Background Brain abnormalities are a concern in COVID-19, so we used minimally invasive autopsy (MIA) to investigate it, consisting of brain 7T MR and CT images and tissue sampling via transethmoidal route with at least three fragments: the first one for reverse transcription polymerase chain reaction (RT-PCR) analysis and the remaining fixed and stained with hematoxylin and eosin. Two mouse monoclonal anti-coronavirus (SARS-CoV-2) antibodies were employed in immunohistochemical (IHC) reactions. Results Seven deceased COVID-19 patients underwent MIA with brain MR and CT images, six of them with tissue sampling. Imaging findings included infarcts, punctate brain hemorrhagic foci, subarachnoid hemorrhage and signal abnormalities in the splenium, basal ganglia, white matter, hippocampi and posterior cortico-subcortical. Punctate brain hemorrhage was the most common finding (three out of seven cases). Brain histological analysis revealed reactive gliosis, congestion, cortical neuron eosinophilic degeneration and axonal disruption in all six cases. Other findings included edema (5 cases), discrete perivascular hemorrhages (5), cerebral small vessel disease (3), perivascular hemosiderin deposits (3), Alzheimer type II glia (3), abundant corpora amylacea (3), ischemic foci (1), periventricular encephalitis foci (1), periventricular vascular ectasia (1) and fibrin thrombi (1). SARS-CoV-2 RNA was detected with RT-PCR in 5 out of 5 and IHC in 6 out 6 patients (100%). Conclusions Despite limited sampling, MIA was an effective tool to evaluate underlying pathological brain changes in deceased COVID-19 patients. Imaging findings were varied, and pathological features corroborated signs of hypoxia, alterations related to systemic critically ill and SARS-CoV-2 brain invasion.

Background COVID‐19 patients on mechanical ventilation are at risk to develop invasive aspergillosis. To provide additional data regarding this intriguing entity, we conducted a retrospective study describing risk factors, radiology and prognosis of this emerging entity in a Brazilian referral centre. Methods This retrospective study included intubated (≥18 years) patients with COVID‐19 admitted from April 2020 until July 2021 that had bronchoscopy to investigate pulmonary co‐infections. COVID‐19‐associated aspergillosis (CAPA) was defined according to the 2020 European Confederation of Medical Mycology/International Society of Human and Animal Mycosis consensus criteria. The performance of tracheal aspirate (TA) cultures to diagnose CAPA were described, as well as the radiological findings, risk factors and outcomes. Results Fourteen patients (14/87, 16%) had probable CAPA (0.9 cases per 100 ICU admissions). The sensitivity, specificity, positive predictive value and negative predictive value of TA for the diagnosis of CAPA were 85.7%, 73.1%, 46.2% and 95% respectively. Most of the radiological findings of CAPA were classified as typical of invasive pulmonary aspergillosis (64.3%). The overall mortality rate of probable CAPA was 71.4%. Age was the only independent risk factor for CAPA [p = .03; odds ratio (OR) 1.072]. CAPA patients under renal replacement therapy (RRT) may have a higher risk for a fatal outcome (p = .053, hazard ratio 8.047). Conclusions CAPA was a prevalent co‐infection in our cohort of patients under mechanical ventilation. Older patients had a higher risk to develop CAPA, and a poor prognosis may be associated with RRT.

SUMMARY OBJECTIVES 1) To evaluate the efficiency of a new method of training laypeople on cardiopulmonary resuscitation (CPR). 2) To assess previous knowledge of the participants. METHODS Instructors were trained according to the 2015 American Heart Association Guidelines, with emphasis on CPR. Dummies made with PET bottles were used, and a questionnaire was applied to the participants before and after training. Statistical analysis was performed in the R commander program. Participants with incomplete documents were excluded from the study. RESULTS Out of 101 participants, 96 were included: 69 lay people, 17 health professionals, and ten health students. There was an improvement in the overall performance after training (mean pre: 62.7%, mean post: 75.8%, p <0.01), also present in the following main concepts: “mouth-to-mouth breathing is not necessary” (p <0.01), “risk of contamination” (p <0.01), “compression technique” (p <0.01). The concepts “recognition of severity” and “what is chest compression” did not improve, but had good pre-test means, 96.8% and 81.2%. There was no statistical difference in the knowledge between the groups (laypeople vs. health professionals and students, pre=0,06 e post=0,33). CONCLUSION The tools used in training were efficient. However, further studies are necessary to assess the long-term impact of this intervention.

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RESUMO:Há oitenta anos, Alexander Fleming descobriu a penicilina. O trabalho enfatiza o contexto no qual foi descoberto a penicilina e suas repercussões na prática clínica e na epidemiologia. DESCRITORES:História da medicina. Microbiologia. Penicilinas/história. O tratamento de infecções na antiguidadeD esde o início dos tempos o homem tentou controlar as doenças a fi m de manter sua sobrevivência. As primeiras informações que concernem a prática da medicina datam do 5º milênio a.C., com os egípcios. Os sacerdotes egípcios uniam a medicina e a teleologia supersticiosa de maneira muito íntima; usavam ervas medicinais e outros produtos como leite, mel, sal ou cerveja, mas nenhum deles era considerado efi caz no tratamento de infecções sem o uso de invocações mágicas 3 .N o e n t a n t o , n ã o p o d e m o s a f i r m a r inexoravelmente que todos os componentes eram inefetivos. O efeito bactericida do açúcar para Staphylococcus aureus e Escherichia coli, entre outros, foi comprovado por Rahal et al., em 1983 6 . Obviamente, os povos antigos não tinham o conhecimento da existência dos microorganismos, e seus tratamentos eram conduzidos de forma bastante empírica. Somente a partir de Robert Koch, que comprovou o papel patogênico dos microorganismos no século XIX a partir da elaboração dos quatro Postulados de Koch (usados até hoje na descoberta de patógenos, como a relação entre a Helicobacter pylori e as úlceras pépticas), cientistas começaram a realizar pesquisas relacionadas à antibiose. O conceito de antibiose em medicina e o isolamento da penicilinaEm meados do século XIX, sabia-se que medidas sanitárias, adotadas previamente a procedimentos cirúrgicos e obstétricos, eram capazes de reduzir significativamente as infecções pós-operatórias. Os exemplos mais claros disso foram a adoção da lavagem das mãos por Semmelweis e a esterilização, introduzida por Joseph Lister nesta mesma época, por meio de uma solução de fenol (ácido carbólico) 5 . No entanto, o fenol possui um efeito tóxico importante, sendo o seu uso em

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Background. Ischemic preconditioning (IPC), either direct (DIPC) or remote (RIPC), is a procedure aimed at reducing the harmful effects of ischemia-reperfusion injury. Aims. To assess the local and systemic effects of DIPC, RIPC, and both combined, in the pig liver transplant model. Methods. Twenty-four pigs underwent orthotopic liver transplantation and were divided into 4 groups according to the procedures applied: direct donor preconditioning; indirect preconditioning at the recipient and a group with direct donor and indirect recipient preconditioning. The following parameters were recorded: donor and recipient weight, graft-to-recipient weight ratio (GRWR), surgery time, hot and cold ischemia time, and intraoperative hemodynamic values. Blood samples were collected before native liver removal (BL) and at 0h, 1h, 3h, 6h, 12h, 18h, and 24h postreperfusion and the following biochemical tests were performed: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), creatinine, BUN, lactate, total and direct bilirubin. Histopathological examination of liver, gut, kidney, and lung fragments were performed, as well as molecular analyses for expression of the apoptosisrelated BAX (pro-apoptotic) and Bcl-XL (anti-apoptotic) genes, eNOS (endothelial nitric oxide synthase) gene, and IL-6 gene related to inflammatory ischemia-reperfusion injury, using real-time polymerase chain reaction (RT-PCR).Results. There were no differences between the groups regarding biochemical and histopathological parameters. We found a reduced ratio between the expression of the pro-apoptotic BAX gene and the expression of the anti-apoptotic Bcl gene in the livers of animals with IPC versus the control group.Conclusions. DIPC, RIPC or a combination of both produce local beneficial effects only at the molecular level but do not translate into biochemical or histological changes. BackgroundPrimary graft dysfunction due to ischemia-reperfusion (I/R) injury is one of the most serious complications of liver transplantation. 1,2 Ischemic preconditioning (IPC) is an important approach to reduce the harmful effects of this process. It consists of producing brief periods of ischemia followed by brief periods of reperfusion prior to the prolonged ischemic insult, which should induce greater