The Incidence and Mortality Impact of Gastrointestinal Bleeding in Hospitalized COVID-19 Patients.

BACKGROUND: Patients requiring hospitalization to critical care units are at a higher risk for gastrointestinal (GI) bleeding. Although severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is predominantly a pulmonary disease, other serious manifestations including thromboembolic phenomenon are reported. Acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, use of steroids and anticoagulation are all known to increase the risk of GI bleeding significantly. AIM: To study the incidence of GI bleeding and its impact on mortality in patients admitted with SARS-CoV-2. METHODS: We retrospectively reviewed all patients admitted with SARS-CoV-2 from February 1, 2020 to April 15, 2020. We collected data including demographics, comorbid conditions, laboratory parameters, steroid and anticoagulant use. Coffee ground emesis, hematemesis, melena and hematochezia were defined as GI bleeding. All-cause mortality was reviewed for all patients included in the study. The relationship between GI bleeding and mortality was studied using logistic regression. RESULTS: We had a total of 1206 patients hospitalized with SARS-CoV-2 infection with an all-cause mortality of 34% (n = 411). The overall incidence of GI bleeding was 3.1% (n = 37) with no significant difference between the patients who survived versus died during hospitalization (1.3% vs 1.5%, p = 0.77). Logistic regression analysis did not identify GI bleeding as an independent predictor of mortality. Therapeutic doses of anticoagulation were administered in 13.3% (n = 161) of patients, of which 6.8% (n = 11) developed GI bleeding. Patients were more likely to develop GI bleeding with use of therapeutic doses of anticoagulation (29.7% vs 12.8%, p = 0.003), steroids (37.8% vs 18.5%, p = 0.003) and mechanical ventilation (48.6% vs 30.4%, p = 0.018). CONCLUSION: Patients hospitalized with SARS-CoV-2 infection are at risk of gastrointestinal bleeding. Therapeutic doses of anticoagulation, mechanical ventilation and steroid use are significant risk factors for GI bleeding. However, GI bleeding did not significantly alter the mortality rates in SARS-CoV-2-infected patients.

COVID-19 in the Healthy Patient Population: Demographic and Clinical Phenotypic Characterization and Predictors of In-Hospital Outcomes.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can infect patients in any age group including those with no comorbid conditions. Understanding the demographic, clinical, and laboratory characteristics of these patients is important toward developing successful treatment strategies. Approach and Results: In a retrospective study design, consecutive patients without baseline comorbidities hospitalized with confirmed COVID-19 were included. Patients were subdivided into ≤55 and >55 years of age. Predictors of in-hospital mortality or mechanical ventilation were analyzed in this patient population, as well as subgroups. Stable parameters in overall and subgroup models were used to construct a cluster model for phenotyping of patients. Of 1207 COVID-19-positive patients, 157 met the study criteria (80≤55 and 77>55 years of age). Most reliable predictors of outcomes overall and in subgroups were age, initial and follow-up d-dimer, and LDH (lactate dehydrogenase) levels. Their predictive cutoff values were used to construct a cluster model that produced 3 main clusters. Cluster 1 was a low-risk cluster and was characterized by younger patients who had low thrombotic and inflammatory features. Cluster 2 was intermediate risk that also consisted of younger population that had moderate level of thrombosis, higher inflammatory cells, and inflammatory markers. Cluster 3 was a high-risk cluster that had the most aggressive thrombotic and inflammatory feature. CONCLUSIONS: In healthy patient population, COVID-19 remains significantly associated with morbidity and mortality. While age remains the most important predictor of in-hospital outcomes, thromboinflammatory interactions are also associated with worse clinical outcomes regardless of age in healthy patients.

Modulation of activated astrocytes in the hypothalamus paraventricular nucleus to prevent ventricular arrhythmia complicating acute myocardial infarction.

BACKGROUND: Sympathetic overactivation after acute myocardial infarction (AMI) contributes to ventricular arrhythmia (VA). Paraventricular nucleus (PVN) of the hypothalamus may play an important role on this context, however, the mechanisms remain unknown. In this study, we investigated whether inhibition of activated astrocytes in the PVN could reduce VA in rats with AMI. METHODS: The anesthetized rats were randomly divided into four groups of sham-operated, AMI, AMI + vehicle and AMI + fluorocitrate (FCA). Electrocardiogram was continuously recorded. RNA sequencing, sympathetic nerve activity (heart rate variability and norepinephrine levels) and ventricular electrical instability (ventricular effective refractory period and ventricular fibrillation inducibility) were measured. Furthermore, brain tissues were extracted to detect expression of inflammatory cytokines (IL-6, and TNF-α), astrocyte and neuro activation. RESULTS: RNA sequencing analysis showed that functions of differentially expressed genes in the PVN of AMI rats were significantly enriched in immune system- and neuroactive-related pathways, along with enhance expression of cytokines and Glial fibrillary acidic protein (GFAP). We further characterized that astrocytes were activated in PVN and intervention of activation astrocytes by FCA significantly inhibited sympathetic nerve activity and decreased the incidence of VA and ventricular electrical instability in rats with AMI. Moreover, FCA significantly attenuated neurons activation and downregulated expression of inflammatory cytokines in the PVN. CONCLUSIONS: Inhibition of activated astrocytes in the PVN could reduce VA occurrence and improve ventricular electrical instability in AMI rats by central neuro-immune pathway. These findings suggest that astrocytes are a potential target for prevention and treatment of VA complicating AMI.

Mesenchymal Stem Cells with Enhanced Bcl-2 Expression Promote Liver Recovery in a Rat Model of Hepatic Cirrhosis.

BACKGROUND/AIMS: Mesenchymal stem cell (MSC) transplantation has emerged as an option for the treatment of chronic hepatic cirrhosis, while its therapeutic efficacy could be improved. The bcl-2 gene is anti-apoptotic and can help cell survival and proliferation. Therefore, we explored whether transplanted MSCs with enhanced bcl-2 expression may be beneficial in the treatment of experimental cirrhosis in rats. METHODS: MSCs were isolated from rat bone marrow, expanded in vitro and transfected with adeno-associated virus (AAV) engineered the bcl-2 gene (AAV-bcl-2). Rats with cirrhosis induced by carbon tetrachloride (CCl4) were treated with AAV-bcl-2 infected BMSCs-AAV-bcl-2, with the cells traced in vivo post transplantation. Liver pathology and function were evaluated 7, 14, 21, and 28 days post transplantation, respectively. RESULTS: On day 7 post transplantation, the infused AAV-bcl-2 had integrated into the hepatocyte-like cells (HLCs) that expressed albumin (ALB), Cytokeratin 18 (CK18), and hepatocytes nuclear factor 4a (HNF4a). On day 28 post transplantation, rats in the cirrhosis + BMSCs-AAV-bcl-2 group showed the most dense HLCs, highest mRNA and protein levels of ALB, CK18, and HNF4a, compared to the other groups. Their liver function recovered most rapidly in 4 week observation, while histological sign of cirrhosis remained at the end of this period. CONCLUSION: BMSCs over expressing bcl-2 gene showed better survival, and enhanced the differentiation into hepatocytes-like cells, and appeared to promote the recovery of liver function in rats with experimental cirrhosis.