Citations

Abstract Importance Respiratory syncytial virus (RSV) hospitalization rates are highest among children <2 years of age. RSV immunization with infant monoclonal antibody or maternal vaccine is recommended to protect all U.S. infants in their first RSV season. For certain high-risk children aged 8−19 months entering their second RSV season, the monoclonal antibody nirsevimab is recommended. Little is known regarding preexisting health conditions as risk factors for RSV-associated respiratory failure in children during their second season. Objectives To describe children admitted to the pediatric intensive care unit (PICU) for RSV during their second RSV season by preexisting health conditions, and to compare demographic and clinical characteristics across groups. Design, Setting, and Participants Surveillance registry of children 8-<24 months old admitted to the PICU in 30 pediatric hospitals in the 2023-2024/2024-2025 RSV seasons. All children had an RSV-positive respiratory sample and received respiratory support with high flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation (IMV). Exposure Preexisting health conditions potentially increasing risk of severe RSV disease. Main Outcomes and Measures Patients were classified into four mutually exclusive groups by preexisting health conditions: 1) U.S. nirsevimab eligible criteria, 2) other identified RSV risk conditions (with some evidence of increased risk for severe RSV), 3) other preexisting conditions, and 4) no preexisting conditions. Patient demographic characteristics and level of respiratory support received were compared. Results Among 574 children: 47 (8.2%) had U.S. nirsevimab eligibility criteria, 76 (13.2%) had other RSV risk conditions, 96 (16.7%) had other preexisting conditions, and 355 (61.8%) had none. A higher proportion of children with nirsevimab eligibility factors (40.4%) than those with other identified RSV risk conditions (17.1%) required IMV, which was higher than other (10.4%) or no (5.9%) preexisting health conditions (p trend <0.001). Conclusions and Relevance Approximately 20% of children admitted to the PICU with severe RSV were in the defined groups that met U.S. nirsevimab-eligibility criteria or that had an identified RSV risk condition associated with known risk for severe RSV. A considerable proportion of both groups of children required IMV for respiratory support. These findings may help inform future deliberations regarding U.S. second season nirsevimab-eligibility recommendations. Key Points Question What preexisting health conditions are present in children aged 8–<24 months admitted to the pediatric intensive care unit for severe RSV disease in their second RSV season and how do clinical outcomes differ? Findings Among 574 children, 8% were eligible for nirsevimab in the U.S. and 13% had other preexisting conditions with known risk for severe RSV. Children with preexisting conditions, particularly those eligible for nirsevimab, were more likely to require invasive mechanical ventilation than those without. Meaning These findings may inform future deliberations regarding which children in their second RSV season might benefit from RSV preventive products.

Abstract Lung fibrosis, including idiopathic pulmonary fibrosis (IPF), represents a spectrum of progressive interstitial lung diseases characterized by disrupted epithelial repair, fibroblast activation, and excess extracellular matrix accumulation. A central feature of fibrotic progression is the loss of alveolar type 2 epithelial (AT2) cell identity and the emergence of aberrant transitional states that fail to support normal regeneration. Based on our re-analysis of multiple publicly available scRNA-seq datasets from the IPF Cell Atlas, S100A2 expression is tightly associated with basal-like reprogramming of AT2 cells and is a top upregulated gene at both mRNA and protein levels in IPF lungs. Furthermore, scRNA-seq data from human lung organoid models reveal that AT2 cells co-cultured with fibroblasts acquire a basal-like phenotype and express high levels of S100A2. Functionally, overexpression of S100A2 in human iPSC-derived lung alveolar epithelial type 2 (iAT2) cells leads to loss of AT2 cellular identity, increased generation of reactive oxygen species, and activation of RAGE signaling pathway. We demonstrate that pharmacologic inhibition of RAGE using Azeliragon preserves AT2 cell populations, associated with reduced oxidative stress in iAT2 cells, and significantly attenuates collagen deposition in bleomycin-induced lung fibrosis models. Collectively, our results indicate that S100A2 is a key driver of epithelial dysfunction in lung fibrosis, promoting loss of AT2 identity, aberrant basal fate acquisition, and persistent epithelial injury. Targeting the unrecognized S100A2–RAGE pathway may offer a new therapeutic strategy to restore epithelial homeostasis in lung fibrosis.

Preserving Cognition and Reducing Dementia Risk in Focal Epilepsy Tai XY, Zhao S, Liem B, Galovic M, Husain M, Sen A, Manohar S. The Relationship Between Sleep, Cognition, and Dementia Risk in People With Focal Epilepsy. Neurology. 2026 May 26;106(10):e214985. doi: 10.1212/WNL.0000000000214985. Epub 2026 Apr 22. PMID: 42018962 Background and objectives: Sleep disruption and cognitive impairment are important comorbidities of focal epilepsy. However, the nature to which sleep affects cognition and long-term dementia risk in focal epilepsy, compared with other brain conditions, remains unclear. We examined the relationship between sleep, cognition, and dementia risk in patients with focal epilepsy compared with healthy controls and stroke patients. Methods: We conducted an analysis of the prospective UK Biobank cohort study, with baseline assessments performed between 2006 and 2010 and follow-up until 2021. Study groups were mutually exclusive participants with focal epilepsy and stroke at baseline assessment and healthy controls. Sleep characteristics included reports of sleep duration, obstructive sleep apnea, insomnia, napping, and dozing. Main outcomes were risk of incident all-cause dementia and Alzheimer’s disease from Cox proportional hazard modeling and comparison of executive function measures and brain total hippocampal and gray matter volumes using generalized linear modeling. Results: We examined a sample of 482,207 participants, aged between 38 and 72 years (mean [SD] 57.6 [8.1] years; 53.8% female), without dementia at baseline and a nested imaging subsample of 42,345 participants. Optimal sleep duration (6-8 h) was associated with better executive function in control, focal epilepsy, and stroke groups. The impact of optimal sleep was significantly higher in individuals with focal epilepsy compared with controls (interaction term, p = 0 . 009), but not in the stroke group (interaction term, p = 0 . 574). Nonoptimal sleep was associated with worse executive function up to 8 years before the diagnosis of focal epilepsy. A fivefold increased risk of developing dementia was seen in individuals with focal epilepsy and nonoptimal sleep (hazard ratio [HR] 5.15, 95% CI: 3.77–7.04, p < 0 . 001) compared with healthy controls with optimal sleep. This was greater than in stroke individuals with poor sleep (HR 3.48, 95% CI: 2.82–4.26, p < 0 . 001). Optimal sleep compared with nonoptimal sleep modified the dementia risk in individuals focal epilepsy, with a significantly greater improvement compared with healthy controls (interaction term p = 0 . 017), while no significant difference was seen in the stroke group (interaction term p = 0 . 991). Discussion: Optimal sleep modified both cognitive performance and dementia risk in individuals with focal epilepsy compared with stroke patients and healthy controls. Based on self-reported sleep data, these findings suggest that improving sleep may be an impactful intervention to improve cognition and reduce dementia risk particularly in focal epilepsy.

Radiation therapy is central to the management of gynecological cancers, including endometrial, cervical, ovarian, and vaginal malignancies. Despite advances in photon-based techniques, treatment-related toxicity remains significant owing to the anatomical proximity of pelvic targets to critical organs at risk (OARs), including the bowel, bladder, and bone marrow. Proton beam therapy exploits the Bragg peak to deliver a precise dose at depth with minimal exit dose, potentially reducing OAR exposure. This review develops the physical principles, dosimetric evidence, and early clinical data for proton therapy in gynecological malignancies, including cervical, endometrial, ovarian, vaginal, and vulvar cancers. Major focus is given to clinical conditions where conventional brachytherapy is not practical, and proton therapy may offer the greatest advantages, such as reirradiation for recurrent disease, post-operative pelvic irradiation, and extended field nodal treatment. This review also emphasizes current constraints that have slowed down wide clinical implementation, such as the lack of mature prospective data, cost, and accessibility. Finally, we emphasize future directions, including well-designed comparative trials, integration with systemic and immunotherapies, and adaptive treatment strategies. As the body of accumulated evidence evolves, the proton beam therapy potential for the treatment of gynecological malignancies has tremendously increased due to its role in safety and personalization of radiation treatment.