Impact of Alteplase on Mortality in Critically Ill Patients with COVID-19 and Pulmonary Embolism.

COVID-19 is an independent risk factor for pulmonary embolism (PE). Little is known about alteplase therapy in this patient group. A retrospective study analyzed 74 patients with PE and acute respiratory distress syndrome (ARDS) due to COVID-19 who were hospitalized in the intensive care unit in 2021. Patients with or without confirmed right heart thrombi (RHT) were treated with unfractionated heparin or alteplase. The mortality rate in patients with RHT treated with heparin was 100% compared to 37.9% and 55.2% in those treated with alteplase without RHT and alteplase with RHT, respectively. The risk of death in the alteplase group increased with delayed thrombolysis (p = 0.009, odds ratio (OR) = 1.73 95% CI (confidence interval) 1.14-2.62), increased D-dimer concentration (p = 0.02, OR = 1.43 95% CI 1.06-1.93), and decreased PaO2/FiO2 ratio (p = 0.001, OR = 0.56 95% CI 0.41-0.78). The receiver operating characteristic method determined that a 1-day delay in thrombolytic treatment, D-dimer concentration >5.844 mg/L, and PaO2/FiO2 <144 mmHg predicted a fatal outcome. The risk of death in patients with severe COVID-19 with ARDS and PE increases with higher D-dimer levels, decreased PaO2/FiO2, and delayed thrombolytic treatment. Thrombolysis seems to be treatment of choice in severe COVID-19 with PE and RHT. It should be carried out as soon as possible after the diagnosis is established.

Efficacy of Sildenafil in Patients with Severe COVID-19 and Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is common in severe coronavirus disease 2019 (COVID-19) and worsens the prognosis. Sildenafil, a phosphodiesterase-5 inhibitor, is approved for PAH treatment but little is known about its efficacy in cases of severe COVID-19 with PAH. This study aimed to investigate the clinical efficacy of sildenafil in patients with severe COVID-19 and PAH. Intensive care unit (ICU) patients were randomly assigned to receive sildenafil or a placebo, with 75 participants in each group. Sildenafil was administered orally at 0.25 mg/kg t.i.d. for one week in a placebo-controlled, double-blind manner as an add-on therapy alongside the patient's routine treatment. The primary endpoint was one-week mortality, and the secondary endpoints were the one-week intubation rate and duration of ICU stay. The mortality rate was 4% vs. 13.3% (p = 0.078), the intubation rate was 8% and 18.7% (p = 0.09), and the length of ICU stay was 15 vs. 19 days (p < 0.001) for the sildenafil and placebo groups, respectively. If adjusted for PAH, sildenafil treatment significantly reduced mortality and intubation risks: OR = 0.21 (95% CI: 0.05-0.89) and OR = 0.26 (95% CI: 0.08-0.86), respectively. Sildenafil demonstrated some clinical efficacy in patients with severe COVID-19 and PAH and should be considered as an add-on therapy in these patients.

Platelet aggregation measurement for assessment of hemostasis failure mechanisms in patients with gastroduodenal ulcer bleeding.

BACKGROUND: The purpose of this study was to identify factors associated with the risk of unsustainable hemostasis in patients with gastric and duodenal ulcer bleeding by in vitro assessment of platelet reactivity using artificial neural networks. METHODS: Patients with gastroduodenal ulcers complicated by bleeding were studied. Platelet aggregation was measured using aggregometry with adenosine diphosphate 5 µM, epinephrine 2.5 µM, 5-hydroxytryptophan 10 µM, collagen 1 µM, and thrombin 0.06 NIH Unit/mL as agonists. Multiple logistic regression was used to evaluate the independent relationship between demographic, clinical, endoscopic, and laboratory data and in vitro assessment of platelet reactivity and local parameters of hemostasis in patients with ulcer bleeding. RESULTS: Analysis of platelet aggregation in patients with gastroduodenal ulcer bleeding allowed the variability of platelet response to different agonists used in effective concentration which induces 50% platelet aggregation (EC50) to be established. The relationship between platelet aggregation and the spatial-temporal characteristics of ulcers complicated by bleeding was demonstrated. Adrenoreactivity of platelets was associated with time elapsed since the start of ulcer bleeding and degree of hemorrhage. The lowest platelet response to collagen and thrombin was detected in patients with active bleeding (P < 0.001) and unsustainable recent bleeding (P < 0.01). Decreased adenosine diphosphate-induced platelet aggregation in patients with ulcer bleeding was correlated with the platelet response to thrombin (r = 0.714, P < 0.001) and collagen (r = 0.584, P < 0.01). CONCLUSION: Estimation of platelet reactivity in vitro indicates the key mechanisms of failure of hemostasis in patients with ulcer bleeding. In addition to gender, an important determinant of unsustainable hemostasis was a decreased platelet response to thrombin and adenosine diphosphate.

Gender risk of nonfatal stroke in type 2 diabetic patients differs depending on the type of treatment.

BACKGROUND: The gender differences in stroke risk among diabetic patients with different treatments have not been studied previously. We aim to determine if there is a gender difference in nonfatal stroke risk in diabetic patients receiving different types of glucose-lowering treatments. METHODS: In December 2005, data of type 2 diabetic patients were extracted from a nationwide population-based diabetes registry covering 11 Ukrainian regions. Male/female odds ratios (OR) for nonfatal stroke were calculated in three treatment groups: diet only 7,273/15,901, oral glucose-lowering drugs 15,109/33,913, and insulin 5,529/12,462 male/female. Male/female ORs of stroke were estimated using a logistic regression model. RESULTS: The age-adjusted ORs of stroke were higher among diabetic men compared with diabetic women with oral glucose-lowering drug treatment (OR 1.37, 95% CI 1.22-1.54) and diet treatment only (OR 1.53, 95% CI 1.35-1.73). No differences were found among patients who used insulin (OR 0.97, 95% CI 0.84-1.11). Further adjustment for duration of type 2 diabetes, body mass index (BMI), systolic blood pressure, total cholesterol, and smoking affected the results only slightly. CONCLUSIONS: The gender risks of nonfatal stroke in patients with type 2 diabetes appear to differ considerably depending on treatment types.