Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One Allele: A Phase 3, Open-Label Clinical Trial.

A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6-11 years with cystic fibrosis (CF) and one or more alleles. To assess long-term safety and efficacy of ELX/TEZ/IVA in children who completed the pivotal 24-week phase 3 trial. In this phase 3, two-part (part A and part B), open-label extension study, children aged ⩾6 years with CF heterozygous for and a minimal function mutation (/MF genotypes) or homozygous for ( genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight.

Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study.

Background: Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele. To assess long-term effects of ELX/TEZ/IVA under real-world conditions of use, a 5-year observational registry-based study is being conducted. We report interim results from the first 2 years of follow-up.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one allele but has not been studied in younger children. To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.

Screening and counseling for nicotine use in youth with diabetes.

Objective: To assess current practice patterns and identify knowledge gaps among pediatric endocrinologists in the United States regarding screening and counseling for combustible tobacco and e-cigarette use in youth with diabetes.

Introduction: Electronic cigarettes (e-cigarettes) are the most used tobacco product among adolescents and may be associated with an increased risk of progression to combustible cigarette smoking, cardiovascular disease, and stroke. Diabetes mellitus is a known risk factor for cardiovascular disease, and nicotine products can increase this risk.

Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells.

Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes. Although >85% of GIST patients treated with the small-molecule inhibitor imatinib mesylate (Gleevec) achieve disease stabilization, complete remissions are rare and a substantial proportion of patients develop resistance to imatinib over time. Upregulation of soluble, non-chromatin-bound histone H2AX has an important role in imatinib-induced apoptosis of GIST cells.

Soluble histone H2AX is induced by DNA replication stress and sensitizes cells to undergo apoptosis.

Background: Chromatin-associated histone H2AX is a key regulator of the cellular responses to DNA damage. However, non-nucleosomal functions of histone H2AX are poorly characterized. We have recently shown that soluble H2AX can trigger apoptosis but the mechanisms leading to non-chromatin-associated H2AX are unclear.

Analysis of centrosome overduplication in correlation to cell division errors in high-risk human papillomavirus (HPV)-associated anal neoplasms.

High-risk HPV-associated anal neoplasms are difficult to treat and biomarkers of malignant progression are needed. A hallmark of carcinogenic progression is genomic instability, which is frequently associated with cell division errors and aneuploidy. The HPV-16 E7 oncoprotein has been previously shown to rapidly induce centriole and centrosome overduplication and to cooperate with HPV-16 E6 in the induction of abnormal multipolar mitoses.