Durable suppression of seizures in a preclinical model of KCNT1 genetic epilepsy with divalent small interfering RNA.

Objective: Gain-of-function variants in the KCNT1 gene, which encodes a sodium-activated potassium ion channel, drive severe early onset developmental epileptic encephalopathies including epilepsy of infancy with migrating focal seizures and sleep-related hypermotor epilepsy. No therapy provides more than sporadic or incremental improvement. Here, we report suppression of seizures in a genetic mouse model of KCNT1 epilepsy by reducing Kcnt1 transcript with divalent small interfering RNA (siRNA), an emerging variant of oligonucleotide technology developed for the central nervous system.

Assessing Second Trimester Ferning in Diagnosing Preterm Prelabor Rupture of Membranes.

Preterm prelabor rupture of membranes (PPROM) diagnosis is made through visualization of amniotic fluid (pooling), nitrizine testing, sonographic low amniotic fluid, and microscopic detection of amniotic fluid arborization (ferning). Data exits on the specificity and sensitivity of ferning detection but has not focused on the second trimester. Our objective is to evaluate the presence of ferning in transvaginally collected amniotic fluid in pregnancies with known second trimester PPROM to determine if there is a difference in ferning based on gestational age and sample drying time.

Patients With Shoulder Labral Tears Search the Internet to Understand Their Diagnoses and Treatment Options.

Purpose: To analyze the most frequently searched questions associated with shoulder labral pathology and to evaluate the source-type availability and quality.

Methods: Common shoulder labral pathology-related search terms were entered into Google, and the suggested frequently asked questions were compiled and categorized. In addition, suggested sources were recorded, categorized, and scored for quality of information using JAMA benchmark criteria.

Patient-Reported Outcomes for Low-Risk Ductal Carcinoma In Situ: A Secondary Analysis of the COMET Randomized Clinical Trial.

Importance: Active monitoring (AM) for low-risk ductal carcinoma in situ (DCIS) has been considered as a potential alternative to guideline-concordant care (GCC; inclusive of surgery with or without radiation). Reported data comparing patient-reported outcomes (PROs) between GCC and AM for DCIS are lacking.

Objective: To compare PROs at baseline and over time in patients with low-risk DCIS randomized to receive either AM or GCC.

Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial.

Importance: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.

Objective: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care.

Design, Setting, And Participants: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023.