Positioning sulphonylureas in a modern treatment algorithm for patients with type 2 diabetes: Expert opinion from a European consensus panel

The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings.     

Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice

ObjectiveRecent studies indicate that regulatory T cells (Tregs) attenuate murine atherosclerosis. Since interleukin (IL)-2 induces Tregs proliferation, we tested the impact of L19-IL2, a fusion antibody specific to extra-domain B of fibronectin (ED-B) containing an active human IL-2 molecule, in experimental atherosclerosis.Methods and resultsL19-IL2 or appropriate controls were given intravenously to 6 month old Western diet-fed apoE^?/? mice on day 1, 3, and 5. Human IL-2 was detected on day 7 within atherosclerotic plaques of L19-IL2-treated mice, and magnetic resonance imaging of the plaques showed a significant adventitial gadolinium enhancement on day 7 and 13, suggesting microvascular leakage as a result of the pharmacodynamic activity of L19-IL2. Treatment with L19-IL2 significantly reduced the size of pre-established atherosclerotic plaques at the thoracic aorta (Sudan III stained area) and in the aortic root area (microscopic, morphometric analysis) on day 7 as compared to controls (L19, D1.3-IL2, NaCl) as well as compared to baseline (day 0). Tregs markers Foxp3 and CTLA4 were highly increased in plaques after L19-IL2 treatment compared to controls (p < 0.01), whereas the macrophage marker Mac3 was significantly reduced (p < 0.03). Co-treatment with IL-2-receptor blocking antibody PC61 abrogated L19-IL2-induced plaque reduction compared with IgG control (p < 0.03).ConclusionL19-IL2 delivers functional IL-2 to pre-established atherosclerotic plaques of WD-fed apoE^?/? mice resulting in significant plaque size reduction mediated by local Tregs.     

Admission Norton scale scores (ANSS) and postoperative complications following hip fracture surgery in the elderly

We sought to determine if low ANSS, usually associated with high pressure ulcer risk, are also associated with postoperative complications and in-hospital mortality following hip fracture surgery in the elderly. This was a retrospective cross-sectional study conducted in a tertiary medical center. The medical charts of consecutive elderly (≥ 65 years) patients admitted for hip fracture surgery were studied for the following measurements: ANSS, demographic data, co-morbidities, postoperative complications, the need for revision procedures, and in-hospital mortality. Except for pressure ulcers, postoperative complications included: acute coronary syndrome, acute renal failure, confusion, pneumonia, urinary tract infection, venous thromboembolism, and wound infection. The final cohort included 269 patients: 198 (73.6%) females and 71 (26.4%) males. Mean age for the entire cohort was 82.8 ± 0.4 years. Most patients underwent an internal fixation (n=146; 54.3%) or hemiarthroplasty (n=92; 34.2%). Overall, 110 (40.9%) patients had low (<15) ANSS. Patients with low ANSS had significantly more postoperative complications relative to patients with high ANSS (0.77 ± 0.09 vs. 0.23 ± 0.04; p<0.0001). Among all postoperative complications, urinary tract infection was independently associated with low ANSS (p<0.0001). ANSS were independently associated with postoperative complications (p<0.0001), the need for revision procedures (p=0.019), and in-hospital mortality (p=0.016). We conclude that the Norton scoring system may be used for predicting postoperative complications and in-hospital mortality following hip fracture surgery in the elderly.     

Graves' disease presenting with severe cholestasis

BACKGROUND: Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported. PATIENT SUMMARY: The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well. CONCLUSION: Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis.