Juvenile Patients Research Articles

Clinical and epidemiological characteristics of amyotrophic lateral sclerosis in an Egyptian cohort.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive loss of motor neurons. It is a growing and underestimated disease, prompting this epidemiological study to describe the characteristics of ALS in Egyptian patients. This is a prospective hospital based study. ALS patients were recruited consecutively from Neuromuscular Unit in Ain Shams university Hospital from December 2018 to June 2023. Demographic data and disease related parameters were recorded. 203 ALS patients had a mean age of onset equal 39years and an inter quartile range IQR of (28.00-51.00). 76% of the cases were spinal onset ALS. Median disease duration was 2years with IQR of (1-4years); male to female ratio was 2.5:1; 18% of patients were familial ALS (FALS), while 19% were Juvenile ALS (JALS). Median diagnostic delay was 12 ± (6-36) months. Median Amyotrophic Lateral Sclerosis Functional Rating Scale Revised scores (ALSFRS-R) at presentation was 34.5 IQR of (26.00-40.00). Also, the mean rate of disease progression ALSFRS-R decline [points/month] was 0.76 ± 0.51. Our cohort was characterized by a younger age of onset, male predominance, more familial cases, within average Initial ALSFRS-R scores as well as diagnostic delay. Juvenile ALS patients were much more common in our population. These findings suggest an influential presence of genetic and epigenetic factors affecting the clinical phenotype of Egyptian ALS patients.

Age, Sex, and Clinical Characteristics of Juvenile Open-Angle Glaucoma Patients in a Saudi Tertiary Hospital: A Retrospective Study of Surgical and Non-Surgical Outcomes.

Background/Objectives: Juvenile Open Angle Glaucoma (JOAG) is a condition that presents peculiar issues because it starts at a very early age and, in the end, causes substantial vision loss. This study aimed to analyze the age and gender distribution and treatment outcomes in JOAG patients. Methods: We carried out a retrospective study at King Abdul Aziz University Hospital, Riyadh, Saudi Arabia, from 2015 to 2022. We extracted data from the medical records. Visual acuity data were converted to the logarithm of the minimum angle resolution (LogMAR) for standardized analysis. The CARL ZEISS Humphrey 745i Field Analyzer/HFA II-i Visual Field Analyzer was used to perform visual field examinations under the 24-2 program SITA standard. Results: The study involved 45 JOAG patients (87 affected eyes) with a mean age of 26.91 years. Myopia was the prevailing trait (93%), and a family history of glaucoma was found in 51.1% of cases. Most of the patients presented with severe visual field defects in both eyes (right-57.1%, left-44.4%). Regarding visual acuity, we found that the majority of affected categories belonged to either mild or moderate in both eyes. Initial and final Intraocular pressure (IOP) measurements together showed a significant reduction (p < 0.001) and clearly demonstrated the need for IOP control. Surgical and non-surgical treatments significantly reduced IOP, with no gender or eye differences Conclusions: This research offers important data concerning JOAG demographics (age and gender), clinical picture, and treatment results. Though early-onset presents challenges, multidimensional therapeutic methods have great potential to get JOAG under control and maintain visual function. Additional research is needed to study the genetic causes of JOAG and assess the long-term treatment outcomes.

Profile of patients with Juvenile Dermatomyositis and Anti-MDA5 autoantibodies.

Anti-MDA5 autoantibody-positive dermatomyositis (MDA5-DM) is associated with clinically amyopathic forms and rapidly progressive interstitial lung disease (ILD); however, data in children are limited. In this study, we described our cohort of anti-MDA5-positive juvenile DM (MDA5-JDM) from a tertiary care center in North India. We performed a retrospective analysis of children with MDA5-JDM who were diagnosed and followed up at our center and compared them with our anti-MDA5-negative cohort. We also compared the published literature on MDA5-DM with the juvenile cohort. Of 66 children with JDM who underwent testing for MSA, 10(15.5%) had anti-MDA5 positivity. The mean age at onset of clinical manifestations was 8.4 years; male: female ratio was 7:3. Five of nine patients who underwent screening HRCT chest had ILD; one amongst them had a fatal rapidly progressive disease. Children with MDA5-JDM had significantly more arthralgia/arthritis (p = 0.006) and ILD (p = 0.0005) compared to anti-MDA5 negative JDM in our cohort. While MDA5-DM had high rates of Raynaud's phenomenon (p = 0.04) and pulmonary involvement (p = 0.001), juvenile patients had a higher prevalence of constitutional symptoms (p = 0.01), skin manifestations (p = 0.003), arthritis (p = 0.001), and muscle weakness (p = 0.001). Arthritis and ILD are commonly seen with MDA5-JDM; however, the frequency of ILD and clinically amyopathic forms are less common compared to adult counterparts. The frequency of anti-MDA5 antibodies in a North Indian cohort of JDM is much lower (15.5%) compared to adult studies in dermatomyositis from Southeast Asia (~25%). Incidence of interstitial lung disease (ILD) and arthritis is high in anti-MDA5 autoantibody-positive JDM. Rates of a rapidly progressive form of ILD and clinically amyopathic dermatomyositis are much lower in children compared to adults with anti-MDA5-associated dermatomyositis.

National Registry for Childhood Onset Scleroderma I: Insights from the first 341 juvenile localized scleroderma patients

Objectives: There is an under recognition of juvenile-onset localized scleroderma and its extracutaneous manifestations leading to delay in systemic treatment. Our study aims to address this gap by describing the demographics, presentation, associated family history, concurrent autoimmune disease, extracutaneous manifestations, laboratory evaluation, treatment, and course of disease in juvenile-onset localized scleroderma patients enrolled in the National Registry for Childhood Onset Scleroderma. Methods: Participants for this study were derived from the National Registry for Childhood Onset Scleroderma and included 341 patients with juvenile-onset localized scleroderma. Demographic, and prospectively collected outcome measures, such as the Localized Scleroderma Cutaneous Assessment Tool, physical exam findings, laboratory values, and patient-reported outcomes were reviewed. Results: Most patients were female (71%), Caucasian (94%), had a linear subtype (56%), and had the onset of disease at age 7.5 (±4.2) years, and diagnosis 1.9 (±2.6) years after symptom onset. Most patients experienced at least one extracutaneous manifestation (70%), most commonly musculoskeletal (57%), followed by neurological (46%), and ophthalmological (11%). Those with musculoskeletal extracutaneous manifestation have significantly abnormal inflammatory and antibody laboratory values. Of patients with 1-year follow-up, a majority were treated with systemic therapy and globally improved with significant reduction in both modified Localized Scleroderma Skin Index ( p &lt; 0.001) and Localized Scleroderma Damage Index ( p = 0.001). Conclusion: The study highlights need for earlier recognition of juvenile-onset localized scleroderma after demonstrating the delay in diagnosis and frequent extracutaneous manifestations with significant disease burden in a juvenile-onset localized scleroderma cohort. The benefits of systemic treatment and full extracutaneous manifestation screening in juvenile-onset localized scleroderma is supported.

Juvenile Behçet syndrome: a contemporary view and differential diagnosis in pediatric practice.

This review aims to provide a comprehensive and contemporary overview of juvenile Behçet syndrome (jBS), highlighting its clinical manifestations, diagnostic challenges, and treatment strategies. Behçet syndrome, with its intricate etiopathogenesis and diverse clinical phenotypes, is more aptly classified as a syndrome than a single disease. Its heterogeneous nature requires a broad diagnostic approach and sophisticated differential diagnosis capabilities. The relatively rare occurrence of Behçet syndrome, combined with incomplete clinical presentations and overlapping differential diagnoses, presents significant diagnostic challenges, particularly in pediatric cases. Nevertheless, substantial progress has been made in treatment, especially in managing inflammatory components and preventing complications. Juvenile patients, given their developmental stage, require distinct therapeutic strategies compared to adults, with careful consideration of treatment side effects on growth and psychosocial development. To ensure early identification of jBS, it is imperative to refine and develop diagnostic criteria specifically tailored to pediatric populations. With a deeper understanding of the disease mechanisms, treatment protocols should be designed to address the developmental, psychosocial, and individual needs of patients, aiming to minimize long-term side effects. Additionally, comprehensive studies considering age, sex, and ethnic differences are necessary to fill gaps in the literature and resolve existing inconsistencies.

Quantitative reliability assessment of brain MRI volumetric measurements in type II GM1 gangliosidosis patients.

GM1-gangliosidosis (GM1) leads to extensive neurodegenerative changes and atrophy that precludes the use of automated MRI segmentation techniques for generating brain volumetrics. We developed a standardized segmentation protocol for brain MRIs of patients with type II GM1 and then assessed the inter- and intra-rater reliability of this methodology. The volumetric data may be used as a biomarker of disease burden and progression, and standardized methodology may support research into the natural history of the disease which is currently lacking in the literature. Twenty-five brain MRIs were included in this study from 22 type II GM1 patients of which 8 were late-infantile subtype and 14 were juvenile subtype. The following structures were segmented by two rating teams on a slice-by-slice basis: whole brain, ventricles, cerebellum, lentiform nucleus, thalamus, corpus callosum, and caudate nucleus. The inter- and intra-rater reliability of the segmentation method was assessed with an intraclass correlation coefficient as well as Sorensen-Dice and Jaccard coefficients. Based on the Sorensen-Dice and Jaccard coefficients, the inter- and intra-rater reliability of the segmentation method was significantly better for the juvenile patients compared to late-infantile (p < 0.01). In addition, the agreement between the two rater teams and within themselves can be considered good with all p-values < 0.05. The standardized segmentation approach described here has good inter- and intra-rater reliability and may provide greater accuracy and reproducibility for neuromorphological studies in this group of patients and help to further expand our understanding of the natural history of this disease.

Impact of the COVID-19 pandemic on the quality of care for juvenile idiopathic arthritis patients: insights from Thailand

BackgroundThe COVID-19 pandemic has significantly impacted individuals with chronic conditions. This investigation assessed the quality of care provided to pediatric and adolescent patients with juvenile idiopathic arthritis (JIA) during the pandemic in Thailand.MethodsThis cross-sectional analysis enrolled JIA patients aged ≤ 18 years at an academic tertiary care facility from April 2022 to March 2023. Retrospective reviews were performed, complemented by patient and caregiver questionnaires to assess the pandemic’s impact on care quality.ResultsSeventy JIA patients (37 males, 33 females) with a mean age of 13.5 ± 3.1 years were included. A total of 41.4% of the caregivers reported negative impacts on JIA care due to the pandemic and the lockdown, and 31.4% of the patients experienced pandemic-related anxiety. A comparison between the pandemic and prepandemic periods revealed a higher incidence of active disease, although the difference was statistically nonsignificant (37.1% vs 14.2%, p = 0.106). Nonadherence significantly predicted active disease status (adjusted OR 15.04, 95% CI 2.48–91.15, p = 0.03). COVID-19 vaccinations were administered to 85.7% of patients; 52.8% of whom contracted mild COVID-19. Most patients (71.4%) postponed clinic visits; 36% due to lockdowns and 28% due to concerns about COVID-19 exposure in healthcare settings. The majority of patients received telephone JIA management advice from rheumatologists during the lockdown (91.4%).ConclusionsThe COVID-19 pandemic and associated lockdown measures affected the care of JIA patients, impacting both physical and mental health. Nonadherence was a critical factor in disease flare-ups. Telemedicine is indispensable for patient care.

Prevalence and risk factors of depression in juvenile systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organ systems, including the central nervous system. Depression is one of the neuropsychiatric manifestations of juvenile SLE . Objective To estimate the prevalence of depressive disorders in juvenile SLE and identify its potential risk factors. Methods This cross-sectional study was conducted in juvenile SLE patients at Dr. Mohammad Hoesin General Hospital, Palembang. Sociodemographic data and medications were recorded. Disease activity of SLE was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Physical activity was measured using the Physical Activity Questionnaire for Children (PAQ-C) and the Physical Activity Questionnaire for Adolescents (PAQ-A). All subjects were screened for depression using the Childhood Depression Inventory (CDI) questionnaire. Multiple linear regression analyses were used to determine risk factors for depressive disorders. Results We included 72 patients, of whom 67 (93.1%) were female. Mean age of the patients was 12 years 4 months (SD 2 years 6 months); most (67; 93.1%) were 10-18 years of age. Depression was found in 24 patients (33.3%). SLEDAI scores of ?3 (flare) were found in 54 patients (75%) and low physical activity was found in 62 (86.1%) patients. The prevalence of depression based on the Children's Depression Inventory was 33.3%. A SLEDAI score of ?3 and low physical activity were significantly associated with depression (P=0.009 and P=0.025, respectively). On multiple linear regression analysis, only SLEDAI score of ?3 remained significantly associated with depression (P= 0.017; OR 12.6; 95%CI 1.6–101.7). Gender, age, family economic status, father's education, mother's education, family history of depression, and duration of illness were not associated with depression. Conclusion A SLEDAI score indicating flare (?3) and low physical activity are significantly associated with an increased risk of depression. A SLEDAI score is an independent risk factor for depression when all other significant risk factors are considered.

Profile of juvenile systemic lupus erythematosus patients with a special reference to monogenic lupus and lupus nephritis: a cross-sectional study.

To study the clinical, laboratory profile and outcome of juvenile Systemic Lupus Erythematosus (jSLE) patients at a tertiary care centre in South India. A retrospective review of the medical records of all jSLE patients visiting the Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, India from February 2017 to December 2023 was performed. The clinical characteristics, treatment and outcomes were recorded and tabulated. Seventy patients diagnosed with jSLE were included in the study. The female-to-male ratio was 4.4:1. Mean age at onset and delay in diagnosis were 120.1 (+/- 56.8) and 11.7 (+/- 22.7) months respectively. The median follow-up period was 13 months (range 4, 29 months). Nine patients presented with early onset SLE (< 5 years). Most common manifestations were constitutional symptoms (n = 56), followed by haematologic (n = 55), and mucocutaneous(n = 50) involvement. Immunological workup showed SLE-specific antibody positivity in 38 patients, hypocomplementemia in 40 patients, and anti-phospholipid antibody positivity in 13 patients. Mortality was observed in five patients with LN while there was no mortality in the non-nephritis group (p 0.004). C1q deficiency was the most common cause of monogenic lupus seen in 5/9 patients; protein kinase C delta (PRKCD) defect and chronic granulomatous disease (CYBB mutation) were seen in one patient each. We describe a large cohort of jSLE from Southern India. Lupus nephritis was noted in 35.7% of our cohort and had a direct correlation with mortality. 10% of patients had monogenic lupus. Serious infections were more frequent in patients with monogenic lupus.

Spatial Transcriptomics Identifies Cellular and Molecular Characteristics of Scleroderma Skin Lesions: Pilot Study in Juvenile Scleroderma.

Juvenile localized and systemic scleroderma are rare autoimmune diseases which cause significant disability and morbidity in children. The mechanisms driving juvenile scleroderma remain unclear, necessitating further cellular and molecular level studies. The Visium CytAssist spatial transcriptomics (ST) platform, which preserves the spatial location of cells and simultaneously sequences the whole transcriptome, was employed to profile the histopathological slides from skin lesions of juvenile scleroderma patients. (1) Spatial domains were identified from ST data and exhibited strong concordance with the pathologist's annotations of anatomical structures. (2) The integration of paired ST data and single-cell RNA sequencing (scRNA-seq) from the same patients validated the comparable accuracy of the two platforms and facilitated the estimation of cell type composition in ST data. (3) The pathologist-annotated immune infiltrates, such as perivascular immune infiltrates, were clearly delineated by the ST analysis, underscoring the biological relevance of the findings. This is the first study utilizing spatial transcriptomics to investigate skin lesions in juvenile scleroderma patients. The validity of the ST data was corroborated by gene expression analyses and the pathologist's assessments. Integration with scRNA-seq data facilitated the cell type-level analysis and validation. Analyses of immune infiltrates through combined ST data and pathological review enhances our understanding of the pathogenesis of juvenile scleroderma.

Evaluating Return to Sports After Surgical Treatment of Unstable Osteochondritis Dissecans of the Knee: A Systematic Review.

Although the incidence of osteochondritis dissecans (OCD) of the knee may be low, an overview and comparison of sports-related outcomes with current surgical management techniques are needed. To summarize the available evidence regarding outcomes for different surgical treatment options for unstable OCD of the knee in both skeletally mature and immature patients by calculating the return to sports (RTS) rate, the mean RTS time, and other sports-related postoperative outcome measures. Systematic review; Level of evidence, 4. A systematic review of studies on RTS after surgical correction of unstable OCD within the knee was conducted utilizing PubMed, Embase, and the Cochrane databases. Included were studies discussing the treatment of unstable OCD with minimum 1-year follow-up outcomes. Multivariate analysis was used to compare studies grouped together based on RTS and skeletal maturity. Of 2229 articles, 6 studies (197 patients; 198 knees) met the inclusion criteria and were included in our analysis. The percentage of patients who returned to the previous level of sport ranged from 52% to 100%; those returning to any level of sport ranged from 87% to 100%. Clinical outcomes did not differ between patients with open versus closed physes. Osteochondral Autograft Transfer System (OATS) procedures had a 100% RTS rate across several studies with skeletally mature and mixed cohorts, and microfracture had the lowest overall RTS rate (52%). For skeletally immature patients, all examined studies that utilized either open or arthroscopic reduction and internal fixation, 77% and 78%, respectively, had acceptable RTS rates. Arthroscopic fixation had a higher rate of revision surgery in both skeletally mature and immature patients. Our analysis indicated that the treatment of unstable OCD lesions using the OATS technique demonstrated high RTS rates across several studies, while microfracture alone exhibited the lowest RTS rate. Both arthroscopic and open internal fixation utilizing bioabsorbable screws yielded satisfactory RTS rates for juvenile patients with OCD.

A novel prediction score determining individual clinical outcome 3 months after juvenile stroke (PREDICT-score)

BackgroundJuvenile strokes (< 55 years) account for about 15% of all ischemic strokes. Structured data on clinical outcome in those patients are sparse. Here, we aimed to fill this gap by systematically collecting relevant data and modeling a juvenile stroke prediction score for the 3-month functional outcome.MethodsWe retrospectively integrated and analyzed clinical and outcome data of juvenile stroke and TIA patients treated at the LMU University Hospital, LMU Munich, Munich. Good outcome was defined as a modified Rankin Scale of 0–2 or return to baseline of function. We analyzed candidate predictors and developed a predictive model. Predictive abilities were inspected using Area Under the ROC curve (AUROC) and visual representation of the calibration. The model was validated internally.Results346 patients were included in the analysis. We observed a good outcome in n = 293 patients (84.7%). The prediction model for an unfavourable outcome had an AUROC of 89.1% (95% CI 83.3–93.1%). The model includes age NIHSS, ASPECTS, blood glucose and type of vessel occlusion as predictors for the individual patient outcome.ConclusionsHere, we introduce the highly accurate PREDICT-score for the 3-month outcome after juvenile stroke derived from clinical routine data. The PREDICT-score might be helpful in guiding individual patient decisions and designing future studies but needs further prospective validation which is already planned.Trial registration The study has been registered at https://drks.de (DRKS00024407) on March 31, 2022.

Association Between Childhood Asthma and Gastroesophageal Reflux Disease in Children: A Systematic Review.

This study aims to comprehensively investigate the association between childhood asthma and gastroesophageal reflux disease (GERD) in children. A thorough search of pertinent databases was done in order to find studies that satisfied the requirements for inclusion. A thorough search of PubMed, Web of Science, SCOPUS, and Science Direct was conducted to find pertinent literature. Twelve studies, including a total of 176,678 patients - 91,447 (51.8%) of them were males - were included in our data. The prevalence of GERD in asthmatic children ranged from 0.7% to 65.3%, with a total prevalence of 3317 (3.6%). The included studies documented that GERD increases the chance of asthma, while asthma raises the risk of GERD. Obesity in asthmatic patients was an independent risk factor for the incidence of GERD. Controlling asthma is significantly impacted by comorbidities like obesity and GRED. The findings of our comprehensive review point to a possible link between juvenile patients with asthma who are referred to secondary and tertiary care facilities and having GERD. Nevertheless, the evidence for this link is weak in a number of situations. Lack of longitudinal research establishing the proper temporal sequence, studies indicating no severity-response relationship, and insufficient data showing a treatment-response relationship all contribute to the uncertainty around the nature and direction of the association. Our findings highlight the need for additional epidemiologic research to investigate the connection between GERD and asthma, including long-term follow-up.

Functional status of Indian children with juvenile idiopathic arthritis.

The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Molecular Regulation of Bone Turnover in Juvenile Idiopathic Arthritis: Animal Models, Cellular Features and TNFα.

We review the abnormal bone turnover that is the basis of idiopathic inflammatory or rheumatoid arthritis and bone loss, with emphasis on Tumor Necrosis Factor-alpha (TNFα)-related mechanisms. We review selected data on idiopathic arthritis in juvenile human disease, and discuss mouse models focusing on induction of bone resorbing cells by TNFα and Receptor Activator of Nuclear Factor kappa B Ligand (RANKL). In both humans and animal models, macrophage-derived cells in the joint, particularly in the synovium and periosteum, degrade bone and cartilage. Mouse models of rheumatoid arthritis share with human disease bone resorbing cells and strong relation to TNFα expression. In humans, differences in therapy and prognosis of arthritis vary with age, and results from early intervention for inflammatory cytokines in juvenile patients are particularly interesting. Mechanisms that contribute to inflammatory arthritis reflect, in large part, inflammatory cytokines that play minor roles in normal bone turnover. Changes in inflammatory cytokines, particularly TNFα, are many times larger, and presented in different locations, than cytokines that regulate normal bone turnover. Recent data from in vitro and mouse models include novel mechanisms described in differentiation of bone resorbing cells in inflammatory arthritis dependent on the Transient Receptor Potential Channel (TRPC) family of calcium channels. Low-molecular weight (MW) inhibitors of TRPC channels add to their potential importance. Associations with inflammatory arthritis unrelated to TNFα are briefly summarized as pointing to alternative mechanisms. We suggest that early detection and monoclonal antibodies targeting cytokines mediating disease progression deserves emphasis.

Cellular Senescence-Related Long Non-coding RNA Signatures Predict Prognosis in Juvenile Osteosarcoma

AbstractOsteosarcoma is the most common malignant bone tumor and is frequently diagnosed in juvenile. Cellular senescence is a fundamental hallmark of osteosarcoma and plays a vital role in the initiation and progression of aging and tumorigenesis. Long non-coding RNAs (lncRNAs) are implicated in tumorigenesis. In this study, six cellular senescence-related lncRNAs with independent prognostic significance in juvenile osteosarcoma patients were identified through univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis. Prognostic significance was further confirmed by Kaplan–Meier (KM) survival curves, co-expression interaction networks, and sankey diagrams. A prognostic model of cellular senescence-related genes in juvenile osteosarcoma patients was then constructed using multivariate Cox regression analysis based on these six genes. High- and low-risk groups were identified according to the median risk score calculated by the prognostic model. The favorable prognostic significance of this model was demonstrated through survival curves, receiver operating characteristic (ROC) curves, distribution scatter plots and lncRNA expression heatmaps. Furthermore, cellular senescence-related lncRNAs were validated by enrichment analysis, immunological correlation analysis, m6A correlation analysis, and drug sensitivity correlation analysis. These findings are important for improving the prognosis of juvenile osteosarcoma patients and understanding the mechanisms underlying cellular senescence in juvenile osteosarcoma development.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups ( P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB ( R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Growth arrest-specific protein 6 as a marker of nephritis in systemic sclerosis and juvenile systemic lupus erythematosus patients.

Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.

Biochemical and molecular analysis of pediatric patients with metachromatic leukodystrophy in South China: functional characterization of five novel ARSA variants.

Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach.

Characteristics and management of juvenile type 2 diabetes mellitus

Background: Over the past two decades, there have been numerous reports on the increasing incidence of type 2 diabetes mellitus (T2DM) in children and adolescents. This trend, which parallels the increase in the prevalence and degree of pediatric obesity, is causing significant concern. This review focuses on the characteristics andcurrent management strategies for juvenile patients with T2DM. Current Concepts: Juvenile T2DM differs from type 1 diabetes mellitus (T1DM) in children and T2DM in adults as it is an aggressive disease with rapidly progressive β-cell decline, high treatment failure rate, and accelerated development of complications. Current management approaches include lifestyle changes such as improved diet and increased physical activity, and pharmacological interventions such as metformin, insulin, and liraglutide.Discussion and Conclusion: Early diagnosis and prevention of T2DM in children and adolescents are essential. Furthermore, compared to adults, there is still a lack of available treatment drugs or research in children and adolescents. Therefore, long-term research on the efficacy and safety of various drug treatments for T2DM in children and adolescents is required. Additionally, as it is often asymptomatic in its early stages, significant efforts by physicians are required for the early diagnosis and prevention of T2DM.