Randomized trial of insulin versus usual care in reducing restenosis after coronary intervention in patients with diabetes. the STent Restenosis And Metabolism (STREAM) study

BackgroundDiabetes status is an independent marker of restenosis after percutaneous coronary intervention (PCI). Previous studies suggest that metabolic abnormalities associated with diabetes increase stent restenosis by promoting intimal hyperplasia. Preclinical studies have indicated that insulin therapy reduces intimal hyperplasia. The objective of this study was to determine whether insulin-mediated glucose lowering reduces in-stent restenosis in patients with diabetes undergoing PCIs.MethodsWe conducted a prospective, randomized, multicenter, open-labeled study with blinded outcomes. Patients were randomized 1:1 to daily bedtime subcutaneous NPH insulin (Novo Nordisk) versus usual therapy with oral hypoglycemic agents. The main outcomes were change in volume of intimal hyperplasia within the stent measured by intravascular ultrasound and late lumen loss by quantitative coronary angiography at 6 months post-PCI.ResultsSeventy-eight patients (36 insulin, 42 usual care) were randomized. Eight patients in each group received drug-eluting stents. The insulin group achieved greater reductions in both glycosylated hemoglobin A1c (mean±S.D.) (insulin: 8.0%±1.2% to 6.7%±0.7% vs. control: 7.5%±1.2% to 7.1%±1.0 %, P=.0038) and fasting glucose (insulin: 9.3±3.8 to 5.8±1.7 vs. usual care: 8.4±2.4 to 7.7±2.0 mmol/l, P<.0001). There were no hypoglycemic events. At 6 months, there were no significant differences in either intravascular-ultrasound-determined neointimal volume (insulin: 41.2±38.9 vs. usual care: 48.4±40.2 mm³, P=.33) or late lumen loss by angiography (insulin: 1.29±0.74 mm vs. usual care: 1.02±0.71 mm, P=.17).ConclusionsAddition of a single bedtime dose of insulin in patients with diabetes does not influence in-stent restenosis.     

Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-Mycobacterium tuberculosis activity

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generated in situ from indenoquinoxaline and l-tryptophan and reacts with various substituted β-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C–C and three C–N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for their in vitro activity against Mycobacterium tuberculosis H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 μg mL⁻¹) to ethambutol against Mycobacterium tuberculosis H37Rv.

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel spiropyrrolidine tethered indole hybrids in excellent yields employing a one-pot multicomponent 1,3-dipolar cycloaddition strategy.     

Factors affecting stresses in cortical bone around miniscrew implants

Abstract Objective: To evaluate various types of stress in cortical bone around miniscrew implants using finite element analysis. Materials and Methods: Twenty-six three-dimensional assemblies of miniscrew models placed in alveolar bone blocks were constructed using Abaqus (Dassault Systèmes Simulia Corp, Providence, RI), a commercial finite element analysis software package. The model variables included implant design factors and bone-related factors. All miniscrew implants were loaded in the mesial direction with a linear force equal to 2 N. Peak von Mises and principal stress values in cortical bone were compared between the different models for each factor. Results: The results demonstrated that some factors affected the stresses in bone (implant diameter, implant head length, thread size, and elastic modulus of cancellous bone), while other factors did not (thread shape, thread pitch, and cortical bone thickness). Conclusions: Miniscrew implant diameter, head length, and thread size as well as the elastic modulus of cancellous bone affect the stresses in cortical bone layer surrounding the miniscrew implant and may therefore affect its stability.     

Diagnostic accuracy of somatosensory evoked potential and electroencephalography during carotid endarterectomy

Background and Purpose: Perioperative stroke risk following carotid endarterectomy (CEA) is reported to be approximately 2–3%. The diagnostic accuracies of intraoperative EEG and SSEP monitoring during CEA have been studied separately. However, to date, the effectiveness of simultaneous EEG and SSEP monitoring during CEA has only been evaluated in small study populations. This study examined the diagnostic accuracy of combined EEG and SSEP monitoring in a large (N = 1165) patient population.

Methods: This study included 1165 patients who underwent CEA from 2000 to 2012 at the University of Pittsburgh Medical Center. The sensitivities, specificities, and diagnostic odds ratio of EEG and SSEP monitoring methods were examined separately and together. Receiver operating characteristic curves were plotted to assess sensitivity and specificity of single and combined Intraoperative monitoring (IONM) methods.

Results: Maximum sensitivity was obtained with multimodality monitoring with an IONM change in either EEG or SSEP of 50.00 (95% CI, 30.66–69.34). The specificity of simultaneous EEG and SSEP changes was 93.95 (95% CI, 92.28–95.35%). Maximum area under ROC curve obtained for IONM change in either EEG or SSEP was 0.660 (95% CI, 0.547–0.773, p-value 0.004).

Conclusion: The diagnostic accuracy of multimodality IONM during CEA is higher than an approach using single modality IONM. Simultaneous EEG and SSEP monitoring improves the likelihood of detecting periprocedural strokes after CEA. Neuro protective therapies to prevent periprocedural strokes can be based on changes in SSEP and EEG during CEA.     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.