoV-2 IgG seropositivity in patients diagnosed with COVID-19 during hospitalization and 2-4 weeks after discharge. A cohort of patients, consisting of 31 individuals with confirmed acute COVID-19 infection and 27 diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), was enrolled in the study. Follow-up clinic appointments were scheduled for 2-4 weeks post-discharge. During admission and follow-up, blood samples were collected from each patient for laboratory analysis. Anti-nucleoprotein SARS-CoV-2 IgG levels were determined using the Enzyme-Linked Immunosorbent Assay (ELISA) method. In this study, a cohort of 58 patients was examined. At admission, 52% (n = 14) of MIS-C patients and 10% (n = 3) of acute COVID-19 patients had positive SARS-CoV-2 IgG test. Only 48 cases were referred to the hospital, and follow-up data was available for 20 cases with MIS-C and 28 cases with acute COVID-19. All patients (n = 15) who initially tested positive for SARS-CoV-2 IgG at admission remained positive serology during follow-up (100%). Among the 33 patients who initially tested negative, 12 (37.5%) showed a positive serology result during follow-up, while 21 (62.5%) remained negative. Within this subgroup, 11 cases (44%) were diagnosed with acute COVID-19, and one patient (12.5%) presented with MIS-C. Fourteen cases with acute COVID-19 infection (56%) and seven cases with MIS-C (87.5%) consistently showed negative serology results throughout the study. During follow-up, the median lymphocyte count demonstrated a significant difference, with 0.96 × 109 cells per L (IQR: 0.75-3.0 × 109 cells per L) in the SARS-CoV-2 IgG-negative group and 2.9 × 109 cells per L (IQR = 1.33-7.22 × 109 cells per L) in the SARS-CoV-2 IgG-positive group (p-value = 0.03). Patients who demonstrated seropositivity during the follow-up were associated with a notably severe disease (p-value = 0.028). Our study highlights the dynamic nature of SARS-CoV-2 IgG antibody responses in pediatric patients with COVID-19 infection. We observed a notable increase in seropositivity rates during follow-up. Furthermore, patients who were seropositive at follow-up demonstrated a severe disease course and lower lymphocyte counts compared to those with persistently negative serology. Our findings underscore the importance of longitudinal serological monitoring in understanding disease progression and immune response dynamics in pediatric COVID-19 cases.

Reduction in kidney function decline and risk of severe clinical events in agalsidase beta-treated Fabry disease patients: a matched analysis from the Fabry Registry.

Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD. Agalsidase beta-treated adult patients (aged ≥16years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16years. Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were -3.19 and -1.47mL/min/1.73 m2/year, respectively (reduction in rate of decline=53.9%, P=.007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were -3.29 and -1.56mL/min/1.73 m2/year, respectively (reduction in rate of decline=52.6%, P<.001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P=.003) and 0.67 (P=.008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6months of treatment initiation. Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients.

Pediatric diffuse intrinsic pontine glioma radiotherapy response prediction: MRI morphology and T2 intensity-based quantitative analyses.

An easy-to-implement MRI model for predicting partial response (PR) postradiotherapy for diffuse intrinsic pontine glioma (DIPG) is lacking. Utilizing quantitative T2 signal intensity and introducing a visual evaluation method based on T2 signal intensity heterogeneity, and compared MRI radiomic models for predicting radiotherapy response in pediatric patients with DIPG. We retrospectively included patients with brainstem gliomas aged ≤ 18 years admitted between July 2011 and March 2023. Applying Response Assessment in Pediatric Neuro-Oncology criteria, we categorized patients into PR and non-PR groups. For qualitative analysis, tumor heterogeneity vision was classified into four grades based on T2-weighted images. Quantitative analysis included the relative T2 signal intensity ratio (rT2SR), extra pons volume ratio, and tumor ring-enhancement volume. Radiomic features were extracted from T2-weighted and T1-enhanced images of volumes of interest. Univariate analysis was used to identify independent variables related to PR. Multivariate logistic regression was performed using significant variables (p < 0.05) from univariate analysis. Of 140 patients (training n = 109, and test n = 31), 64 (45.7%) achieved PR. The AUC of the predictive model with extrapontine volume ratio, rT2SRmax-min (rT2SRdif), and grade was 0.89. The AUCs of the T2-weighted and T1WI-enhanced models with radiomic signatures were 0.84 and 0.81, respectively. For the 31 DIPG test sets, the AUCs were 0.91, 0.83, and 0.81, for the models incorporating the quantitative features, radiomic model (T2-weighted images, and T1W1-enhanced images), respectively. Combining T2-weighted quantification with qualitative and extrapontine volume ratios reliably predicted pediatric DIPG radiotherapy response. Combining T2-weighted quantification with qualitative and extrapontine volume ratios can accurately predict diffuse intrinsic pontine glioma (DIPG) radiotherapy response, which may facilitate personalized treatment and prognostic assessment for patients with DIPG. Early identification is crucial for radiotherapy response and risk stratification in diffuse intrinsic pontine glioma. The model using tumor heterogeneity and quantitative T2 signal metrics achieved an AUC of 0.91. Using a combination of parameters can effectively predict radiotherapy response in this population.

IMMU-17. A PHASE I STUDY OF INTRATUMORAL/PERITUMORAL HERPES SIMPLEX VIRUS-1 MUTANT HSV1716 IN PATIENTS WITH REFRACTORY OF RECURRENT HIGH-GRADE GLIOMAS: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY

Abstract BACKGROUND Immune-modulatory strategies, including checkpoint inhibition and tumor vaccines, have been tested in efforts to mitigate the pro-tumor microenvironment in pediatric high-grade glioma (pHGG). HSV1716 is a first-generation oncolytic virus that was previously reported safe with evidence of response in pediatric patients with relapsed or refractory extracranial tumors and in adults with high-grade glioma. METHODS PBTC-037 was a multicenter, phase I trial developed and performed by the Pediatric Brain Tumor Consortium (PBTC) to estimate the maximum tolerated dose or recommended phase II dose of HSV1716 administered during surgical resection. Patients aged 12 to 21 years with recurrent or refractory pHGG for whom surgical resection was clinically indicated were eligible. After maximal tumor resection, patients received one intraoperative dose of HSV1716. RESULTS Two patients were enrolled; one was later deemed ineligible (due to out-of-window screening evaluations) yet was continued in follow up for safety. Shortly after enrollment of the 2 patients, the study was closed to accrual due to a change in the sponsor’s investment focus. One patient completed the 8-week reporting period without toxicities. The only grade 3 or higher adverse event noted was grade 3 hyperglycemia at 2- and 3-months post injection. The second patient that was later deemed ineligible received the injection of HSV1716 and had no evidence of dose-limiting toxicity. The two patients had progressive disease 1.9 and 2.9 months after enrollment; both eventually died due to progressive disease at 7.5 months. CONCLUSIONS We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger trials and in combinatorial trials in other tumor types. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors.

Efficacy and safety of entrectinib in children with extracranial solid or primary central nervous system (CNS) tumors harboring NTRK or ROS1 fusions.

10000 Background: Entrectinib previously yielded durable responses in children with NTRKor ROS1fusion-positive extracranial solid or primary CNS tumors in STARTRK-NG (NCT02650401). We present updated data from STARTRK-NG, TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267): pediatric patients from these trials were combined to enable an integrated efficacy and safety analysis on a larger cohort than previously. Methods: Eligible patients were TRK or ROS1 inhibitor naïve and aged &lt; 18 years, had locally advanced or metastatic extracranial solid or primary CNS tumors harboring an NTRK or ROS1 fusion, and had measurable or evaluable-only disease. Once enrolled, patients received ≥1 daily dose of oral entrectinib until disease progression, unacceptable toxicity, or consent withdrawal. Tumor responses were confirmed by blinded independent central review (BICR) per RECIST v1.1 or RANO criteria. Patients were included if they had been followed for ≥6 months. The primary endpoint was confirmed objective response rate (ORR) per BICR. Key secondary endpoints included ORR in patients with baseline measurable disease per BICR, duration of confirmed response (DoR), time to confirmed response (TTR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results: At clinical cutoff (16 July 2023), out of 91 safety-evaluable patients (regardless of fusion), 44 patients in the NTRKcohort and 20 patients in the ROS1cohort were efficacy evaluable. Median duration of survival follow-up was 24.2 months ( NTRK: range 1–66) and 27.6 months ( ROS1: range 1–73). The ORR was 68.2% (95% CI 52.4–81.4) in the NTRK cohort and 65.0% (95% CI 40.8–84.6) in the ROS1 cohort. In patients with baseline measurable disease, the ORR was 77.8% ( NTRK: n = 28/36; 95% CI 60.9–89.9) and 62.5% ( ROS1: n = 10/16; 95% CI 35.4–84.8). Efficacy outcomes are shown in the Table. The most common adverse events were pyrexia (50.5%), vomiting (40.7%) and anemia (40.7%). Conclusions: Entrectinib continued to yield rapid and durable responses in pediatric patients with extracranial solid or primary CNS tumors harboring an NTRK or ROS1 fusion. The safety profile of entrectinib was in line with previous reports. Clinical trial information: NCT02650401 / NCT04589845 / NCT02568267 . [Table: see text]

T cell responses in pediatric patients with severe influenza disease.

T cell responses in pediatric patients with severe influenza disease.

Effect of ultrasound-guided quadratus lumborum block on neuroendocrine stress response and postoperative analgesia in paediatric patients undergoing elective open pyeloplasty - A randomised clinical trial.

Quadratus lumborum block (QLB) is a compartmental block of the anterior abdominal wall. Surgical trauma produces neuroendocrine surgical stress responses, which are modified by anaesthetic blocks. The aim of this study was to evaluate the effect of ultrasound (US)-guided QLB on analgesia and surgical neuroendocrine stress response in paediatric patients undergoing pyeloplasty. A randomised trial was conducted in 60 children aged 1-7 years undergoing elective open pyeloplasty. Patients were randomised into Group QLB [US-guided QLB with 0.5 ml/kg of 0.25% ropivacaine after induction of general anaesthesia (GA)], and Group GA, which received only GA. Perioperative haemodynamic parameters, serum cortisol, blood glucose, analgesic consumption and postoperative FLACC scores were recorded. Unpaired t-test, Wilcoxon rank-sum test or Mann-Whitney U test was used to compare variables between the two groups. Two-way analysis of variance or the Friedmann test was used to compare quantitative variables at various points within a group. A decrease in serum cortisol and blood glucose values was observed in Group QLB at 30 min after surgical incision and 24 h after surgery compared to the preoperative value and compared to Group GA (P < 0.05). The quality of analgesia assessed by the FLACC scale was significantly better in group QLB. Dose of fentanyl consumption (µg/kg) was higher in Group GA compared to Group QLB in the intraoperative and postoperative period (P < 0.05). QLB is effective as part of multimodal analgesia and attenuates the neuroendocrine stress in paediatric patients undergoing open pyeloplasty.

Interstitial Cells of Cajal and P2X3 Receptors at Ureteropelvic Junction Obstruction and Their Relationship with Pain Response.

Introduction: Etiopathogenesis and the symptomatology of ureteropelvic junction obstruction (UPJO) in the pediatric population has not yet been definitely clarified, suggesting a multifactorial nature of the condition. The aim was to analyze the association between the number of Interstitial Cells of Cajal (ICCs), as well as P2X3 receptors in ureteropelvic junction (UPJ) and the pain response in pediatric patients with hydronephrosis. Methods: 50 patients with congenital hydronephrosis underwent open or laparoscopic pyeloplasty at one of two departments of pediatric surgery and urology in Poland. Patients were divided into two groups according to the pain symptoms before surgery. A total of 50 samples of UPJ were obtained intraoperatively and underwent histopathological and immunohistochemical (IHC) analysis. Quantitative assessment of ICCs was based on the number of CD117(+) cells of adequate morphology in the subepithelial layer and the muscularis propria. Expression of P2X3 receptors was evaluated as the intensity of IHC staining. Results: Patients with hydronephrosis and accompanying pain were on average 60 months older (77 vs. 17 months) than children with asymptomatic hydronephrosis (p = 0.017). Symptomatic children revealed higher numbers of ICCs in both the subepithelial layer and in the lamina muscularis propria. In particular, symptomatic patients aged 2 years or more exhibited significantly higher numbers of ICCs in the subepithelial layer. Significant differences in the distribution of ICCs between the subepithelial layer and the lamina muscularis propria were observed in both groups. Expression of P2X3 receptors was limited to the urothelium and the muscle layer and correlated between these structures. There was no relationship between pain response and the expression of P2X3 receptors. Conclusions: ICCs and P2X3 receptors may participate in the pathogenesis of UPJO and in the modulation of pain response to a dilatation of the pyelocaliceal system. Explanation of the role of ICCs and P2X3 receptors in propagation of ureteral peristaltic wave and the modulation of pain stimuli requires further studies.

Analysis of pupillary responses in pediatric patients with vitamin D deficiency.

To evaluate the effects of vitamin D deficiency on pupillary responses in the pediatric population. The study was conducted using data from the right eyes of 52 children with vitamin D deficiency and 52 healthy children. Measurements were taken under static and dynamic conditions with automatic pupillometry. Static measurements were performed at scotopic, mesopic, and photopic light intensities. The mean pupil dilation speed was calculated by observing the changes in pupil dilation over time according to dynamic measurements. Differences between patient and control groups were analyzed for the static and dynamic measurements and the mean pupil dilation speed. While the two groups were similar in terms of scotopic, mesopic, the first dynamic measurements, and the pupil dilation speed data (p > 0.05), a significant difference was found in the photopic conditions (p = 0.001). The mean pupil diameter of the patient group was 4.46 ± 0.928mm and 3.95 ± 0.556mm in the control group under photopic conditions. Pediatric patients with vitamin D deficiency have significantly larger pupil diameters in photopic conditions than healthy children. These results suggest that there is an autonomic dysfunction in vitamin D deficiency in the pediatric population, especially pointing to the parasympathetic system.

Pediatric Wound Infections Following 2023 Kahramanmaras Earthquakes: Case Series

Background. The Kahramanmaras earthquakes in Turkey on February 6, 2023, resulted in more than 100 000 injuries and 50 500 deaths. The main causes of morbidity and mortality in earthquake-affected patients include crush syndrome, trauma-related extremity injuries, and wound infections. Objective. To investigate infective complications, causative microorganisms, treatments, and treatment responses in pediatric patients. Methods. The case series involved 12 earthquake victims admitted to a tertiary treatment center between February 9 and 24, 2023. Wound sample cultures were obtained from patients with infected wounds via wound secretions and tissue samples collected during surgery. Results. Nine patients were male (75%), and the mean age of patients was 12.6 ± 3.7 years. Seven patients (58.3%) experienced crush syndrome. Seven patients (58.3%) underwent fasciotomy operations. The main infectious complications were wound infections (58.3%) and urinary tract infections (25%). Nine different organisms were found to cause wound infection, with Enterococcus faecium (41.6%), Acinetobacter baumanii (33.3%), and Pseudomonas aeruginosa (16.6%) being the major bacterial isolates. All Acinetobacter strains were multidrug-resistant (MDR). Conclusion. Major disasters such as earthquakes are rare, and infections are the major complications that increase morbidity and mortality. Initial appropriate treatment contributes to improved outcomes, as MDR strains are common pathogens in these patients.

Pediatric Psoriasis with or without Arthritis: Does It Make a Difference?

Psoriasis and psoriatic arthritis can present simultaneously or separately in children and may pose a diagnostic challenge. To compare the dermatological manifestations in pediatric psoriatic patients with and without arthritis. A retrospective case-control study of psoriatic patients ≤ 18 years old at Sheba Medical Center was conducted between 2011 and 2021. Patients with psoriatic arthritis versus psoriasis-only were compared according to body surface area (BSA) involvement, cutaneous distribution, severity of skin disease, response to treatment and related side effects. The study cohort included 29 psoriatic arthritis and 64 psoriasis-only patients matched by age and sex. The psoriasis-only group had a significantly higher mean BSA (19.7%, SD ± 18.7) than the psoriatic arthritis group (6.1%, SD ± 11.4), (p = 0.029). The skin distribution differed with the psoriasis group showing more involvement of the extremities, scalp, trunk, and genitals. Both groups primarily experienced partial responses to methotrexate, whereas the psoriasis group mainly saw complete responses to biologics. Adverse events were rare, with a higher incidence in the psoriasis group. This retrospective study highlights the differences in cutaneous disease characteristics, severity, and treatment response in pediatric patients with psoriasis and psoriatic arthritis, providing valuable insights for diagnosis and disease course in the pediatric population.

Genome Sequencing-Based Prognosis, Mutational Analysis, and Survival Rate of Pediatric Acute Myeloid Leukemia

Abstract Introduction/Objective Pediatric Acute Myeloid Leukemia (AML) is a rare diagnosis that once carried a poor prognosis, but with recent improvement, the survival rate now reaches 80%. Although studies of most genetic mechanisms of AML involved adult studies, but dissimilar mutational profiles and treatment responses in pediatric patients have become evident. Information regarding pediatric AML-specific whole genome sequencing, a prognostic prediction system, and overall survival is limited. Hence, we aimed to analyze the genomic profile, epidemiological characteristics, and overall survival of pediatric AML. Methods/Case Report We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study genetic mutations associated with pediatric AML. Epidemiological characteristics and genetic profiles available on cBioportal were evaluated. Gene mutations with the most statistically significant shortest overall survival and survival in days from the samples were used for gene query, and survival rate with the most common mutations was calculated. Log-rank test and Kaplan–Meier estimators were used in analyzing the survival function. Patients with two or more overlapping mutations were excluded. Results (if a Case Study enter NA) We identified 899 patients with Pediatric AML, out of 886 had all demographic data available, 50.8% were males, 71.6% were Caucasian, and 11.3% were African American. 568 (63.2%) were alive, and 318 (35.4%) were deceased. 159 patients were diagnosed at less than or equal to 2 years of age, and 150 patients had 80-90% blasts in their samples. 440 (42.9%) had relapse of disease at the bone marrow, whereas 72 (7.0%) had relapse at other sites. The common mutations associated with reduced survival were C4ORF36, HERC5, GPRIN3, NFKB1, NUP88, QRFPR, SPRY1, and UNC5C. Median survival data of patients was available for GPRIN3, NFKB1, NUP88, SPRY1, UNC5C, and was 25.00, 11.00, 15.00, 59.00, and 14.00 months respectively. Comparison with the unaltered group was not available (p &amp;lt; 0.0001). Survival was lowest amongst NFKB1 (11.00 months), NUP88 (15.00 months), and UNC5C (14.00 months). In survival analysis, the same genes were associated with lowest survival after initial diagnosis (p = 7.301e-4). Conclusion Our study found that NFKB1, NUP88, and UNC5C genes were associated with the worst prognosis in pediatric AML with median survival of 11.00, 15.00, and 14.00 months. Furthermore it may result in improve the prognosis of these patients.

Clinical and Hematopoietic Profiles Associated with Sustained Hydroxyurea Response for Patients with Sickle Cell Disease

Background: Hydroxyurea improves the lives of patients with sickle cell disease (SCD) by inducing expression of fetal hemoglobin (HbF). Higher HbF levels are associated with improved clinical outcomes. However, there is significant heterogeneity in long-term response to the drug. The impact of quantitative changes in hematopoietic stem and progenitor cells (HSPCs) during hydroxyurea treatment remains poorly characterized. Objectives: (1) Determine the prevalence and clinical impact of declining hydroxyurea response in pediatric patients with SCD; and (2) Characterize HSPC profiles associated with hydroxyurea response. Methods: We conducted a retrospective review of longitudinal clinical data from 760 pediatric patients with SCD seen at Texas Children's Hematology Center between 2010-2021. We selected patients consistently on hydroxyurea for &amp;gt;5 years for this study. We classified each subject according to their individual HbF response to hydroxyurea into: 1) Sustained-Response if the patient maintained an absolute HbF level &amp;gt;20% or 2) Decreased-Response if a patient's HbF levels decreased to &amp;lt;10% over time despite medication compliance. We obtained clinical and laboratory hydroxyurea treatment information for each individual. We isolated peripheral blood mononuclear cells (PBMCs) from whole blood collected from these patients during outpatient appointments. Patients were on a stable hydroxyurea dose without recent blood transfusions prior to collection. Flow cytometry was used to quantify the frequencies of ten HSPC populations in the PBMC samples. Results: In total, 208 children with HbSS or HbSβ 0-Thalassemia were included in our analysis: 148 individuals (71%) had a Sustained Response and 60 (29%) experienced a Decreased Response to hydroxyurea. Subjects with a Decreased Response had a median initial hydroxyurea induced HbF of 23.9% that decreased to 9.8% over time compared to stable values of HbF &amp;gt;20% in the HU-Sustained Response group (p&amp;lt;0.001). These differences were consistent after adjusting for age ( Figure 1). We found that patients who developed a Decreased Response to hydroxyurea experienced a significantly higher incidence of clinical complications, including number of visits to the emergency department (153.3 vs. 120.3 events per 100 patient-years), number of transfusions (37.4 vs. 11.9), and SCD-related hospitalizations (57.7 vs. 42.0). The causes of SCD-related hospitalizations included vaso-occlusive events requiring admission (27.7 vs 21.1 events per 100 patient-years), acute chest syndrome (13 vs 9.9), splenic sequestration (6.4 vs 3.5), and surgical procedures (7.47 vs 3.02). We also profiled HSPCs by flow cytometry using PBMCs collected from a subset of 40 patients (20 Sustained Response individuals vs. 20 Decreased Response). Individuals with a Sustained Response had increased numbers of hematopoietic multipotent cells (51.75% vs. 43%), hematopoietic stem cells positive for CD49F ++ (20.5% vs. 13.55%), and CD235a +/CD71 + cells (11.55% vs. 4.54%). In contrast, individuals with a Decreased Response had an increased percentage of unipotent hematopoietic progenitor cells (38.55% vs. 52.9%) and committed megakaryocyte erythroid progenitor cells (33.2% vs 46.2%; Figure 2). Conclusions: Nearly 30% of children with SCD taking hydroxyurea had a significant decline in their HbF levels after years of treatment and consequently suffered an increased number of clinical complications. While higher dosages of hydroxyurea may restore some HbF induction in these patients, we have quantified broad changes in specific HSPC levels that may be responsible for this decline in HbF. Patients with a Decreased Response had a lower percentage of multipotent progenitor cells that maintain self-regeneration capacity and increase numbers of committed erythroid progenitor cells. Although many stressors can impact quantitative and functional changes seen in HSPCs, these findings suggest that premature aging of the hematopoietic system plays an important role in long-term hydroxyurea response. Better understanding of why certain individuals are more susceptible to this phenomenon would enable the development of personalized strategies to enhance HbF induction and facilitate early selection of alternative treatments for these individuals with SCD.

Steroid-induced ocular hypertensive response in pediatric patients with acute lymphoblastic leukemia.

To report the characteristics of the steroid-induced ocular hypertensive response in pediatric patients with acute lymphoblastic leukemia (ALL) treated with prednisolone (PSL) during induction therapy and with dexamethasone (DEX) during reinduction therapy. Retrospective. This study included pediatric patients diagnosed with B-cell precursor ALL and treated with systemic corticosteroids sometime during the period from 2016 to 2018 at Shizuoka Children's Hospital. Data were extracted from the hematology/oncology records related to the type, dose, and duration of systemic corticosteroids as well as to the ophthalmologic examination findings, intraocular pressure (IOP) data, symptoms of high IOP, and antiglaucoma medications obtained during corticosteroid administration. The maximal IOPs of the PSL and DEX groups were compared. Twenty-eight patients (18 boys and 10 girls; mean age 5.5years) were treated with systemic corticosteroids. Twelve of the 22 courses of PSL and 33 of the 44 courses of DEX were found to be associated with high IOP. The maximal IOP was higher with the use of DEX than with the use of PSL, including in those who received prophylactic therapy (PSL 25.2mmHg, DEX 33.6mmHg; P = 0.02). Antiglaucoma medication was given to 21 patients; 6 patients had symptoms of ocular hypertension. The maximal IOPs were 52.8mmHg and 70.8mmHg in the PSL and DEX groups, respectively. Both groups of patients reported severe headache. Increased IOP was frequently observed during systemic corticosteroid therapy in pediatric patients with ALL. Although most patients were asymptomatic, they occasionally presented with severe systemic symptoms. Regular ophthalmologic examinations should be included in the treatment guidelines for ALL.

Bifidobacteria modulate immune response in pediatric patients with cow's milk protein allergy.

In children with an allergy to cow's milk proteins (CMA), the altered composition of intestinal microbiota influences the immune tolerance to milk proteins (CMP). This study aims to investigate the effect of probiotics on the phenotype and activation status of peripheral basophils and lymphocytes in a pediatric CMA cohort. CMA children underwent 45 days of treatment with Bifidobacteria. The basophil degranulation and the immune phenotype of B cells, T helper cells, and regulatory T cells were analyzed in peripheral blood at diagnosis (T0), after a 45-day probiotic treatment (T1), and 45 days after the probiotic wash-out (T2). We observed in probiotic-treated CMA patients a decrease in naive T lymphocytes. Among the CD3+ cell subsets, both naive and activated CD4+ cells resulted markedly reduced after taking probiotics, with the lowest percentages at T2. A decreased basophil degranulation was observed in response to all analyzed CMP at T1 compared to T0. The probiotic treatment resulted in a decrease of circulating naive and activated CD4+ T cells, as well as degranulating basophils. These data suggest that the Bifidobacteria could have a beneficial effect in the modulation of oral tolerance to CMP. ISRCTN69069358. URL of registration: https://www.isrctn.com/ISRCTN69069358 . Probiotic treatment with Bifidobacteria induces a reduction of both naive and activated circulating CD4+ T cells in pediatric patients with cow's milk allergy (CMA). The probiotic supplementation induces a decreased basophil degranulation. The immunological tolerance persists even after 45 days of the probiotic wash-out. Bifidobacteria in vivo supplementation down-modulates the activation of innate and adaptive immunity in pediatric patients with cow's milk allergy. Bifidobacteria contribute to the development of immune tolerance in CMA patients.

Development of a clinical model to predict vagus nerve stimulation response in pediatric patients with drug-resistant epilepsy.

Epilepsy impacts 470,000 children in the United States. For patients with drug-resistant epilepsy (DRE) and unresectable seizure foci, vagus nerve stimulation (VNS) is a treatment option. Predicting response to VNS has been historically challenging. The objective of this study was to create a clinical VNS prediction tool for use in an outpatient setting. The authors performed an 11-year retrospective cohort analysis with 1-year follow-up. Patients < 21 years of age with DRE who underwent VNS (n = 365) were included. Logistic regressions were performed to assess clinical factors associated with VNS response (≥ 50% seizure frequency reduction after 1 year); 70% and 30% of the sample were used to train and validate the multivariable model, respectively. A prediction score was subsequently developed. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated. Variables associated with VNS response were < 4-year epilepsy duration before VNS (p = 0.008) and focal motor seizures (p = 0.037). The variables included in the clinical prediction score were epilepsy duration before VNS, age at seizure onset, number of pre-VNS antiseizure medications, if VNS was the patient's first therapeutic epilepsy surgery, and predominant seizure semiology. The final AUCs were 0.7013 for the "fitted" sample and 0.6159 for the "validation" sample. The authors developed a clinical model to predict VNS response in a large sample of pediatric patients treated with VNS. Despite the large sample size, clinical variables alone were not able to accurately predict VNS response. This score may be useful after further validation, although its predictive ability underscores the need for more robust biomarkers to predict treatment response.

Evaluation of Hepatitis A and B Vaccine Antibody Response in Pediatric Patients with Type 1 Diabetes Mellitus

Evaluation of Hepatitis A and B Vaccine Antibody Response in Pediatric Patients with Type 1 Diabetes Mellitus