Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Perfil citológico pulmonar de bezerros sadios nos três primeiros meses de vida

Resumo: A citologia é um importante exame complementar utilizado para a detecção de alterações no perfil celular do trato respiratório e auxílio no diagnóstico de doenças. No entanto, como os primeiros meses de vida compõem o período de adaptação à vida extrauterina resultando em possíveis alterações das populações celulares, é essencial a padronização das características comuns aos animais sadios, possibilitando a identificação e análise de qualquer mudança no quadro esperado. O objetivo desta pesquisa foi caracterizar o perfil celular por citologia do lavado broncoalveolar obtido semanalmente por broncoscopia de dez bezerros durante os três primeiros meses de vida. A análise estatística foi realizada utilizando-se o software Minitab® 15.0, empregando-se o teste T pareado para as amostras paramétricas e Mann-Whitney para as amostras não paramétricas, considerando nivel de significância P≤0,05. Os resultados obtidos apontaram que o perfil celular do lavado broncoalveolar de bezerros hígidos durante os primeiros 90 dias de vida apresentou predomínio de macrófagos, com média geral de 63,17%, seguido de 33,69% de neutrófilos. Porém observou-se diminuição significativa na porcentagem de macrófagos (P=0,04) e aumento de neutrófilos (P=0,05) ao longo dos momentos, comprovada pela forte correlação negativa entre as porcentagens de macrófagos e neutrófilos ao longo dos momentos. Não houve diferença entre as porcentagens de células gigantes, células epiteliais, linfócitos, eosinófilos e basófilos durante o experimento. Apesar dos resultados serem influenciados por fatores ambientais e de manejo, os resultados dessa pesquisa fornecem subsídios para a identificação de alterações críticas que descaracterizem o perfil celular de bezerros acometidos por doenças respiratórias

Acute and Chronic Effects of Isometric Handgrip Exercise on Cardiovascular Variables in Hypertensive Patients: A Systematic Review

The aim of this study was to describe, through a systematic review, the acute and chronic effects of isometric handgrip exercise on cardiovascular variables in hypertensive individuals. In this systematic review, we included studies that analyzed whether a single bout or a program with isometric exercises affect cardiovascular variables in hypertensive adults. The electronic database PubMed/Medline was searched for relevant studies published until May 2017. Of the 2927 studies initially identified, 2916 were excluded based on title and abstract and five on the basis of full-text assessment, leaving six studies remaining. In addition, one further study cited in the references of the included articles was included in this review, totaling seven studies included (five studies on the chronic effects of isometric handgrip exercise on cardiovascular parameters). None of the acute studies observed post-exercise hypotension. The majority of the chronic studies found decreases in office blood pressure after isometric handgrip training, with training ranging from 6 to 10 weeks, while heart rate variability parameters were improved in one study and did not change in another. Reduction in oxidative stress was observed; however, this variable was only analyzed in one study. In hypertensives, acute responses to isometric handgrip exercise are very limited due to the small number of studies, therefore more research is required. Furthermore, chronic isometric handgrip training reduces blood pressure; however, there is still a gap in the knowledge on the effects of this modality of exercise on other cardiovascular variables-such as endothelial function, oxidative stress, and cardiac autonomic modulation-which should be addressed in future studies.status: publishe

A marinha destronada: ou a famigerada São Vicente derrotada pela Rochela paulista. A afirmação de São Paulo como cabeça de capitania (1681-1766)

A vila de São Vicente, primeira criada na América portuguesa, foi sede da capitania de mesmo nome e, apesar de muito "famigerada noutro tempo", como diz Frei Gaspar da Madre de Deus, acaba, no século XVIII, "tão desconhecida que nem o nome primitivo conserva para memória de sua antiga existência". A primeira tentativa de mudança ocorreu em 1681, por obra do marquês de Cascais, donatário da capitania, que contou com a resistência da câmara de São Vicente. Após a restauração da capitania em 1765 o Morgado de Mateus, novo governador da capitania restaurada, transfere definitivamente o governo, a Sé, a junta de fazenda, a guarnição e a provedoria para São Paulo. A Marinha perde definitivamente o governo para o Sertão de serra acima. O objetivo deste artigo é compreender como a cidade de São Paulo adquiriu sua dominância em relação às demais vilas, chegando a renomear a própria capitania, colocando no esquecimento a anteriormente famigerada São Vicente

Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study

OBJECTIVES: Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs. DESIGN: A multicentre, international, collaborative cohort study. SETTING: 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020. PARTICIPANTS: Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer. MAIN OUTCOME MEASURE: All-cause mortality at 30 days and 90 days. RESULTS: 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001). CONCLUSIONS: The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally