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X-linked myotubular myopathy (XL-MTM) is a rare life-threatening congenital myopathy caused by mutations in the MTM1 gene that encodes myotubularin, a ubiquitous enzyme required for normal development and function of skeletal muscle. The incidence of XLMTM in newborn males is 1:50,000. Recent evidence has revealed a previously unrecognized cholestatic tendency in patients with XL-MTM. EXCEL is a 48-week, prospective, observational, multicenter study to evaluate hepatobiliary health in patients with XLMTM. Approximately 50 male participants <18 years of age (up to half <5 years of age) with genetically confirmed XLMTM will be enrolled at 15–25 specialist sites in Canada, UK, and USA. The primary objective is to assess hepatobiliary health by estimating the incidence and prevalence of cholestatic complications in participants with XL-MTM. Secondary objectives are to evaluate the: (1) association between genetic variants of MTM1 and cholestasis; (2) association between environmental modifiers and cholestasis; and (3) healthcare utilization related to hepatobiliary and cholestatic complications. Participant assessments will be performed at the investigator's discretion based on standard of care at the site. A recommended schedule of assessments includes liver function tests (including serum bile acids), blood clotting parameters, creatinine, triglycerides and total cholesterol, and vitamin panel. Further clinical evaluation including liver ultrasound and Fibroscan will be used where appropriate. To reduce patient and caregiver burden, home healthcare services will collect laboratory tests when possible. Remote data collection may be used for healthcare resource utilization and patient medical history. Findings are expected to improve our understanding of cholestatic tendencies in participants with XL-MTM and provide critical information to improve the current management and treatment of XL-MTM, as well as future clinical trial designs. *Co-first authors. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study is among the largest to assess persistent airflow limitation and the first to evaluate a wide range of potential risk factors in high-risk patients with severe or difficult-to-treat asthma. A better understanding is needed regarding factors associated with persistent airway obstruction; this study was performed to determine demographic and clinical characteristics associated with persistent airflow limitation. METHODS: Data from adult patients (>or= 18 years old) with severe or difficult-to-treat asthma were evaluated. Patients with COPD, obesity with a restrictive respiratory pattern, or a >or= 30 pack-year history of smoking were excluded. Patients with persistent airflow limitation (postbronchodilator FEV1/FVC ratio

Objective: To examine the descriptive epidemiologic features of incident thyroid cancers diagnosed among Los Angeles County residents between 1972 and 1995.Methods: The Los Angeles County/University of Southern California Cancer Surveillance Program (CSP) collected data on 8820 newly diagnosed thyroid cancer of cases occurring in Los Angeles County. Average annual age-adjusted incidence rates were calculated to study the epidemiology of each of the major histologic types of thyroid carcinoma.Results: For all races combined, the age-adjusted incidence rates were 2.5 per 100,000 males and 6.0 per 100,000 females. Differences in incidence by ethnicity were particularly striking, with Filipinos demonstrating the highest incidence rates (4.44 per 100,000 males, 11.3 per 100,000 females). Over the 23-year period, thyroid cancer incidence rates increased 1.5% per year for males and 1% per year for females. By histology, papillary carcinoma rates increased over time and follicular carcinoma rates decreased. Non-Spanish surnamed white men employed in certain white-collar occupations and radiologic technicians were at greater risk of thyroid cancer.Conclusions: Additional research on the epidemiologic risk factors for thyroid cancer, particularly for gender and ethnicity, is needed to explain the marked elevated incidence rates among females and the Filipino population in Los Angeles County. [ABSTRACT FROM AUTHOR]

Centronuclear myopathies (CNMs) are a group of rare inherited congenital myopathies for which there is currently no cure. The most common form is X-linked myotubular myopathy (XL-MTM) with an estimated incidence of 1 in 50,000 male births and a typically severe clinical phenotype. The international Myotubular and Centronuclear Myopathy Patient Registry collects demographic, genetic and clinical data for affected individuals (living and deceased) and female carriers of XL-MTM. In the past few years two clinical trials have taken place, ASPIRO & Unite-CNM, both of which were halted prematurely because of liver-related serious adverse events, ranging from reversible liver function abnormalities to fatal cholestatic liver failure. These events have led to an increasing awareness of liver-related pathology, including pre-existing liver dysfunction in XL-MTM and CNM which may predispose patients to treatment-related adverse events, as highlighted in a recent publication on the ASPIRO gene therapy trial for XL-MTM. Driven by two patient organisations (MTM-CNM Family Connection and Myotubular Trust UK), a group of international experts was assembled to create the 'Liver Collaborative' to better understand liver challenges experienced in the community from both a natural history perspective and in the context of emerging clinical trials. Working with the MTM & CNM Patient Registry, a liver health questionnaire was developed and implemented into the registry platform in April 2023, with 168 questionnaires completed. The Collaborative is responsive to emerging new research which is advancing the understanding of potential liver dysfunction in XLMTM and CNM. The liver health questionnaire will be updated to capture additional data on nutritional diet and patient liver testing results. Findings from the current and expanded questionnaire will be presented. The registry has been a key instrument for the longitudinal collection of this data. [ABSTRACT FROM AUTHOR]