Chest
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Germline mutations in the gene encoding TERT cause haploinsufficiency with subsequent telomere shortening. TERT mutations are associated with short telomere syndromes, such as pulmonary fibrosis (PF), which is often the first manifestation of a short telomere syndrome. Telomere length is heritable, and progeny of telomerase mutation carriers are known to have shorter telomeres. In families with TERT mutations, genetic anticipation, the earlier onset of symptoms with successive generation, is described. Little is known on the number of generations that may pass before disease occurs in families with a TERT mutation. ⋯ The TERT c.2005T mutation is a pathogenic mutation and associates with PF. This study learns that a latency period of > 300 years may pass before the cumulative effect of telomere shortening eventually leads to PF. This finding underlines the complexity of the clinical interpretation of TERT mutations because, not the presence of the mutation, but the result of genetic anticipation, is associated with disease. Therefore, multidisciplinary discussion between pulmonary physicians, clinical geneticists, and genetic laboratory experts is recommended.
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Mepolizumab was the first licensed anti-IL5 monoclonal antibody for severe eosinophilic asthma (SEA). To date there are few data to confirm its efficacy in the real-world setting or assessment of baseline characteristics associated with response. ⋯ In a real-world SEA cohort, treatment with mepolizumab reduced exacerbation frequency and mOCS requirements. Nasal polyposis, a lower BMI, and a lower maintenance prednisolone requirement at baseline were associated with better outcomes. Twelve-month response was identifiable in >90% of patients by week 24.
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Multicenter Study
Rurality, Stage-Stratified Use of Treatment Modalities and Survival of Non-small Cell Lung Cancer.
To eliminate them, non-small cell lung cancer (NSCLC) care and outcome disparities need to be better understood. ⋯ Rurality-associated treatment and survival disparities were present at the patient and institution levels, but the institution-level disparity was greater. Rural residents receiving care at urban institutions had similar outcomes to urban residents receiving care at urban hospitals. To overcome rurality-associated NSCLC survival disparity, interventions should preferentially target the institution level, including expanding access to higher-quality guideline-concordant care.