Background: Angiotensin receptor blockers (ARBs), such as telmisartan, have been postulated to treat Covid-19-induced lung inflammation. Methods: This is a parallel-group, randomized, two-arm, open-label, adaptive, multicenter superiority trial with 1:1 allocation ratio. Participants included patients from 18 years of age hospitalized with Covid-19 with 4 or fewer days since symptom onset enrolled at a university and a community hospital in Buenos Aires, Argentina. Exclusion criteria included prior intensive care unit (ICU) admission and use of ARBs/angiotensin converting enzyme inhibitors at randomization. Control arm received standard care alone and treatment arm telmisartan 80 mg twice daily for 14 days. Primary outcomes were C-reactive protein (CRP) plasma levels at day 5 and 8 after randomization. Secondary outcomes included time to discharge within 15 days, admission to ICU and death at 15-and 30-days. NCT04355936 (Completed). Findings: A pragmatic decision to end the study before the third interim analysis was made on Oct. 30th due to sharp reduction in recruitment. A total of 162 patients were randomized. 158 patients enrolled between May 14 and October 30 2020, were included in the analysis, 80 in the standard care and 78 in the telmisartan added to standard care group. Baseline absolute CRP serum levels were 5.53 § 6.19 mg/dL (95% CI 6.91 to 4.15, n = 80) and 9.04 § 7.69 (95% CI 9.04 to 10.82, n = 74) in the standard care and telmisartan added to standard care groups, respectively. Day 5 control-group CRP levels were 6.06 § 6.95 mg/dL (95% CI 7.79À4.35, n = 66) while telmisartan group were 3.83 § 5.08 mg/dL (95% CI 5.08À2.59, n = 66, p = 0.038). Day 8 CRP levels were 6.30 § 8.19 mg/dL (95% CI 8.79À3.81, n = 44) and 2.37 § 3.47 mg/dL (95% CI 3.44À1.30, n = 43, p = 0.0098) in the control and telmisartan groups, respectively (all values expressed as mean § SD). Kaplan-Meier analysis showed that telmisartan-treated patients had a lower median time-to-discharge (control=15 days; telmisartan=9 days). Death by day 30 was reduced in the telmisartan-treated group (control 22.54%,

No abstract

One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.

AIM:To investigate the effects of chronic drinking of cola beverages on metabolic and echocardiographic parameters in rats. METHODS:Forty-eight male Wistar rats were divided in 3 groups and allowed to drink regular cola (C), diet cola (L), or tap water (W) ad libitum during 6 mo. After this period, 50% of the animals in each group were euthanized. The remaining rats drank tap water ad libitum for an additional 6 mo and were then sacrificed. Rat weight, food, and beverage consumption were measured regularly. Biochemical, echocardiographic and systolic blood pressure data were obtained at baseline, and at 6 mo (treatment) and 12 mo (washout). A complete histopathology study was performed after sacrifice. RESULTS:After 6 mo, C rats had increased body weight (+7%, P < 0.01), increased liquid consumption (+69%, P < 0.001), and decreased food intake (-31%, P < 0.001). C rats showed mild hyperglycemia and hypertriglyceridemia. Normoglycemia (+69%, P < 0.01) and sustained hypertriglyceridemia (+69%, P < 0.01) were observed in C after washout. Both cola beverages induced an increase in left ventricular diastolic diameter (C: +9%, L: +7%, P < 0.05 vs W) and volumes (diastolic C: +26%, L: +22%, P < 0.01 vs W; systolic C: +24%, L: +24%, P < 0.05 vs W) and reduction of relative posterior wall thickness (C: -8%, L: -10%, P < 0.05 vs W). Cardiac output tended to increase (C: +25%, P < 0.05 vs W; L: +17%, not significant vs W). Heart rate was not affected. Pathology findings were scarce, related to aging rather than treatment.CONCLUSION: This experimental model may prove useful to investigate the consequences of high consumption of soft drinks.

PurposeThis study evaluates whether the daily practice of an exercise routine might protect from endocrine pancreas damage in cola drinking rats.MethodsForty-eight Wistar rats were randomly assigned to 4 groups depending on a) beverage consumption ad libitum, water (W) or cola beverage (C), and b) physical activity, sedentary (S) or treadmill running (R). Accordingly, 4 groups were studied: WS (water sedentary), WR (water runner), CS (cola sedentary) and CR (cola runner). Body weight, nutritional data, plasma levels of glucose, creatinine, total cholesterol and cholesterol fractions, and triglycerides (enzymocolorimetry), and systolic blood pressure (plethysmography) were measured. After 6 months, euthanasia was performed (overdose sodium thiopental). Pancreatic tissue was immediately excised and conventionally processed for morphometrical and immunohistochemical determinations.ResultsThe effects of running and chronic cola drinking on pancreas morphology showed interaction (p<0.001) rather than simple summation. Cola drinking (CS vs WS) reduced median pancreatic islet area (-30%, 1.8 104 μm2 vs 2.58 104 μm2, p<0.0001) and median β-cell mass (-43%, 3.81 mg vs 6.73 mg, p<0.0001), and increased median α/β ratio (+49%, 0.64 vs 0.43, p< 0.001). In water drinking rats (WR vs WS), running reduced median α-cell mass (-48%, 1.48 mg vs 2.82 mg, p<0.001) and α/β ratio (-56%, 0.19 vs 0.43, p<0.0001). Differently, in cola drinking rats (CR vs CS), running partially restored median islet area (+15%, 2.06 104 μm2 vs 1.79 104 μm2, p<0.05), increased median β-cell mass (+47%, 5.59 mg vs 3.81 mg, p <0.0001) and reduced median α/β ratio (-6%, 0.60 vs 0.64, p<0.05).ConclusionThis study is likely the first reporting experimental evidence of the beneficial effect of exercise on pancreatic morphology in cola-drinking rats. Presently, the increase of nearly 50% in β cells mass by running in cola drinking rats is by far the most relevant finding. Moderate running, advisably indicated in cola consumers and patients at risk of diabetes, finds here experimental support.

The authors hypothesized that preeclampsia may change the phenotype of umbilical cord vessels. Segments of umbilical cords were obtained from 29 pregnant women (20 healthy and 9 with preeclampsia), which were histomorphometrically assessed. Birth weight was 2928±613 g for the control group vs 1749±656 g for the preeclampsia group (P<.0001). A significantly shorter gestational period was noted in the preeclampsia group: 35 weeks vs 39 weeks in the healthy group. Measurements of the outer layer area (116.4±55 μm2 vs 56.5±25 μm2; P=.0038), the inner layer area (63.1±16 μm2 vs 28.6±8 μm2; P<.0001), the lumen area (8.4±1 μm2 vs 3.4±2 μm2; P=.0003), and the wall/lumen ratio (20.3±9 vs 3.1±0.6; P<.0001) of arteries were significantly larger in the preeclampsia umbilical cords. Concerning veins, the wall/lumen ratio was higher in the preeclampsia group. In this study, the umbilical cord in preeclampsia showed significant changes in the structure of umbilical arteries, with increases in wall areas and wall/lumen ratios. J Clin Hypertens (Greenwich). 2011;13:30–34. ©2010 Wiley Periodicals, Inc.

Background. Covid-19, the disease caused by SARS-CoV-2, is associated with significant respiratory-related morbidity and mortality. Angiotensin receptor blockers (ARBs) have been postulated as tentative pharmacological agents to treat Covid-19-induced lung inflammation. Trial design. This trial is a parallel group, randomized, two arm, open label, multicenter superiority trial with 1:1 allocation ratio. Methods. Participants included patients who were 18 years of age or older and who had been hospitalized with confirmed Covid-19 with 4 or fewer days since symptom onset. Exclusion criteria included intensive care unit admission prior to randomization and use of angiotensin receptor blocker or angiotensin converting enzyme inhibitors at admission. Participants in the treatment arm received telmisartan 80 mg bid during 14 days plus standard care. Participants in the control arm received standard care alone. Primary outcome was to achieve significant reductions in plasma levels of C-reactive protein in telmisartan treated Covid-19 patients at day 5 and 8 after randomization. Key secondary outcomes included time to discharge evaluated at 15 days after randomization and admission to ICU and death at 15- and 30-days post randomization. We present here a preliminary report. Results. A total of 78 patients were included in the interim analysis, 40 in the telmisartan and 38 in the control groups. CRP levels at day 5 in the control group were 51.1 +/- 44.8 mg/L (mean +/- SD; n=28) and in the telmisartan group were 24.2 +/- 31.4 mg/L (mean +/- SD; n=32, p<0.05). At day 8, CRP levels were 41.6 +/- 47.6 mg/L (mean +/- SD; n=16) and 9.0 +/- 10.0 mg/L (mean +/- SD; n=13, p < 0.05) in the control and telmisartan groups, respectively. Also, analysis of time to discharge by Kaplan-Meier method showed that telmisartan treated patients had statistically significant lower time to discharge (median time to discharge control group=15 days; telmisartan group=9 days). No differences were observed for ICU admission or death. No significant adverse events related to telmisartan were reported. Conclusions. In the present preliminary report, despite the small number of patients studied, ARB telmisartan, a well-known inexpensive safe antihypertensive drug, administered in high doses, demonstrates anti-inflammatory effects and improved morbidity in hospitalized patients infected with SARS -CoV-2, providing support for its use in this serious pandemia (NCT04355936).

The prevalence of coronary intimal thickening (IT) was assessed in fetuses and pediatric population. We studied the coronary arteries of 63 hearts obtained from fetuses, infants, children, and adolescents, deceased from noncardiac disease or trauma. Histomorphometric analysis, planimetry, and immunohistochemical studies were conducted. Intimal thickening consisted of proliferation of smooth muscle cells and scarce monocytes embedded in amorphous deposits within the internal elastic membrane (IEM). Intermingled lesions of intimal hyperplasia and parietal nonstenotic plaques were also observed. Intimal thickening was found in 10% of 20 fetuses, in 33.3% of 18 infants, 73.3% of 15 children, and 100% of 10 adolescents. A significant correlation ( r = 0.671, P < 0.001) was found between the extent of IT and age. The IEM was duplicated or interrupted in 43% of patients, showing a positive correlation with the degree of IT ( P = 0.01). Intimal thickening was predominantly found near bifurcation sites in the left anterior descending coronary artery (55.6%) and in zones free of bifurcation in the right coronary artery (75%). In conclusion, the prevalence and extension of IT lesions are higher at older ages within a young population. Intimal thickening may be regarded as the first event occurring in coronary preatherosclerosis, preceding lipid deposition.