Existing findings regarding the relationship between comorbidities and the severity of coronavirus disease 2019 (COVID-19) are inconsistent and insufficient. The aim of this study was to evaluate the association between different comorbidities and the severity of COVID-19. The PubMed, Embase, and Cochrane Library databases were searched to identify studies reporting the rates of comorbidities in COVID-19 patients with severe/fatal outcomes. Subgroup analyses were conducted according to disease severity and the country of residence. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using random-effects models. A total of 34 eligible studies were identified. In patients with severe/fatal COVID-19, the most prevalent chronic comorbidities were obesity (42%, 95% CI 34–49%) and hypertension (40%, 95% CI 35–45%), followed by diabetes (17%, 95% CI 15–20%), cardiovascular disease (13%, 95% CI 11–15%), respiratory disease (8%, 95% CI 6–10%), cerebrovascular disease (6%, 95% CI 4–8%), malignancy (4%, 95% CI 3–6%), kidney disease (3%, 95% CI 2–4%), and liver disease (2%, 95% CI 1–3%). In order of the prediction, the pooled ORs of the comorbidities in patients with severe or fatal COVID-19 when compared to patients with non-severe/fatal COVID-19 were as follows: chronic respiratory disease, OR 3.56 (95% CI 2.87–4.41); hypertension, OR 3.17 (95% CI 2.46–4.08); cardiovascular disease, OR 3.13 (95% CI 2.65–3.70); kidney disease, OR 3.02 (95% CI 2.23–4.08); cerebrovascular disease, OR 2.74 (95% CI 1.59–4.74); malignancy, OR 2.73 (95% CI 1.73–4.21); diabetes, OR 2.63 (95% CI 2.08–3.33); and obesity, OR 1.72 (95% CI 1.04–2.85). No correlation was observed between liver disease and COVID-19 aggravation (OR 1.54, 95% CI 0.95–2.49). Chronic comorbidities, including obesity, hypertension, diabetes, cardiovascular disease, cerebrovascular disease, respiratory disease, kidney disease, and malignancy are clinical risk factors for a severe or fatal outcome associated with COVID-19, with obesity being the most prevalent and respiratory disease being the most strongly predictive. Knowledge of these risk factors could help clinicians better identify and manage the high-risk populations.

Since 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed. In July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized. One hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis. The spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.

Context: The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM).Design: Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled.Results: A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories.Conclusions: Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.