Safety and efficacy of ivacaftor in infants aged 1 to less than 4 months with cystic fibrosis.

Background: Ivacaftor (IVA) has been shown to be safe and efficacious in children aged ≥4 months with cystic fibrosis (CF) and CFTR gating variants. We evaluated safety, pharmacokinetics (PK), and efficacy of IVA in a small cohort of infants aged 1 to <4 months with CF.

Methods: In this phase 3, open-label study, infants 1 to <4 months with CF and an IVA-responsive CFTR variant received an initial low dose of IVA based on age and weight.

Long-term tezacaftor/ivacaftor safety and efficacy in people with cystic fibrosis and an F508del-CFTR mutation: 96-week, open-label extension of the EXTEND trial.

Background: Study 661-110 (EXTEND) is a phase 3, open-label, three-part rollover study designed to assess the long-term safety and efficacy of tezacaftor/ivacaftor (TEZ/IVA) in participants aged ≥12 years homozygous for F508del (F/F) or heterozygous for F508del and a residual function mutation (F/RF). TEZ/IVA was shown to be safe and efficacious for up to 120 weeks in Part A. Here we report results from Part B, which evaluated safety and efficacy for an additional 96 weeks.

A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children ≥ 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant.

Background: Two previous Phase 3 studies ("parent studies") showed that tezacaftor/ivacaftor was generally safe and efficacious for up to 24 weeks in children 6 through 11 years of age with cystic fibrosis (CF) and F508del/F508del (F/F) or F508del/residual function (F/RF) genotypes. We assessed the safety and efficacy of tezacaftor/ivacaftor in an open-label, 96-week extension study.

Methods: This was a Phase 3, 2-part, multicenter, open-label, extension study in children 6 through 11 years of age at treatment initiation (Study VX17-661-116; NCT03537651).

Synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma in a patient with severe and long-standing hyperparathyroidism.

Objective: To describe a patient presenting with the rare constellation of synchronous parathyroid carcinoma, parathyroid adenoma, and papillary thyroid carcinoma.

Methods: We summarize the clinical presentation, diagnostic work-up, surgical management, and pathologic features of our patient and review the pertinent literature.

Results: The patient was a 59-year-old man who presented with severe clinical manifestations of long-standing primary hyperparathyroidism, a serum calcium concentration of 14.

Thyroid function in the critically ill newborn and child.

Purpose Of Review: Here we review typical thyroid function alterations observed in the critically ill pediatric patient.

Recent Findings: Abnormalities in the hypothalamic-pituitary-thyroid axis have recently been confirmed to be prevalent in similar proportions in pediatric and adult patients. Significant benefits of therapy have yet to be demonstrated.

Insulin signaling in alpha cells modulates glucagon secretion in vivo.

Glucagon plays an important role in glucose homeostasis by regulating hepatic glucose output in both normo- and hypoglycemic conditions. In this study, we created and characterized alpha cell-specific insulin receptor knockout (alphaIRKO) mice to directly explore the role of insulin signaling in the regulation of glucagon secretion in vivo. Adult male alphaIRKO mice exhibited mild glucose intolerance, hyperglycemia, and hyperglucagonemia in the fed state and enhanced glucagon secretion in response to L-arginine stimulation.

Cell polarity protein Spa2P associates with proteins involved in actin function in Saccharomyces cerevisiae.

Spa2p is a nonessential protein that regulates yeast cell polarity. It localizes early to the presumptive bud site and remains at sites of growth throughout the cell cycle. To understand how Spa2p localization is regulated and to gain insight into its molecular function in cell polarity, we used a coimmunoprecipitation strategy followed by tandem mass spectrometry analysis to identify proteins that associate with Spa2p in vivo.

Peripheral keratitis associated with erythema elevatum diutinum.

Purpose: To describe a case of peripheral keratitis associated with erythema elevatum diutinum (EED), an unusual immune-complex-mediated cutaneous vasculitis.

Design: Observational case report.

Methods: A 25-year-old man who was diagnosed 15 months previously with erythema elevatum diutinum presented with an inflammatory peripheral keratitis of the left eye.