Pediatric Disease Research Articles

Bone health: Quality versus quantity

Healthy bone has the ability to resist deformation and fracture, while adapting to applied mechanical loads. These properties of bone depend on characteristics of its extracellular matrix. This review focuses on the contribution of bone quality and quantity to bone health and highlights current and promising future clinical approaches to measure bone health in the pediatric population. Bone’s unique material properties are derived from its highly organized, hierarchical composite structure, together with its modeling and remodeling dynamics and microdamage mechanisms. Pediatric bone diseases and disorders affect the biological processes that regulate its quality, negatively impacting the extracellular matrix and causing bone fragility. Laboratory bone analysis from human biopsies or animal models of human bone diseases allows high detail examination of the mechanisms contributing to bone fragility. Conversely, clinical measurements of bone fragility are difficult and limited due to the inaccessibility of the material. Because bone quality directly affects fracture resistance, both structure and composition should be used in fracture risk calculation rather than bone mineral density or bone quantity alone. Thus, to advance clinical evaluation of bone fragility, future studies are needed to determine which characteristics of bone quality can be applied to clinical practice to predict bone fragility. New and effective clinical tools are needed to predict fracture risk taking bone quality into consideration. Key Concepts(1)Bone quality and bone quantity are both fundamental for resistance to deformity and fracture.(2)Pediatric bone diseases and disorders alter bone’s composition and structure, compromising bone quality and increasing vulnerability to fracture.(3)Current clinical approaches to assess bone fragility and fracture risk rely mainly on bone quantity measurements from DEXA scans.(4)DEXA bone mineral density poorly correlates with bone’s resistance to fracture, both in adults and children.(5)Future clinical approaches to measure bone health should account for bone quality in order to predict fracture risk.

Nitric oxide regulation of fetal and newborn lung development and function

In the developing lung, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signaling are essential in regulating lung formation and vascular tone. Animal studies have linked many anatomical and pathophysiological features of newborn lung disease to abnormalities in the NO/cGMP signaling system. They have demonstrated that driving this system with agonists and antagonists alleviates many of them. This research has spurred the rapid clinical development, testing, and application of several NO/cGMP-targeting therapies with the hope of treating and potentially preventing significant pediatric lung diseases. However, there are instances when the therapeutic effectiveness of these agents is limited. Studies indicate that injury-induced disruption of several critical components within the signaling system may hinder the promise of some of these therapies. Recent research has identified basic mechanisms that suppress NO/cGMP signaling in the injured newborn lung. They have also pinpointed biomarkers that offer insight into the activation of these pathogenic mechanisms and their influence on the NO/cGMP signaling system's integrity in vivo. Together, these will guide the development of new therapies to protect NO/cGMP signaling and safeguard newborn lung development and function. This review summarizes the important role of the NO/cGMP signaling system in regulating pulmonary development and function and our evolving understanding of how it is disrupted by newborn lung injury.

Molecular Dynamic Simulations to Determine Individualized Therapy: Tetrabenazine for the GNAO1 Encephalopathy E246K Variant.

GNAO1 encephalopathy is characterized by severe hypotonia, psychomotor retardation, epilepsy, and movement disorders. Genetic variations in GNAO1 have been linked to neurological symptoms including movement disorders like dystonia. The correlation between the E246K mutation in the Gα subunit and aberrant signal transduction of G proteins has been established but no data are reported regarding the efficacy of medical treatment with tetrabenazine. Molecular modeling studies were performed to elucidate the molecular mechanisms underlying this mutation. We developed drug efficacy models using molecular dynamic simulations that replicated the behavior of wild-type and mutated proteins in the presence or absence of ligands. We demonstrated that the absence of the mutation leads to normal signal transduction upon receptor activation by the endogenous ligand, but not in the presence of tetrabenazine. In contrast, the presence of the mutation resulted in abnormal signal transduction in the presence of the endogenous ligand, which was corrected by the drug tetrabenazine. Tetrabenazine was identified as a promising therapeutic option for pediatric patients suffering from encephalopathy due to an E246K mutation in the GNAO1 gene validated through molecular dynamics. This is a potential first example of the use of this technique in arare neurological pediatric disease.

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05g/dL vs. 6.31g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Diagnostic Challenges and Emerging Pathogeneses of Selected Glomerulopathies.

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3). Second, we examine advances in techniques for paraffin and light chain immunofluorescence (IF), including the former's function as a salvage technique and their necessity for diagnosis in adolescent cases of membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) and proliferative glomerulonephritis with monotypic Ig deposits (PGNMID), respectively. Finally, progress in understanding the roles of complement in pediatric glomerular disease is reviewed, with specific attention to overlapping clinical, histologic, and genetic or functional alternative complement pathway (AP) abnormalities among C3 glomerulopathy (C3G), infection-related and post-infectious GN, "atypical" post-infectious GN, immune complex mediated membranoproliferative glomerulonephritis (IC-MPGN), and atypical hemolytic uremic syndrome (aHUS).

Higher incidence of paediatric inflammatory bowel disease by increasing latitude in Norway, but stable incidence by age.

To examine possible geographical and temporal differences in the incidence of childhood-onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry-based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD-10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south-to-north gradient and the incidence by period of birth. By the end of follow-up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two-fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47-2.57; Mid region: HR = 1.68, 95% CI = 1.29-2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004-2006 and 2010-2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007-2009. We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non-causal explanations cannot be ruled out.

Division of Responsibility in Child Feeding and Eating Competence: A Cross-Sectional Study in a Sample of Caregivers of Brazilian Children with Celiac Disease.

The objective of this cross-sectional study was to assess eating competence (EC) and the adherence to the division of responsibility in child feeding (sDOR) of Brazilian caregivers of children with celiac disease (CD). It also examined the association between EC and sDOR, children's adherence to a gluten-free diet, and sociodemographic data. This study administered a survey set that included sociodemographic data, health-related data, eating habits, and the instruments ecSI2.0TMBR and sDOR.2-6yTM BR, validated for a Brazilian population. The sample comprised 50 caregivers of children with CD (between 24 and 72 months of age). The participants following a gluten-free diet (GFD) presented higher scores for all EC domains and the total EC. The total EC scores were higher for the participants over 40 y/o, frequently having meals as a family, with their children consuming more than three servings of fruit and at least one serving of vegetables daily and complying with a GFD. Different from the EC, the sDOR.2-6yTM scores did not differ between the participants complying with a GFD. The sDOR.2-6yTM mealtime structure domain scores were significantly associated with the EC eating attitude, food acceptance, contextual skills, and total. These findings support the need for greater attention to exploring the division of responsibility in feeding and EC in pediatric celiac disease, potentially enhancing intervention strategies for patients and their families.

A rat model of adenoid hypertrophy constructed by using ovalbumin and lipopolysaccharides to induce allergy, chronic inflammation, and chronic intermittent hypoxia.

Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

Prognostic markers in hepatitis A-related pediatric acute liver failure and validation of the Peds-hepatitis A virus prognostic model.

Hepatitis A virus (HAV) is the commonest cause for pediatric acute liver failure (PALF) in India. The objective of the study was to identify the predictors of mortality and to evaluate the utility of Peds-HAV model in a cohort of non-LT HAV-PALF. The study included HAV-related PALF from two non-transplant centers. The predictors of outcome were identified by univariate analysis followed by Cox regression analysis. The prognostic accuracy of Peds-HAV model, King's College Hospital (KCH) criteria and pediatric end-stage liver disease score (PELD) were evaluated. As many as 140 children with PALF were included, of whom 96 (68.6%) children had HAV-PALF. On Cox regression analysis, international normalized ratio (INR) (p < 0.001), jaundice to encephalopathy (JE) interval (p < 0.001) and hepatic encephalopathy (HE) grade 3/4 (p = 0.01) were independent predictors of mortality. The mortality rates were 0% (0/42), 14.3% (3/21), 60% (9/15) and 94.4% (17/18) when none, 1, 2 or 3 criteria of the Peds-HAV were met, respectively. Peds-HAV model at a listing cut-off of ≥ 2 criteria predicted death with 89.7% sensitivity and 89.6% specificity. In contrast, KCH criteria had a lower sensitivity of 62.1%. PELD score had a sensitivity of 89.7% and specificity of 85.1% at a cut-off of 30. The overall prognostic accuracy of Peds-HAV model (89.6%) was higher than those of KCH (83.3%) and PELD (86.5%). INR, HE grade and JE interval were independent predictors of mortality. The study provides an external validation of Peds-HAV model as a prognostic score in HAV-PALF. Not applicable as this is a retrospective study.

Vitamin D and pediatric bone health: Important information and considerations for the pediatric orthopaedic surgeon

Vitamin D is an essential fat-soluble vitamin produced in the skin during sun exposure. It plays a considerable role in musculoskeletal health and is largely responsible for the regulation of calcium and phosphate metabolism to maintain a healthy, mineralized skeleton. Optimizing bone mineral density in childhood and adolescence is essential to the foundation of skeletal health; however, the literature lacks consensus on values for normal, deficient, and insufficient serum 25-hydroxyvitamin D levels making supplementation and treatment somewhat challenging.The pediatric orthopaedic surgeon is important to optimizing bone health, particularly in the context of bony pathology/injury. Up to 60% of boys and 40% of girls sustain a fracture in childhood. On top of this baseline incidence, children with low vitamin D levels have been noted to be subject to a higher incidence of fractures from normal activities. While the prevalence of vitamin D deficiency in children in the general population has been determined to be 9%, the prevalence of vitamin D deficiency in the pediatric fracture population can be as high as 75% and 61% of the pediatric population has been determined to have vitamin D insufficiency. The pediatric orthopedist also often is the first to diagnose nutritional rickets as these patients can present solely for complaints of limb deformity. Knowledge of appropriate evaluation, vitamin D supplementation, and indications for pediatric endocrinology referral is vital for the treatment of these patients.In the pediatric population, there is a lack of consensus regarding risk factors that warrant screening for vitamin D deficiency, determining insufficient thresholds, and identifying optimal supplementation recommendations and treatment dosages. More research is needed to clarify the ideal amounts of vitamin D necessary through critical growth periods to prevent rickets and to mitigate fracture risk. Regardless, pediatric Orthopaedic surgeons should promote supplementation to all children and treat diagnosed vitamin D deficiency. Key Concepts(1)Vitamin D plays a vital role in musculoskeletal health and optimizing vitamin D levels in childhood and adolescence is crucial to proper bone development.(2)Vitamin D deficiency and insufficiency in the general population is common; 9% of the pediatric population, representing 7.6 million US children and adolescents, are vitamin D deficient and 61%, representing 50.8 million US children and adolescents, are vitamin D insufficient. The prevalence of vitamin D deficiency in the pediatric fracture population can be as high as 75%.(3)Vitamin D deficiency can lead to nutritional rickets which is the most frequent cause of pediatric bone disease in the world, is entirely preventable, and is characterized by deficient mineralization and subsequent architectural disruption of the physis.(4)Vitamin D supplementation is widely recommended and believed to be beneficial, but there are inconsistent guidelines regarding target levels for optimal vitamin D status.

Pre-Diagnosis Diet Predicts Response to Exclusive Enteral Nutrition and Correlates with Microbiome in Pediatric Crohn Disease.

Exclusive enteral nutrition (EEN) is effective in inducing remission in pediatric Crohn disease (CD). EEN alters the intestinal microbiome, but precise mechanisms are unknown. We hypothesized that pre-diagnosis diet establishes a baseline gut microbiome, which then mediates response to EEN. We analyzed prospectively recorded food frequency questionnaires (FFQs) for pre-diagnosis dietary patterns. Fecal microbiota were sequenced (16SrRNA) at baseline and through an 18-month follow-up period. Dietary patterns, Mediterranean diet adherence, and stool microbiota were associated with EEN treatment outcomes, disease flare, need for anti-tumor necrosis factor (TNF)-α therapy, and long-term clinical outcomes. Ninety-eight patients were included. Baseline disease severity and microbiota were associated with diet. Four dietary patterns were identified by FFQs; a "mature diet" high in fruits, vegetables, and fish was linked to increased baseline microbial diversity, which was associated with fewer disease flares (p < 0.05) and a trend towards a delayed need for anti-TNF therapy (p = 0.086). Baseline stool microbial taxa were increased (Blautia and Faecalibacterium) or decreased (Ruminococcus gnavus group) with the mature diet compared to other diets. Surprisingly, a "pre-packaged" dietary pattern (rich in processed foods) was associated with delayed flares in males (p < 0.05). Long-term pre-diagnosis diet was associated with outcomes of EEN therapy in pediatric CD; diet-microbiota and microbiota-outcome associations may mediate this relationship.

Indirect revascularization for pediatric moyamoya disease.

Indirect revascularization is a common and effective treatment for pediatric moyamoya disease. However, in several cases postoperative angiogenesis is not sufficient. It is not fully understood which factors are involved in the development of postoperative collateral circulation. In this study, the authors aimed to elucidate the factors related to postoperative angiogenesis in indirect revascularization. Among the patients who underwent indirect revascularization for moyamoya disease from January 2015 to December 2022, those whose angiogenesis was evaluated using angiography were included. Age, onset symptoms, comorbidities, preoperative imaging findings, surgical details, perioperative complications, postoperative imaging findings, and modified Rankin Scale (mRS) score at the last outpatient visit were retrospectively examined. Ninety cases (53 patients; 37 bilateral, 16 unilateral) were included. Sixty-eight cases (75.6%) were symptomatic. The mean age at surgery was 7.9 years, and the mean postoperative follow-up duration was 48.5 months. Frontotemporal encephalo-duro-arterio-synangiosis (EDAS) was performed in all cases, and simultaneous frontal encephalo-galeo-synangiosis (EGS) was performed in 34 cases. Postoperative angiography revealed insufficient angiogenesis in 14 of 90 cases (15.6%) after frontotemporal EDAS and in 8 of 34 cases (23.5%) after frontal EGS. A high degree of ivy sign depicted on preoperative MRI was found to be significantly correlated with good angiogenesis after both surgical procedures (p = 0.00030 for EDAS and p = 0.0039 for frontal EGS). In addition, an advanced preoperative Suzuki stage was significantly correlated with good postoperative angiogenesis after EDAS (p = 0.00040). Good angiogenesis was significantly correlated with postoperative improvement of the ivy sign in both procedures (p = 0.0005 in EDAS and p = 0.030 in frontal EGS) as well as correlated with a better mRS score at long-term follow-up after EDAS (p = 0.018). Preoperative ivy sign and Suzuki classification are related to the degree of angiogenesis achieved after indirect revascularization for pediatric moyamoya disease.

Reverse-engineered exclusive enteral nutrition in pediatric Crohn's disease: A pilot trial.

In pediatric Crohn's disease (CD), commercial formulas used as exclusive enteral nutrition (EEN) are effective at inducing remission. This study aims to assess the impact of a whole-food blended smoothie as EEN on CD activity and the intestinal microbiome. A 4-week prospective trial assessed the impact of EEN with a whole-food smoothie on newly diagnosed mild-to-moderate active pediatric CD. The smoothie with a multivitamin were developed to meet age-appropriate nutritional requirements. Assessment over 4 weeks included Pediatric Crohn's Disease Activity Index (PCDAI), serum laboratories, fecal calprotectin (FCP), and stool collection for metagenomic shotgun sequencing and microbiota composition analysis. Clinical remission was defined as PCDAI ≤ 10 at week 4. Ten participants were enrolled with median age 14.5 years, and 8 completed the trial. Baseline mean PCDAI was 26.3 ± 9.1 and mean FCP 1149 ± 718 µg/g. At week 4, 80% of participants achieved clinical remission. FCP decreased by over half in 60% of participants, with FCP below 250 µg/g in 60% and below 100 µg/g in 40%. Microbiome analysis showed a significant increase in species richness over 4 weeks (p = 0.01). Compared to baseline, the relative abundance at week 2 and at week 4 was significantly increased for Bifidobacterium and Streptococcus and decreased for Blautia (p < 0.05 for all). A whole-food blended smoothie was effective for inducing clinical remission and decreasing FCP in pediatric CD similar to commercial EEN formulas. Further research may give insight into data-driven whole-food dietary approaches for CD management. gov NCT03508193.

Meta-analysis of the adoption of omalizumab in the treatment of pediatric allergic diseases

IntroductionAllergic diseases are common chronic conditions in children, omalizumab has a wide range of adoptions in various diseases. A meta-analysis was implemented to demonstrate the efficacy of omalizumab in the therapy of pediatric allergic diseases. Materials and methodsEnglish databases were searched. The search terms included “Omalizumab”, “Children”, “Allergic asthma”, and “Atopic dermatitis”. The literature was screened regarding inclusion and exclusion criteria, and data were extracted and analyzed using RevMan5.3. Resultsa total of six suitable studies, comprising 2761 patients, were selected for inclusion. The meta-analysis results implied that at 24 weeks, OR for worsening of symptoms in children was 0.10 (95 % confidence interval [CI] 0.03–0.41), Z = 3.24, P = 0.001 (P < 0.05); at 52 weeks, OR was 0.27 (95 % CI 0.09–0.83), Z = 2.28, P = 0.02 (P < 0.05); and during treatment, OR for adverse events in children was 0.87 (95 % CI 0.60–1.29), Z = 0.68, P = 0.49 (P > 0.05). Conclusionthe study comprised six investigations that examined the effectiveness of omalizumab in treating pediatric allergic diseases. The findings demonstrated that, in comparison to standard treatment, omalizumab can greatly alleviate allergy-related clinical symptoms in children, slow down disease progression, and has a higher safety profile with fewer adverse reactions. These results have practical implications and highlight the potential value of omalizumab in pediatric allergy treatment.

The Application of Umbilical Cord Blood-derived Platelet Gel for Skin Ulcers Associated With Chronic Graft-Versus-Host Disease in Pediatrics: A Randomized Trial

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities, and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. To assess the safety and efficacy of the application of platelet gel-containing dressing for the management of ulcerative skin cGVHD in pediatric patients. This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (4 females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = .019). In addition, the mean reduction in the ulcers’ surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = .001 for day 5 and P < .001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including 6 completely healed ulcers) versus 1 (6.25%, which was not completely healed) in the control arm (P < .001). None of the patients exhibited any localized or systemic treatment-related adverse events. In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020.

Serum Zonulin as a Marker of Intestinal Mucosal Barrier Function in Chronic Liver Diseases in Pediatrics

Serum Zonulin as a Marker of Intestinal Mucosal Barrier Function in Chronic Liver Diseases in Pediatrics

321 The Use of AI in Pediatric Congenital Heart Disease: How Far Have We Come?

OBJECTIVES/GOALS: Artificial Intelligence (AI) is gaining popularity in a variety of disciplines. While clinical applications for AI have increased in recent years, the use of AI in pediatric congenital heart disease (CHD) is limited. The goal of this systematic review was to assess how AI is currently used in this patient population and to describe knowledge gaps. METHODS/STUDY POPULATION: A systematic search was performed up to July 2023 using PubMed and Scopus databases and revealed 814 articles. Upon initial screening, 161 duplicates, 76 non-AI articles, and an additional 318 irrelevant articles were removed. A total of 259 full-text articles were reviewed for relevance. Articles that did not include a retrospective or prospective review of human subject data were excluded. Articles that had only results in the adult, prenatal, or non-CHD population were excluded. The remaining 68 articles were included in this review. RESULTS/ANTICIPATED RESULTS: Of the 68 articles in this review, 19 were performed within cardiac surgery, 41 were within cardiology, and the remaining 8 included articles were combined cardiac surgery and cardiology. Upon initial review, 24 used AI for diagnostic purposes, 40 for predicting survival or adverse outcomes, 2 for developing training tools, and 2 for surveillance of CHD trends. We anticipate that upon further review of these 68 articles, there will be a wide variety in the types of AI models that were used. The results will reveal a multitude of challenges and limitations that future studies will need to further address. DISCUSSION/SIGNIFICANCE: While technical innovations in pediatric CHD have dramatically improved survival rates, we have hit a plateau in improving the complications of these patients. AI has created an opportunity to build new diagnostic, predictive, teaching, and surveillance tools for advancing CHD care, but it seems we still have a long way to go.

Multicenter registry of pediatric inflammatory bowel disease from a developing country

BackgroundDespite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry.MethodsFour teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up.ResultsWe included 35 Crohn’s disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up.ConclusionsA high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

Parental stress in the relationship with children affected by chronic hematologic disease.

Sickle cell disease (SCD) and autoimmune thrombocytopenic purpura (AITP) are pediatric diseases which frequently are associated with cognitive, social and emotional complications and can lead caregivers to important consequences. The aim of this study was to examine the potential psychologic parental distress and the plausible interference with suffering of their children. We recruited 39 parents of 44 pediatric patients and divided them into two groups: patients affected by SCD and patients affected by AITP. Parenting Stress Index Short-form (PSI-SF) was proposed to the parents. We investigated the statistical correlations between the PSI-SF variables of the test, the patients scores at the cognitive test, the patients age, and the scores obtained at the mood test. The analysis of the parents scores obtained by the test reported that the stress levels of the parents of children affected by SCD are higher than those the other group. The analysis of the data showed that 72% of the patients score was average in the cognitive test, whereas 28% of them obtained a score below average; in the mood assessment tests: 35% of the patients reported elevated scores in the depression subscale; 21% showed an elevated score in the anxiety subscale. The data obtained provide us useful indications about pattern of behavior between the parents and the children affected by chronic hematological diseases. The differences in the perception of the parental distress were associated with children's disease, social problems increased parental distress, which was correlated with depression symptoms of the children.

The Role of Fibroblast Growth Factor-Receptor Pathway Aberrations in Pediatric Diseases

The fibroblast growth factor receptors play a crucial role in binding to fibroblast growth factor and are involved in various pathological conditions. These receptors consist of an extracellular ligand domain, a transmembrane helix domain, and an intracellular domain with tyrosine kinase activity. There are over 48 different isoforms of FGFR. Each FGF receptor in ligand-binding properties and kinase domains. The FGF/FGFR signaling pathway is implicated in various pediatric cancers and therefore are both non-selective and selective FGFR inhibitors available. Additionally, there are five distinct membrane FGF receptors dentified in vertebrates. All belonging to the tyrosine kinase superfamily. In this manuscript, the focus is based on an analysis of the role of FGF receptor signaling pathways and aberrations especially in pediatric diseases. Erk 1 and Erk 2 seem to have an important role as a mediator of FGF signaling in different biological and developmental processes. FGF signaling plays an important role in conserved developmental functions in skeletal growth, palate closure, ear development, cranial suture ossification and neuronal development in the child. Aberrant FGF signaling causes different congenital disorders and different forms of cancer in childhood. Modulating FGF signaling is of great importance for the treatment of rare diseases in childhood.