American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2021
Mast Cell Tryptase Release Contributes to Disease Progression in Lymphangioleiomyomatosis.
Rationale: Lymphangioleiomyomatosis (LAM) is a multisystem disease that causes lung cysts and respiratory failure. Loss of TSC (tuberous sclerosis complex) gene function results in a clone of "LAM cells" with dysregulated mTOR (mechanistic target of rapamycin) activity. LAM cells and fibroblasts form lung nodules that also contain mast cells, although their significance is unknown. ⋯ In vivo, SCG reduced mast-cell activation and Tsc2-null lung tumor burden (vehicle: 32.5.3% ± 23.6%; SCG: 5.5% ± 4.3%; P = 0.0035). Conclusions: LAM-cell/fibroblast interactions attract mast cells where tryptase release contributes to disease progression. Repurposing SCG for use in LAM should be studied as an alternative or adjunct to mTOR inhibitor therapy.
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Am. J. Respir. Crit. Care Med. · Aug 2021
Glycemic Trajectories After Tuberculosis Diagnosis and Treatment Outcomes of New Tuberculosis Patients: A Prospective Study in Eastern China.
Rationale: Patients with newly diagnosed tuberculosis often have inconsistent glycemic measurements during and after treatment. Distinct glycemic trajectories after the diagnosis of tuberculosis are not well characterized, and whether patients with stress hyperglycemia have poor treatment outcomes is not known. Objectives: To identify distinct glycemic trajectories from the point of tuberculosis diagnosis to the posttreatment period and to assess the relationship between glycemic trajectories and tuberculosis treatment outcomes. ⋯ Compared with participants with a consistently normal glycemic trajectory, patients with transient hyperglycemia were more likely to experience treatment failure (adjusted odds ratio [AOR], 4.20; 95% confidence interval [CI], 1.57-11.25; P = 0.004) or erratic glycemic instability (AOR, 5.98; 95% CI, 2.00-17.87; P = 0.001). Patients living with diabetes also had a higher risk of experiencing treatment failure (AOR, 6.56; 95% CI, 2.22-19.35; P = 0.001), and this was modified by glycemic control and metformin use. Conclusions: Among patients with tuberculosis without diabetes, glycemic changes were common and may represent an important marker for patient response to tuberculosis treatment.