The effect of BCG vaccination on infection and antibody levels against SARS-CoV-2-The results of ProBCG: a multicenter randomized clinical trial in Brazil.

OBJECTIVES: Evatuate if Bacillus Calmette-Guérin (BCG) vaccine could be used as a tool against SARS-CoV-2 based on the concept of trained immunity. METHODS: A multicenter, double-blinded, randomized clinical trial recruited health care workers (HCWs) in Brazil. The incidence rates of COVID-19, clinical manifestations, absenteeism, and adverse events among HCWs receiving BCG vaccine (Moreau or Moscow strains) or placebo were compared. BCG vaccine-mediated immune response before and after implementing specific vaccines for COVID-19 (CoronaVac or COVISHIELD) was analyzed. Cox proportional hazard and linear mixed effect modeling were used. RESULTS: A total of 264 volunteers were included for analysis (BCG = 134 and placebo = 130). The placebo group presented a COVID-19 cumulative incidence of 0.75% vs 0.52% of BCG. The Moreau strain also presented a higher incidence rate (1.60% × 0.22%). BCG did not show a protective hazard ratio against COVID-19. In addition, the log (immunoglobulin G) level against SARS-CoV-2 presented a higher increase in the BCG group, whether or not participants had COVID-19, but also without statistical significance. CONCLUSION: Our results suggest that BCG has a tendency of protection against SARS-CoV-2 and higher immunoglobulin G levels than placebo. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04659941).

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Sternal fractures in a level III trauma intensive care unit. / Fraturas de esterno em uma unidade de tratamento intensivo especializada em trauma.

OBJECTIVE: to evaluate epidemiology, anatomical characteristics, management, and prognosis of critical patients with sternum fractures. METHODS: retrospective analysis of patients admitted to intensive care unit (ICU) of a Level III trauma center in Sao Paulo, Brazil. RESULTS: 1552 trauma patients were admitted from January 2012 to April 2016. A total of 439 patients had thoracic trauma and among these, 13 patients had sternum fracture, making up 0.9% of all trauma admissions and 3% of all thoracic trauma cases. Three of these 13 patients had unstable chest, two underwent surgical management for fracture fixation, and three died (mortality was of 29%). In one of the deaths, sternum fracture was assessed as the main contributor to the outcome. CONCLUSION: sternum fracture was diagnosed in 0.9% of critical trauma patients in a specialized ICU. Only 15% of patients required specific surgical management in the acute phase. In most cases, mortality was due to other injuries.

OBJETIVO: avaliar epidemiologia, características anatômicas, manejo e prognóstico de pacientes críticos com fraturas de esterno. MÉTODOS: análise retrospectiva de pacientes internados em unidade de terapia intensiva (UTI) de emergências cirúrgicas e trauma de um centro de trauma Tipo III em São Paulo, Brasil. RESULTADOS: foram admitidos 1552 pacientes traumatizados no período de janeiro de 2012 a abril de 2016. Desses, 439 apresentavam trauma torácico e 13 apresentavam fratura de esterno, configurando 0,9% das admissões de trauma e 3% dos traumas torácicos. Desses pacientes, três apresentavam tórax instável e dois foram submetidos à conduta cirúrgica para fixação da fratura. A mortalidade de pacientes com fratura de esterno foi de 29% (três pacientes). Em um dos óbitos pôde-se atribuir a fratura do esterno como contribuinte principal para o desfecho. CONCLUSÃO: a fratura de esterno foi diagnosticada em 0,9% dos pacientes críticos vítimas de trauma em UTI especializada. Somente 15% dos pacientes necessitaram de conduta cirúrgica específica na fase aguda e a mortalidade foi decorrente das outras lesões na maior parte dos casos.

Fraturas de esterno em uma unidade de tratamento intensivo especializada em trauma / Sternal fractures in a level III trauma intensive care unit

RESUMO Objetivo: avaliar epidemiologia, características anatômicas, manejo e prognóstico de pacientes críticos com fraturas de esterno. Métodos: análise retrospectiva de pacientes internados em unidade de terapia intensiva (UTI) de emergências cirúrgicas e trauma de um centro de trauma Tipo III em São Paulo, Brasil. Resultados: foram admitidos 1552 pacientes traumatizados no período de janeiro de 2012 a abril de 2016. Desses, 439 apresentavam trauma torácico e 13 apresentavam fratura de esterno, configurando 0,9% das admissões de trauma e 3% dos traumas torácicos. Desses pacientes, três apresentavam tórax instável e dois foram submetidos à conduta cirúrgica para fixação da fratura. A mortalidade de pacientes com fratura de esterno foi de 29% (três pacientes). Em um dos óbitos pôde-se atribuir a fratura do esterno como contribuinte principal para o desfecho. Conclusão: a fratura de esterno foi diagnosticada em 0,9% dos pacientes críticos vítimas de trauma em UTI especializada. Somente 15% dos pacientes necessitaram de conduta cirúrgica específica na fase aguda e a mortalidade foi decorrente das outras lesões na maior parte dos casos.

ABSTRACT Objective: to evaluate epidemiology, anatomical characteristics, management, and prognosis of critical patients with sternum fractures. Methods: retrospective analysis of patients admitted to intensive care unit (ICU) of a Level III trauma center in Sao Paulo, Brazil. Results: 1552 trauma patients were admitted from January 2012 to April 2016. A total of 439 patients had thoracic trauma and among these, 13 patients had sternum fracture, making up 0.9% of all trauma admissions and 3% of all thoracic trauma cases. Three of these 13 patients had unstable chest, two underwent surgical management for fracture fixation, and three died (mortality was of 29%). In one of the deaths, sternum fracture was assessed as the main contributor to the outcome. Conclusion: sternum fracture was diagnosed in 0.9% of critical trauma patients in a specialized ICU. Only 15% of patients required specific surgical management in the acute phase. In most cases, mortality was due to other injuries.

Comparison between ultrasound- and bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients: a retrospective cohort study.

INTRODUCTION: Percutaneous dilational tracheostomy (PDT) is routinely performed in the intensive care unit with bronchoscopic guidance. Recently, ultrasound (US) has emerged as a new safety adjunct tool to increase the efficacy of PDT. However, the available data are limited to case series without any control group. Hence, a retrospective cohort study was designed to evaluate the efficacy of US-guided PDT compared with bronchoscopy-guided PDT. METHODS: All patients who were submitted to PDT after the standardization of US-guided PDT technique in our institution were analyzed. Demographic and procedure-related variables, complications, and clinical outcomes were collected and compared in patients undergoing US- or bronchoscopy-guided PDT. RESULTS: Sixty patients who had been submitted to PDT were studied, including 11 under bronchoscopy guidance and 49 under US guidance. No surgical conversion was necessary in any of the procedures, and bronchoscopy assistance was only required in 1 case in the US group. The procedure length was shorter in the US group than in the bronchoscopy group (12 vs 15 minutes, P = .028). None of the patients had any major complications. The minor complication rates were not significantly different between the groups, nor was the probability of breathing without assistance within 28 days, intensive care unit length of stay, or hospital mortality. CONCLUSION: Ultrasound-guided PDT is effective, safe, and associated with similar complication rates and clinical outcomes compared with bronchoscopy-guided PDT.

Atendimento às vítimas de lesão inalatória por incêndio em ambiente fechado: o que aprendemos com a tragédia de Santa Maria / Assistance of inhalation injury victims caused by fire in confined spaces: what we learned from the tragedy at Santa Maria

Em janeiro de 2013, uma catástrofe ocorrida em Santa Maria (RS), decorrente de um incêndio em ambiente fechado, resultou em 242 mortes, a maioria por lesões inalatórias. Em novembro de 2013, quatro vítimas necessitaram de suporte intensivo após inalação de fumaça em incêndio no Memorial da América Latina, em São Paulo (SP). Este artigo relata a evolução clínica e o manejo dos pacientes com lesão inalatória vítimas de uma catástrofe. Os pacientes ERL e OC apresentaram insuficiência respiratória precoce com broncoaspiração de material carbonáceo e intoxicação por monóxido de carbono. Foi instituído suporte ventilatório com oxigênio a 100%, retirada do material aspirado por broncoscopia, e terapia empírica com nitrito de sódio e tiossulfato de sódio para intoxicação por cianeto. O paciente RP apresentou tosse e queimação retroesternal. Evoluiu com insuficiência respiratória por edema de via aérea alta e infecção pulmonar precoce, manejados com ventilação pulmonar protetora e antimicrobianos. Foi extubado após melhora do edema no seguimento broncoscópico. O paciente MA, asmático, apresentou intoxicação por monóxido de carbono e broncoespasmo, sendo tratado com hiperóxia normobárica, broncodilatadores e corticoterapia. A estadia na unidade de terapia intensiva variou de 4 e 10 dias, e todos os pacientes apresentaram boa recuperação funcional no seguimento. Em conclusão, nos incêndios em ambientes fechados, as lesões inalatórias têm papel preponderante. O suporte ventilatório invasivo não deve ser postergado em caso de edema significativo de via aérea. A hiperóxia deve ser instituída precocemente como terapêutica para intoxicação por monóxido de carbono, bem como terapia farmacológica empírica para intoxicação por cianeto em caso de suspeita.

On January 2013, a disaster at Santa Maria (RS) due to a fire in a confined space caused 242 deaths, most of them by inhalation injury. On November 2013, four individuals required intensive care following smoke inhalation from a fire at the Memorial da América Latina in São Paulo (SP). The present article reports the clinical progression and management of disaster victims presenting with inhalation injury. Patients ERL and OC exhibited early respiratory failure, bronchial aspiration of carbonaceous material, and carbon monoxide poisoning. Ventilation support was performed with 100% oxygen, the aspirated material was removed by bronchoscopy, and cyanide poisoning was empirically treated with sodium nitrite and sodium thiosulfate. Patient RP initially exhibited cough and retrosternal burning and subsequently progressed to respiratory failure due to upper airway swelling and early-onset pulmonary infection, which were treated with protective ventilation and antimicrobial agents. This patient was extubated following improvement of edema on bronchoscopy. Patient MA, an asthmatic, exhibited carbon monoxide poisoning and bronchospasm and was treated with normobaric hyperoxia, bronchodilators, and corticosteroids. The length of stay in the intensive care unit varied from four to 10 days, and all four patients exhibited satisfactory functional recovery. To conclude, inhalation injury has a preponderant role in fires in confined spaces. Invasive ventilation should not be delayed in cases with significant airway swelling. Hyperoxia should be induced early as a therapeutic means against carbon monoxide poisoning, in addition to empiric pharmacological treatment in suspected cases of cyanide poisoning.

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study.

INTRODUCTION: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). METHODS: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. RESULTS: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. CONCLUSIONS: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.

Assistance of inhalation injury victims caused by fire in confined spaces: what we learned from the tragedy at Santa Maria.

On January 2013, a disaster at Santa Maria (RS) due to a fire in a confined space caused 242 deaths, most of them by inhalation injury. On November 2013, four individuals required intensive care following smoke inhalation from a fire at the Memorial da América Latina in São Paulo (SP). The present article reports the clinical progression and management of disaster victims presenting with inhalation injury. Patients ERL and OC exhibited early respiratory failure, bronchial aspiration of carbonaceous material, and carbon monoxide poisoning. Ventilation support was performed with 100% oxygen, the aspirated material was removed by bronchoscopy, and cyanide poisoning was empirically treated with sodium nitrite and sodium thiosulfate. Patient RP initially exhibited cough and retrosternal burning and subsequently progressed to respiratory failure due to upper airway swelling and early-onset pulmonary infection, which were treated with protective ventilation and antimicrobial agents. This patient was extubated following improvement of edema on bronchoscopy. Patient MA, an asthmatic, exhibited carbon monoxide poisoning and bronchospasm and was treated with normobaric hyperoxia,bronchodilators, and corticosteroids. The length of stay in the intensive care unit varied from four to 10 days, and all four patients exhibited satisfactory functional recovery. To conclude, inhalation injury has a preponderant role in fires in confined spaces. Invasive ventilation should not be delayed in cases with significant airway swelling. Hyperoxia should be induced early asa therapeutic means against carbon monoxide poisoning, in addition to empiric pharmacological treatment in suspected cases of cyanide poisoning.

[Acute renal injury in polytrauma patients]. / Injúria Renal Aguda no paciente politraumatizado.

Acute Kidney Injury (AKI) in trauma is, in most cases, multifactorial. Factors related to the initial ressuscitation protocol, degree of the systemic inflamatory response to trauma, contrast nephropathy in diagnostic procedures, rhabdomyolysis and abdominal compartment syndrome are some of those factors. Nowadays a uniformization in diagnostic criteria for AKI has been proposed by the Acute Kidney Injury Network (AKIN) and as a result the incidence of AKI and its impact in outcomes in trauma patients also needs to be reconsider. In this review we aim to approach epidemiologic, physiologic and clinical relevant data in the critical care of patients victims of trauma and also to expose the risks of indiscriminate use of volume expanders and the interaction between renal replacement theraphy and intracranial hypertension.

Injúria Renal Aguda no paciente politraumatizado / Acute Renal Injury in polytrauma patients

A Injúria Renal Aguda (IRA) no contexto do paciente politraumatizado ocorre, na maioria das vezes, por uma conjuntura de fatores que passam por eventos correlacionados à ressuscitação volêmica inicial, ao grau de resposta inflamatória sistêmica associada ao trauma, ao uso de contraste iodado para procedimentos diagnósticos, à rabdomiólise e à síndrome compartimental abdominal. Atualmente, passamos por uma fase de uniformização dos critérios diagnósticos da IRA com o Acute Kidney Injury Network (AKIN), sendo a referência mais aceita. Consequentemente, o estudo da IRA no politraumatismo também passa por uma fase de reformulação. Esta revisão da literatura médica visa trazer dados epidemiológicos, fisiológicos e de implicação clínica para o manuseio destes pacientes, bem como expor os riscos do uso indiscriminado de expansores volêmicos e particularidades sobre a instituição de terapia renal substitutiva em indivíduos sob risco de hipertensão intracraniana.

Acute Kidney Injury (AKI) in trauma is, in most cases, multifactorial. Factors related to the initial ressuscitation protocol, degree of the systemic inflamatory response to trauma, contrast nephropathy in diagnostic procedures, rhabdomyolysis and abdominal compartment syndrome are some of those factors. Nowadays a uniformization in diagnostic criteria for AKI has been proposed by the Acute Kidney Injury Network (AKIN) and as a result the incidence of AKI and its impact in outcomes in trauma patients also needs to be reconsider. In this review we aim to approach epidemiologic, physiologic and clinical relevant data in the critical care of patients victims of trauma and also to expose the risks of indiscriminate use of volume expanders and the interaction between renal replacement theraphy and intracranial hypertension.