Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Age-dependent increase of cytoskeletal components in sensory axons in human skin.

Aging is a complex process characterized by several molecular and cellular imbalances. The composition and stability of the neuronal cytoskeleton is essential for the maintenance of homeostasis, especially in long neurites. Using human skin biopsies containing sensory axons from a cohort of healthy individuals, we investigate alterations in cytoskeletal content and sensory axon caliber during aging via quantitative immunostainings. Cytoskeletal components show an increase with aging in both sexes, while elevation in axon diameter is only evident in males. Transcriptomic data from aging males illustrate various patterns in gene expression during aging. Together, the data suggest gender-specific changes during aging in peripheral sensory axons, possibly influencing cytoskeletal functionality and axonal caliber. These changes may cumulatively increase susceptibility of aged individuals to neurodegenerative diseases

Durale arteriovenöse Fistel (DAVF) als Ursache eines pulssynchronen Tinnitus

Background and purpose. In September 2011 the cornea section of the German Ophthalmological Society (DOG) established the first German Acanthamoeba keratitis registry. The data of this multicenter survey are being collected, compiled and evaluated at the Department of Ophthalmology at the Saarland University. The aim of this article is to present an intermediate report. Patients and methods. Data from 172 eyes with Acanthamoeba keratitis were collected during the last 10 years. For this interim report we actually evaluated 121 eyes (60.2 % female patients, average age 41.3 years) and collected the following data: date of onset of symptoms, date and method of diagnosis, initial diagnosis, anamnestic data, clinical symptoms and signs at diagnosis and during follow-up, conservative and surgical therapy. Criteria for inclusion in the Acanthamoeba registry was the established diagnosis of an Acanthamoeba keratitis with at least one of the methods described in this article. Results. Acanthamoeba keratitis could be histologically proven in 55.3 % of the cases, via PCR in 25.6 %, with confocal microscopy in 20.4 % and using in vitro cultivation in 15.5 %. Clinical symptoms and signs in Acanthamoeba keratitis were pain in 67.0 %, ring infiltrates in 53.4 %, pseudodendritiform epitheliopathy in 11.7 % and keratoneuritis in 5.8 %. In 47.6 % of the cases the initial diagnosis was herpes simplex virus keratitis followed by bacterial keratitis in 25.2 % and fungal keratitis in 3.9 %. Acanthamoeba keratitis was the correct initial diagnosis in only 23.2 % of cases. The average time period between first symptoms and diagnosis was 2.8 +/- 4.0 months (range 0-23 months). A triple therapy with BroleneA (R) LavaseptA (R) and antibiotic eye drops at least 5 x/day was used in 54.5 % of eyes (n = 66). Penetrating keratoplasty was performed in 40.4 %, in 18 cases in combination with cryotherapy of the cornea. The mean graft diameter was 7.9 A +/- 1.1 mm (range 3.5-11.0 mm). The final visual acuity (Snellen visual acuity chart at 5 m) was comparable in the two groups of eyes with (5/40 A +/- 5/25) and without (5/32 A +/- 5/25) keratoplasty. Conclusion. Acanthamoeba keratitis is a rare and often very late diagnosed disease and two thirds of the cases were initially misdiagnosed. The early recognition of the typical symptoms is crucial for the prognosis of the disease. All ophthalmological departments in Germany are invited to submit further data of all confirmed cases ([email protected]), whether retrospectively or prospectively in order to generate an adequate standardized diagnostic and therapeutic approach for this potentially devastating disease