Background: Convalescent plasma is a potential therapeutic option for critically ill patients with coronavirus disease 19 (COVID-19), yet its efficacy remains to be determined. The aim was to investigate the effects of convalescent plasma (CP) in critically ill patients with COVID-19.Methods: This was a single-center prospective observational study conducted in Rio de Janeiro, Brazil, from March 17th to May 30th, with final follow-up on June 30th. We included 113 laboratory-confirmed COVID-19 patients with respiratory failure. Primary outcomes were time to clinical improvement and survival within 28 days. Secondary outcomes included behavior of biomarkers and viral loads. Kaplan–Meier analyses and Cox proportional-hazards regression using propensity score with inverse-probability weighing were performed.Results: 41 patients received CP and 72 received standard of care (SOC). Median age was 61 years (IQR 48–68), disease duration was 10 days (IQR 6–13), and 86% were mechanically ventilated. At least 29 out of 41CP-recipients had baseline IgG titers ≥ 1:1,080. Clinical improvement within 28 days occurred in 19 (46%) CP-treated patients, as compared to 23 (32%) in the SOC group [adjusted hazard ratio (aHR) 0.91 (0.49–1.69)]. There was no significant change in 28-day mortality (CP 49% vs. SOC 56%; aHR 0.90 [0.52–1.57]). Biomarker assessment revealed reduced inflammatory activity and increased lymphocyte count after CP.Conclusions: In this study, CP was not associated with clinical improvement or increase in 28-day survival. However, our study may have been underpowered and included patients with high IgG titers and life-threatening disease.Clinical Trial Registration: The study protocol was retrospectively registered at the Brazilian Registry of Clinical Trials (ReBEC) with the identification RBR-4vm3yy (http://www.ensaiosclinicos.gov.br).

Background Aneurysmal subarachnoid hemorrhage (SAH) is an acute cerebrovascular disease associated with high mortality and long-term functional impairment among survivors. Systemic inflammatory responses after acute injury and nosocomial infections are frequent complications, making the management of these patients challenging. Here, we hypothesized that sepsis might be associated with early and long-term mortality and functional outcomes. Our objective was to define the incidence of sepsis, diagnosed prospectively with the Sepsis-3 criteria, and to determine its impact on mortality and functional outcomes of patients with SAH. Methods We prospectively included all adult patients with aneurysmal SAH admitted to the intensive care unit (ICU) of a reference center between April 2016 and May 2018. Daily clinical and laboratory follow-up data were analyzed during the first 14 days, with data collected on sepsis according to the Sepsis-3 criteria. The main outcome was the functional outcome using the Modified Rankin Scale (mRS), which was assessed at hospital discharge and 3, 6 and 12 months post-discharge. Results In total, 149 patients were enrolled. The incidence of sepsis was 28%. Multivariable logistic regression analysis revealed that death or functional dependence (defined as an mRS score of 4 to 6) at hospital discharge was independently associated with sepsis (OR 3.4, 95% CI 1.16–9.96, p = 0.026) even after controlling for World Federation of Neurological Surgeons (WFNS) Scale (OR 4.66, 95% CI 1.69–12.88, p = 0.003), hydrocephalus (OR 4.55, 95% CI 1.61–12.85, p = 0.004) and DCI (OR 3.86, 95% CI 1.39–10.74, p = 0.01). Long-term follow-up mortality rates were significantly different in the septic and nonseptic groups (log-rank test p < 0.0001). The mortality rate of septic patients was 52.5%, and that of nonseptic patients was 16%. Conclusion Sepsis plays a significant role in the outcomes of patients with SAH, affecting both mortality and long-term functional outcomes. Combining high-level neurocritical care management of neurological complications and the optimal diagnosis and management of sepsis may effectively reduce secondary brain injury and improve patients’ outcomes after SAH.

ObjectiveTo evaluate the relationships of brain iron and heme with the inflammatory response of the systemic and central nervous systems and to investigate the role of defensive systems against the toxicity of iron and heme in the central nervous system.MethodsWe assessed a prospective cohort of patients presenting with intracerebral and subarachnoid hemorrhage. We assayed plasma and cerebrospinal fluid samples for the presence of iron, heme, hemopexin, haptoglobin, enolase, S100-β and cytokines for the first three days following hemorrhagic stroke. We also analyzed the dynamic changes in these components within both fluids and their relationship with early mortality rates.ResultsHemopexin and haptoglobin concentrations were nearly negligible in the brain after intracerebral and subarachnoid hemorrhage. Cerebrospinal fluid iron and heme concentrations correlated with a pro-inflammatory response in the central nervous system, and plasmatic and cerebrospinal fluid inflammatory profiles on the third day after hemorrhagic stroke were related to early mortality rates. Interleukin 4 levels within the cerebrospinal fluid during the first 24 hours after hemorrhagic stroke were found to be higher in survivors than in non-survivors.ConclusionIron and heme are associated with a pro-inflammatory response in the central nervous system following hemorrhagic stroke, and protections against hemoglobin and heme are lacking within the human brain. Patient inflammatory profiles were associated with a poorer prognosis, and local anti-inflammatory responses appeared to have a protective role.

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Introduction Noninvasive ventilation is a safe and eff ective method to treat acute respiratory failure, minimizing the respiratory workload and oxygenation. Few studies compare the effi cacy of diff erent types of noninvasive ventilation interfaces and their adaptation. Objective To identify the most frequently noninvasive ventilation interfaces used and eventual problems related to their adaptation in critically ill patients. Methods We conducted an observational study, with patients older than 18 years old admitted to the intensive care and step-down units of the Albert Einstein Jewish Hospital that used noninvasive ventilation. We collected data such as reason to use noninvasive ventilation, interface used, scheme of noninvasive ventilation used (continuously, periods or nocturnal use), adaptation, and reasons for nonadaptation. Results We evaluated 245 patients with a median age of 82 years (range of 20 to 107 years). Acute respiratory failure was the most frequent cause of noninvasive ventilation used (71.3%), followed by pulmonary expansion (10.24%), after mechanical ventilation weaning (6.14%) and sleep obstructive apnea (8.6%). The most frequently used interface was total face masks (74.7%), followed by facial masks in 24.5% of the patients, and 0.8% used performax masks. The use of noninvasive ventilation for periods (82.4%) was the most common scheme of use, with 10.6% using it continuously and 6.9% during the nocturnal period only. Interface adaptation occurred in 76% of the patients; the 24% that did not adapt had their interface changed to improve adaptation afterwards. The total face mask had 75.5% of interface adaptation, the facial mask had 80% and no adaptation occurred in patients that used the performax mask. The face format was the most frequent cause of nonadaptation in 30.5% of the patients, followed by patient's related discomfort (28.8%), air leaking (27.7%), claustrophobia (18.6%), noncollaborative patient (10.1%), patient agitation (6.7%), facial trauma or lesion (1.7%), type of mask fi xation (1.7%), and 1.7% patients with other causes. Conclusion Acute respiratory failure was the most frequent reason for noninvasive ventilation use, with the total face mask being the most frequent interface used. The most common causes of interface nonadaptation were face format, patient-related discomfort and air leaking, showing improvement of adaptation after changing the interface used. P2 Exercise training reduces oxidative damage in skeletal muscle of septic rats