Search Results (829)

Background and Objectives: Transcatheter aortic valve implantation (TAVI) has become the mainstay of treatment for symptomatic aortic stenosis (AS) in patients over 70 years of age. It is also indicated for younger patients with significant comorbidities, for valve-in-valve interventions, and in selected patients with severe aortic insufficiency. We aimed to evaluate procedural and clinical outcomes of transfemoral TAVI performed over the course of 12 years by the same operators using different bioprosthetic valves. Materials and Methods: Between 2012 and 2023, 375 patients underwent TAVI in our clinic, with six types of bioprosthetic valves (Edwards Sapien XT, Medtronic Valves [CoreValve and Evolut R], Portico, Myval, Acurate Neo, and Direct Flow Medical). A transfemoral approach was used in all patients. The procedural and clinical outcomes were defined according to Valve Academic Research Consortium-3 (VARC-3) criteria. Results: The mean age of the patients was 78.4 ± 7.3, and their median STS score was 4.2 (2.9–5.9). Of the 375 patients, 361 had severe AS, 4 had severe aortic insufficiency, 5 were valve-in-valve, and 5 were valve-in-TAVI. Seven patients required a second valve implantation: four due to embolization of the prosthetic valve and three due to deep implantation of the prosthetic valve. Based on the VARC-3 criteria, the rates of technical success and device success were 90.4% and 85.3%, respectively. Major vascular complications were observed in 18 (4.8%) patients. Also, 42 (11.2%) patients required permanent pacemaker implantation. The incidence of moderate or worse paravalvular leak was 2.9%. The peri-procedural, 30-day, 1-year, and 5-year mortality rates were 5.1%, 4.3%, 15.2%, and 45.6%, respectively. STS scores (HR:1.129, 95%CI: 1.068–1.192, p < 0.001) and post-TAVI acute kidney injury (HR:3.993, 95%CI:1.629–9.785, p = 0.002) were detected as independent predictors of mortality in Cox regression analysis. Conclusions: This registry demonstrated the evolution of TAVI procedures at a single center over 12 years. A high level of collaboration between experienced operators and innovations in devices seem to be the key features for achieving high procedural success and low complication rates. Full article

Background/Objectives: Endoscopic submucosal dissection (ESD) is a state-of-the-art en bloc resection for early gastro-intestinal cancers and precursors developed and validated in Japan. Western expertise with this complex technique remains limited. Tutored training might be optimal for patients and ESD learning. We established ESD tutoring courses led by experienced Japanese experts to provide (i) optimal long-term curative outcomes and low complication rates for patients and (ii) hands-on training on difficult lesions for European endoscopists under direct expert supervision. Methods: Prospective data from 2011 to 2015 (follow-up to 12/2024) were analyzed. A total of 118 neoplasms (50% HGIEN and cancer) in 101 patients (median age 68 [37–91] years; 38% with significant comorbidities) were treated with expert or tutored ESD. Japanese experts performed 28 ESDs, while 22 trained beginners conducted 90 supervised procedures on difficult lesions during 5 live and 20 tutoring events (1–4 days each). Results: Analysis of the complete data showed curative and en bloc resection rates of 88% and 95%, respectively, with no recurrence after R0 resections during a median follow-up of 9.8 [1.5–14.9] years. Long-term survival remained recurrence-free after endoscopic resection of 3 recurrent adenomas (at R1/Rx) and curative surgery/2nd ESD for 5 non-curative ESDs. Adverse events occurred in 9.3% without emergency surgery or 30-day mortality. Comparing expert-only vs. tutored ESD procedures, beginners correctly applied curative ESD indications in 94% of 118 neoplasms. Experts resected larger lesions (22 cm²) at a rate of 9.3 cm²/h in 121 min. Tutored beginners achieved a 75% [25–100] self-completion rate on 33% smaller lesions in 112 min. Conclusions: ESD tutoring courses led by Japanese experts ensure excellent patient outcomes and standardized procedural training. This model may foster professional ESD performance across European referral centers. Full article

Background/Objectives: Obstructive sleep apnea (OSA) affects approximately 1 billion adults worldwide with extensive comorbidities, including cardiovascular disease, metabolic disorders, and cognitive decline, yet pharmacological therapies remain limited. Conventional bottom-up omics approaches identify numerous genes overlapping with other diseases, hindering therapeutic translation. This study introduces a top-down, comorbidity-driven approach to identify actionable molecular targets and develop rational dual kinase inhibitors for OSA management. Methods: We implemented a five-tier modeling workflow: (1) comorbidity network analysis, (2) disease module identification through NetworkAnalyst, (3) mechanistic pathway reconstruction of the CK1δ-(HIF1A)-PINK1 signaling cascade, (4) molecular docking analysis of Nigella sativa alkaloids and reference inhibitors (IC261, PF-670462) against CK1δ (PDB: 3UYS) and PINK1 (PDB: 5OAT) using AutoDock Vina, and (5) rational design and computational validation of novel dual inhibitors (ICL, PFL) integrating pharmacophoric features from natural alkaloids and established kinase inhibitors. Results: Extensive network analysis revealed a discrete OSA disease module centered on two interconnected protein kinases—CK1δ and PINK1—that mechanistically bridge circadian disruption and neurodegeneration. Among natural alkaloids, Nigellidine showed strongest CK1δ binding (−8.0 kcal/mol) and Nigellicine strongest PINK1 binding (−8.6 kcal/mol). Rationally designed dual inhibitors demonstrated superior binding: ICL (−7.2 kcal/mol PINK1, −8.9 kcal/mol CK1δ) and PFL (−10.8 kcal/mol CK1δ, −11.2 kcal/mol PINK1), representing −2.6–2.8 kcal/mol improvements over reference compounds. Conclusions: This study establishes a comorbidity-driven translational framework identifying the CK1δ-PINK1 axis as a therapeutic target in OSA. The rationally designed dual inhibitors represent third-generation precision therapeutics addressing OSA’s multi-dimensional pathophysiology, while the five-tier workflow provides a generalizable template for drug discovery in complex multimorbid diseases. Full article

Background: Glaucoma is an age-related optic neuropathy frequently accompanied by systemic comorbidities. Vitamin D deficiency (VDD) has been associated with cardiovascular and renal diseases in the general population, yet its relationship with long-term systemic outcomes in glaucoma remains unclear. This study evaluated the association between baseline vitamin D status and subsequent mortality and cardiorenal events in patients with primary glaucoma. Methods: We conducted a retrospective cohort study using deidentified electronic health records from the TriNetX U.S. Collaborative Network, a federated network of participating healthcare organizations. Adults (≥18 years) with incident primary glaucoma (2005–2020) and a serum 25-hydroxyvitamin D (25(OH)D) test within 12 months prior to diagnosis were categorized as VDD (<30 ng/mL) or vitamin D adequacy (VDA; ≥30 ng/mL). After 1:1 propensity score matching across 47 demographic, clinical, medication, and laboratory variables, 11,855 patients per group were followed for up to 5 years. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), and renal function decline (eGFR < 60 mL/min/1.73 m²). Analyses incorporated Kaplan–Meier curves, Cox models, landmark tests, sensitivity analyses, and competing risk methods. Results: Among the 35,100 eligible patients, the matched cohorts demonstrated higher 5-year risks associated with VDD for all-cause mortality (HR 1.104; 95% CI 1.001–1.217), MACE (HR 1.151; 95% CI 1.078–1.229), and AKI (HR 1.154; 95% CI 1.056–1.261), whereas the risks of renal function decline did not differ (HR 0.972; 95% CI 0.907–1.042). Risk divergence emerged within the first year of follow-up and persisted through the 5-year observation period. Conclusions: In patients with primary glaucoma, vitamin D deficiency was associated with higher long-term risks of mortality and cardiorenal complications, but not renal function decline. Taken together, the results are consistent with vitamin D status serving as a marker of broader systemic vulnerability in glaucoma and highlight the need for prospective studies to further clarify its prognostic significance. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity, mortality, and healthcare utilization. Lung volume reduction surgery improves outcomes in a select cohort but portends high morbidity. Bronchoscopic lung volume reduction (BLVR) is a less invasive, reversible manner of lung volume reduction, using one-way valves to improve lung function, quality of life, and exercise capacity. Nevertheless, knowledge gaps persist regarding factors that predict procedural success. Methods: We retrospectively reviewed 142 patients who underwent BLVR at the University of Chicago between December 2018 and July 2024 to assess the relationship between comorbidities and procedural outcomes. Using logistic and multinomial regression, we determined odds ratios (ORs) for a binary outcome of success and failure and relative risk ratios (RRRs) for failure sub-categories relative to procedural success. Results: We observed a procedural success rate of 48.1% and pneumothorax prevalence of 21.8%. After adjusting for age, sex, race, and body mass index (BMI), comorbidities associated with procedural failure included chronic kidney disease (CKD), congestive heart failure (CHF), anemia, and a BMI, Obstruction, Dyspnea and Exercise (BODE) Index of 5 or greater. Obstructive sleep apnea (OSA) was associated with procedural success. Conclusions: Comorbidities associated with dyspnea appear to have a significant effect on procedural success in BLVR. Full article

Background/Objectives: The aim of the present systematic review is to evaluate the performance of AI models for length of stay prediction. Methods: This SR was carried out in accordance with PRISMA 2020 and registered in PROSPERO database (CRD420251039985). Using the PICOS framework, we formulated the following research question: “Can artificial intelligence models accurately predict hospital length of stay (LOS) in patients undergoing head and neck (H&N) cancer surgery?” We searched the Cochrane Library, Embase, PubMed, and Scopus, with additional gray literature identified through Google Scholar and ProQuest. Risk of bias (RoB) was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST), and a narrative synthesis was performed to summarize qualitative findings. Results: Of 1304 identified articles, 5 met inclusion criteria, covering 5009 patients. All studies used supervised learning to predict LOS with different variables presenting stronger associations with increased hospital LOS. Age, race, ASA score, BMI, and comorbid factors like smoking and arterial hypertension were comon variables across studies but not always the ones most strongly associated with LOS. One study also predicted discharge to non-home facilities and prolonged LOS; only one applied data balancing. Model accuracies ranged from 0.63 to 0.84, and area under the receiver operator characteristics curve (AUROC) values from 0.66 to 0.80, suggesting moderate discriminative performance. All studies had a high risk of bias, though no applicability concerns were noted. Conclusions: AI models show potential for LOS prediction after H&N cancer surgery; however, an elevated RoB and methodological shortcomings constrain the current evidence. Methodological improvements, external validation, and transparent reporting is essential to enhance reliability and generalizability, enabling integration into clinical decision-making. Full article

Background and Objectives: Psychomotor developmental delay is a frequent comorbidity in children with congenital heart defects (CHD), especially after surgical correction of the CHD and exposure to risk factors such as anesthesia, cardiopulmonary bypass and postoperative complications. Yet psychomotor delay is present in these patients before surgical correction but is under-recognized. Evidence focusing solely on unrepaired CHD remains limited. Materials and Methods: This prospective cross-sectional study evaluated 153 and included 77 children under 6 years of age with unrepaired CHD, stratified into cyanotic (n = 31) and non-cyanotic (n = 46) CHD, admitted to a pediatric cardiology department over a period of 5 years. Psychomotor development was assessed using the Denver Developmental Screening Test II (DDST-II), standardized for pediatric population. Associations with clinical, perinatal, and demographic factors were analyzed using univariate and multivariate methods. Results: Developmental delay was identified in 97% of cyanotic and 54% of non-cyanotic patients. Compared to healthy norms, CHD patients had significantly lower global developmental scores (p = 0.03). Gross motor and personal-social domains were most frequently affected. Prenatal CHD diagnosis correlated with better global developmental scores (p = 0.012), and breastfeeding was associated with improved outcomes compared with formula or mixed feeding (p = 0.008). Conclusions: Infants and young children with CHD are at increased risk of early psychomotor developmental delay, particularly in the gross motor and personal–social domains, even before exposure to surgical or intensive care damaging factors. Systematic psychomotor surveillance, integration of protective factors such as prenatal diagnosis and breastfeeding, and timely access to multidisciplinary interventions are essential to optimize long-term outcomes in this vulnerable population. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is characterized by recurrent episodes of complete or partial upper airway collapse during sleep, leading to apnea or hypopnea and recurrent oxygen desaturation. Intermittent hypoxia (IH) and sleep fragmentation have been proposed as key mechanisms contributing to the adverse cardiovascular consequences observed in OSA. The present study aimed to identify clinical variables independently associated with IH in patients with OSA and to examine their relationships with common comorbid conditions. Methods: This retrospective study included 569 adult patients diagnosed with obstructive sleep apnea (OSA) by overnight polysomnography (apnea–hypopnea index [AHI] ≥ 5 events/hour) between February 2020 and January 2025 at the Sleep Laboratory of Trakya University Hospital. Demographic characteristics, body mass index (BMI), AHI values, comorbid medical conditions, average nocturnal oxygen saturation, and the duration of intermittent hypoxia (time below 90% SpO₂ [T90]) were retrieved from the laboratory database. Normality of distribution was assessed using the Kolmogorov–Smirnov test. Group differences were evaluated using the Mann–Whitney U test and the Kruskal–Wallis test with Dunn–Bonferroni post hoc analysis. Correlations were examined using Spearman’s correlation analysis, and variables independently associated with average nocturnal oxygen saturation and intermittent T90 were assessed using multivariable linear regression analysis. Results: The presence of hypertension, diabetes mellitus, and comorbid conditions was associated with significant differences in T90 among patients with OSA. T90 also differed significantly across AHI severity grades. Significant negative correlations were observed between nocturnal oxygen saturation and BMI, hypertension, diabetes, comorbidities, and age. Nocturnal oxygen saturation values likewise differed significantly across BMI-defined obesity groups. In the multivariable regression analysis, BMI, AHI, and age were independently associated with lower nocturnal oxygen saturation and longer T90. Conclusions: This study provides important insight into the complex relationships among OSA severity, patient demographics, comorbidities, and intermittent hypoxia. In multivariable analysis, BMI, AHI, and age showed independent associations with reduced nocturnal oxygen saturation and prolonged T90. These findings highlight the importance of a multidimensional clinical assessment in OSA and support the use of intermittent hypoxia metrics as additional indicators of disease burden and potential clinical impact. Full article

Background/Objectives: Ankylosing spondylitis (AS) has been associated with various comorbidities, including cardiovascular morbidity. Recent studies suggest that certain arrhythmias may be more frequent in AS patients than in the general population. The aim of this study was to analyze the prevalence of electric heart disorders (EHD) in patients with AS in real-world conditions and compare them with those reported in the general population. Methods: Descriptive cross-sectional study aiming to determine the prevalence of EHD in AS in pre-COVID-19 period. EHD were analyzed in a resting ECG and 24 h Holter monitoring. Additionally, the association between clinical and demographic variables was analyzed. Results: Among 121 patients with AS (62% men; mean ± SD age 54.6 ± 15.6 years; median [IQR] disease duration 14 (8–20) years), 18.2% presented any EHD, including 9.1% with supraventricular tachyarrhythmias (SVT) (5% atrial fibrillation [AF]) and 7.4% with atrioventricular block (AVB). Clinically relevant disorders (≥2nd-degree AVB or SVT) were observed in 9.9% of patients. In adjusted analyses, SVT was independently associated with older age and higher BMI, while any conduction delay and clinically relevant EHD were associated with age, hypertension, and disease-modifying antirheumatic-drug treatment duration. Comparisons with previous population-based studies showed similar data, with a non-significant trend toward higher AF prevalence in AS patients. Conclusions: There appears to be a trend toward a higher prevalence of arrhythmias in patients with AS in real-world conditions, which could have clinical and therapeutic implications. An association between EHD and pro-inflammatory conditions such as age and BMI was observed, supporting the hypothesis that underlying inflammation might contribute to increased arrhythmogenicity. Full article

Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case–control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23–63] years), compared to 69 (69 [65–84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3–3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1–15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04–1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies. Full article

Background and Objectives: This study aimed to evaluate the prognostic impact of baseline body composition measurements and changes in muscle and adipose tissue during treatment on overall survival (OS) in metastatic non-small cell lung cancer (NSCLC) patients treated with nivolumab. Materials and Methods: Eighty-eight metastatic NSCLC patients who were initiated on nivolumab between January 2022 and December 2024 were retrospectively analyzed. Body composition parameters were derived from baseline and 3-month ¹⁸F-FDG PET/CT scans at the L3 level, including psoas muscle index (PMI), skeletal muscle index (SMI), intramuscular adipose content (IMAC), and subcutaneous fat density (SFD). Treatment-related changes in body composition were evaluated, and survival analyses were performed using Kaplan–Meier estimates and Cox regression models. Results: Overall, 34.1% (n = 30) of patients were classified as sarcopenic. Median OS was significantly longer in non-sarcopenic patients (19 months vs. 5 months, p < 0.001). In univariate analysis, older age, higher comorbidity burden, liver metastasis, baseline sarcopenia, and adverse treatment-related changes in muscle and nutritional parameters were found to be associated with OS. In multivariate analysis, only unfavorable changes in skeletal muscle (ΔSMI; HR 3.39, p = 0.003) and subcutaneous fat radiodensity (ΔSFD; HR 2.45, p = 0.02) remained independent adverse prognostic factors. Baseline body composition parameters did not maintain their independence in multivariate models. Conclusions: Our study demonstrates that muscle loss or insufficient gain and unfavorable changes in subcutaneous fat radiodensity during nivolumab treatment more strongly predict overall survival compared to baseline measurements. These findings highlight the clinical importance of monitoring dynamic body composition throughout treatment, rather than static assessments, in NSCLC patients receiving immunotherapy. Full article

Toxoplasmosis is a parasitic disease associated with significant morbidity and mortality. This cross-sectional study aimed to determine the prevalence, associated risk factors, and ocular health outcomes related to Toxoplasma gondii seropositivity in 161 residents from four Quilombolas communities in the northern region of Tocantins, Brazilian Legal Amazon. Peripheral blood samples were collected and tested by Enzyme-Linked Immunosorbent Assay (ELISA) for Immunoglobulin G (IgG) and/or Immunoglobulin M (IgM) and Polymerase Chain Reaction (PCR), while a standardized form was used to collect sociodemographic, health, and behavioral data. Statistical analysis, conducted using Epi-Info 3.3.2, considered T. gondii seropositivity as the primary outcome, with a significance level less than 5% (p ≤ 0.05). An overall seroprevalence of 62.11% (100/161) was observed. Key risk factors significantly, as measured by the Odds Ratio (OR), associated with T. gondii seropositivity included being elderly (OR: 4.07, CI: 2.05–8.06, p < 0.01), having cats (OR: 5.56, CI: 2.74–22.27, p < 0.01), a low parental education level (OR: 2.97, CI: 1.46–6.02, p < 0.01), children playing on the ground (OR: 2.50, CI: 1.30–4.82, p < 0.01), and having a home vegetable garden (OR: 3.80, CI: 1.94–7.47, p < 0.01). Regarding ocular health, no conclusive direct association was established between T. gondii seropositivity and specific ocular manifestations when analyzed for children and the elderly separately. Observed ocular problems in the grouped population were primarily linked to age-related comorbidities rather than parasitic infection. High rates of T. gondii seropositivity, driven by specific environmental and socioeconomic factors, highlight the vulnerability of these communities, emphasizing the need for targeted preventive strategies. Full article

Background and Objectives: Pancreatoduodenectomy (PD) is the primary treatment for patients with resectable, non-metastatic pancreatic adenocarcinoma and periampullary tumors. Although surgical methods and perioperative management have improved, the procedure still carries a high risk of complications, with postoperative pancreatic fistula (POPF) being the most significant. This study focuses on identifying current risk factors for POPF after PD in a single HPB center. Materials and Methods: We retrospectively analyzed prospectively collected data from patients undergoing PD in our department between October 2018 and April 2024. Data included demographics, comorbidities, lifestyle factors, preoperative tests (bilirubin, CA19-9, HbA1c), intraoperative variables (pancreatic texture, duct diameter), and postoperative outcomes. POPF was classified using the International Study Group of Pancreatic Surgery (ISGPS) criteria. Univariate and multivariate logistic regression analyses were performed. Results: A total of 118 patients underwent PD (82 males, 36 females; mean age 67 (45–85) years; mean body mass index (BMI) 26.6 kg/m²). POPF occurred in 37 patients (31%), with 27 Grade B (23%) and 10 Grade C (9%). The 30- and 90-day mortality rates were 5% and 12.7%, respectively. Univariate analysis showed associations between POPF and soft pancreas (p = 0.018), c-reactive protein (CRP) on postoperative day (POD) 5 (p = 0.004), and serum amylase on POD 0 (p = 0.008). Diabetes mellitus was associated with a lower incidence of POPF (p = 0.014). Multivariate analysis confirmed CRP on POD 5 (OR 1.007, p = 0.025) and DM (OR 0.254, p = 0.015), as independent factors. ROC analysis identified POD 0 amylase >113.5 U/L (AUC 0.717) and POD 5 CRP >125.3 mg/dL (AUC 0.669) as predictive values. Conclusions: POPF remains an important complication after PD. CRP > 126 mg/dL on POD 5 was associated with POPF and may serve as an adjunctive signal to guide further assessment, including imaging. The observed inverse association with diabetes mellitus is hypothesis-generating and should be interpreted cautiously, considering potential confounding and the influence of center volume, surgeon heterogeneity, and institutional protocols. Full article

Background: Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract illness and hospitalizations in children aged ≤5 years worldwide. The aim of this study was to characterize the Polish population of patients aged ≤5 years who were hospitalized due to RSV infection, focusing on their clinical and epidemiological characteristics as well as treatment patterns. Methods: This retrospective observational study was conducted between November 2023 and February 2024 in 41 hospitals with pediatric departments across Poland. Data from patients aged ≤5 years admitted due to RSV infection confirmed with antigen test or RT-PCR were collected. The dataset was weighted and extrapolated to allow conclusions applicable to the general population of patients aged 0–5 years hospitalized with RSV infection in Poland. Results: Data from 419 patients were analyzed. Over half (57.4%) were younger than 12 months, 84% were born at term, and 85.8% had no comorbidities. The most frequent manifestations of RSV infections were pneumonia (56.8%), bronchiolitis (35.9%), and bronchitis (12.4%). Viral co-infections were identified in 8% of patients. Regarding treatment, 21.1% of patients required respiratory support, 67.6% received inhaled steroid therapy, 61.5% were treated with antibiotics, 48.1% received beta2-mimetics and anticholinergics, and 44.3% underwent systemic steroid therapy. Conclusions: Our findings confirm that severe RSV primarily affects the youngest children with no comorbidities who do not present high risk conditions. To reduce the overall disease burden, preventive strategies should be offered to all children, not being limited to those in risk groups. Full article

Background/Objectives: Sleep disorders represent a significant health burden among children and adolescents with autism spectrum disorder (ASD), affecting their core symptoms, behavior, and quality of life. While physical activity has shown promise in managing sleep disorders in the general pediatric population, its effectiveness for children and adolescents with ASD remains understudied. Methods: This retrospective cohort study analyzed electronic health records from 132 healthcare organizations, examining 155,860,529 individuals to determine sleep disorder prevalence in ASD populations and evaluate the impact of physical activity interventions. We identified 248,940 children and adolescents with ASD aged 5–18 years, of whom 38,976 had documented sleep disorders. Propensity score matching was performed to compare patients with ASD and sleep disorders who received physical activity interventions with matched controls. Primary outcomes included sleep disorder resolution and medication utilization changes at 1- and 5-year follow-up. Bonferroni correction was applied to secondary analyses to account for multiple comparisons. Results: The prevalence of sleep disorders was markedly higher in children and adolescents with ASD (19.25%) compared to non-ASD peers (3.37%), with risk ratios escalating from childhood (RR = 5.34, 95% CI: 5.28–5.40) to adolescence (RR = 6.12, 95% CI: 6.05–6.19). After matching, 3709 patients were included in each group. Physical activity interventions were associated with significantly higher sleep disorder resolution at 1 year (−59.9% vs. −5.05%, p = 0.001) and sustained benefit at 5 years (−49.83% vs. +7.26%, p = 0.001). After Bonferroni correction, improvement in sleep apnea at 1 year remained statistically significant (−62.26% vs. +9.39%, Bonferroni-adjusted p = 0.040). Improvements in parasomnia and insomnia did not survive correction and were considered exploratory. Age emerged as a key effect modifier: adolescents (12–18 years) demonstrated sustained improvements in overall sleep outcomes at both 1- and 5-year follow-up that met Bonferroni-corrected thresholds, whereas younger children (5–11 years) showed limited and inconsistent responses. Among comorbidity groups, anxiety-comorbid patients exhibited the strongest overall improvement (−58.7% vs. −12.4%, p < 0.01), while reductions in amphetamine use and changes in melatonin prescribing patterns should be interpreted as exploratory findings requiring prospective confirmation. Conclusions: This large-scale observational study suggests structured physical activity interventions are associated with sustained improvements in overall sleep disorders among children and adolescents with ASD. While subtype- and subgroup-specific associations were observed, many attenuate after multiple comparison adjustments, highlighting the need for cautious interpretation. Findings support exploring physical activity in comprehensive care plans, with prospective randomized trials needed to confirm causality, optimize protocols, and address multiplicity. Full article