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Summary: Background: The European Society of Paediatric Gastroenterology, Hepatology and Nutrition established guidelines in 2012 for a no‐biopsy approach to diagnose coeliac disease in children. This guideline required symptoms suggestive of coeliac disease, positive human leukocyte antigen (HLA) DQ2/DQ8 haplotypes, tissue transglutaminase type‐2 immunoglobulin A antibody titre at levels greater than 10 times the upper limit of normal, and positive endomysial immune‐globulin A antibody test. An updated 2020 guideline excluded the need for symptoms and positive HLA. Aims: To assess the pooled positive predictive value (PPV) of the no‐biopsy approach with small bowel biopsy (SBB) data as the reference standard for comparison. Methods: Database searches (October 2023) provided data that we combined using a random‐effects meta‐analysis to provide a pooled PPV, representing the probability that a positive test result means that an individual truly has the condition. Results: We included 23 studies. Study sample sizes totalled 23,769 but only 3007 children had comparative SBB. The proportion of coeliac disease confirmed by the no‐biopsy approach and SBB ranged from 79.2% to 100%, with an overall pooled PPV of 97.4% (95% confidence interval 96.0, 98.6). Sensitivity analysis showed higher PPV for the criteria that included HLA (98.5% vs. 96.8%; p = 0.017). Conclusion: Both no‐biopsy criteria exhibit high PPV when compared to the reference standard. These results provide a consistent message of accuracy and feasibility to inform change and improve outcomes. [ABSTRACT FROM AUTHOR]

The specificities of the current clinical practice demand a constant reflection regarding the symbolizing and containing potential of our therapeutic settings as a means to support families whose backgrounds are often marked by traumatic migratory experiences. Clinicians need to modify traditional therapeutic settings in order to culturally, socially and intrapsychically permit injured families to adhere to the proposed clinical interventions. As a way of better responding to the demands of those families, both in terms of time and content, we have set up a parent/child space. This multi-disciplinary observation place enables us to elaborate about the child's care, but it also constitutes a first therapeutic space that supports the institutional transfer which is often weakened by the traumatic impact of the history of the families we receive at the CMP. Inspired by Françoise Dolto's Maison Verte, this space encourages the parents' involvement in their child's development, by enhancing their investment in the institution and in their child. The aim is to provide a more individualized support so that children can regain a subjective position, and their parents can be heard and supported in their suffering while dealing with their child's disorders and disorganization. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing juvenile idiopathic arthritis (JIA) is challenging. Our study aimed to investigate the clinical significance of anti-α-1,4-D-polygalacturonic acid (PGA) antibodies in JIA, focusing on their role in diagnosis and assessing disease activity. Methods: In this prospective case–control study, we examined variations in serum levels of PGA-IgA and PGA-IgG among children with different types of JIA and healthy controls. Serum PGA-IgA and PGA-IgG levels were assessed concurrently in children with active and inactive JIA. Results: This study included 126 patients diagnosed with JIA, 13 neonates, and 76 healthy children. Serum PGA-IgA and PGA-IgG levels were assessed, which revealed significant differences in PGA-IgA levels between various JIA subtypes and controls. An analysis of PGA-IgA levels in various JIA states revealed a statistically significant difference. Receiver operating characteristic (ROC) analysis demonstrated the robust predictive capability of PGA-IgA, with an AUC of 0.879 (p < 0.001), along with a specificity of 0.842 and sensitivity of 0.848. Conclusion: Increased levels of anti-PGA antibodies, particularly PGA-IgA, were significantly associated with JIA. PGA-IgA may serve as a sensitive biomarker for disease activity in JIA and could potentially aid in the diagnosis of JIA. Key Points • This study found a significant correlation between blood levels of PGA-IgA and juvenile idiopathic arthritis (JIA), which may provide valuable diagnostic insights. • PGA-IgA shows potential as a sensitive biomarker for the assessment of disease activity in JIA patients, helping to determine disease activity. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify and characterise the determinants influencing the occurrence of diarrheal diseases in children aged 6–24 months undergoing complementary feeding within a low‐income urban community in Kenya. Methods: This study followed a cross‐sectional design and recruited caregivers of children aged 6–24 months from 302 households. The dependent variable was the 2‐week diarrhoea prevalence among children, with independent variables including sociodemographic characteristics, child immunisation and feeding status, and water and sanitation facilities. Data analysis was performed using SPSS. Descriptive statistics and logistic regression analyses were used to assess associations between independent variables and the occurrence of diarrheal diseases. Results: The majority of caregivers were female (n = 282, 93.4%), aged 25–34 years (n = 156, 51.7%), had attained secondary school education (n = 154, 51%), were unemployed (n = 162, 53.6%), and earned Ksh 10,000 (USD 100) or less. 296 (98%) indexed children were fully vaccinated against rotavirus. Most households used improved drinking water sources (n = 272, 90.1%). Most caregivers did not regularly wash their hands with soap and water (n = 225, 74.5%). The 2‐week diarrhoea prevalence among children was 34.1% (103/302), with 69.9% (72/103) of these cases seeking care at a healthcare facility. Logistic regression analysis revealed that children of caregivers earning Ksh 20,000 and below (aOR = 2.9[1.3–6.5], p = 0.01), and those from households using unimproved sanitation facilities (aOR = 1.9 [CI 1–3.4], p = 0.042), had significantly higher odds of having diarrhoea. Conclusion: The study found a high prevalence of diarrhoea in Kenyan children aged 6–24 months, with caregiver income and household sanitation facilities significantly impacting the occurrence of the disease. The study suggests integrated approaches, including education, income generation, hygiene, and improved nutrition, to address the burden of diarrheal disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Few studies have focused on the outcomes of Wilson's disease (WD) diagnosed before age of 5 years. This study aimed to summarize the clinical features of early diagnosed WD and analyse treatment outcomes and the risk factors associated with treatment failure. Methods: A total of 139 children confirmed with WD before 5 years were enrolled in this study. Only patients with follow‐up over 1 year were analysed with Kaplan–Meier survival analysis. The composite outcomes included death, progression to liver failure or acute hepatitis, development of renal or neurological symptoms and persistent elevation of alanine aminotransferase (ALT). The treatment failure was defined as occurrence of at least one of above outcomes. Results: Among 139 WD patients at diagnosis, two (1.4%) WD patients presented with symptomatic liver disease, whereas 137 (98.6%) were phenotypically asymptomatic, including 135 with elevated ALT and 2 with normal liver function. Median serum ceruloplasmin (Cp) was 3.1 mg/dL, and urinary copper excretion was 87.4 μg/24‐h. There were 71 variants identified in the the copper‐transporting ATPase beta gene, and 29 were loss of function (LOF). 51 patients with LOF variant were younger at diagnosis and had lower Cp than 88 patients without LOF. Among 93 patients with over 1 year of follow‐up, 19 (20.4%) received zinc monotherapy, and 74 (79.6%) received a zinc/D‐penicillamine combination therapy. 14 (15.1%) patients underwent treatment failure, and its occurrence was associated with poor compliance (p <.01). Conclusions: Cp is a reliable biomarker for early diagnosis, and zinc monotherapy is an effective treatment for WD during early childhood. Good treatment compliance is critical to achieve a favourable outcome. [ABSTRACT FROM AUTHOR]

Aim: To compare the adherence to gluten‐free diet between children with serology‐based and biopsy‐proven coeliac disease. Methods: Medical records were retrospectively reviewed in 257 Swedish children diagnosed with coeliac disease between 2012 and 2019 at a tertiary hospital. Adherence to a gluten‐free diet was systematically assessed by trained dietitians at follow‐up. Mixed models were used to analyse the dietary adherence by mode of diagnosis (serology‐based vs. biopsy‐proven). Results: After mean 6.3 (SD 2.4) years, there was neither a difference in the dietary adherence over time depending on the mode of diagnosis (OR 0.64 [95% confidence interval (CI) 0.26, 1.60], p = 0.342), nor if coeliac disease was detected in screening studies (OR 0.74 [95% CI 0.25, 2.17], p = 0.584) or in risk‐groups (OR 1.01 [95% CI 0.26, 3.91], p = 0.991) compared to clinically detected diagnosis. Non‐adherence to a gluten‐free diet increased with age (OR 1.19 [95% CI 1.06, 1.33], p = 0.003). There was no difference in the proportion of patients improving their dietary adherence from non‐adherent to adherent over time (p = 0.322). Conclusion: Mode of diagnosis did not influence the dietary adherence in Swedish children with coeliac disease, although adherence to a gluten‐free diet was inversely associated with increasing age. [ABSTRACT FROM AUTHOR]

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Background Methods Results Conclusion The course of late‐onset Behçet's disease (LBD) is unknown. This study aimed to determine the characteristics and systemic involvement of LBD.In this retrospective, cross‐sectional, and comparative study, 700 patient files from 4100 patients diagnosed with Behçet's disease (BD) were selected and divided into three groups: LBD, adult BD (ABD), and juvenile BD (JBD). The age limits for LBD and JBD were determined to be 42 and 16, respectively. LBD patients were compared to ABD and JBD patients in terms of demographics, systemic involvement, and disease duration.The LBD rate among BD patients was 4.7% (183/4,100). The time from initial symptom occurrence to the age at which the BD criteria were met was longer in LBD than in ABD or JBD. Except for genital ulcers, the frequencies of involvement in LBD were similar to those in ABD and JBD. The frequency of family history was significantly lower in LBD (12%) than in ABD (15.9%) or JBD (18.2%). The time from the initial symptom to oral aphthae, genital ulcers, and eye involvement was longer in LBD than in ABD or JBD. Furthermore, erythema nodosum was observed after a longer duration in LBD than in ABD.Considering that involvement occurs much later in LBD and there are no differences in the frequencies of involvement except for genital ulcers, LBD patients should be followed up as closely as ABD and JBD patients. [ABSTRACT FROM AUTHOR]

Background: Whole blood host transcript signatures show great potential for diagnosis of infectious and inflammatory illness, with most published signatures performing binary classification tasks. Barriers to clinical implementation include validation studies, and development of strategies that enable simultaneous, multiclass diagnosis of febrile illness based on gene expression. Methods: We validated five distinct diagnostic signatures for paediatric infectious diseases in parallel using a single NanoString nCounter® experiment. We included a novel 3-transcript signature for childhood tuberculosis, and four published signatures which differentiate bacterial infection, viral infection, or Kawasaki disease from other febrile illnesses. Signature performance was assessed using receiver operating characteristic curve statistics. We also explored conceptual frameworks for multiclass diagnostic signatures, including additional transcripts found to be significantly differentially expressed in previous studies. Relaxed, regularised logistic regression models were used to derive two novel multiclass signatures: a mixed One-vs-All model (MOVA), running multiple binomial models in parallel, and a full-multiclass model. In-sample performance of these models was compared using radar-plots and confusion matrix statistics. Results: Samples from 91 children were included in the study: 23 bacterial infections (DB), 20 viral infections (DV), 14 Kawasaki disease (KD), 18 tuberculosis disease (TB), and 16 healthy controls. The five signatures tested demonstrated cross-platform performance similar to their primary discovery-validation cohorts. The signatures could differentiate: KD from other diseases with area under ROC curve (AUC) of 0.897 [95% confidence interval: 0.822–0.972]; DB from DV with AUC of 0.825 [0.691–0.959] (signature-1) and 0.867 [0.753–0.982] (signature-2); TB from other diseases with AUC of 0.882 [0.787–0.977] (novel signature); TB from healthy children with AUC of 0.910 [0.808–1.000]. Application of signatures outside of their designed context reduced performance. In-sample error rates for the multiclass models were 13.3% for the MOVA model and 0.0% for the full-multiclass model. The MOVA model misclassified DB cases most frequently (18.7%) and TB cases least (2.7%). Conclusions: Our study demonstrates the feasibility of NanoString technology for cross-platform validation of multiple transcriptomic signatures in parallel. This external cohort validated performance of all five signatures, including a novel sparse TB signature. Two exploratory multi-class models showed high potential accuracy across four distinct diagnostic groups. [ABSTRACT FROM AUTHOR]

Background: Enthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis with high disease burden. The objectives of this study were to explore the prevalence of HLA-B27, clinical characteristics, and treatment outcomes in children with ERA and compare the differences between HLA-B27 positive and negative patients. Methods: A retrospective cohort study at a pediatric rheumatology clinic in a tertiary referral hospital in Bangkok, Thailand, including ERA patients with at least 6 months of follow-up (July 2011-April 2022) was performed. Data were collected from medical records from diagnosis to recent follow-up, assessing disease activity and treatment outcomes, with an analysis comparing HLA-B27 positive and negative patients. Descriptive statistics were used for data analysis. Results: There were 59 ERA patients with mean age ± SD at diagnosis 11.2 ± 2.5 years, 53 males (89.8%), and positive HLA-B27 in 38 patients (64.4%). The HLA-B27 positive group had significantly higher levels of inflammatory markers at initial diagnosis (p = 0.001), lower baseline hemoglobin (p = 0.001) and hematocrit (p = 0.002), higher disease activity assessed by the Juvenile Spondyloarthritis Disease Activity score at 6 and 12 months of follow-up (p = 0.028 and 0.040, respectively), increased utilization of bridging systemic corticosteroids (60.5% vs. 14.3%, p = 0.001) and anti-TNF (39.5% vs. 9.5%, p = 0.018), and longer duration of methotrexate (median[IQR] 1.7[1.1–3.1] vs. 1.3[0.6–1.9] years, p = 0.040). The HLA-B27 negative group had more prevalent hip arthritis than the positive group at initial diagnosis (66.7% vs. 28.9%, p = 0.005) and during the course of the disease (71.4% vs. 36.8%, p = 0.011). Conclusion: Most of the ERA patients tested positive for HLA-B27. Throughout the follow-up period, these patients demonstrated greater disease activity, greater use of corticosteroids and anti-TNF, and longer duration of methotrexate to control the disease. Key points: • HLA-B27 was tested positive in nearly two-thirds of enthesitis-related arthritis (ERA) patients. • ERA patients with positive HLA-B27 had significantly higher levels of inflammatory markers with lower hemoglobin and hematocrit at initial diagnosis, increased disease activity assessed by the Juvenile Spondyloarthritis Disease Activity (JSpADA) score at 6 and 12 months of follow-up, greater utilization of bridging systemic corticosteroids and anti-TNF, and longer duration of methotrexate use. • ERA patients with negative HLA-B27 had more prevalent hip arthritis at initial diagnosis and during disease course. • Application of the Assessment of SpondyloArthritis international Society (ASAS) classification for adult spondyloarthritis in ERA patients who entered adulthood showed the predominance of peripheral spondyloarthritis in more than half of the patients. [ABSTRACT FROM AUTHOR]

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions. [ABSTRACT FROM AUTHOR]

Renal fibrosis is the common outcome of practically all progressive forms of chronic kidney disease (CKD), a significant societal health concern. Glutamate dehydrogenase (GDH) 1 is one of key enzymes in glutamine metabolism to catalyze the reversible conversion of glutamate to α‐ketoglutarate and ammonia. However, its function in renal fibrosis has not yet been proven. In this study, GDH1 expression was significantly downregulated in kidney tissues of both children with kidney disease and animal models of CKD. In vivo, the use of R162 (a GDH1 inhibitor) significantly improved renal fibrosis, as indicated by Sirius red and Masson trichrome staining. These findings are consistent with the impaired expression of fibrosis indicators in kidneys from both the unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (5/6 Nx) models. In vitro, silencing GDH1 or pretreatment with R162 inhibited the induction of fibrosis indicators in tissue kidney proximal tubular cells (TKPTS) treated with Transforming growth factor Beta 1 (TGF‐β1), whereas activating GDH1 worsened TGF‐β1's induction impact. Using RNA‐sequence, luciferase reporter assays and Biacore analysis, we demonstrated that GDH1 interacts with Peroxisome proliferator‐activated receptor gamma (PPARγ) and blocks its transcriptional activity, independent of the protein's expression. Additionally, R162 treatment boosted PPARγ transcriptional activity, and blocking of this signaling pathway reversed R162's protective effect. Finally, we discovered that R162 treatment or silencing GDH1 greatly lowered reactive oxygen species (ROS) and lipid accumulation. These findings concluded that suppressing GDH1 or R162 treatment could prevent renal fibrosis by augmenting PPARγ transcriptional activity to control lipid accumulation and redox balance. [ABSTRACT FROM AUTHOR]

Background: Determining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets. Aim: We aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA. Materials and methods: This cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children's Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann–Whitney, Kruskal–Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination. Results: Forty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve. Conclusion: The significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination. [ABSTRACT FROM AUTHOR]

AbstractAlthough school-aged children often suffer from multiple several allergic diseases concurrently, most studies on stress coping have examined allergic diseases separately. Herein, semi-structured interviews were conducted to evaluate stress-coping patterns associated with allergic diseases among ten children aged 9–12 years, and obtained data were subjected to qualitative thematic analysis. Characteristic word contents were grouped into categories to explore themes. After the analysis, e themes—objection, support, rescue, distraction, concealment, catharsis, conversion, and positive thoughts—and 13 categories were identified. Furthermore, a thematic map was used on the following three coping domains of coping: problem-focused and behavioral coping, emotion-focused and behavioral coping, and emotion-focused and cognitive coping. Behavioral coping could be easily implemented in children. This study revealed that it is critical for children with allergic diseases to have various coping methods and functional coping strategies should be implemented. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane’s Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006–0.103, p = 0.026) and genus Ruminococcaceae UCG003 (β: 0.06, 95%CI: 0.003–0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD. [ABSTRACT FROM AUTHOR]

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases are common in children and adolescents. It is important to assess the prevalence and risk factors of environmental diseases to implement tailored countermeasures. Methods: This questionnaire study investigated factors associated with environmental diseases in elementary school children with an environmental disease from 150 households in Daejeon Metropolitan City, South Korea in 2021. Results: The participants comprised 55.7% girls and 44.3% boys, and the mean age was 10.1 years with an even age distribution. The typical risk factors observed were the type of roads nearby, the presence of mold or stains within the residence, pet ownership, and frequency of indoor ventilation and cleaning. Notably, 73.2% of the households had an eight-lane road nearby, 40.2% reported leaks, stains, or mold within their homes during the past year, and 37.1% ventilated their homes for less than 30 min. After education on preventing and managing environmental diseases, significant changes were observed in bedding washing frequency, average ventilation duration per session, and duration of humidifier usage (p < 0.05–0.001), with improvements in lifestyle. Conclusions: Our study can be used as a reference for expanding indoor air quality control education for parents with children with an environmental disease and providing tailored environmental consultations. [ABSTRACT FROM AUTHOR]

Otitis media with effusion (OME) is a common presentation to the Otorhinolaryngology clinic. Besides hearing impairment, recent evidence shows that approximately 30% of these children have some degree of vestibular and balance impairment. To assess the presence of vestibular dysfunction among children with OME. Children between 4 and 17, with and without OME, underwent vestibular assessment using video head impulse test (VHIT), subjective visual subjective (SVV), and single leg raising test (SLS). Data were recorded and analysed. 24 OME children were included with male predominance. No statistical significance was found between the VOR gain (p > 0.05), SVV (p = 0.056) and SLS (p = 0.06). Simple linear regression analysis showed that age and gender are potential factors for VOR gain. Our study found that children with OME have normal vestibular function. [ABSTRACT FROM AUTHOR]

Ustekinumab is an effective therapy for adult Crohn's disease (CD), but data in paediatric CD patients are scarce. The aim of the study was to describe the real-life effectiveness and safety of ustekinumab in paediatric CD. This is a multicentre review of children with Crohn's disease treated with ustekinumab. The aim of our study was to describe the effectiveness and safety of ustekinumab in paediatric real-life practice. This is a study of the Paediatric IBD (inflammatory bowel disease) Porto group of ESPGHAN. Corticosteroid (CS)- and exclusive enteral nutrition (EEN)-free remission, defined as weighted Paediatric Crohn's Disease Activity Index (wPCDAI) < 12.5, and physician global assessment (PGA) were determined at weeks 12 and 52. A total of 101 children were included at a median age of 15.4 years (IQR 12.7–17.2) with a median follow-up of 7.4 months (IQR 5.6–11.8). Ninety-nine percent had received prior anti-TNF, 63% ≥ 2 anti-TNFα therapies and 22% vedolizumab. Baseline median wPCDAI was 39 (IQR 25–57.5) (71 (70%) patients with moderate-severe activity). Weeks 12 and 52 CS- and EEN-free remission were both 40.5%. Clinical response at week 6, iv induction route and older age at onset of ustekinumab treatment were predictive factors associated with clinical remission at week 12. Seven minor adverse events probably related to ustekinumab were reported. One patient died from an unrelated cause. Conclusion: Our results suggest that ustekinumab is effective and safe in children with chronically active or refractory CD. What is Known: • Ustekinumab is an effective therapy for adult moderate to severe Crohn's disease (CD). • Off-label use of ustekinumab in children is increasing especially in anti-TNF refractory CD. What is New: • Is the largest cohort of real-world use of ustekinumab in paediatric CD to date. • Clinical response at week 6, iv induction and older age at onset of ustekinumab were predictive factors associated with clinical response at week 12. [ABSTRACT FROM AUTHOR]

We aimed to provide a detailed phenotypic description of status epilepticus (SE) in a large cohort of patients with POLG disease and identify prognostic biomarkers to improve the management of this life-threatening condition. In a multinational, retrospective study with data on patients with POLG disease from seven European countries, we identified those who had SE. The age of SE onset, accompanying clinical, laboratory, imaging and genetic findings were analysed. One hundred and ninety-five patients with genetically confirmed POLG disease were recruited, of whom 67% (130/194) had epilepsy. SE was identified in 77% (97/126), with a median age of SE onset of 7 years. SE was the presenting symptom of the disease in 43% (40/93) of those with SE, while 57% (53/93) developed SE during the disease course. Convulsive SE was reported in 97% (91/94) followed by epilepsia partialis continua in 67% (56/84). Liver impairment 78% (74/95), ataxia 69% (60/87), stroke-like episodes 57% (50/88), were the major comorbidities. In the majority (66%; 57/86) with SE this became refractory or super-refractory. The presence of seizures was associated with significantly higher mortality compared to those without (P ≤ 0.001). The median time from SE debut to death was 5 months. SE is a major clinical feature of POLG disease in early and juvenile to adult-onset disease and can be the presenting feature or arise as part of a multisystem disease. It is associated with high morbidity and mortality, with the majority of patients with SE going on to develop refractory or super-refractory SE. [ABSTRACT FROM AUTHOR]

Background: Asthma is the most common chronic respiratory disease in childhood. Aspergillus fumigatus sensitivity may be involved in the pathogenesis of asthma by leading to different clinical presentations. Objective: To investigate the demographic, clinical, laboratory, and radiological characteristics of A. fumigatus sensitivity in childhood asthma and identify associated risk factors and diagnostic parameters. Methods: A total of 259 children with asthma were included in the study, 7 (2.7%) with allergic bronchopulmonary aspergillosis (ABPA), 84 (32.4%) with A. fumigatus‐sensitized asthma (Af‐SA), and 168 (64.9%) with A. fumigatus‐unsensitized asthma (Af‐UA). Results: Aspergillus sensitivity was associated with early asthma onset and longer asthma duration. Total IgE level and asthma severity are highest in ABPA and higher in Af‐SA. Absolute eosinophil count was higher, and FEV1 was lower in Af‐SA and ABPA. Aspergillus fumigatus was associated with greater odds of being male (odds ratio [OR], 2.45), having atopic dermatitis (OR, 3.159), Alternaria sensitivity (OR, 10.37), and longer asthma duration (OR, 1.266). The best cut‐off values for detecting A. fumigatus positivity were 363.5 IU/mL for total IgE and 455 cells/μL for absolute eosinophil count. In Af‐SA compared to Af‐UA, centrilobular nodules and peribronchial thickening were more common, and the bronchoarterial ratio was higher. Conclusions: Aspergillus sensitivity is a strong allergic stimulus in asthma, leading to laboratory, structural, clinical, and functional consequences. Af‐SA is a distinct asthma endotype independent of ABPA that is characterized by increased risk of severe clinical presentations and impaired lung function. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Necrotizing pneumonia (NP) is the destruction of the interstitial part of the lung due to severe infection. One cause of this rare and fatal condition in pediatrics is Acinetobacter. Severe infections, especially pneumonia, can prone pediatric patients to ischemic stroke. This study reports an 8‐year‐old girl presented to the emergency department complaining of shortness of breath, fever, and fatigue. She was admitted to the intensive care unit due to respiratory distress and pericardial effusion. Swab and respiratory secretion tests for COVID‐19 and Acinetobacter were positive. In her admission course, her condition deteriorated, and on the fifth day, she underwent a craniotomy due to the signs of increased intracranial pressure (ICP). The computed tomography (CT) scan showed an ischemic stroke. Despite all efforts and medical efforts, the patient's clinical condition got worse, and she died 10 days after the surgery. COVID‐19 can lead to vulnerability to severe bacterial infections such as NP in pediatrics. Severe infections are a significant risk factor for ischemic stroke. The presentation might be different in intubated unconscious patients, such as detecting increased ICP signs. In severe and extensive cases of NP and ischemia, the destruction of the lungs and brain tissue might be irreversible and even lethal. Doctors and parents should consider neurologic complaints in children with infectious diseases as a serious issue since infections make children vulnerable to complications such as stroke. [ABSTRACT FROM AUTHOR]

Allergic rhinitis is a common childhood disease. Although various drugs have been used to treat allergic rhinitis, including nasal corticosteroids, antileukotrienes, and antihistamines, there is still controversy about the optimal dose and the best combination with the highest efficacy. Higher doses of antihistamines are recommended for better control of urticaria, but there is insufficient evidence regarding the efficacy of increased doses of antihistamines in allergic rhinitis. The aim of the study was to evaluate the effectiveness of different drug combinations in the treatment of children with allergic rhinitis. Sixty-four children with persistent moderate to severe allergic rhinitis were enrolled and randomly divided into 4 groups. All children received mometasone furoate nasal spray once daily. In addition to mometasone, each group received one of the following drugs or drug combinations: daily desloratadine, twice daily desloratadine, montelukast, or a combination of desloratadine and montelukast. The severity of symptoms before and after the intervention was evaluated based on the total nasal symptoms score, including sneezing, nasal congestion, nasal itching, and rhinorrhea. Sixty patients completed the study. The reduction of nasal congestion score and total nasal symptoms score in the groups receiving desloratadine twice a day and desloratadine plus montelukast was superior to the daily desloratadine group and daily montelukast groups. According to this work, the treatment of allergic rhinitis with mometasone nasal spray with desloratadine twice a day or with the combination of desloratadine and montelukast was more effective than other treatment regimens. [ABSTRACT FROM AUTHOR]

Cesarean section delivery is associated with microbiota disruption and immuno-dysregulation during childhood, but the association with Kawasaki disease remains uncertain. We aimed to evaluate the association between Cesarean section and Kawasaki disease. We examined the association between Kawasaki disease between six and eighteen months and Cesarean section within a birth cohort of 15,796 mother-infant pairs in Taiwan. The associations were assessed with Poisson regression in the study population, in the 1:2 propensity score-matched subpopulation, and compared with febrile convulsion, trauma and accidents during the same interval as negative control outcomes. Cesarean section was found to increase the risk of Kawasaki disease among overall population (adjusted relative risk [aRR]: 2.22, 95 % confidence interval (CI): 1.14–4.34) and the matched subpopulation (aRR: 2.29, 95 % CI: 1.14–4.68 in PS-matched subpopulation). Meanwhile, there was no association between Cesarean section and the clinic visits for febrile convulsion, trauma and accidents. In conclusion, this study identified a potential association between Cesarean section delivery and a higher risk of Kawasaki disease during six-to eighteen months of the prospective birth cohort in Taiwan. [Display omitted] • Cesarean section delivery disrupts microbiota and immune regulation but its association with Kawasaki disease is uncertain. • This study examined the association between Cesarean section and Kawasaki disease in 15,796 mother-infant pairs in Taiwan. • Cesarean section increased Kawasaki disease risk, while it was not associated with the risk of negative control outcomes. [ABSTRACT FROM AUTHOR]

Background: An increasing number of people around the world suffer from Crohn's disease (CD), one of the inflammatory bowel diseases (IBDs). Recent evidence suggests that the endogenous cannabinoid system plays an important role in IBD. The main endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are ligands of the CB1 and CB2 receptors that are expressed on immune cells. These receptors as well as endocannabinoids are believed to mediate inflammatory activity and participate in the pathophysiology of CD. Objective: Very little is known about the secretion of endogenous cannabinoids throughout the course of CD. Therefore, the aim of this study was to determine and analyze the 2-AG and AEA concentrations in children who suffered from CD. Methods: We studied 34 adolescents with CD, mean age 13.5 years ± 2.0. Blood samples were collected three times in the active phase of the disease (during admission to hospital, before treatment), 2–4 weeks later, during the treatment and clinical improvement of the patients, and 3–6 months later, in the period of remission. The control group included 33 healthy teenagers of the same age who were examined once. In all patients, fasting blood samples were collected in the morning. 2AG and AEA concentrations in serum were measured using EIA kits (Abclonal, Woburn, MA, USA and ELK Biotechnology Co., Ltd. Wuhan, China, respectively). Results: The median 2-AG concentration in the study group was stable: acute phase 907.4 [379.3; 1300.5] pg/mL, during treatment 715.1 [416.7; 1302.5] pg/mL; remission 991.1 [381.1; 1652.5] pg/mL, and similar to the values observed in the control group 761.8 [504.3; 1497.0] pg/mL. No significant differences were found between the results obtained at all time points in the study group and compared to the control group (in all cases p > 0.44). In the case of AEA, in the study group before treatment, the median concentration was 2.63 [2.24; 2.79] ng/mL and similar to values obtained during treatment 2.56 [2.33; 3.06] ng/mL, and in remission, with 2.61 [2.46; 2.85] ng/mL. All these concentrations were lower compared to the values measured in the control group of 3.18 [2.57; 3.88] ng/mL (p = 0.023, p = 0.035, p = 0.056, respectively). Conclusions: While 2-AG levels remained stable throughout the disease course and were comparable to controls, AEA concentrations were consistently lower in CD patients. Therefore, therapeutic interventions aimed at increasing AEA-related signaling, such as administration of its analogues or fatty acid amide hydrolase inhibitors, may improve symptoms associated with Crohn's disease in children. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non‐TNFi biologic following discontinuation of a TNFi for patients with polyarticular‐course juvenile idiopathic arthritis (pJIA). Methods: Using the Childhood Arthritis and Rheumatology Research Alliance Registry, patients with pJIA who started receiving a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on the index date and a visit six months after the index date. Outcome measures included Clinical Juvenile Arthritis Disease Activity Score with a maximum of 10 active joints (cJADAS10), cJADAS10 inactive disease (ID; ≤2.5) and cJADAS10 minimal disease activity (MiDA; ≤5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aORs) were calculated using propensity score quintiles to compare outcomes at six months following second biologic initiation. Results: There were 216 patients included, 84% initially received etanercept, and most patients stopped receiving it because of its ineffectiveness (74%). A total of 183 (85%) started receiving a second TNFi, and 33 (15%) started receiving a non‐TNFi. Adalimumab was the most common second biologic received (71% overall, 84% of second TNFi), and tocilizumab was the most common non‐TNFi second biologic received (9% overall, 58% of non‐TNFi). There was no difference between receiving TNFi versus non‐TNFi in cJADAS10 ID (29% vs 25%; aOR 1.23, 95% confidence interval [CI] 0.47–3.20) or at least MiDA (43% vs 39%; aOR 1.11, 95% CI 0.47–2.62) at six months. Conclusion: Most patients with pJIA started receiving TNFi rather than non‐TNFi as their second biologic, and there were no differences in disease activity at six months. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Heterogeneous nuclear ribonucleoprotein A1 is involved in nucleic acid homeostatic functions. The encoding gene HNRNPA1 has been associated with several neuromuscular disorders including an amyotrophic lateral sclerosis‐like phenotype, distal hereditary motor neuropathy, multisystem proteinopathy, and various myopathies. We report two unrelated individuals with monoallelic stop loss variants affecting the same codon of HNRNPA1.Two individuals with unsolved juvenile‐onset myopathy were enrolled under approved institutional protocols. Phenotype data were collected and genetic analyses were performed, including whole‐exome sequencing (WES).The two probands (MNOT002‐01 and K1440‐01) showed a similar onset of slowly progressive extremity and facial weakness in early adolescence. K1440‐01 presented with facial weakness, winged scapula, elevated serum creatine kinase (CK) levels, and mild neck weakness. MNOT002‐01 also exhibited elevated CK levels along with facial weakness, cardiomyopathy, respiratory dysfunction, pectus excavatum, a mildly rigid spine, and loss of ambulation. On quadriceps muscle biopsy, K1440‐01 displayed rounded myofibers, mild variation in fiber diameter, and type 2 fiber hypertrophy, while MNOT002‐01 displayed rimmed vacuoles. Monoallelic stop‐loss variants in HNRNPA1 were identified for both probands: c.1119A>C p.*373Tyrext*6 (K1440‐01) and c.1118A>C p.*373Serext*6 (MNOT002‐01) affect the same codon and are both predicted to lead to the addition of six amino acids before termination at an alternative stop codon.Both stop‐loss variants in our probands are likely pathogenic. Our findings contribute to the disease characterization of pathogenic variants in HNRNPA1. This gene should be screened in clinical diagnostic testing of unsolved cases of sporadic or dominant juvenile‐onset myopathy. [ABSTRACT FROM AUTHOR]

Purpose Methods Findings Conclusions Implications for nursing practice This study aimed to determine the clinical validation of the nursing diagnosis (ND) of “spiritual distress (00066)” and the sensitivity, specificity, likelihood ratio, and predictive value in parents of children with chronic diseases.This cross‐sectional study was conducted using the clinical diagnostic validity method proposed by Fehring. The data were collected through structured interviews and using a researcher‐made list that included 5 parts of demographic information, parents’ opinions about spiritual distress, the researcher's diagnosis, 74 defining characteristics (DCs) of the ND of spiritual distress, and the Spiritual Well‐being Questionnaire. Data were analyzed using descriptive statistics as well as sensitivity, specificity, likelihood ratio, and predictive value.The prevalence of diagnosis was 70% in a sample of 120 parents. Out of the 74 DCs, 39 criteria were validated. Questioning meaning of illness and suffering had the highest sensitivity (98.8%), the highest negative predictive value (88.88%), and the lowest negative likelihood ratio (0.05%). Expressing the lack of meaning in life demonstrated the highest specificity (97.22%), the highest positive predictive value (98.33%), and the highest positive likelihood ratio (25.26%).Parents who search for meaning of illness and suffering related to a lack of meaning in life are in spiritual distress. The ND was validated.These findings can empower clinical nurses to confidently assess and identify patients experiencing spiritual distress, bridging the gaps caused by the absence of standardized tools for assessing spiritual distress in the inpatient setting. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion To provide guidance for follow‐up and monitoring of children and adolescents identified as positive to islet autoantibodies (IA) in the general population screening for type 1 diabetes (T1D) in Italy.Detection of IA helps to diagnose pre‐symptomatic T1D, prevent diabetic ketoacidosis (DKA) and identify persons for new therapies to delay symptomatic diabetes. Italy recently became the first country to approve by law a general autoantibody screening program for T1D and celiac disease in all children and adolescents (age 1‐17yr). A pilot study is currently underway in four Italian regions addressing feasibility issues to be used in the scale up to nationwide screening. Meanwhile, a group of experts developed guidance recommendations for follow‐up and monitoring of identified IA positive persons.Ten key components have been identified: establishment of a registry for children and adolescents at risk; close collaboration with the national network of family paediatricians; creation of T1D centers with expertise in follow‐up and monitoring; educational measures; assurance of solid IA tests; identification of appropriate metabolic tests; feed‐back feasibility and acceptability questionnaires; potential access to available therapeutic interventions; valuable outcome measures including DKA incidence; costs monitoring. Distinctive features of this program include single (in addition to multiple) IA antibody‐positive persons in follow‐up and the use of CGM to assess risk progression, rather than the cumbersome OGTT.It is expected that the proposed follow‐up and monitoring program will be effective, affordable and acceptable to children and families identified in general T1D screening in Italy. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids are widely used in inhalation aerosol therapy for wheezing diseases. This study aims to explore guardians' knowledge and attitude towards inhaled corticosteroids (ICS) aerosol therapy and the medication compliance of children with wheezing diseases in China. Methods: This cross-sectional study enrolled guardians of children with wheezing diseases at the First Hospital Affiliated to Shaoyang College between October 2022 and February 2023. A self-administered questionnaire was developed to collect demographic information of the participants and evaluate their knowledge and attitude towards ICS aerosol therapy. The 8-item Morisky Medication Adherence Scale was used to assess the medication compliance of children. Results: A total of 506 valid questionnaires were collected. 260 (51.38%) participants were guardians of a ≤ 3-year-old child and 327 (64.62%) were children's mothers. The knowledge, attitude, and medication compliance scores of all participants were 12.61 ± 5.78, 20.95 ± 2.37, and 4.69 ± 2.18, respectively. Multivariate logistic regression showed that knowledge scores [OR = 1.053, 95% CI (confidence interval): 1.017–1.090, P = 0.003], attitude scores (OR = 1.121, 95% CI: 1.030–1.219, P = 0.008), guardians of children aged 4–6 years (OR = 0.385, 95% CI: 0.242–0.612, P < 0.001), and grandparents of children (OR = 2.633, 95% CI: 1.104–6.275, P = 0.029) were independently associated with children's medication compliance. Conclusions: In conclusion, guardians of children with wheezing diseases in China had insufficient knowledge, unsatisfactory attitude, and poor medication compliance towards ICS aerosol therapy. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Pompe disease, a rare autosomal recessive disorder caused by acid alpha-glucosidase deficiency, results in progressive glycogen accumulation and multisystem dysfunction. Enzyme replacement therapy with recombinant human acid alpha-glucosidase is the standard of care; however, some patients develop anti-recombinant human acid alpha-glucosidase antibodies, leading to reduced efficacy. This case report presents two infants with early-onset Pompe disease who developed IgG antibodies to enzyme replacement therapy and were subsequently treated with methotrexate, highlighting the importance of monitoring antibody development and exploring alternative therapeutic approaches. Case presentation: Patient 1, a 10-month-old female from Bogota, Colombia, presented with generalized hypotonia, macroglossia, hyporeflexia, and mild left ventricular hypertrophy. Diagnostic tests confirmed early-onset Pompe disease, and enzyme replacement therapy was started at 12 months. Due to a lack of improvement and high anti-recombinant human acid alpha-glucosidase IgG antibody titers (1:1800), methotrexate was started at 18 months. After 8 months of combined therapy, antibody titers were negative and significant improvement in motor function was observed using the Gross Motor Function Measure 88. Patient 2, a 7-year-old female from Bogota, Colombia, was diagnosed with early-onset Pompe disease at 12 months and initiated enzyme replacement therapy. At 5 years of age, she experienced frequent falls and grip strength alterations. Functional tests revealed motor development delay, generalized hypotonia, and positive anti-recombinant human acid alpha-glucosidase IgG antibody titers (6400). Methotrexate was initiated, leading to a reduction in falls and antibody titers (3200) after 6 months, with no adverse events or complications. Motor function improvement was assessed using the Motor Function Measurement 32. Conclusions: The presented cases highlight the importance of monitoring patients for anti-recombinant human acid alpha-glucosidase antibody development during enzyme replacement therapy and the potential benefit of methotrexate as an immunomodulatory agent in early-onset Pompe disease. Early diagnosis and timely initiation of enzyme replacement therapy, combined with prophylactic immune tolerance induction, may improve clinical outcomes and reduce the development of anti-recombinant human acid alpha-glucosidase antibodies. The cases also highlight the importance of objective motor function assessment tools, such as Gross Motor Function Measure 88 and Motor Function Measurement 32, in assessing treatment response. Further research is needed to optimize treatment regimens, monitor long-term effects, and address the current limitations of enzyme replacement therapy in Pompe disease. [ABSTRACT FROM AUTHOR]

Background: Infantile tibia vara (ITV) is a rare proximal tibia deformity in infancy, leading to progressive knee varus. High tibial osteotomy is commonly practiced but has high recurrence rates. This study analyzed factors affecting treatment failure and recurrence in children undergoing opening-wedge high tibial osteotomy (OWHTO) for ITV. Methods: We retrospectively studied children with ITV who had OWHTO with a press-fit cancellous bone allograft between 2000 and 2020, with ≥2-year follow-up. Outcomes included recurrence (knee varus with tibiofemoral angle > 10°), complications, and reintervention. Results: We analyzed 39 knees in 29 patients (mean age: 4.8 ± 1.9 years; median follow-up: 7.4 years). Recurrence occurred in 22 cases (56%). Age at surgery significantly influenced recurrence, with rates of 16% before age 5 versus 95% later (hazard ratio: 12.0, p = 0.001). Langenskiöld stage also affected recurrence (β-coefficient: 2.7, 95% C.I. 1.0–4.5, p = 0.002; pseudo-R-squared: 0.50, p = 0.001), with recurrence in all stage IV or higher cases. Conclusions: Early diagnosis and treatment before age 5, ideally with Langenskiöld stage III or lower, are crucial for stable correction with OWHTO alone. Late, high-grade ITV may require combined, acute or gradual, and/or staged correction. Further evidence is needed for optimal management. [ABSTRACT FROM AUTHOR]

Summary: Background: Both corticosteroids and exclusive enteral nutrition (EEN) have been used as induction therapy in children with Crohn's disease (CD). Aim: To compare in a nationwide study the long‐term outcomes of children with CD receiving either EEN or corticosteroids as induction therapy. Methods: We retrieved data of all children diagnosed with CD (2005–2020) from the epi‐IIRN cohort covering 98% of the Israeli population. The primary outcome was time to complicated disease course (i.e., surgery, steroid‐dependency, or at least 2 biologic class). Patients were matched individually utilising propensity score adjustments. Results: We included 410 children treated with EEN and 375 with corticosteroids without other treatments (median follow‐up, 4.73 [IQR: 2.2–7.2] years [1433 patient‐years]). For 274 matched children, the probability of a complicated course was higher with corticosteroids than EEN at 0.5, 3 and 5 years (14% vs. 4%, 42% vs. 27% and 54% vs. 41%, respectively, p = 0.0066), despite similar use of biologics. Steroid‐dependency (10% vs. 2%, 15% vs. 3%, and 20% vs. 5%, respectively, p = 0.00018), and hospitalisations (20% vs. 11%, 37% vs. 26%, and 55% vs. 38%, respectively, p = 0.002) were higher with corticosteroids. During follow‐up, children receiving corticosteroids as induction treatment were more often further exposed to corticosteroids, and those on EEN were more often further exposed to nutritional treatment (p < 0.001). Induction with EEN had no advantage over corticosteroids regarding survival probability of surgeries, biologic use and growth. Conclusions: EEN in paediatric CD is associated with lower long‐term risks of corticosteroid dependency and hospitalisation than corticosteroids. These results may lend support to favouring nutritional therapy in paediatric CD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of electrocardiogram QT interval dispersion (QTd) combined with 25-hydroxyvitamin D [25-(OH) D], growth differentiation factor-15 (GDF-15) and pentraxin 3 (PTX3) in the evaluation of coronary artery lesions (CAL) in children with Kawasaki disease. Methods: 180 children with Kawasaki disease admitted to our hospital from June 2018 to June 2023 were selected, and patients were divided into CAL group (36 cases) and non-CAL group (144 cases) according to whether CAL occurred. All children received electrocardiogram examination to obtain QTd and corrected QT dispersion (QTcd), and serum 25-(OH)D, GDF-15 and PTX3 levels were detected. The factors affecting the occurrence of CAL in children with Kawasaki disease were analyzed by multivariate Logistic regression analysis, and a Log P model of multi-index combined application was constructed. The predictive value of QTd, 25-(OH)D, GDF-15 and PTX3 for CAL in children with Kawasaki disease were analyzed by receiver operating characteristic (ROC) curve. Results: The levels of QTd, QTcd, GDF-15 and PTX3 in CAL group were higher than those in non-CAL group (P<0.05), and the level of 25-(OH)D was lower than that in non-CAL group(P<0.05). Treatment non-response, high QTd, high QTcd, high GDF-15, and high PTX3 were risk factors for CAL in children with Kawasaki disease (P<0.05), and high 25-(OH)D was a protective factor (P<0.05). The Log P models of multi-index combined application were constructed as follows: A: electrocardiogram parameter model: Ln (P/1-P)=0.512 ×QTd+0.596 QTcd; B: serum 3 index model: Ln (P/1-P)=0.712×GDF-15+0.626×PTX3-0.609×25- (OH)D; C: 5-factor joint application model (above A+B model): Ln (P/1-P)=0.512×QTd+0.596 QTcd+0.712×GDF-15+0.626×PTX3-0.609×25-(OH)D. ROC analysis showed that, models A, B and C had certain predictive efficacy for CAL in children with Kawasaki disease, and their ROC-AUC (0.95CI) were 0.709 (0.490~0.921), 0.787 (0.579~0.966) and 0.835 (0.699~0.955) respectively. C combined application model has the highest prediction efficiency. Conclusion: The QTd increase, QTcd increased, GDF-15 increase, PTX3 increase, and 25-(OH)D decrease in children with Kawasaki disease with CAL, the combined detection of the above indicators has a high predictive efficiency for the occurrence of CAL in children with Kawasaki disease. [ABSTRACT FROM AUTHOR]

Domino liver transplantation and domino‐auxiliary partial orthotopic liver transplantation are emerging techniques that can expand the liver donor pool and provide hope for children with liver disease. The innovative technique of domino liver transplantation has emerged as a pioneering strategy, capitalizing on structurally preserved livers from donors exhibiting single enzymatic defects within a morphologically normal context, effectively broadening the donor pool. Concurrently, the increasingly prevalent domino‐auxiliary partial orthotopic liver transplantation method assumes a critical role in bolstering available donor resources. These advanced transplantation methods present a unique opportunity for pediatric patients who, despite having structurally and functionally intact livers and lacking early signs of portal hypertension or extrahepatic involvement, do not attain priority on conventional transplant lists. Utilizing optimal clinical conditions enhances posttransplant outcomes, benefiting patients who would otherwise endure extended waiting periods for traditional transplantation. The perioperative management of children undergoing these procedures is complex and requires careful consideration of some factors, including clinical and metabolic conditions of the specific metabolic disorder, and the need for tailored perioperative management planning. Furthermore, the prudent consideration of de novo disease development in the recipient assumes paramount significance when selecting suitable donors for domino liver transplantation, as it profoundly influences prognosis, mortality, and morbidity. This narrative review of domino liver transplantation will discuss the pathophysiology, clinical evaluation, perioperative management, and prognostic expectations, focusing on perioperative anesthetic considerations for children undergoing domino liver transplantation. [ABSTRACT FROM AUTHOR]

Background: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans. Methods: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children's infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed. Results: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed. Conclusions: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction. Systematic review registration: The research protocol of this systematic review is registered and accessible at the Open Science Framework (https://doi.org/10.17605/OSF.IO/5M2VU). [ABSTRACT FROM AUTHOR]

Background: The World Health Organisation Essential Medicines List (WHO EML) guides National Essential Medicines Lists and Standard Treatment Guidelines for clearly identified disease priorities especially in low- and middle-income countries. This study compares the degree to which the basket of medicines recommended for rheumatic diseases in children and young people in National Essential Medicines Lists of countries in the WHO Africa region, corresponds to the 2021 WHO EML and WHO EML for children, as a proxy of availability. Methods: An online search of the WHO medicines and health technology portal, the Health Ministry websites of the 54 African countries, PUBMED and Google Scholar, with search terms for 'National Essential Medicines List', AND/OR 'standard treatment guidelines' AND/OR 'Lista Nacional de Medicamentos Essenciais' AND/ OR 'Liste Nationale de Medicaments Essentiels' AND Africa AND/OR < Name of African country > was conducted. The number of medicines on the national lists were compared according to a predefined template of medicines; and the percentage similarity calculated. Descriptive statistics were derived using STATA. Results: Forty-seven countries in the WHO Africa region have developed a National Essential Medicines List. Eleven countries do not have any medicines listed for rheumatic diseases. The majority of countries had less than or equal to 50% similarity with the WHO EML for rheumatic disease in children and young people, median 3 medicines (IQR 1— 4). The most common medicines on the national lists from Africa were methotrexate, sulfasalazine and azathioprine, with etanercept available in 6 countries. Seven countries had only one medicine, acetylsalicylic acid listed in the section 'Juvenile Joint diseases'. A multiple linear regression model for the predictors of the number of medicines on the national lists established that 20% of the variability was predicted by health expenditure per capita, socio-demographic index and the availability of rheumatology services (adult and/or paediatric) p = 0.006, with socio-demographic index (p = 0.035, 95% CI 0.64—16.16) and the availability of rheumatology services (p = 0.033, 95% CI 0.13 – 2.90) significant. Conclusion: Four countries (8.5%) in Africa have updated their National Essential Medicines Lists to reflect adequate care for children and young people with rheumatic diseases. Moving forward, efforts should focus on aligning available medicines with the WHO EML, and strengthening healthcare policy for rheumatology and pharmaceutical services, for affordable access to care and medicines. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 15-year-old girl with juvenile-onset ankylosing spondylitis (JoAS). The study found that tumor necrosis factor-alpha inhibitor agents were effective in treating JoAS without any adverse events. The article emphasizes the importance of considering JoAS as a possible diagnosis in cases of low back pain and generalized pain since childhood, and highlights the prompt administration of TNF inhibitors after diagnosis. The case study also discusses the treatment approach taken, including the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and different TNF inhibitors. It concludes that prompt diagnosis and treatment with TNF inhibitors can lead to positive outcomes for patients with JoAS. [Extracted from the article]

Background: The management of mitral valve disease in young children is challenging. Mechanical mitral valves could provide long-term durability; however, the need for anticoagulation increases the risk profile of mechanical valves. We report our experience in mechanical mitral valve replacement (MVR) in children under 2 years of age and evaluate factors affecting the outcomes. The study included all patients younger than 2 years who underwent mechanical MVR between 2000 and 2023. The study outcomes were mitral valve reoperation, bleeding, valve-related thrombosis, and survival. Results: Twenty-three patients were included, with a mean age of 10.2 ± 5.9 months. The mitral valve sizes ranged from 16 to 25 mm, and 6 (26%) were placed in the supra-annular position. Complete heart block occurred in seven patients (30%), and operative mortality occurred in three patients (13%). Postoperative warfarin was used in 17 patients (74%). After discharge, bleeding occurred in five patients (22%), four were managed conservatively, and one had intracranial hemorrhage treated with craniotomy. Nine patients (39%) had valve-related thrombosis; two underwent reoperation, while seven were treated with alteplase in 26 patients. Valve-related thrombosis was more common in patients with supra-annular valves (p < 0.001) and in those who were not on warfarin (p < 0.001). A total of seven patients (30%) underwent redo MVR, and redo was more common in young patients (p = 0.029) and in patients with supra-annular valves (p < 0.001). Survival of the whole cohort was 73% at 5 years. Among the annular position group, 5-year survival was 88%, while among the supra-annular position group, survival was 50% after 3 months and 25% after 14 months (p = 0.009). Conclusions: Mechanical MVR in children younger than 2 years is associated with high complication rates, including thrombosis and bleeding. The supra-annular valve position appears to be a risk factor for thrombosis and reoperation. Anticoagulation with warfarin remains challenging. However, further studies evaluating alternative options are needed. [ABSTRACT FROM AUTHOR]

Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France. [ABSTRACT FROM AUTHOR]

To describe the diffusion-weighted imaging (DWI) findings in young children with moyamoya disease (MMD) during the acute period of the condition. Clinical data were collected from 12 children with MMD aged less than six years, in whom abnormalities were observed on DWI scans obtained within one week after the appearance of symptoms related to MMD. The DWI abnormalities were classified into gyral, atypical territorial, honeycomb, classical territorial, multiple-dot, border zone, and deep lacunar patterns. The severity of arterial stenosis was graded by angiographic stages that have been previously described. In all but one child, the DWI abnormalities were restricted to the cerebral cortex. The lesions were gyral in nature in seven children and atypical territorial in five; all differed from those of typical arterial strokes. Internal carotid artery stenosis was observed in all 12 children, although the stenosis was mild in 11. The severity of arterial stenosis did not match the regions of ischemic lesions in some children. There was no statistically significant difference in the severity of arterial stenosis according to the presence or absence of ischemic lesions or the pattern of the lesions. Lesions located mainly in the cerebral cortex, i.e., not in arterial territories, are characteristic of young children with MMD. [ABSTRACT FROM AUTHOR]

Quantitative muscle fat fraction (FF) responsiveness is lower in younger Charcot–Marie–Tooth disease type 1A (CMT1A) patients with lower baseline calf‐level FF. We investigated the practicality, validity, and responsiveness of foot‐level FF in this cohort involving 22 CMT1A patients and 14 controls. The mean baseline foot‐level FF was 25.9 ± 20.3% in CMT1A patients, and the 365‐day FF (n = 15) increased by 2.0 ± 2.4% (p < 0.001 vs controls). Intrinsic foot‐level FF demonstrated large responsiveness (12‐month standardized response mean (SRM) of 0.86) and correlated with the CMT examination score (ρ = 0.58, P = 0.01). Intrinsic foot‐level FF has the potential to be used as a biomarker in future clinical trials involving younger CMT1A patients. ANN NEUROL 2024;96:170–174 [ABSTRACT FROM AUTHOR]

This article discusses a case of pediatric Behçet's disease in an 11-year-old boy who initially presented with symptoms that mimicked pulmonary malignancy. The boy had a paravertebral mass, along with pyrexia of unknown origin, weight loss, myalgias, and orogenital ulcers. Further examination and imaging revealed thrombophlebitis, anemia, leukocytosis, and raised inflammatory markers. After ruling out other conditions, the boy was diagnosed with Behçet's disease based on the pediatric Behçet's criteria. Treatment with medication resulted in improvement, and the boy is currently doing well. The article also provides information on the pulmonary manifestations of Behçet's disease. [Extracted from the article]

Skin lesions are frequently observed in children with rheumatic diseases, particularly in conditions such as IgA vasculitis (IgAV) and Kawasaki disease (KD). In paediatric vasculitis, the presence of skin lesions serves as an early indicator, emphasising the importance of timely diagnosis to prevent complications, such as cardiac or renal involvement. Conversely, autoinflammatory disorders like juvenile systemic lupus erythematosus (SLE) and juvenile dermatomyositis (DM) may manifest with cutaneous manifestations either at the onset of disease or during its progression. Identifying these skin lesions prior to the appearance of systemic symptoms offers an opportunity for early diagnosis and treatment, which has a positive influence on the outcomes. Additionally, it is noteworthy that specific rheumatological conditions, such as acute rheumatic fever (ARF) or oligoarticular or polyarticular forms of juvenile idiopathic arthritis (JIA), may exhibit occasional, but significant skin involvement, which is strongly correlated with an unfavourable prognosis. The assessment of skin is important in the holist approach to assessing patients for potentially systemic/multisystem disorder and helps distinguish discrete conditions. [ABSTRACT FROM AUTHOR]

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early‐life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early‐life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to monitor the cranial parameters of patients with sagittal craniosynostosis. We will mainly focus on the differences between endoscopic and open-surgical treatment and their influence on changes in cranial parameters in patients with craniosynostosis of the sagittal suture. Craniosynostosis has various consequences, including reduced self-confidence and problems fitting in among other children due to craniofacial deformity. Therefore, monitoring aesthetic results of craniosynostosis treatment in pediatric patients is important. Patients and Methods: The sample of patients included in this study comes from patients monitored by the neurosurgeon at the Department of Paediatric Neurosurgery of the National Institute of Child Diseases in Bratislava, Slovakia. Standardized anthropometric methods and tools to monitor cranial dimensions were used. Results: In our study, we noted no differences in aesthetic results between open and endoscopic surgical treatment. However, surgical treatment, regardless of the type of chosen treatment, produced the desired aesthetic results, and these results improved over time. Conclusion: The benefit of the work will be the longitudinal monitoring of the growth of children's cranium, and the evaluation of the effectiveness of surgical treatment in patients with neurocranial growth disorders and the prevention of late consequences of growth disorders. [ABSTRACT FROM AUTHOR]

Dietary measures based on the exclusion of fermentable oligo-, di-, monosaccharides, and polyols (low-FODMAP diet) are increasingly being used in treating certain gastrointestinal diseases in children. The following text summarizes essential recommendations for using the low-FODMAP diet, based on the position paper of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) issued in September 2022. It includes recommendations on initiation, duration, gradual cessation, monitoring, professional guidance, safety, and risks. Currently, there is limited evidence supporting the use of this diet in children, primarily only for some pediatric patients suffering from functional gastrointestinal disorders (FGID), specifically children with functional abdominal pain (FAP), such as irritable bowel syndrome (IBS) according to the Rome IV criteria from 2016. There is no evidence for the use of the low-FODMAP diet in other gastrointestinal diseases in children, such as constipation, inflammatory bowel disease, celiac disease, non-celiac gluten sensitivity, or small intestinal bacterial overgrowth. [ABSTRACT FROM AUTHOR]