Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

BACKGROUND:The calculation of the glycemic index of food mirrors a rise in blood sugar levels. A loweglycemic index carbohydrate diet in pregnancy has been associated with normal infant birthweight. Thus, strategies to lower the food glycemic index could be successful in improving pregnancy outcomes. OBJECTIVE: The purpose of this study was to compare different prescribed diets on food glycemic index intake and its relationship with rate of large-for-gestational-age infants. STUDY DESIGN: At the 9the12th week of gestation (with a gynecologist and a dietitian both present), 273 Italian women with a body mass index of !25 kg/m 2 were assigned randomly either to a customized loweglycemic index diet that was detailed by a dietitian (customized intervention; n¼139 women; 1800 kcal/dþ30 minutes walking 4 times/ wk) or to generic lifestyle advice (standard care; n¼134 women) with counseling about a prudent diet and physical activity, according to Italian guidelines. At enrollment and at the 36th week of gestation, the food frequency questionnaire was completed. In 73 Italian foods, the glycemic index was assessed with the use of a classic formula (available carbo-hydrateÂglycemic index prescribed/total carb content of the meal) then was subdivided according to meal pattern. The main outcome was the change in foode glycemic index. RESULTS: Sociodemographic features were similar between the groups. One hundred fifty-six women completed the study (customized intervention¼81; standard care¼75). The mean daily glycemic index decreased from 58.4AE19 to 52.5AE11.2 (P¼.008) in the customized intervention group although it remained unchanged in the standard care group. After the intervention, women in the customized intervention group reported a significant decrease in the diet glycemic index at dinner compared with both lunch and breakfast values (P<.02). Lower birthweight and fewer large-for-gestational-age infants were observed in the customized intervention group. CONCLUSION: A customized loweglycemic index, calorie-restricted diet that was associated with constant physical activity effectively reduced the food glycemic index. This reduced food glycemic index is associated with lower rate of large-for-gestational-age newborn infants.

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OBJECTIVE: To determine the influence of weight gain on the odds of cesarean delivery for obese women (as determined by pre-pregnancy body mass index [BMI]), specifically by class of obesity. STUDY DESIGN: This is a secondary data analysis of the Pregnancy Risk Assessment Monitoring System (PRAMS) in the United States (Centers for Disease Control and Prevention). The unadjusted odds ratios for cesarean delivery were determined for each class of BMI (underweight, normal weight, overweight, class I obesity, class II obesity, and class III obesity). These odds were then adjusted by demographic and prenatal care factors (maternal age, marital status, race, ethnicity, education) influencing either weight gain during pregnancy or risk of cesarean delivery on univariate analysis. The association of weight gain (insufficient <11 lbs, appropriate 11-20 lbs, and excessive >20 lbs) on the odds ratios of cesarean delivery in obese women was evaluated via multivariate logistic regression analysis. RESULTS: Thirty-two states contributed to the dataset (n¼57,866 women), (Figure 1). The adjusted odds ratios (aOR) of cesarean delivery by BMI were: underweight 0.92 (95% CI 0.83, 1.01), normal weight (referent group), overweight 1.38 (95% CI 1.32, 1.45), class I obesity 1.77 (95% CI 1.68, 1.88), class II obesity 2.17 (95% CI 2.02, 2.34), and class III obesity 3.07 (95% CI 2.82, 3.34). Class I and II obese women were more likely to have a cesarean with excessive weight gain, with class I OR 1.20 (95% CI 1.06, 1.36) and class II OR 1.24 (1.04,1.48) when compared to women in their same class of obesity with appropriate weight gain (Figure 2). CONCLUSION: Although obesity is a known risk factor for cesarean delivery, this risk is thought to be mitigatable by appropriate weight gain during the pregnancy. Weight gain of <20 pounds was associated with the least risk of cesarean delivery among obese (specifically Class I and II) individuals.

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