To describe the clinical characteristics, laboratory results, imaging findings, and in-hospital outcomes of COVID-19 patients admitted to Brazilian hospitals. Methods: A cohort study of laboratory-confirmed COVID-19 patients who were hospitalized from March 2020 to September 2020 in 25 hospitals. Data were collected from medical records using Research Electronic Data Capture (REDCap) tools. A multivariate Poisson regression model was used to assess the risk factors for in-hospital mortality. Results: For a total of 2,054 patients (52.6% male; median age of 58 years), the in-hospital mortality was 22.0%; this rose to 47.6% for those treated in the intensive care unit (ICU). Hypertension (52.9%), diabetes (29.2%), and obesity (17.2%) were the most prevalent comorbidities. Overall, 32.5% required invasive mechanical ventilation, and 12.1% required kidney replacement therapy. Septic shock was observed in 15.0%, nosocomial infection in 13.1%, thromboembolism in 4.1%, and acute heart failure in 3.6%. Age >= 65 years, chronic kidney disease, hypertension, C-reactive protein ! 100 mg/dL, platelet count < 100 Â 10 9 /L, oxygen saturation < 90%, the need for supplemental oxygen, and invasive mechanical ventilation at admission were independently associated with a higher risk of in-hospital mortality. The overall use of antimicrobials was 87.9%. Conclusions: This study reveals the characteristics and in-hospital outcomes of hospitalized patients with confirmed COVID-19 in Brazil. Certain easily assessed parameters at hospital admission were independently associated with a higher risk of death. The high frequency of antibiotic use points to an over-use of antimicrobials in COVID-19 patients.

Background Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. Methods Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. Results Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. Conclusion The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium’s clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.

Objective Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (1H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using 1H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3T 1H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. The association between brain lactate with mitochondrial activity and antidepressant efficacy were also assessed. Methods Twenty medication-free outpatients with short length of illness BD (80% drug-naive) in a current major depressive episode were matched with healthy controls. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood levels 0.48±0.19mmL). CC lactate was measured before (week 0) and after lithium therapy (week 6) using 1H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. Results Subjects with BD depression showed a significantly higher CC lactate in comparison to healthy controls. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared to baseline (p=0.002). No association between reduction in CC lactate levels over time and remission at week 6 was observed. Conclusions This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium’s therapeutic actions. Clinical trial number NCT01919892

Objectives The majority of available scores to assess mortality risk of coronavirus disease 19 (COVID-19) patients in the emergency department have high risk of bias. Therefore, our aim was to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients, and to compare this score with other existing ones. Methods Consecutive patients (≥18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. Results Median (25th-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO 2 /FiO 2 ratio, platelet count and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829 to 0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833 to 0.885]) and Spanish (0.894 [95% CI 0.870 to 0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions We designed and validated an easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation, for early stratification for in-hospital mortality risk of patients with COVID-19.

Cholesterol is an essential component in the structure and function of cell membranes and has been associated with the major pathological signatures of Alzheimer's disease (AD). To maintain brain cholesterol homeostasis, it is converted into 24(S)-hydroxycholesterol (24OHC) which can be driven through the blood-brain barrier. Several studies have already described a decrease in 24OHC and an increase of 27(S)-hydroxycholesterol (27OHC) in AD, as a reflection of disease burden, the loss of metabolically active neurons and the degree of structural atrophy. It is also well known that peripheral cholesterol is altered in AD patients. However, there are no data regarding effects of AD treatment in this cholesterol pathway. Since a study from our group indicated a significant increase in membrane phospholipid metabolism by donepezil, the aim of this study was to evaluate the effect of short- and long-term donepezil treatment on cholesterol and metabolites 24OHC and 27OHC in plasma of AD patients and in healthy volunteers. At baseline, we found a decrease of 24OHC (p = 0.003) in AD patients. Cholesterol levels increased with donepezil treatment (p = 0.04) but no differences were observed regarding 24OHC and 27OHC. However, these results confirm and extend previous studies demonstrating disturbed cholesterol turnover in Alzheimer's disease.