Effect of Remote Ischaemic Conditioning on the Inflammatory Cytokine Cascade of COVID-19 (RIC in COVID-19): a Randomized Controlled Trial.

PURPOSE: Patients hospitalized with COVID-19 may develop a hyperinflammatory, dysregulated cytokine "storm" that rapidly progresses to acute respiratory distress syndrome, multiple organ dysfunction, and even death. Remote ischaemic conditioning (RIC) has elicited anti-inflammatory and cytoprotective benefits by reducing cytokines following sepsis in animal studies. Therefore, we investigated whether RIC would mitigate the inflammatory cytokine cascade induced by COVID-19. METHODS: We conducted a prospective, multicentre, randomized, sham-controlled, single-blind trial in Brazil and South Africa. Non-critically ill adult patients with COVID-19 pneumonia were randomly allocated (1:1) to receive either RIC (intermittent ischaemia/reperfusion applied through four 5-min cycles of inflation (20 mmHg above systolic blood pressure) and deflation of an automated blood-pressure cuff) or sham for approximately 15 days. Serum was collected following RIC/sham administration and analyzed for inflammatory cytokines using flow cytometry. The endpoint was the change in serum cytokine concentrations. Participants were followed for 30 days. RESULTS: Eighty randomized participants (40 RIC and 40 sham) completed the trial. Baseline characteristics according to trial intervention were overall balanced. Despite downward trajectories of all cytokines across hospitalization, we observed no substantial changes in cytokine concentrations after successive days of RIC. Time to clinical improvement was similar in both groups (HR 1.66; 95% CI, 0.938-2.948, p 0.08). Overall RIC did not demonstrate a significant impact on the composite outcome of all-cause death or clinical deterioration (HR 1.19; 95% CI, 0.616-2.295, p = 0.61). CONCLUSION: RIC did not reduce the hypercytokinaemia induced by COVID-19 or prevent clinical deterioration to critical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04699227.

RIC in COVID-19-a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19.

PURPOSE: Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. "RIC in COVID-19" is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. METHODS: A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. CONCLUSIONS: The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. TRIAL REGISTRATION: NCT04699227, registered January 7th, 2021.

Adiposidade em adolescentes e obesidade materna / Relationship between maternal obesity and adiposity in adolescents

OBJETIVO: Descrever a relação entre adiposidade na adolescência e obesidade materna. MÉTODOS: Foi realizado estudo transversal com 660 indivíduos de 8 a 18 anos, de ambos os sexos, matriculados em uma escola pública e outra privada do município de São Paulo. A coleta de dados foi realizada por meio de entrevista, medidas antropométricas e inquérito alimentar. A adiposidade na adolescência foi mensurada a partir do índice de massa corporal e, por meio de análise de regressão, verificou-se sua relação com a obesidade materna, ajustada por sexo, idade, estágio de maturação sexual, valor energético total da dieta, atividade física, sedentarismo, peso ao nascer e escolaridade materna. RESULTADOS: Dos adolescentes estudados, 64,7 por cento eram do sexo feminino. A média (desvio-padrão) de idade foi de 12,4 (1,80), variando de 8 a 17 anos. Verificou-se maior prevalência de excesso de peso e obesidade entre os indivíduos do sexo masculino, não sendo observada associação significativa entre estado nutricional e sexo. Após ajuste pelas covariáveis, detectou-se que filhos de mães obesas têm risco quatro vezes maior de ser obesos, quando comparados aos adolescentes filhos de mães não obesas. CONCLUSÃO: Conclui-se que a obesidade materna representa fator de risco importante para o desenvolvimento da obesidade na adolescência.

OBJECTIVE: This study aimed to describe the relationship between teenager's adiposity and maternal obesity. METHODS: A cross-sectional study was done with 660 teenagers aged 8 to 18 years, of both genders, students of private and public schools of São Paulo. The data were collected by interviews, anthropometric measurements and food intake records. Teenagers' adiposity was determined by body mass index and regression analyses was used to verify its relationship with maternal obesity adjusted for gender, age, stage of sexual development, energy intake, physical activity, sedentary lifestyle, birth weight and mother's education level. RESULTS: Most (64.7 percent) of the teenagers were female. The mean age was 12.4 years (SD=1.80), aged 8 to 17 years. The prevalence of obesity and overweight was higher in boys. No statistical difference was found between nutritional status and gender. After the adjustments, the data show that children of obese mothers were 4 times more likely to be at risk of obesity than children of normal weight mothers. CONCLUSION: Maternal obesity is a great risk factor for adolescent obesity.