MicroRNA-155-5p (miR-155-5p) is a proinflammatory, oncogenic miRNA, involved in various physiological processes, including hematopoiesis, immunity, inflammation, and cell lineage differentiation. It regulates important transcription factors, such as E2F2, hypoxia-inducible factor 1 (HIF1), and FOXO3. Recently, the dysregulation of miR-155-5p expression has been linked to chronic lymphocytic leukemia (CLL) pathogenesis. In this research study, we investigated the potential diagnostic and prognostic value of miR-155-5p in CLL. To achieve our goal, we isolated total RNA from peripheral blood mononuclear cells (PBMCs) collected from 88 CLL patients and 36 nonleukemic blood donors and performed polyadenylation of total RNA and reverse transcription. Next, we quantified miR-155-5p levels using an in-house-developed real-time quantitative PCR method, before proceeding to extensive biostatistical analysis. Thus, it appears that miR-155-5p is significantly overexpressed in PBMCs of CLL patients and can distinguish them from nonleukemic population. Kaplan-Meier OS analysis and bootstrap univariate Cox regression showed that high miR-155-5p expression predicts inferior OS for CLL patients (p < 0.001). Interestingly, miR-155-5p overexpression retains its unfavorable prognostic role in CLL patients stratified according to established prognostic factors [CD38 expression and mutational status of the immunoglobulin heavy chain variable region (IGHV)]. Thus, miR-155-5p appears as a promising, independent molecular biomarker of unfavorable prognosis in CLL.

COVID-19 is a global pandemic associated with increased morbidity and mortality. Convalescent plasma (CP) infusion is a strategy of potential therapeutic benefit. We conducted a multicenter phase II study to evaluate the efficacy and safety of CP in patients with COVID-19, grade 4 or higher. To evaluate the efficacy of CP, a matched propensity score analysis was used comparing the intervention (n = 59) to a control group (n = 59). Sixty patients received CP within a median time of 7 days from symptom onset. During a median follow-up of 28.5 days, 56/60 patients fully recovered and 1 patient remained in the ICU. The death rate in the CP group was 3.4% vs. 13.6% in the control group. By multivariate analysis, CP recipients demonstrated a significantly reduced risk of death [HR: 0.04 (95% CI: 0.004–0.36), p: 0.005], significantly better overall survival by Kaplan–Meir analysis (p < 0.001), and increased probability of extubation [OR: 30.3 (95% CI: 2.64–348.9), p: 0.006]. Higher levels of antibodies in the CP were independently associated with significantly reduced risk of death. CP infusion was safe with only one grade 3 adverse event (AE), which easily resolved. CP used early may be a safe and effective treatment for patients with severe COVID-19 (trial number NCT04408209).

Combined aerobic interval and strength training induces a greater benefit than interval training alone on muscle strength in CHF patients. Adaptations other than hypertrophy, such as muscle fiber type alterations and/or neuromuscular adjustments, may account for these results.

Graphical AbstractSARS-CoV-2 infection has significant effects on red blood cells that seems to be associated with disease severity in these patients. (A) Non-Intensive care unit hospitalized patients due to severe COVID-19 disease were included in this study (n = 36). (B) The control group included healthy subjects without renal or hepatic impairment, no diagnosis of anemia or myeloid malignancy, and no blood transfusion over the past 3 months (n = 18). (C) Demographic data, clinical, laboratory and chest Computed Tomography (CT) findings at time of admission were recorded. Hematological tests, standard biochemical analysis of serum components were performed both in the patient and in the control group and coagulation analysis were evaluated in the patient group. A peripheral blood smear examination was also performed in all patients and control samples. (D) Plasma free hemoglobin and red blood cell (RBC) osmotic fragility and free hemoglobin (Free-Hb) after mechanical stress (MECH) by mechanical hemolysis were assesed in both patients and controls. Intracellular (i) calcium (iCa2 +) levels, RBCs phosphatidylserine exposure (PS), RBC membrane-bound immunoglobulins G (IgGs), and activate RBC caspase-3 levels as cell clearance and apoptotic markers were measured by flow cytometry. A spectrophotometric assay was used to quantify the activity of G6PD enzyme. Intracellular RBC reactive oxidative species (iROS) were assesed in both patients and controls. (E) Elevated hemolysis markers (Free-Hb) and Lactate Dehydrogenase (LDH) were observed in patients compared to the control group. Patients’ RBCs were more vulnerable to mechanical stress, and exhibited significantly elevated apoptotic markers (iCa2 + and RBC-PS+). Erythrocyte iROS levels were significantly lower in the patients’ group compared to healthy controls. This finding possibly correlates with the increased G6PDH activity levels in this group, suggesting a compensatory mechanism against the virus. (F) Patients’ D-Dimers correlated with RBC-PS +, implying a possible contribution of the erythrocytes in the thrombotic diathesis associated with the SARS-CoV-2 disease. (G) Free-Hb levels correlated with the extend of pulmonary infiltrates on chest CT in COVID-19 patients. RBC-IgGs+ correlated with the severity of pulmonary CT imaging features as well as the abnormality of lung function, expressed by the PO2/FiO 2 ratio. This finding suggests that hypoxia may lead to RBC senescence.