INTRODUCTION:Antiandrogen therapy can reduce the expression of transmembrane protease 2, which is essential for severe acute respiratory syndrome coronavirus-2 to enter the host cells. Prior trials suggested the efficacy of antiandrogen agents in patients with COVID-19. We investigated whether antiandrogen agents reduce mortality compared to placebo or usual care. EVIDENCE ACQUISITION:We searched for randomized controlled trials comparing antiandrogen agents with placebo or usual care alone in adults with COVID-19 in PubMed, EMBASE, the Cochrane Library, the reference lists of retrieved articles, and publications by manufacturers of antiandrogen agents. The primary outcome was mortality at the longest follow-up available. The secondary outcomes included clinical worsening, the need for invasive mechanical ventilation, admission to the intensive care unit, hospitalization, and thrombotic events. We registered this systematic review and meta-analysis in PROSPERO International Prospective Register of Systematic Reviews (CRD42022338099). EVIDENCE SYNTHESIS:We included 13 randomized controlled trials enrolling 1934 COVID-19 patients. We found that antiandrogen agents reduced mortality at the longest follow-up available (91/1021 [8.9%] vs. 245/913 [27%]; risk ratio =0.40; 95% confidence interval, 0.25-0.65; P=0.0002; I2=54%). Antiandrogen therapy also reduced clinical worsening (127/1016 [13%] vs. 298/911 [33%]; risk ratio =0.44; 95% confidence interval, 0.27-0.71; P=0.0007; I2=70%) and hospitalization (97/160 [4.4%] vs. 24/165 [15%]; risk ratio =0.24; 95% confidence interval, 0.10-0.58; P=0.002; I2=44%). There was no significant difference in the other outcomes between the two treatment groups. CONCLUSIONS:Antiandrogen therapy reduced mortality and clinical worsening in adult patients with COVID-19.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages. We performed a systematic literature review to assess efficacy and safety of awake ECMO without invasive ventilation in patients with respiratory failure. DATA SOURCES: PubMed, Web of Science, and Scopus were searched for studies reporting outcome of awake ECMO for adult patients with respiratory failure. STUDY SELECTION: We included all studies reporting outcome of awake ECMO in patients with respiratory failure. Studies on ECMO for cardiovascular failure, cardiac arrest, or perioperative support and studies on pediatric patients were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of awake ECMO failure, and mortality. Primary outcome was rate of awake ECMO failure (need for intubation). Pooled estimates with corresponding 95% CIs were calculated. Subgroup analyses by setting were performed. DATA SYNTHESIS: A total of 57 studies (28 case reports) included data from 467 awake ECMO patients. The subgroup of patients with acute respiratory distress syndrome showed a pooled estimate for awake ECMO failure of 39.3% (95% CI, 24.0–54.7%), while in patients bridged to lung transplantation, pooled estimate was 23.4% (95% CI, 13.3–33.5%). Longest follow-up mortality was 121 of 439 (pooled estimate, 28%; 95% CI, 22.3–33.6%). Mortality in patients who failed awake ECMO strategy was 43 of 74 (pooled estimate, 57.2%; 95% CI, 40.2–74.3%). Two cases of cannula self-removal were reported. CONCLUSIONS: Awake ECMO is feasible in selected patients, although the effect on outcome remains to be demonstrated. Mortality is almost 60% in patients who failed awake ECMO strategy.

Introduction: Coronary angiography (CAG) frequently reveals coronary artery disease (CAD) after out-of-hospital cardiac arrest (OHCA), but its use is not standardized and often reported in different subpopulations. This systematic review and meta-analysis accurately describes angiographic features in resuscitated and refractory OHCA.Methods: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to October 31, 2022. Studies reporting coronary angiography findings after OHCA were considered eligible. The primary outcome was location and rate of coronary lesions. Coronary angiography findings with 95% confidence intervals were pooled with a meta-analysis of proportion.Results: 128 studies (62,845 patients) were included. CAG, performed in 69% (63-75%) of patients, found a significant CAD in 75% (70-79%), a culprit lesion in 63% (59-66%), and a multivessel disease in 46% (41-51%). Compared to patients with return of spontaneous circulation, refractory OHCA was associated with more severe CAD due to a higher rate of left main involvement (17% [12-24%] vs 5.7% [3.1-10%]; p = 0.002) and acute occlusion of left anterior descending artery (27% [17-39%] vs 15% [13-18%]; p = 0.02). Nonshockable patients without ST-elevation were those receiving CAG less frequently, despite significant disease in 54% (31-76%). Left anterior descending artery was the most frequently involved (34% [30-39%]).Conclusions: Patients with OHCA have a high prevalence of significant CAD caused by acute and treatable coronary lesions. Refractory OHCA was associated with more severe coronary lesions. CAD was also present in patients with nonshockable rhythm and without ST elevation. However, heterogeneity of studies and selection of patients undergoing CAG limit the certainty of findings.

•COVID-19 related thrombosis are immune-mediated and detectable as lung MicroCLOTS.•COVID-19 radiological pattern confirms that in situ thrombosis are not embolisms.•Full anticoagulation may prevent MicroCLOTS in non-ICU COVID-19 patients.•Routine full anticoagulation might increase bleeding risk in advanced stages.•Anti-inflammatory drugs play a pivotal role in the management of MicroCLOTS.

The novel coronavirus disease (COVID-19) affected females less than males, as demonstrated by sex-disaggregated data present in the literature. During the first wave, females hospitalized at San Raffaele Hospital, Milan, Italy were few in number, presented symptoms later and had less critical clinical conditions than males. The present study aimed to evaluate the epidemiological status of the female population during the second wave, which occurred in Autumn 2020 in Italy. This prospective cohort study included all patients, with a positive real-time reverse-transcriptase polymerase chain reaction for COVID-19, who attended the emergency department or were hospitalized in wards and/or intensive care unit (ICU) from 29th September 2020 to 29th November 2020. A total of 1216 COVID-19 patients were included, of whom 459 (37.8%) were females. The percentage of females admitted was 41.3% in the first period and 36.3% in the second period, without significant increase over time (p = 0.3). Females accounted for 25% of all COVID-19 intensive care unit admissions. There was significantly sex-based difference in the overall hospital mortality (4.1% for females and 11.3% for males, p < 0.0001). At San Raffaele Hospital, Milan, Italy during the second wave, female patients were few and affected by a less severe form of COVID-19. An increase over time of females hospitalized patients was not reported, unlike what was previously demonstrated during the first wave.

BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.