RESUMEN
BACKGROUND: Since its first outbreak, coronavirus disease 2019 (COVID-19) has led to a great deal of published literature highlighting the short-term determinants of morbidity and mortality. Recently, several studies have reported radiological and functional sequelae from 3 months to 1 year among hospitalized COVID-19 survivors; however, long-term (more than 1 year) respiratory consequences in this population remain to be evaluated. OBJECTIVE: To assess the long-term radiological and pulmonary function outcomes of patients with COVID-19 2 years after resolution of the initial infection. METHODS: Hospitalized COVID-19 patients with moderate to severe disease who survived acute illness were included in this prospective and partially retrospective study. Clinical assessment, laboratory tests, high-resolution computed tomography scans, and pulmonary function tests (PFTs) were performed at baseline, followed by radiological and lung function assessments at 6 and 24 months. RESULTS: Among 106 enrolled participants (mean age 62 ± 13.5 years; males: 61), 44 (41.5%) and 27 (25.4%) underwent radiological assessment at 6 and 24 months, respectively. Overall, 22.6% (24) of patients had residual radiological abnormalities. Overt fibrosis was observed in 12.2% of patients. Computed tomography disease severity and extent diminished significantly at 6 (13 ± 6, P < 0.001) and 24 months (11 ± 6, P < 0.001) from baseline. PFTs were performed in 65 (61.3%), 22 (20.7%), and 34 (32%) patients at baseline, 6 and 24 months, respectively. Impaired diffusion capacity (median diffusion capacity for carbon monoxide: 60%, interquartile range [IQR]: 51-80), restrictive lung defect (mean total lung capacity: 73.4% ± 18% predicted), and reduced exercise tolerance (median 6-min walk distance: 360 m, IQR: 210-400) were the predominant features at baseline. With the exception of exercise tolerance, a statistically significant improvement was observed in lung function parameters at the extended follow-up (2 years). CONCLUSIONS: Hospitalized COVID-19 survivors are at increased risk of developing long-term pulmonary complications, including lung fibrosis. A protocol-based approach to the management of post-COVID-19 patients is mandatory to improve future outcomes.
RESUMEN
Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.