Coronavirus disease-19 (COVID-19) may result in serious complications involving several organ systems, including myocardial tissue. An exaggerated host inflammatory response, described as a cytokine storm, has been linked to play a major role in these complications. Colchicine and other pharmaceutical agents have been proposed to counter the cytokine storm and improve outcomes. In this exploratory review, we utilized a PubMed and Cochrane Database search aiming to identify the biochemical characteristics of the cytokine storm as well as to identify the potential effect of colchicine on these inflammatory biomarkers. The research yielded 30 reports describing the characteristics of the cytokine storm and 44 reports describing the effect of colchicine on various inflammatory biomarkers. According to our research, colchicine may be an agent of interest in the treatment of COVID-19 via its anti-inflammatory properties. However, there are potential drug interactions with cytochrome P450 3A4 inhibitors resulting in acute colchicine toxicities. Additionally, there is scarce evidence regarding the efficacy of colchicine in the acute phase of disease, since most trials evaluated its effect in chronic conditions. In this direction, our team proposes three different hypotheses for evaluating the place of colchicine in the treatment of COVID-19.

BACKGROUND Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following “hard” efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I 2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I 2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I 2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I 2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I 2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I 2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I 2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I 2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, th...

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Cardiovascular disease is the leading cause of mortality in patients with end‐stage‐kidney disease. Evidence on the possible echocardiographic differences between hemodialysis and peritoneal dialysis (PD) is scarce. This study aimed to evaluate differences in left (LA) and right atrial (RA), left (LV) and right ventricular (RV) geometry, systolic and diastolic function in hemodialysis, and PD patients. Thirty‐eight hemodialysis and 38 PD patients were matched for age, sex, and dialysis vintage. Two‐dimensional and tissue‐Doppler echocardiography, and lung ultrasound were performed during an interdialytic day in hemodialysis and before a programmed follow‐up visit in PD patients. Vena cava diameter (11.09 ± 4.53 vs. 14.91 ± 4.30 mm; p < 0.001) was significantly lower in hemodialysis patients. Indices of LA, RA, LV, and RV dimensions were similar between the two groups. LVMi (116.91 [38.56] vs. 122.83 [52.33] g/m2; p = 0.767) was similar, but relative wall thickness was marginally (0.40 [0.14] vs. 0.45 [0.15] cm; p = 0.055) lower in hemodialysis patients. LV hypertrophy prevalence was similar between groups (73.7% vs. 71.1%; p = 0.798), but hemodialysis patients presented eccentric and PD patients concentric LVH. Regarding ventricular systolic function, stroke volume (p = 0.030) and cardiac output (p = 0.036) were higher in hemodialysis, while RV systolic pressure (RVSP) (20.37 [22.54] vs. 27.68 [14.32] mm Hg; p = 0.009) was higher in PD. No significant differences were evidenced in diastolic function indices and lung water excess between the two groups. A moderate association was noted between ultrasound B‐lines score and LA volume index (r = 0.465, p < 0.001), RVSP (r = 0.431, p < 0.001), and E/e′ ratio (r = 0.304, p = 0.009). Hemodialysis and PD patients present largely similar echocardiographic indices reflecting cardiac geometry, systolic, and diastolic function, but different patterns of abnormal LV remodeling.

To the Editor:Diabetes represents a pandemic that has been recognized as an independent risk factor for severe infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the context of the coronavirus disease 19 (COVID-19) pandemic, 1 although it may not actually increase the risk for SARS-CoV-2 transmission for patients with diabetes compared with the general population. 2,3 Patients with diabetes feature a twofold increase in the odds for severe SARS-CoV-2 infection and a two-to threefold increase in the odds for death because of disease. 1,4,5 Patients with diabetes experience a significant increase in the risk for in-hospital death because of SARS-CoV-2 infection, as shown in a recent, large nationwide study. 6 Therefore, optimal treatment strategy for these patients becomes a top priority. 7 Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, an antidiabetic drug class with multiple, pleiotropic and beneficial effects, especially in patients with concomitant cardiovascular or renal disease, should be used with caution in the context of infection, because of the increased risk for diabetic ketoacidosis. 8 The anti-inflammatory properties of SGLT-2 inhibitors might be beneficial for infected patients, as they could hypothetically ameliorate the cytokine storm. 9,10 Previous studies have shown the significant reduction in inflammatory markers, such as C-reactive protein, ferritin and interleukin-6, with SGLT-2 inhibitors. 9 In addition, this drug class exerts beneficial effects on endothelial function, a finding that could have potential applicability for the prevention of thrombotic complications among SARS-CoV-2 patients. 11 Recently published observational studies support that SGLT-2 inhibitors are not inferior to incretin-based agents concerning surrogate COVID-19 outcomes, 12 while they might decrease the risk for mechanical ventilation. 13 However, more evidence from clinical practice is required, to identify the impact of antidiabetic drugs administered prior to infection on outcomes of interest among infected patients. 14,15 In addition, the ongoing DARE-19 trial, whose protocol has recently been published in Diabetes, Obesity and Metabolism, will provide answers on whether dapagliflozin could prevent COVID-19-related complications and all-cause mortality in patients admitted with SARS-CoV-2 infection. 16 We sought to determine whether SGLT-2 inhibitors influence the risk for respiratory tract infections and acute respiratory distress syndrome (ARDS), pooling data from the published cardiovascular and renal outcome, placebo-controlled trials until November 2020.