ABSTRACT Objective: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. Methods: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. Results: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. Conclusions: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

RESUMO Objetivo: Avaliar se o uso do ELMO, um capacete para ventilação não invasiva criado no Brasil, teve impacto positivo no prognóstico de pacientes com insuficiência respiratória hipoxêmica por COVID-19 grave. Métodos: Estudo retrospectivo com 50 pacientes críticos com COVID-19. Dados epidemiológicos, clínicos e laboratoriais foram coletados na admissão na UTI e antes, durante e após o uso do ELMO. Os pacientes foram divididos em dois grupos (sucesso e falha) de acordo com o desfecho. Resultados: O uso do ELMO melhorou parâmetros de oxigenação como Pao2, Fio2 e relação Pao2/Fio2, e isso contribuiu para uma redução gradual da Fio2, sem aumento do CO2, conforme determinado pela gasometria arterial. Os pacientes do grupo sucesso apresentaram sobrevida significativamente maior (p < 0,001), conforme determinado pela análise de Kaplan-Meier, menor necessidade de intubação (p < 0,001), menos dias de hospitalização e menor incidência de lesão renal aguda em comparação com os do grupo falha. Conclusões: A significativa melhora nos parâmetros de oxigenação, a maior sobrevida, refletida pela menor necessidade de intubação e pela taxa de mortalidade, e a ausência de lesão renal aguda sugerem que o sistema ELMO CPAP é uma ferramenta promissora para o tratamento da SDRA e de condições clínicas semelhantes.

Abstract Pitaya is a rich source of bioactive compounds, such as polyphenols and betalains. Moreover, these compounds has been associated with reduced risk of type 2 diabetes mellitus. The aim of this study is to evaluate the effect of this fruit on glycemia and oxidative stress in aloxan-induced diabetic mice. Thus, considering that In the in vivo assays, the mice were divided into 5 groups (n = 6): (a) healthy group treated with water; (b) diabetic mice treated with metformin at 200 mg/kg body weight diluted in water; (c) untreated diabetic mice; (d) diabetic mice treated with pitaya at 200 mg/kg and (e) diabetic mice treated with pitaya at 400 mg/kg of body weight diluted in water. The results shows that pitaya was able significantly to reduce blood glucose (p < 0.05) (200 mg/kg); significantly reduce cholesterol (200 and 400 mg/kg) and significantly increase HDL-c (400 mg/kg) levels. In the oxidative stress experiment, Malondialdehyde levels in the liver were significantly reduced (p < 0.05) in the groups treated with pitaya, when compared to the other groups, suggesting lower lipid peroxidation. The consumption of pitaya reduced the blood glucose and cholesterol and increase the HDL, in addition, the lipid peroxidation - which is common in diabetic patients, was reduced.

BACKGROUND A positive Trypanosoma cruzi polymerase chain reaction (PCR) is associated with a worse prognosis in patients with chronic Chagas disease (CD). OBJECTIVES To study the association of clinical, electrocardiographic, and echocardiographic characteristics and biomarker blood levels with positive T. cruzi PCR in chronic CD. METHODS This is a single-centre observational cross-sectional study. Positive T. cruzi PCR association with clinical, electrocardiographic, and echocardiographic characteristics, and biomarker blood levels were studied by logistic regression analysis. p values < 0.05 were considered significant. FINDINGS Among 333 patients with chronic CD (56.4% men; 62 ± 10 years), T. cruzi PCR was positive in 41.1%. Stepwise multivariate logistic regression showed an independent association between positive T. cruzi PCR and diabetes mellitus {odds ratio (OR) 0.53 [95% confidence interval (CI) 0.30-0.93]; p = 0.03}, right bundle branch block [OR 1.78 (95% CI 1.09-2.89); p = 0.02], and history of trypanocidal treatment [OR 0.13 (95% CI 0.04-0.38); p = 0.0002]. Among patients with a history of trypanocidal treatment (n = 39), only four (10%) patients had a positive T. cruzi PCR. MAIN CONCLUSIONS Among several studied parameters, only diabetes mellitus, right bundle branch block, and history of trypanocidal treatment showed an independent association with positive T. cruzi PCR. History of trypanocidal treatment was a strong protective factor against a positive T. cruzi PCR.

RESUMO Objetivo: Avaliar a viabilidade do uso de uma nova interface do tipo capacete para CPAP, denominada ELMO, para o tratamento da insuficiência respiratória aguda (IRpA) hipoxêmica por COVID-19 fora da UTI. Métodos: Estudo de prova de conceito envolvendo pacientes com IRpA hipoxêmica moderada a grave secundária à COVID-19, internados na enfermaria geral de um hospital público. A intervenção consistiu na aplicação de CPAP por meio da interface ELMO integrada a fluxômetros de oxigênio e ar comprimido (30 L/min cada) e a uma válvula de PEEP (níveis de CPAP = 8-10 cmH2O), formando o sistema ELMOcpap. Os pacientes foram monitorados quanto a parâmetros cardiorrespiratórios, eventos adversos e conforto. Resultados: Dez pacientes completaram o protocolo do estudo. O sistema ELMOcpap foi bem tolerado, sem efeitos adversos relevantes. Seu uso foi viável fora da UTI por tempo prolongado e mostrou-se bem-sucedido em 60% dos pacientes. Uma CPAP de 10 cmH2O com fluxo total de gás de 56-60 L/min melhorou a oxigenação após sessões de ELMOcpap de 30-60 min, permitindo redução significativa da FIO2 estimada (p = 0,014) e aumento da PaO2/FIO2 estimada (p = 0,008) na primeira hora, sem reinalação de CO2. Conclusões: O uso do ELMOcpap mostrou-se viável e eficaz no fornecimento de CPAP de alto fluxo a pacientes com IRpA hipoxêmica por COVID-19 fora da UTI. Não houve nenhum efeito adverso importante, e o ELMO foi considerado confortável. As sessões de ELMOcpap melhoraram significativamente a oxigenação, reduzindo a FIO2 sem reinalação de CO2. A taxa global de sucesso foi de 60% neste estudo piloto, e novos ensaios clínicos devem ser realizados. (ClinicalTrials.gov identifier: NCT04470258 [http://www.clinicaltrials.gov/])

ABSTRACT Objective: To assess the feasibility of using a new helmet interface for CPAP, designated ELMO, to treat COVID-19-related acute hypoxemic respiratory failure (AHRF) outside the ICU. Methods: This was a proof-of-concept study involving patients with moderate to severe AHRF secondary to COVID-19 admitted to the general ward of a public hospital. The intervention consisted of applying CPAP via the ELMO interface integrated with oxygen and compressed air flow meters (30 L/min each) and a PEEP valve (CPAP levels = 8-10 cmH2O), forming the ELMOcpap system. The patients were monitored for cardiorespiratory parameters, adverse events, and comfort. Results: Ten patients completed the study protocol. The ELMOcpap system was well tolerated, with no relevant adverse effects. Its use was feasible outside the ICU for a prolonged amount of time and was shown to be successful in 60% of the patients. A CPAP of 10 cmH2O with a total gas flow of 56-60 L/min improved oxygenation after 30-to 60-min ELMOcpap sessions, allowing a significant decrease in estimated FIO2 (p = 0.014) and an increase in estimated PaO2/FIO2 ratio (p = 0.008) within the first hour without CO2 rebreathing. Conclusions: The use of ELMOcpap has proven to be feasible and effective in delivering high-flow CPAP to patients with COVID-19-related AHRF outside the ICU. There were no major adverse effects, and ELMO was considered comfortable. ELMOcpap sessions significantly improved oxygenation, reducing FIO2 without CO2 rebreathing. The overall success rate was 60% in this pilot study, and further clinical trials should be carried out in the future. (ClinicalTrials.gov identifier: NCT04470258 [http://www.clinicaltrials.gov/])

ABSTRACT Objective: To evaluate the influences of respiratory muscle efforts and respiratory rate setting in the ventilator on tidal volume and alveolar distending pressures at end inspiration and expiration in volume-controlled ventilation and pressure-controlled ventilation modes in acute respiratory distress syndrome. Methods: An active test lung (ASL 5000™) connected to five intensive care unit ventilators was used in a model of acute respiratory distress syndrome. Respiratory muscle efforts (muscle pressure) were configured in three different ways: no effort (muscle pressure: 0cmH2O); inspiratory efforts only (muscle pressure:-5cmH2O, neural inspiratory time of 0.6s); and both inspiratory and expiratory muscle efforts (muscle pressure:-5/+5cmH2O). Volume-controlled and pressure-controlled ventilation modes were set to deliver a target tidal volume of 420mL and positive end-expiratory pressure of 10cmH2O. The tidal volume delivered to the lungs, alveolar pressures at the end of inspiration, and alveolar pressures at end expiration were evaluated. Results: When triggered by the simulated patient, the median tidal volume was 27mL lower than the set tidal volume (range-63 to +79mL), and there was variation in alveolar pressures with a median of 25.4cmH2O (range 20.5 to 30cmH2O). In the simulated scenarios with both spontaneous inspiratory and expiratory muscle efforts and with a mandatory respiratory rate lower than the simulated patient's efforts, the median tidal volume was higher than controlled breathing. Conclusion: Adjusting respiratory muscle effort and pulmonary ventilator respiratory rate to a value above the patient’s respiratory rate in assisted/controlled modes generated large variations in tidal volume and pulmonary pressures, while the controlled mode showed no variations in these outcomes.

RESUMO Objetivo: Avaliar a influência dos esforços musculares respiratórios e do ajuste da frequência respiratória no ventilador sobre o volume corrente e as pressões de distensão alveolar ao final da inspiração e expiração com ventilação sob os modos controle por volume e controle por pressão na síndrome do desconforto respiratório agudo. Métodos: Utilizou-se um simulador mecânico de pulmão (ASL 5000™) conectado a cinco tipos de ventiladores utilizados em unidade de terapia intensiva, em um modelo de síndrome do desconforto respiratório agudo. Os esforços musculares respiratórios (pressão muscular) foram configurados de três formas distintas: sem esforço (pressão muscular: 0cmH2O), apenas esforços inspiratórios (pressão muscular: - 5cmH2O, tempo inspiratório neural de 0,6 segundos) e esforços musculares inspiratórios e expiratórios (pressão muscular:-5/+5cmH2O). Foram configuradas ventilação sob os modos controle por volume e ventilação com controle por pressão para oferecer um volume corrente de 420mL e pressão positiva expiratória final de 10cmH2O. Avaliaram-se o volume corrente fornecido aos pulmões, as pressões alveolares no final da inspiração e as pressões alveolares no final da expiração. Resultados: Quando disparado pelo paciente simulado, o volume corrente mediano foi 27mL menor do que o volume corrente ajustado (variação-63 a +79mL), e ocorreu uma variação nas pressões alveolares com mediana de 25,4cmH2O (faixa de 20,5 a 30cmH2O). Nos cenários simulados com esforço muscular tanto inspiratório quanto expiratório e com frequência respiratória mandatória inferior à dos esforços do paciente simulado, o volume corrente mediano foi maior com ventilação controlada. Conclusão: O ajuste do esforço muscular respiratório e da frequência respiratória no ventilador em um valor acima da frequência respiratória do paciente nos modos de ventilação assistida/controlada gerou maiores variações no volume corrente e nas pressões pulmonares, enquanto o modo controlado não mostrou variações nesses desfechos.

RESUMO Objetivo: Avaliar a associação da ventilação mecânica (VM) protetora, com base no VT e na pressão de distensão máxima (PDM), com a mortalidade em pacientes com fator de risco para SDRA. Métodos: Este estudo de coorte prospectivo foi conduzido em uma UTI e incluiu 116 pacientes em VM que apresentavam pelo menos um fator de risco para o desenvolvimento de SDRA. Os parâmetros ventilatórios foram coletados duas vezes ao dia durante sete dias, e os pacientes foram divididos em dois grupos (VM protetora e VM não protetora) com base na PDM (diferença entre pressão máxima de vias aéreas e PEEP) ou no VT. Os desfechos foram mortalidade em 28 dias, mortalidade na UTI e mortalidade hospitalar. Os fatores de risco associados com a adoção da VM não protetora também foram avaliados. Resultados: A VM não protetora com base no VT e na PDM ocorreu em 49 (42,2%) e em 38 (32,8%) dos pacientes, respectivamente. A regressão multivariada de Cox mostrou que a VM protetora com base na PDM associou-se a menor mortalidade hospitalar (hazard ratio = 0,37; IC95%: 0,19-0,73) e em UTI (hazard ratio = 0,40; IC95%, 0,19-0,85), após ajuste para idade, Simplified Acute Physiology Score 3, uso de vasopressor e valores basais de PaO2/FiO2, PEEP, pH e PaCO2. Essas associações não foram observadas quando a VM não protetora foi baseada no VT. Conclusões: A PDM parece ser uma ferramenta útil, melhor do que o VT, para o ajuste da VM em pacientes sob risco para SDRA.

ABSTRACT Objective: To evaluate the association that protective mechanical ventilation (MV), based on VT and maximum distending pressure (MDP), has with mortality in patients at risk for ARDS. Methods: This was a prospective cohort study conducted in an ICU and including 116 patients on MV who had at least one risk factor for the development of ARDS. Ventilatory parameters were collected twice a day for seven days, and patients were divided into two groups (protective MV and nonprotective MV) based on the MDP (difference between maximum airway pressure and PEEP) or VT. The outcome measures were 28-day mortality, ICU mortality, and in-hospital mortality. The risk factors associated with the adoption of nonprotective MV were also assessed. Results: Nonprotective MV based on VT and MDP was applied in 49 (42.2%) and 38 (32.8%) of the patients, respectively. Multivariate Cox regression showed that protective MV based on MDP was associated with lower in-hospital mortality (hazard ratio = 0.37; 95% CI: 0.19-0.73) and lower ICU mortality (hazard ratio = 0.40; 95% CI: 0.19-0.85), after adjustment for age, Simplified Acute Physiology Score 3, and vasopressor use, as well as the baseline values for PaO2/FiO2 ratio, PEEP, pH, and PaCO2. These associations were not observed when nonprotective MV was based on the VT. Conclusions: The MDP seems to be a useful tool, better than VT, for adjusting MV in patients at risk for ARDS.

Abstract INTRODUCTION We aimed to describe the sociodemographic, epidemiological, and clinical characteristics of patients with chronic Chagas disease (CD) at an infectious disease referral center. Changes in patient profiles over time were also evaluated. METHODS This retrospective study included patients with CD from November 1986-December 2019. All patients underwent an evaluation protocol that included sociodemographic profile; epidemiological history; anamnesis; and physical, cardiologic, and digestive examinations. Trend differences for each 5-year period from 1986 to 2019 were tested using a nonparametric trend test for continuous and generalized linear models with binomial distribution for categorical variables. RESULTS A total of 2,168 patients (52.2% women) were included, with a mean age of 47.8 years old. White patients with low levels of education predominated. The reported transmission mode was vectorial in 90.2% of cases. The majority came from areas with a high prevalence (52.2%) and morbidity (67.8%) of CD. The most common clinical presentation was the indeterminate form (44.9%). The number of patients referred gradually decreased and the age at admission increased during the study period, as did the patients’ levels of education. CONCLUSIONS The clinical profile of CD is characterized by a predominance of the indeterminate form of the disease. Regarding the patients who were followed up at the referral center, there was a progressive increase in the mean age and a concomitant decrease in the number of new patients. This reflects the successful control of vector and transfusion transmission in Brazil as well as the aging population of patients with CD.

Abstract INTRODUCTION: Herein, we aimed to identify the factors associated with adverse drug events (ADEs) in chronic Chagas disease (CD) patients. METHODS: We analyzed 320 medical notes from 295 patients. The Naranjo algorithm was applied to determine the cause of ADEs. Mixed effects logistic regression was performed to evaluate the factors associated with ADEs. RESULTS: ADEs were described in 102 medical notes (31.9%). Captopril was most frequently associated with ADEs. Age (RR 0.96; 95%CI 0.94-0.99) and cardiac C/D stages (RR 3.24; 95%CI 1.30-4.58) were the most important clinical factors associated with ADEs. CONCLUSIONS: Close follow-up is warranted for CD patients.

Resumo Fundamentos: Novas técnicas ecocardiográficas são utilizadas no diagnóstico e prognóstico de diversas cardiopatias. No entanto, muitos desses novos índices ainda carecem de valores de referência em diferentes populações. Estudamos esses novos parâmetros ecocardiográficos em um grupo de brasileiros sem doença cardiovascular conhecida. Objetivo: Estudar valores dos novos índices ecocardiográficos em brasileiros sem doença cardiovascular conhecida e sua correlação com a idade. Métodos: Estudo transversal composto por indivíduos saudáveis que realizaram ecocardiograma tridimensional (E3D) e ecocardiograma bidimensional com análise de deformação (e) por speckle tracking (EST). Foram analisadas as funções atrial esquerda (AE) e ventricular esquerda (VE) por E3D e EST, e a função ventricular direita (VD) por EST. Valores de p < 0,05 foram considerados significantes. Resultados: Foram incluídos setenta e sete indivíduos (46,7% homens; 40,4 ± 10,4 anos). Os volumes AE máximo, mínimo e pré-contração atrial (pré-A) (ml/m2) foram 21,2 ± 5,5, 7,8 ± 2,5 e 11,0 ± 3,1, respectivamente. O pico da e global positiva do AE (LAScd), pico da e global negativa do AE e e global total do AE (LASr) foram 17,4±5,2%, -13,2 ± 2,0% e 30,5 ± 5,9%, respectivamente. Os volumes diastólico final e sistólico final do VE (ml/m2) mediram 57 ± 12 e 24 ± 6 e a fração de ejeção tridimensional do VE mediu 58 ± 6%. A e longitudinal, circunferencial e radial global do VE foi de -19 ± 2%, -19 ± 3% e 46 ± 12%, respectivamente. A torção do VE mediu 1,6 ± 0,7(0)/cm. A e longitudinal global do VD (SLG-VD) e a deformação da parede livre do VD foram de -22 ± 3% e -24 ± 5%. Os volumes mínimo e pré-A do AE, rotação apical do VE, torção e SLG-VD aumentaram com a idade, enquanto as frações de esvaziamento total e passivo do LA, LAScd, LASr, volumes diastólico final e sistólico final do VE diminuíram com a idade. Conclusão: Apresentam-se os valores para os novos índices ecocardiográficos em brasileiros sem doença cardiovascular conhecida e sua correlação com a idade.

Abstract Background: New echocardiographic techniques are used in the diagnosis and prognosis of many heart diseases. However, reference values in different populations are still needed for several of these new indexes. We studied these new echocardiographic parameters in a group of Brazilians with no known cardiovascular disease. Objective: To study values for new echocardiographic indexes in Brazilians without known cardiovascular disease and their correlation with age. Methods: Cross-sectional study that included healthy individuals who underwent three-dimensional echocardiography (3DE) and two-dimensional speckle tracking echocardiography (STE) strain (e) analysis. Left atrial (LA) and left ventricular (LV) function were analyzed by 3DE and STE, and right ventricular (RV) function by STE. P values < 0.05 were considered significant. Results: Seventy-seven subjects (46.7% men; 40.4 ± 10.4 years) were included. Maximum, minimum and pre-atrial contraction (pre-A) LA volumes (ml/m2) were 21.2 ± 5.5, 7.8 ± 2.5, and 11.0 ± 3.1, respectively. Peak positive global LA e (LAScd), peak negative global LA e and total global LA e (LASr) were 17.4 ± 5.2%, -13.2 ± 2.0% and 30.5 ± 5.9%, respectively. LV end-diastolic and end-systolic volumes (ml/m2) measured 57 ± 12 and 24 ± 6, and 3D LV ejection fraction measured 58 ± 6%. Global LV longitudinal, circumferential and radial e were -19 ± 2%, -19 ± 3%, and 46 ± 12%, respectively. LV torsion measured 1.6 ± 0.70 /cm. Global longitudinal RV e (RV-GLS) and RV free wall strain were -22 ± 3% and -24 ± 5%. Minimum LA and pre-A volumes, LV apical rotation, torsion and RV-GLS increased with age, while total and passive LA emptying fractions, LAScd, LASr, LV end-diastolic and end-systolic volumes decreased with age. Conclusion: Values for new echocardiographic indexes in Brazilians without known cardiovascular disease and their correlation with age are presented.

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.