A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Index of microcirculatory resistance as predictor for microvascular functional recovery in patients with anterior myocardial infarction.

IMR is useful for assessing the microvascular dysfunction after primary percutaneous coronary intervention (PCI). It remains unknown whether index of microcirculatory resistance (IMR) reflects the functional outcome in patients with anterior myocardial infarction (AMI) with or without microvascular obstruction (MO).This study was performed to evaluate the clinical value of the IMR for assessing myocardial injury and predicting microvascular functional recovery in patients with AMI undergoing primary PCI. We enrolled 34 patients with first anterior AMI. After successful primary PCI, the mean distal coronary artery pressure (P(a)), coronary wedge pressure (P(cw)), mean aortic pressure (P(a)), mean transit time (T(mn)), and IMR (P(d)* hyperemic T(mn)) were measured. The presence and extent of MO were measured using cardiac magnetic resonance image (MRI). All patients underwent follow-up echocardiography after 6 months. We divided the patients into two groups according to the existence of MO (present; n = 16, absent; n = 18) on MRI. The extent of MO correlated with IMR (r = 0.754; P < 0.001), P(cw) (r = 0.404; P = 0.031), and P(cw)/P(d) of infarct-related arteries (r = 0.502; P = 0.016). The IMR was significantly correlated with the ΔRegional wall motion score index (r = -0.61, P < 0.01) and ΔLeft ventricular ejection fraction (r = -0.52, P < 0.01), implying a higher IMR is associated with worse functional improvement. Therefore, Intracoronary wedge pressures and IMR, as parameters for specific and quantitative assessment of coronary microvascular dysfunction, are reliable on-site predictors of short-term myocardial viability and Left ventricle functional recovery in patients undergoing primary PCI for AMI.

A case of severe pulmonary thromboembolism in a young male with klinefelter syndrome.

A young male patient diagnosed with Klinefelter syndrome was admitted to our hospital via the emergency room with chief complaints of acute chest pain and dyspnea. Pulmonary thromboembolism was diagnosed from his chest CT images. His symptoms improved after he underwent thrombolysis and anticoagulation treatment. Klinefelter syndrome has a tendency towards hypercoagulability due to hormonal imbalance and one or more inherited thromophilic factors. Thus, Klinefelter syndrome patients with a past medical history of venous thromboembolism require continuous oral anticoagulation therapy for a period of at least six months.