Purpose To assess the efficacy of tasimelteon to improve sleep in Smith–Magenis syndrome (SMS). Methods A 9-week, double-blind, randomized, two-period crossover study was conducted at four US clinical centers. Genetically confirmed patients with SMS, aged 3 to 39, with sleep complaints participated in the study. Patients were assigned to treatment with tasimelteon or placebo in a 4-week crossover study with a 1-week washout between treatments. Eligible patients participated in an open-label study and were followed for >3 months. Results Improvement of sleep quality (DDSQ50) and total sleep time (DDTST50) on the worst 50% of nights were primary endpoints. Secondary measures included actigraphy and behavioral parameters. Over three years, 52 patients were screened, and 25 patients completed the randomized portion of the study. DDSQ50 significantly improved over placebo (0.4, p = 0.0139), and DDTST50 also improved (18.5 minutes, p = 0.0556). Average sleep quality (0.3, p = 0.0155) and actigraphy-based total sleep time (21.1 minutes, p = 0.0134) improved significantly, consistent with the primary outcomes. Patients treated for ≥90 days in the open-label study showed persistent efficacy. Adverse events were similar between placebo and tasimelteon. Conclusion Tasimelteon safely and effectively improved sleep in SMS.

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INTRODUCTION: Ehlers Danlos syndrome (EDS) is a heritable disorder of the connective tissue usually inherited as an autosomal dominant trait. We observe an enrichment of EDS cases in a gastroparesis clinical study. METHODS: We explored the frequency of EDS cases in 2 consecutive gastroparesis clinical studies. To explore the genetic surrogates of EDS, we have performed whole-genome sequencing analysis and we focused the analyses on the frequencies of consequential variants in core EDS genes. RESULTS: We report a significant enrichment of EDS cases in a set of patients with gastroparesis (14/686 vs 1/5,000 OR 104 (confidence interval 13.7–793.3) P value <0.0001). We report a significant enrichment of variants in EDS genes in patients with idiopathic gastroparesis. DISCUSSION: The enrichment may be suggestive of converging pathways at the heart of etiology or predisposing patients to EDS with gastroparesis.

Introduction: Gastric cancer is the third leading cause of cancer-related mortality in the world. Although various epidemiologic and clinical characteristics are reported to be associated with the development of gastric cancer, there are no large studies that demonstrate their relative risk of gastric malignancy. Our study describes the prevalence of gastric cancer in the US population and quantifies the risk factors associated with the development of gastric cancer. Methods: We used a multi-institutional database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. Based on Systematized Nomenclature of Medicine -Clinical Terms (SNOMED-CT), we identified all patients (age .18 years) with a diagnosis of primary malignant neoplasm of the stomach and compared them with individuals without a diagnosis of gastric cancer. Epidemiologic characteristics and risk factors for the development of gastric cancer were recorded for each group and compared. A univariate binary logistic model was constructed using gastric cancer as the dependent variable. Results: Of the 70, 301,380 individuals in the database between 1999 to 2022, we identified 34,370 (0.04%) patients with primary malignant neoplasm of the stomach. Demographic characteristics such as elderly ( .65 years), male gender, Asian, African American, and White races were at higher odds of gastric cancer when compared with controls (P , 0.0001). Risk factors such as hypertension, diabetes mellitus, obesity, coronary atherosclerosis, end-stage renal disease, cirrhosis, congestive heart failure, alcohol abuse, tobacco use, family history of gastrointestinal cancer, H. pylori infection, history of gastritis, history of gastric ulcer, history of pernicious anemia and history of chronic atrophic gastritis were all associated with higher odds of gastric cancer (P , 0.0001). Finally, patients with history of intestinal polyposis syndrome were more likely to have gastric cancer (P 5 0.0001) (Table ). Conclusion: In our large cohort of patients with primary malignant neoplasm of the stomach, we demonstrate an increased association of gastric cancer with several epidemiological and clinical risk factors. In the absence of screening practices, our study can help guide decision-making and facilitate the early diagnosis of gastric cancer.

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