Citations

Abstract Objective To assess the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) stratified by age, number of previously attempted antiseizure medications (ASMs), and SCN1A pathogenic variant status. Methods In this post hoc analysis, data from three randomized controlled trials (RCTs) in patients with DS (2–18 years) were pooled and stratified by age (<4; ≥4 years), number of previous ASMs (1–3; 4–6; ≥7), and SCN1A pathogenic variant status ( SCN1A +; SCN1A −). Stratified groups were assessed and compared with the pooled placebo group (change in monthly convulsive seizure frequency [MCSF], longest convulsive seizure‐free interval, and Clinical Global Impression–Improvement [CGI–I] scale scores rated by parents/caregivers and investigators), and safety (treatment‐emergent adverse events [TEAEs]: frequency, days to onset, and proportion resolved). Results Among 348 patients included in the RCTs, 216 were randomized to fenfluramine (0.7 mg/kg/day, n = 88; 0.4 mg/kg/day [with stiripentol], n = 43; 0.2 mg/kg/day, n = 85) and 132 to placebo. Compared with placebo, fenfluramine treatment (all doses combined) resulted in greater MCSF reductions, greater increases in longest convulsive seizure‐free intervals, and a higher proportion of parents/caregivers and investigators reporting clinically meaningful improvement (“Much Improved”, “Very Much Improved”) on CGI–I scores across all stratified groups. CGI–I scores were consistent across fenfluramine doses in most stratified groups, but patients with the fewest number of previous ASMs had the greatest frequency of clinically meaningful improvement on investigator‐rated CGI–I scores. Safety outcomes were similar across all strata. Most TEAEs resolved by end‐of‐study. Significance Fenfluramine treatment was associated with improved seizure outcomes and global functioning compared with placebo regardless of age, number of previous ASMs, and SCN1A status in patients with DS. Fenfluramine was well‐tolerated; no new safety signals were identified. Further studies with larger sample sizes (including adults) and a priori inferential analyses of stratified groups are warranted. Plain Language Summary Patients with Dravet syndrome struggle with seizures and everyday life. In three studies, patients aged 2–18 years received fenfluramine or placebo (sugar pill). Fenfluramine lowered seizures without many side effects. Researchers combined results from these studies to see how fenfluramine worked in different patient groups based on age, number of previous medications, and a gene called SCN1A . They looked at seizure reduction and whether doctors felt patients had improved. In all groups, fenfluramine worked better than placebo, with similar side effects. Researchers believe fenfluramine helped these patients, but some groups were small, so these results need to be confirmed.

Background : Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality. Optimal treatment decisions are challenging, and existing treatment allocation frameworks may not fully reflect the evolving therapeutic landscape or contemporary clinical practices in North America. Methods : Using a modified Delphi process, a multidisciplinary panel of 20 North American experts in hepatology, medical oncology, surgery, radiology, and radiation oncology developed a consensus-based treatment framework for HCC, termed the BEACON-HCC system. The framework was informed by current evidence and expert opinion through iterative discussion and voting. In a pilot study using 29 real-world patient cases, we assessed concordance between external expert recommendations and BEACON-HCC recommendations and Barcelona Clinic Liver Cancer (BCLC) 2025 treatment recommendations. Results : The BEACON-HCC treatment allocation framework diverges from prior frameworks by incorporating nuanced clinical features such as degree of intrahepatic tumor burden and vascular invasion, and adverse tumor prognostic markers, to align treatment allocation with tumor biology and therapeutic potential. Key innovations include the incorporation of emerging modalities such as external beam radiation therapy (EBRT), transarterial radioembolization (TARE), and systemic-locoregional combination therapies. In the pilot exercise, expert treatment decisions showed 96.6% concordance with BEACON-HCC recommendations and 72.4% concordance with BCLC recommendations. Conclusions : BEACON-HCC is a consensus-based framework for treatment allocation that incorporates the expanding range of therapeutic options available to patients in the North American HCC population. Expert treatment decisions showed a high concordance with the BEACON-HCC system; further validation using empiric clinical data is planned through the HCC-Live Consortium.

Abstract INTRODUCTION Associations of arterial stiffness, measured through pulse wave velocity (PWV), with incident dementia may be driven by age‐related structural changes to the arterial wall or by elevated blood pressure. METHODS Dementia‐free White or Black participants in the community‐based Atherosclerosis Risk in Communities (ARIC) cohort study with measures of PWV were examined. The associations of carotid‐femoral PWV (cfPWV) and total, structural, and load‐dependent PWV with dementia were estimated using Poisson regression models and Cox proportional hazards models. Dementia cases were defined by physician‐adjudicated review, telephone interviews, hospitalization records, and death certificates. RESULTS Of 4818 participants included in the study population (mean age: 75 years; 41% male, 21% Black), 1067 (22%) developed dementia over a median follow‐up of 9.0 years. Higher cfPWV, total PWV, structural PWV, and load‐dependent PWV were associated with greater dementia risk. DISCUSSION Both structural and pressure‐related arterial stiffness mechanisms may underlie the link between PWV and dementia.

Abstract Background: Glioma diagnosed during pregnancy and pregnancy following glioma treatment present complex management challenges. The safety of glioma treatment during pregnancy is not well established. The ability to counsel patients on timing of conception after treatment remains limited. The aim of this study was to review our institution’s experience with glioma during and before pregnancy. Methods: In this single-institution study, we retrospectively identified patients diagnosed with glioma during or prior to pregnancy and reviewed treatment course and maternal and neonatal outcomes. Results: Twenty-one female patients were included in our study. Glioma diagnoses included 12 high-grade tumors and 9 low-grade tumors. Cohort A consisted of 8 patients who presented with glioma during pregnancy, of which, 7 underwent glioma treatment during pregnancy. All pregnancies in cohort A were without significant maternal complications and resulted in delivery of a healthy neonate. Cohort B consisted of 13 patients who experienced pregnancy after a prior diagnosis of glioma, totaling 23 pregnancies. Antepartum course was complicated by seizure in three pregnancies. Functionally inconsequential anatomic abnormalities in childhood offspring of cohort B occurred in 5 (27.8%) of the pregnancies. Four of the offspring with anatomic abnormalities had exposure to TMZ prior to conception. Conclusions: In this retrospective series, diagnosis of glioma before or during pregnancy was associated with generally favorable maternal, fetal and childhood outcomes. We observed a higher-than-expected rate of anatomic abnormalities in the post-diagnosis cohort, though none carried meaningful functional consequences. These findings add to the limited literature exploring maternal and fetal outcomes in patients with glioma.

Abstract Objectives This study used both researcher and patient perspectives to identify high-priority research questions related to clinical reasoning. Methods This study integrates findings from two previously published research prioritization exercises aimed at advancing the science of diagnostic safety, focusing on questions relevant to clinical reasoning. In Study 1 (April 2019), 97 researchers submitted 177 unique research questions that could be useful “to reduce patient harm in the diagnosis process”. In Study 2 (November 2019), 41 patients/caregivers/advocates submitted 84 unique research questions on the same topic. In an in-person meeting, a subset of these participants identified 81 of these questions as high-priority (51 from Study 1; 30 from Study 2). For the current study, five investigators identified questions that focused on clinical reasoning, first independently and then by consensus. They then categorized the clinical reasoning questions into inductively identified themes. Results Twenty-nine of the 81 high-priority research questions addressed clinical reasoning and were categorized into 5 themes: understanding clinical reasoning and cognition (12 questions), decision support/technology (6 questions), team-based decision making (5 questions), how to learn from cases/scenarios (3 questions), and patient engagement (3 questions). Questions addressed a range of basic/foundational science and clinical applications, and involved individuals, teams, and/or systems. Conclusions Identification of high-priority clinical reasoning research questions can help medical educators, clinicians, researchers, and funders catalyze research and discovery of interventions to improve clinical reasoning and ultimately improve patient outcomes.

Background: We describe an investigation of a cluster of eight Corynebacterium amycolatum sternal surgical site infections (SSIs) that occurred among cardiac surgery patients from February to October 2025. Although C. amycolatum is a member of the skin microbiota, clinically significant infections caused by this organism may occur in cardiac surgery patients. Methods: The investigation included retrospective reviews of SSIs, clinical cultures and medical records, surgical observations, and operating room (OR) assessment. Line lists of surgical case criteria and infection prevention practices were created to assess common factors among cases (e.g., staffing, instrumentation, equipment, skin preparation and antisepsis, nasal decolonization, antibiotic protocols, and closure). Whole genome sequencing of isolates was performed and analyzed using SNIPPY for single-nucleotide polymorphism (SNP)-based phylogenetic analysis. Results: Phylogenetic analysis indicated isolates from five of eight case patients who had cardiac surgeries occurring over a six-week period from February to April 2025 were genetically related (?7 SNPs across the genome), suggesting a common source of infection. These five isolates were ceftriaxone, meropenem, and penicillin resistant. The other three case patient isolates were unrelated (<3181 to <15,000 SNPs); two were ceftriaxone, meropenem and penicillin resistant (one also doxycycline intermediate resistant), and the third penicillin resistant. Use of sternal tape for closure was identified as a recent practice change. Four of five genetically related cases involved the same surgeons and suture tape for sternal closure (wire for all other cases). Sternal tape was discontinued with three cases occurring afterwards. Seven patients completed chlorhexidine gluconate bathing and nasal decolonization. Hair was removed in the OR with reusable surgical clippers. All received the same skin antiseptic, and antibiotic prophylaxis was appropriate. No trends were identified in instrument or equipment use. Broad infection control measures were implemented, including surgical clipper replacement, OR cleaning and ultraviolet light disinfection, headlamp cleaning, and environmental repairs. Leadership was engaged through frequent meetings and audits. Infection control practices such as minimizing OR traffic, double gloving, glove changes, and strict adherence to hand hygiene and attire were reinforced. Two of eight cases occurred after these recommendations were completed but were not genetically related to the primary cluster. Conclusion: We describe a cluster of invasive C. amycolatum sternotomy SSIs. Only two genetically unrelated cases of C. amycolatum occurred following infection control investigation and interventions, underscoring the effectiveness of a comprehensive, multidisciplinary approach. This organism has rarely been reported as a cause of SSIs and may be an emerging pathogen.

Background: Measles is a highly transmissible virus. A single case can result in significant exposures within a healthcare facility and prompt action is needed to prevent secondary cases. In October 2025, Infection Prevention and Control (IPAC) was notified of a patient being admitted to our facility with recent international travel and symptoms consistent with measles. The patient was unvaccinated and had five healthcare facility visits prior to measles being suspected and subsequently confirmed. Objective: To describe our facility’s effective identification, prioritization, and prophylaxis of individuals exposed to measles. Methods: IPAC leveraged the electronic medical record to identify potentially exposed patients. Patients were quickly assessed for age and immune status, then prioritized and assigned to primary care teams. These teams promptly contacted patients and coordinated PEP administration. Results: Across five encounters, the index patient exposed 539 other patients. Due to delayed notification, our teams had less than four days to administer PEP for those exposed and still within PEP window. PEP administration began within hours of the index case’s positive test and patients received PEP within three days (Table 1). No secondary measles cases occurred within our facility. Conclusion: Timely and coordinated multidisciplinary effort enabled us to rapidly respond to our first measles case and control secondary transmission. Although the index case resulted in a large exposure, patients that were exposed and eligible for PEP were quickly prioritized to prevent secondary transmission.

Background: Advanced planning and adaptable response strategies are essential for preventing measles transmission in healthcare facilities. Objective: To describe a measles management plan and subsequent modifications in response to a cluster of measles cases. Methods: Drawing on previously published work (doi:10.1017/ice.2025.49), the Infection Prevention and Control (IPAC) team initiated a multi-disciplinary team and developed a measles preparedness plan with the following domains: Guidance and education; early detection and testing; isolation and patient movement; contact tracing and exposure management (Table 1). In October 2025, a patient was admitted during their fifth healthcare encounter and was diagnosed with measles. Two family members were later hospitalized with measles. Delayed recognition of the first case prompted enhancements to our preparedness framework (Table 1). Results: The first case resulted in 539 exposed patients. The second resulted in 87 exposures, and the third resulted in no exposure. Despite the extensive exposure, zero secondary measles were reported. Conclusion: Proactive planning enabled rapid response to our first case and controlled secondary transmission. Despite extensive planning, delayed identification of the first case caused significant exposures. As the cluster unfolded, we refined our plan, resulting in zero exposures from the last patient and zero secondary cases, despite over 850 exposures. These efforts may guide other healthcare facilities in improving their measles preparedness and response.