BACKGROUND:Sustained seizure freedom without intolerable adverse events is the main goal of epilepsy treatment, but may be challenging to achieve for some patients, particularly following the failure of multiple anti-seizure medications (ASMs). A majority of days without seizures is another important clinical outcome that can lead to meaningful improvement in quality of life. The objective of this post-hoc analysis was to evaluate the percentage of seizure-free days by responder groups during the open-label extension (OLE) of study C017 with a focus on patients who achieved near-seizure freedom that was sustained during the duration of the study (≥ 90%-< 100% responders group). The study also evaluated retention rates and the impact of concomitant antiseizure medications. METHODS:Study C017 (NCT01866111) was a double-blind, randomized, placebo-controlled, dose-response trial evaluating adults 18-70 years old who were taking 1-3 concomitant ASMs. Participants completed the 18-week double-blind treatment period and entered the OLE. This post-hoc analysis quantified the proportion of seizure-free days by responder category and by number and type of concomitant ASMs. The occurrence and severity of treatment-emergent adverse events during the OLE were also reported. RESULTS:Sixty (16.9%) of the 354 study participants were ≥ 90%-< 100% responders (median age 42.5 years, 46.7% [n = 28] female, median number of concomitant ASMs at baseline was 2). The study population also included 91 (25.7%) patients who were ≥ 50%-< 75% responders, 62 (17.5%) patients who were ≥ 75%-< 90% responders, and 13 (3.7%) patients who were 100% responders. The median duration of cenobamate exposure was 5.6 years for the ≥ 90%-< 100% responders; 1.8 years for the non-responders; 5.5 years for the ≥ 50%-< 75% responders; 5.5 years for the ≥ 75%-< 90% responders; and 5.6 years for the 100% responders. The percentage of seizure-free days during the entire OLE was 97.9% in the ≥ 90%-< 100% responder group, compared to 93.5% in the ≥ 75%-< 90% group and 83.9% in the ≥ 50%-< 75% group. The number and mechanism of action of concomitant ASMs did not meaningfully impact the proportion of days without seizures. The percentage of days with seizures in the ≥ 90%-< 100% responder group declined from 33.2% at baseline to 1.2% at Year 5. At Year 5, the ≥ 90%-< 100% responder group had a high retention rate (90%). The most commonly occurring adverse events were dizziness, somnolence, and headache. CONCLUSIONS:Participants taking cenobamate who achieved ≥ 90%-< 100% responder rates were seizure-free for nearly 98% of days during the 5 years of the OLE. These results suggest that a high reduction of seizure burden can be achieved and maintained by many people with epilepsy taking cenobamate.
To assess 2-year biochemical control, radiological progression, late side effects, and survival outcomes following stereotactic body radiotherapy (SBRT) for localized prostate cancer in a multicenter Spanish cohort. A total of 250 patients with localized prostate cancer treated with SBRT across 12 Spanish centers between January 2020 and December 2023 were analyzed. Biochemical recurrence was defined according to the Phoenix criterion (nadir PSA + 2 ng/mL). Late genitourinary (GU), gastrointestinal (GI), and sexual adverse events were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Univariate and multivariate analyses were performed to identify factors associated with outcomes. Survival was estimated using the Kaplan–Meier method and the log-rank test (p < 0.05). The median age was 72 years (IQR: 65–76), and the median baseline PSA was 6.7 ng/mL (5.3–8.7). According to the NCCN classification, 30
A T-shaped uterus is a uterine malformation, which can be either congenital or acquired, potentially impairing fertility and increasing the risk of miscarriage. Diagnosis primarily relies on three-dimensional ultrasound and hysteroscopy. Hysteroscopic metroplasty is the standard surgical intervention aimed at restoring normal uterine anatomy and potentially improving reproductive outcomes. This narrative review, conducted in accordance with SANRA (Scale for the Assessment of Narrative Review Articles) guidelines, is based on a comprehensive database search and critically evaluates observational and interventional studies on the definition, diagnosis, and management of T-shaped uterus in the context of in vitro fertilization. Recent studies indicate that correction of this anomaly might not only improve spontaneous conception rates but also enhance the outcomes of IVF. However, the precise role of metroplasty in patients undergoing IVF outcomes remains controversial. Some evidence indicates that surgical correction might improve embryo implantation and endometrial perfusion. Despite these promising observations, randomized controlled trials are necessary to define optimal patient selection criteria and to confirm the true benefit of metroplasty in the context of IVF. Future research should also address the potential risks associated with the procedure. A standardized diagnostic and therapeutic approach might contribute to improved reproductive outcomes in affected patients.
Fenfluramine (FFA) is approved as an adjunctive treatment for epileptic seizures associated with Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) in patients aged 2 years and older. Owing to its pharmacological characteristics and history of cardiovascular adverse effects, specific cardiological monitoring is required throughout the course of treatment. A set of recommendations for FFA was developed by a multidisciplinary panel comprising specialists in neurology/paediatric neurology, epilepsy, and cardiology (both adult and paediatric). The process involved a literature review, methodological design, working group sessions, and preparation of recommendations structured around three key phases: before treatment, during treatment, and after treatment discontinuation. An expert-led algorithm for the use of FFA was developed, helping to establish a common language that promotes a better understanding between cardiologists and neurologists/paediatric neurologists, facilitating the prevention and early management of potential cardiovascular events. The management of FFA treatment should be holistic, with coordinated follow-up involving neurologists, paediatric neurologists, and cardiologists. Implementing a structured, expert-based protocol will help enhance treatment safety and optimize clinical outcomes for patients with developmental and epileptic encephalopathies.
Introdução: O alendronato (ALN) é um bisfosfonato usado na prática clínica para reduzir as consequências adversas de condições ósseas patológicas. Objetivo: Investigar os efeitos da administração de alendronato (ALN) na imunoexpressão de Na+K+ATPase e v-ATPase na mucosa das vias aéreas superiores e no bulbo olfativo de ratos. Método: Dezesseis animais foram distribuídos igualmente em grupos controle e experimental, com estes últimos recebendo doses diárias intraperitoneais de ALN (2,5 mg/kg). Após sete dias, os ratos foram eutanasiados e suas cabeças processadas para avaliação histológica e quantificação imunohistoquímica de ambas as bombas de prótons alvo para avaliar a integridade estrutural do tecido. Resultados -. Amostras tratadas com ALN apresentaram diminuição da presença de Na+K+ATPase e v-ATPase tanto no epitélio respiratório quanto no bulbo olfatório. Esses achados coincidiram com vacuolização e perda de polaridade dentro do epitélio respiratório, juntamente com profunda degeneração celular no bulbo olfatório. Conclusão: A administração de alendronato pode alterar a histomorfologia do epitelial respiratório, comprometendo adicionalmente a integridade do bulbo olfatório devido à regulação negativa da expressão de Na+K+ATPase e de v-ATPase.
