Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is mediated by the androgen-promoted protease, transmembrane protease, serine 2 (TMPRSS2). Previously, we have shown that treatment with proxalutamide, a non-steroidal androgen receptor antagonist, accelerates viral clearance and clinical remission in outpatients with coronavirus disease 2019 (COVID-19) compared to placebo. The effects in hospitalized COVID-19 patients were unknown. Methods: Men and women hospitalized but not requiring mechanical ventilation were randomized (1:1 ratio) to receive 300 mg of proxalutamide per day or placebo for 14 days. The study was conducted at eight sites in the state of Amazonas, Brazil. The primary outcome measure was the clinical status (8-point ordinal scale) at 14-days post-randomization. The primary efficacy endpoint was the 14-day recovery ratio (alive hospital discharge [scores 1, 2]). Findings: A total of 645 patients were randomized (317 received proxalutamide, 328 placebo) and underwent intention-to-treat analysis. The 14-day median ordinal scale score in the proxalutamide group was 1 (interquartile range [IQR]=1-2) versus 7 (IQR=2-8) for placebo, P<0.001. The 14-day recovery rate was 81.4% for proxalutamide and 35.7% for placebo (recovery ratio, 2.28; 95% CI 1.95-2.66 [P<0.001]). The 28-day all-cause mortality rate was 11.0% for proxalutamide versus 49.4% for placebo (hazard ratio, 0.16; 95% CI 0.11-0.24). The median post-randomization time to recovery was 5 days (IQR=3-8) for proxalutamide versus 10 days (IQR=6-15) for placebo. Interpretation: Hospitalized COVID-19 patients not requiring mechanical ventilation receiving proxalutamide had a 128% higher recovery rate than those treated with placebo. All-cause mortality was reduced by 77.7% over 28 days. (ClinicalTrials.gov number, NCT04728802).

CT scan seems to measure 2 important markers of MS: visceral adiposity and hepatic fatty infiltration. In morbidly obese patients, both visceral adiposity and hepatic fatty infiltration increase the risk for the presence of MS.

Background. Obesity is considered a low-grade inflammatory state and has been associated with increased acute phase proteins as well as changes in serum fatty acids. Few studies have assessed associations between acute phase proteins and serum fatty acids in morbidly obese patients. Objective. To investigate the relationship between acute phase proteins (C-Reactive Protein, Orosomucoid, and Albumin) and serum fatty acids in morbidly obese patients. Methods. Twenty-two morbidly obese patients were enrolled in this study. Biochemical and clinical data were obtained before bariatric surgery, and fatty acids measured in preoperative serum. Results. Orosomucoid was negatively correlated with lauric acid (P = 0.027) and eicosapentaenoic acid (EPA) (P = 0.037) and positively with arachidonic acid (AA) (P = 0.035), AA/EPA ratio (P = 0.005), and n-6/n-3 polyunsaturated fatty acids ratio (P = 0.035). C-Reactive Protein (CRP) was negatively correlated with lauric acid (P = 0.048), and both CRP and CRP/Albumin ratio were negatively correlated with margaric acid (P = 0.010, P = 0.008, resp.). Albumin was positively correlated with EPA (P = 0.027) and margaric acid (P = 0.008). Other correlations were not statistically significant. Conclusion. Our findings suggest that serum fatty acids are linked to acute phase proteins in morbidly obese patients.

Background The year 2020 was marked by the new coronavirus pandemic, resulting in millions of cases and deaths, placing healthcare workers at high risk of infection. Aims The aim of this study was to describe the role of an occupational health service during coronavirus disease 2019 pandemic in an oncologic hospital and characterize the most likely sources of viral infection. Methods The information of all healthcare workers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from 11 March to 15 December 2020 was collected through an epidemiological survey conducted during contact tracing. The data extracted included gender, age, comorbidities, occupational group, source of infection, clinical presentation, duration of the disease, need for hospitalization and persistent or late symptoms after disease or upon returning to work. Results Out of a total of 2300 workers, 157 were infected, consisting of nurses (36%), nurse assistants (33%) and diagnostic and therapeutic professionals (10%). Physicians and administrative staff accounted for 8% each. The most frequently reported source of infection was occupational (43%), owing to worker-to-worker transmission (45%) and patient-to-worker transmission (36%). The most frequent moments of infection perceived corresponded to the removal of protective equipment during meals and moments of rest in the staff and changing rooms. Conclusions The study revealed that occupational transmission from patients and colleagues might be an important source of SARS-CoV-2 infection in healthcare workers. Spread between colleagues accounted for 45% of the occupational source infections reported. Implementing physical distancing measures and limiting the number of people in changing and rest rooms could significantly reduce infection and related absenteeism.

Roux-en-Y gastric bypass promoted a decrease in plasma concentrations of CRP and Alpha-1-acid glycoprotein, improving lipid and inflammatory profiles.

Introduction: Proxalutamide, a second generation non-steroidal antiandrogen (NSAA), primarily developed for castration-resistant prostate cancer, demonstrated reduction in 28-day mortality rate of 77.7% in hospitalized COVID-19 patients in a double-blind, placebo-controlled, two-arm randomized clinical trial (RCT), through intention-to-treat (ITT) analysis. However, the intriguingly high 28-day mortality rate of patients that did not complete the 14-day treatment with proxalutamide, compared non-completers of the placebo arm and overall placebo arm, raised the hypotheses of the existence of non-neglectable differences between ITT and on-treatment (OT) analysis in terms of drug efficacy. Despite the inherent limitations of OT analysis, we aimed to respond to unanswered questions regarding the drug efficacy when the 14-day treatment with proxalutamide was complete, and secondarily understand the causality relationship between treatment interruption and mortality rate. Methods: This is a post-hoc exploratory analysis of a double-blinded, randomized, placebo-controlled, prospective, multicentric, two-arm RCT of 300mg-daily 14-day proxalutamide therapy for hospitalized COVID-19 patients not requiring mechanical ventilation, using OT population, i.e., excluding patients that did not complete treatment or interrupted at least 24 hours before death. Patients above 18 years old with confirmed COVID-19 not presenting kidney, liver, or heart failure were eligible. The primary outcome was 8-point COVD-19 ordinal scale at day 14. Secondary outcomes included 28-day 8-point COVID-19 ordinary scale, 14-day and 28-day all-cause mortality rate, and median hospital length. Results: In total, 580 patients completed the 14-day treatment or died during treatment, including 288 patients in the proxalutamide arm and 292 patients in the placebo arm, with similar baseline characteristics between groups. The 28-day all-cause mortality rate was 4.2% in the proxalutamide group and 49.0% in the placebo group. The mortality risk ratio (RR) was 0.08 (95% CI, 0.05-0.15), with a number needed to treat (NNT) of 2.2 to prevent death. The median hospital length stay after randomization was 05 days (interquartile range - IQR = 3 to 7.2 days) in the proxalutamide group and 09 days (IQR = 6 to 15 days) in the placebo group (p < 0.001). The 28-day all-cause mortality rate of patients that received proxalutamide but interrupted treatment before 14 days was 79.3%, while those that received placebo and interrupted before 14 days was 52.8% (p = 0.054 between groups). Conclusion: The reduction in 28-day all-cause mortality rate with 14-day proxalutamide treatment for hospitalized COVID-19 patients was more significant treatment completers (92%), compared to the reduction when all patients enrolled in the proxalutamide arm were considered (77.7%). However, the magnitude of statistical significance of the reduction in all-cause mortality and the NNT were similar between the OT and ITT analysis. The apparent high mortality risk rate with early interruption of proxalutamide treatments suggests that strategies for treatment compliance should be reinforced for future RCTs with proxalutamide. (NCT04728802)

Highlights The most common imaging findings of COVID-19 in our patient group were multilobar ground-glass opacities and parenchymal consolidation. Older age, opacities with diffuse distribution in the axial plane and a higher CT severity index were associated with worse short-term prognosis. The presence of rounded opacities or patterns resembling organizing pneumonia were associated with favorable short-term prognosis.

Introduction: Antiandrogen are good candidates against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) due to the inhibition of its entry into host cells by the suppression of TMPRSS2, an enzyme that primes the SARS-CoV-2 spike (S) protein and is key for its cell entry. Proxalutamide is a second-generation nonsteroidal anti-androgen (NSAA) with strong activities on androgen receptor (AR) antagonism, suppression of AR nuclear expression, and downregulation of the membrane-attached angiotensin converting enzyme-2 (ACE2). The efficacy of proxalutamide was previously demonstrated for early COVID-19 patients, and has now demonstrated efficacy to reduce deaths in hospitalized COVID-19 patient in a double-blind, placebo-controlled randomized clinical trial (RCT). Whether radiological changes would follow the improvement in clinical outcomes with proxalutamide is not established. The present post-hoc analysis aims to evaluate whether proxalutamide improves lung injury observed through chest computed tomography (CT) scans, in addition to the clinical improvement, thus providing further objective evidence of the drug response in COVID-19. Methods: This is a post-hoc analysis of the radiological findings of a double-blinded, placebo-controlled, prospective, two-arm RCT (The Proxa-Rescue AndroCoV Trial) with all enrolled patients from the three participating institutions of the city of Manaus, Amazonas, Brazil, that had at least two chest CT scans during hospitalization. The quantification of lung parenchyma involvement was performed by independent board-certified radiologists with expertise in analysis of COVID-19 images, that were blind to the assigned intervention in the RCT. A first chest CT scan was performed upon randomization and a second CT scan was performed approximately five days later, whenever patient transportation was feasible. Results: Of the 395 patients initially evaluated, 72 and 179 patients from the proxalutamide and placebo arms, respectively, were included (n=251). Baseline and clinical characteristics, interval between first and second chest CT scans, and percentage of lung parenchyma affected in the baseline chest CT scan were similar between groups. In the second chest CT scan, the percentage of lungs affected (Median - IQR) was 35.0% (25.0-57.5%) in the proxalutamide group versus 67.5% (50.0-80.0%) in the placebo group (p < 0.001). The absolute and relative change between the second and first chest CT scans (Median - IQR) were -15.0 percent points (p.p.) (-30.0 - 0.0p.p.) and -25.0% (-50.0 - 0.0%) in the proxalutamide group, respectively, and +15.0p.p. (0.0 - +30.0p.p.) and +32.7% (0.0 - +80.0%) in the placebo group, respectively (p < 0.001 for both absolute and relative changes). Conclusion: Proxalutamide improves lung opacities in hospitalized COVID-19 patients when compared to placebo. (NCT04728802)