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Summary: Background: Growing evidence indicates that incretin‐based therapies (IBTs), glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), and dipeptidyl peptidase‐4 inhibitors (DPP4is) are effective and safe for treating pediatric obesity patients with or without type 2 diabetes. Therefore, we aimed to perform a systematic review and meta‐analysis for updating current evidence. Methods: We searched the PubMed, the Cochrane Library, and the EMBASE database for articles published until September 15, 2023, and limited to randomized control trials. The primary outcomes were changed from baseline in weight metrics and the cardiometabolic profile. A random effects model will be used, as high heterogeneity is expected. All analyses were performed using STATA 17.0. Results: Fifteen trials with a total number of 1286 participants were included in our meta‐analysis. Overall, the mean difference in weight change between the IBTs group and the control group was −2.89 kg (95% confidence interval, −5.12 to −0.65, p = 0.011). Additionally, IBTs significantly reduced the HbA1c level and fasting plasma glucose by 0.37% and 6.99 mg/dl, compared with control groups. IBTs showed a little increased risk of GI side effects and hypoglycemia events, but none of the severe hypoglycemia events were occurred in IBTs group. Conclusions: Our study results have proved that GLP‐1 RAs are safe, acceptable, and effective in weight reduction and sugar control for children with obesity. In addition, DPP‐4is seems to have no effect on glycemic control and weight loss in childhood obesity. Further research is needed to confirm these findings, especially in younger children. [ABSTRACT FROM AUTHOR]

Aim: A population pharmacokinetic (PPK) study of the correlation of adverse drug reactions (ADRs) with the 3HP regimen (weekly high‐dose rifapentine plus isoniazid for 12 doses) for latent tuberculosis infection (LTBI) remains lacking. The purpose of this study is to determine the association of rifapentine or isoniazid concentration and ADRs. Methods: This prospective, multicentre, observational study enrolled LTBI contacts receiving 3HP treatment between January 2017 and August 2020. The concentrations of rifapentine, isoniazid and their metabolites (25‐desacetyl‐rifapentine and acetyl‐isoniazid) in plasma samples collected monthly after 3HP treatment were determined. A PPK model was constructed to predict the maximum concentration (Cmax) and area under the concentration–time curve from 0 to 24 h (AUC). Their association with ADRs was evaluated by applying three multivariate logistic regression models with adjustment for various covariates. Results: A total of 415 LTBI cases were ultimately enrolled; 355 (85.5%) completed the 3HP treatment. Among them, 47 (11.3%) experienced systemic drug reactions and 291 (70.0%) experienced one or more flu‐like symptom. The plasma concentration–time profiles of isoniazid, rifapentine and their metabolites were adequately described by the developed models. A higher Cmax of isoniazid was significantly correlated with a higher risk of any ADR (adjusted odds ratio and 95% confidence interval: 3.04 [1.07–8.65]) and any or at least two flu‐like symptoms (all severity grades) (2.76 [1.06–7.17]). Conclusions: Isoniazid may be responsible for ADRs, especially flu‐like symptoms, during 3HP treatment. [ABSTRACT FROM AUTHOR]

Rac GTPases act as molecular switch in various morphogenic events. However, the regulation of their activities during the development of multicellular organisms is not well understood. Caenorhabditis elegans rac genes ced-10 and mig-2 have been shown to act redundantly to control P cell migration and the axon outgrowth of D type motoneurons. We showed that ced-10 and mig-2 also control amphid axon outgrowth and amphid dendrite fasciculation in a redundant fashion. Our biochemical and genetic data indicate that unc-73, which encodes a protein related to Trio-like guanine nucleotide exchange factor, acts as a direct activator of ced-10 and mig-2 during P cell migration and axon outgrowth of D type motoneurons and amphid sensory neurons. Furthermore, rac regulators ced-2/crkII and ced-5/dock180 function genetically upstream of ced-10 and mig-2 during axon outgrowth of D type motoneurons and act upstream of mig-2 but not ced-10 during P cell migration. However, neither ced-2/crkII nor ced-5/dock180 is involved in amphid axon outgrowth. Therefore, distinct fac regulators control ced-10 and mig-2 differentially in various cellular processes. Key Words: axon outgrowth; cell migration; guanine nucleotide exchange factor; rac; ced-2; ced-5; ced-10; ced-12; mig-2; unc-73.

Background: Survival after post-transplant recurrence of HCC is dismal, and almost all treatments for recurrent HCC are off-labeled, without an extensive large-scale analysis. We aimed to delineate their post-recurrence courses and define benchmarks for comparing future treatment effectiveness. Methods: Three national databases, including health insurance, catastrophic illness, and the cause of death, were linked for cohort establishment and data collection during the period from 2005 to 2016. Patients with HCC recurrence ≥6 months after transplant surgery and under treatment were recruited for survival analysis. Selection of treatment strategies for HCC recurrence after liver transplant was based on the same criteria for those without liver transplant. Results: Of 2,123 liver transplant recipients, 349 developed HCC recurrence ≥6 months after liver transplant, and the median recurrence time was 17.8 months post-transplant. Within 2 years of treatment, 61% patients showed recurrence (early recurrence group), and survival in these patients was poorer than in the late recurrence group. According to a multivariable analysis, the transplant era before 2008 and radiofrequency ablation were associated with good prognosis, whereas receiving sorafenib and radiotherapy was associated with poor prognosis. The effect of transplant era became insignificant after stratification by recently receiving pretransplant transarterial chemoembolization. Conclusion: Timing of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration. [ABSTRACT FROM AUTHOR]