Incidence, Risk Factors and Mortality Associated with Major Bleeding Events in Hospitalized COVID-19 Patients.

Thromboprophylaxis is a mainstay of treatment of hospitalized COVID-19 patients, due to the high occurrence of thrombotic events. This increases the risk of bleeding. However, data on bleeding events and associated risk factors are scarce. Thus, we aimed to investigate the incidence, predictors and clinical outcomes associated with major bleeding in hospitalized COVID-19 patients. We retrospectively evaluated a cohort of 4014 consecutively hospitalized COVID-19 patients treated in a tertiary-level institution in the period 3/2020-3/2021. Bleeding of any kind was documented in 322 (8%) and major bleeding in 129 (3.2%) patients. A total of 129 (40.1%) bleeding events were present at the time of hospital admission, and 193 (59.9%) occurred during hospitalization. In the multivariate logistic regression analysis, intensive-care-unit treatment (adjusted odds ratio (aOR) 6.55; p < 0.001), atrial fibrillation (aOR 2.55; p = 0.029), higher white-blood-cell count (WBC) (aOR 1.03; p = 0.021), lower hemoglobin (aOR 0.97; p = 0.002) and history of bleeding (aOR 17.39; p < 0.001) were recognized as mutually independent predictors of major bleeding. Major bleeding was significantly associated with increased in-hospital mortality compared to non-major-bleeding patients (59.7% vs. 34.8%, p < 0.001), especially if occurring during hospitalization. Median time from major bleeding to death was 5 days. Bleeding events are frequent in hospitalized COVID-19 patients, with a significant proportion of patients presenting at the time of hospital admission, and others almost universally exposed to anticoagulant and corticosteroid therapies. Major bleeding is associated with high mortality, especially if occurring during hospitalization. The recognition of patients at risk and implementation of timely interventions are of high clinical importance.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

No Evident Prognostic Benefit of Statin Use in Diffuse Large B-Cell Lymphoma Patients with Unfavorable Disease Features Treated with R-DA-EPOCH.

Recent reports indicate that patients with aggressive non-Hodgkin lymphomas might benefit if concomitantly receiving statins with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin) and prednisone immunochemotherapy. We retrospectively analyzed a cohort of 130 newly diagnosed diffuse large B-cell lymphomas with unfavorable clinical features treated with first-line rituximab, dose-adjusted etoposide, prednisone, vincristine [Oncovin], cyclophosphamide, hydroxydaunorubicin (R-DA-EPOCH) immunochemotherapy in period 2005-2019. A total of 17/130 (13.1%) patients received statins concomitantly with immunochemotherapy, mostly atorvastatin and in intermediate statin dose intensity. Besides tendency to be associated with older age (p = 0.070), there were no other significant associations of statins use with neither sex, disease stage, R-IPI, or other unfavorable disease features (p > 0.05 for all analyses). Also, no significant differences were present considering feasibility (number of cycles with dose escalation/reduction), toxicity (number of cycles with anemia, thrombocytopenia, neutropenia, febrile neutropenia, and septic complications) nor efficacy (response rates) of R-DA-EPOCH regimen (p > 0.05 for all analyses). Also, statin use had no significant association with neither OS (p = 0.480) nor PFS (p = 0.891). Lack of associations of statin use with relevant clinical outcomes was further corroborated by multivariate analyses.