Background The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. Methods We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. Results A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P=0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. Conclusions Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114 .)

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Summary:Purpose: To study the interaction between gabapentin (GBP) and high-protein meals, 12 patients with epilepsy were administered this drug both while in a fasting state and after a high-protein meal.Methods: After having acquired their informed consent, the patients (suffering from partial complex seizures resistant to other anticonvulsants) were randomly assigned to 2 groups of 6 subjects. Each subject was treated in a fasting state with a single 400 (group A) or 800 (group B) mg GBP oral dose. After 24 h, the GBP dose regimen was repeated, but was given after a high-protein meal. Serum GBP concentrations were measured by LC-Mass at baseline and 0.5, 1, 2, 3, 5, 7, 9, 12, and 24 h. Saliva GBP concentrations were determined at baseline and 2, 4, 8, and 12 h. GBP urinary excretion was determined at 0-4, 4-8, and 8-12 h intervals. The following kinetic parameters were calculated: area under the concentration time curve from zero time to 24 h after the dose, AUC 0-24 h; maximal serum concentration, C, , , ; time to the maximal serum concentration, T,,,; absorption rate constant, ka; elimination rate constant, p;elimination half-time, t%P. Student's t test for paired data, with significance assigned at P < 0.05, was used. Results:No statistically significant differences were seen in GBP serum or saliva concentrations or in its urinary excretion (both in A or B group) between fasting and after the highprotein meal.Conclusions: High-protein meals do not seem to interfere with oral disposition of GBP.

Background and objectivesPatients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR.Design, setting, participants, & measurementsThe DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2.ResultsThe effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2.ConclusionsThe effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.

OBJECTIVETo determine the prevalence of renal artery stenosis (RAS) in patients who have undergone cineangiocoronariography. METHODSProspective study of cineangiocoronariography and aortography examinations conducted between January 2002 and February 2004 on 1,656 hypertensive and normotensive patients who underwent the examinations to confirm the diagnosis of obstructive coronary artery disease or valve disease. RESULTSThe average age of the 1,656 patients was 61.6 ± 11.8 years. Eight hundred and ninety-one (53.8%) were male, 169 (10.2%) were diabetic and 1,054 (63.8%) presented obstructive coronary artery disease. Renal stenosis greater than 50% was observed in 228 (13.8%) patients, and 25 (1.5%) had bilateral stenosis. Obstructive coronary artery disease was defined as stenosis greater than or equal to 50% of the vessel lumen, in one, two or three main arteries, classified as single, double or triple vessels, respectively. Quantification was conducted using visual analysis of the angiography. Comparison of the revealed significant statistical differences in relation to gender, age, diabetes mellitus, blood pressure and left ventricular function. However, no statistical difference was noted in relation to the occurrence of coronary relation to blood pressure, coronary artery obstructions in the renal artery obstruction group. M a i l i n g A d d r e s s : R o g é r i o T a d e u T u m e l e r o CONCLUSIONThe prevalence of RAS found in our study was comparable to that reported by major medical literature case studies. RAS is associated with systemic hypertension (SH), endstage renal disease (ESRD) and its sequelae, emphasizing how important it is that we are aware of possible candidates for angiographic diagnosis of this disease. KEY WORDSRenal artery stenosis, atherosclerosis, end-stage kidney disease, systemic hypertension, angiography with contrast medium.

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