Pharmacological interventions for pediatric obstructive sleep apnea (OSA): Network meta-analysis.

IMPORTANCE: Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking. OBJECTIVE: This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population. DATA SOURCES: PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA. STUDY SELECTION: Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children. DATA EXTRACTION AND SYNTHESIS: Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839). MAIN OUTCOME(S) AND MEASURE(S): The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2). RESULTS: 17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %). CONCLUSIONS AND RELEVANCE: The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.

LncRNA MEG3 aggravates adipocyte inflammation and insulin resistance by targeting IGF2BP2 to activate TLR4/NF-κB signaling pathway.

Recently, emerging evidence has shown that LncRNA MEG3 is involved in adipocyte inflammation and insulin resistance progression, however, the specific mechanism of action remains unclear. In this study, we found that LncRNA MEG3 expression was increased in TNF-α stimulated 3T3-L1 mature adipocytes, and inflammatory factors IL-6 and MCP-1 secretion levels were increased, cell apoptosis and caspase3 activity was enhanced, ROS content was increased, and iNOS protein expression was increased. Moreover, TNF-α treatment attenuated glucose uptake, promoted triglyceride accumulation, inhibited GLUT4 protein expression at the plasma membrane, and reduced the phosphorylation levels of AMPK and ACC in the cells. Interestingly, we found that transfection of si-MEG3 reversed TNF-α caused inflammatory injury and insulin resistance of 3T3-L1 mature adipocytes. Next, we found that IGF2BP2 is an RNA binding protein of LncRNA MGE3 and transfection of si-IGF2BP2 reversed TNF-α caused inflammatory injury and insulin resistance in 3T3-L1 mature adipocytes, the same effects as transfection of si-MEG3. Mechanistically, LncRNA MGE3 was able to aggravate adipocyte inflammatory injury and dysregulation of insulin sensitivity by activating TLR4 pathway through upregulating the protein expression of IGF2BP2. In vivo findings showed that HFD mice with knockdown of MEG3 had reduced body weight, lower glucose concentrations and insulin levels in plasma, decreased inflammatory factors secretion, and reduced MEG3 and IGF2BP2 expression in epididymal adipose tissues and reduced fat accumulation in mice compared with HFD mice. Our results indicate that LncRNA MEG3 can aggravate chronic inflammation and insulin resistance in adipocytes by activating TLR4/NF-κB signaling pathway via targeting IGF2BP2.

Early-life weight gain patterns of term small-for-gestational-age infants and the predictive ability for later childhood overweight/obesity: A prospective cohort study.

Objectives: We aimed to identify the weight gain patterns of small-for-gestational age (SGA) infants in early life and to explore the predictive value for later overweight/obesity in childhood. Methods: We obtained data from a prospective cohort including term SGA infants born between January 2006 and November 2015 who received regular health care from birth to 5 years in West China Second University Hospital, Chengdu, China. A latent class growth analysis (LCGA) was applied to group children with similar growth trajectory patterns. Multiple logistic regression was performed to examine the association between weight gain patterns and later overweight/obesity. Results: A total of 296 term SGA infants were finally included. Five weight gain trajectories were identified, including excessive rapid catch-up growth (ERCG) (class 1, 10.9%), rapid catch-up growth (RCG) (class 2, 17.9%), appropriate catch-up growth (ACG) (class 3, 53.0%), slow catch-up growth (SCG) (class 4, 13.4%) and almost no catch growth (NCG) (class 5, 4.8%). SGA infants in class 1 and class 2 had a higher BMI according to age- and sex-specific Z scores from 2-5 years of age. In addition, 25% of SGA infants in class 1 and 13.2% of SGA infants in class 2 were found to be overweight/obese at 2-5 years of age. After adjusting for confounders, we found that extremely rapid weight gain (class 1) in the first 2 years of life increased the risk of overweight/obesity by 2.1 times at 2 to 5 years of age (aOR=2.1, 95% CI: 1.3~4.8; P<0.05). Furthermore, the increment of ΔWAZ between 0 and 4 mo was prominently related to the risk of overweight/obesity at 2 to 5 years for term SGA infants (aOR=3.2, 95% CI: 1.7~8.1; P<0.001). A receiver operating characteristic (ROC) curve showed the area under curve (AUC) was 0.7, with a 95% confidence interval (CI) from 0.6 to 0.8 (P<0.001). Conclusions: The extremely rapid weight gain pattern of term SGA infants in the first 2 years of life increased the risk of overweight/obesity at 2 to 5 years of age. It suggests monitoring weight gain across the infant period represents a first step towards primary prevention of childhood obesity.

SLC10A2 deficiency-induced congenital chronic bile acid diarrhea and stunting.

BACKGROUND: Diarrhea is a common occurrence in children below the age of 5 years. In chronic cases, it induces malnutrition that severely stunts growth. Bile acid diarrhea (BAD), caused by malabsorption of bile acid (BA), is a rare form of chronic diarrhea seldom observed in pediatric patients. Here, we present a clinical report on a novel case of chronic BAD, with severe stunting in an infant, induced by a homozygous mutation of SLC10A2. METHODS: We performed DNA extraction, whole-exome sequencing analysis, and mutation analysis of SLC10A2 to obtain genetic data on the patient. We subsequently analyzed the patient's clinical and genetic data. RESULTS: The patient's clinical manifestations were chronic diarrhea with increased BAs in the feces and extreme stunting, which was diagnosed as BAD. A homozygous mutation of SLC10A2 at the c.313T>C (rs201206937) site was detected. CONCLUSION: Our report reveals the youngest case illustrating the characteristics of BAD induced by genetic variant at 313T>C, and the second case entailing a clear association between a SLC10A2 genetic mutation and the onset of BAD. Our findings expand the mutant spectrum of the SLC10A2 gene and contribute to the refinement of the genotype-phenotype mapping of severe stunting induced by pediatric BAD. Moreover, they highlight the value of molecular genetic screening for diagnosing BAD in young patients.

Clinical manifestations of Kawasaki disease in different age groups: retrospective data from Southwest China.

OBJECTIVES: The aim of the present study is to identify the clinical manifestations and laboratory findings of children with Kawasaki disease (KD) in different age groups and to recognize and treat KD in a timely manner. METHODS: A total of 213 children with KD were divided into the following age groups: (1) infants, (2) toddlers, and (3) preschool age. Retrospective analysis of clinical data was performed among the groups. Categorical data were statistically compared by Chi-square analysis, and measurement data were compared using one-way ANOVA analysis. RESULTS: Our study showed that (1) cough (40.5%), diarrhea (16.9%), and vomiting (8.5%) were also very common in KD patients. (2) Patients in the infant group more commonly developed cough and diarrhea, but were less frequently documented with lymphadenopathy and skin rash. (3) Elevation of platelets was more common in the infant group. When urine tests were compared among the three groups, the toddler group had a higher proportion of sterile pyuria, and infants younger than 1 year old had a lower proportion of proteinuria and positive urine ketones. CONCLUSION: Cough, diarrhea, vomiting, and sterile pyuria were very common in infant KD patients less than 1 year old. They should be noted in patients with suspected KD for earlier diagnosis and timely treatments. Key Points • Patients with Kawasaki disease (KD) in different age groups showed different clinical manifestations and laboratory findings. • Cough, diarrhea, vomiting, and sterile pyuria were very common in infant KD patients less than 1 year old. • Paying more attentions to respiratory, gastrointestinal, and urinary manifestations or abnormalities might be helpful for earlier diagnosis of KD, especially incomplete KD, though they were not list in the diagnostic criteria.

Acute myelitis of children with positive anti-GM1 antibody: Case series and literature review.

RATIONALE: To explore the clinical features, treatment, and prognosis of acute myelitis (AM) of children with positive blood anti- ganglioside (GM1) antibodies. PATIENT CONCERNS: Two cases of AM of children with positive anti-GM1 antibody were retrospectively collected and followed up for 6 months. Two cases had positive helicobacter pylori IgG antibody, and Case 2 also had positive mycoplasma IgM antibody. DIAGNOSES: Two cases had typical symptoms of myelitis, abnormal spinal magnetic resonance imaging (MRI), and positive serum anti-GM1 IgM. INTERVENTIONS: They were treated with steroid, immunoglobulin and rehabilitation. OUTCOMES: Symptoms of AM were relieved after treatment. After 6 months of follow-up, case 1 was fully recovered and case 2 was partially recovered. Summarizing previous reports in literature and our 2 cases, AM with positive anti-GM1 antibody can be induced by multiple pathogen infections. About 35.7% were fully recovered, 42.9% had mild sequelae, and 21.4% had severe sequelae. LESSONS: Post-infection immune injury plays an important role in the pathogenesis of AM with positive anti-GM1 antibody. H pylori and Mycoplasma pneumoniae infection may also induce AM with positive anti-GM1 antibody. Screening and treatment of pathogens were required and only 21.4% patients had severe sequelae after treatment.

Plasma exchange successfully treated macrophage activation syndrome in rheumatoid factor-positive polyarticular juvenile idiopathic arthritis with co-existing pneumonia.

Macrophage activation syndrome (MAS) is one of the serious complications associated with rheumatic diseases, especially systemic juvenile idiopathic arthritis (sJIA). Here we describe a 9-year-old girl with rheumatoid factor (RF)-positive polyarticular JIA, not sJIA, combined with pneumonia who was successfully treated by plasma exchange. She was diagnosed with RF-positive polyarticular JIA based on positive RF and multiple joint swelling and tenderness 3 years ago. She was admitted in our hospital with myalgia for 2 days and a high fever for half a day. Physical examination revealed relapsing joints symptoms and rough breathing sounds of lungs. The laboratory examination showed increased liver enzymes, elevated serum ferritin and procalcitonin (PCT), decreased percentage of nature killer (NK) cells and fibrinogen, and activated macrophage phagocytosing hematopoietic elements in bone marrow. The elevated PCT and chest computed tomography scan confirmed she also had pneumonia. Intravenous methylprednisolone and oral cyclosporine A followed by intravenous immunoglobulin were added on the basis of antibiotics therapy, but clinical symptoms and laboratory findings did not improve. Finally, we changed to plasma exchange once every other day for a total of three times. Within 1 week, the girl recovered from the MAS completely.

[Efficacy of different doses of recombinant human growth hormone in the treatment of short stature in children born small for gestational age].

OBJECTIVE: To investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA). METHODS: A total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups. RESULTS: ΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function. CONCLUSIONS: rhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.