Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease

Diabetes Mellitus is a multifactorial disease with a critical impact worldwide. During prediabetes, the presence of various inflammatory cytokines and oxidative stress will lead to the pathogenesis of type 2 diabetes. Furthermore, insulin resistance and chronic hyperglycemia will lead to micro- and macrovascular complications (cardiovascular disease, heart failure, hypertension, chronic kidney disease, and atherosclerosis). The development through the years of pharmacological options allowed us to reduce the persistence of chronic hyperglycemia and reduce diabetic complications. This review aims to highlight the specific mechanisms with which the new treatments for type 2 diabetes reduce oxidative stress and insulin resistance and improve cardiovascular outcomes

Percutaneous transfemoral-transseptal implantation of a second-generation CardiAQ™ mitral valve bioprosthesis: first procedure description and 30-day follow-up

Transcatheter mitral valve implantation for mitral valve regurgitation is in the very early phase of development because of challenging anatomy and device dimensions. We describe the procedure of a transfemoral-transseptal implantation of the second-generation CardiAQ™ mitral valve bioprosthesis and 30-day follow-up

Clinical results with the 31 mm CoreValve™ in large aortic annuli: The importance of implantation technique

The CoreValve Revalving System (CRS) (Medtronic Inc., Minneapolis, MN, USA) is currently available in four sizes: 23 mm, 26 mm, 29 mm and 31 mm. Aim of our study was to assess the acute clinical results after implantation of a 31 mm CRS

Identification of MOR-positive B cell as possible innovative biomarker (Mu lympho-marker) for chronic pain diagnosis in patients with fibromyalgia and osteoarthritis diseases

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease

Prediction of All-Cause Mortality Following Percutaneous Coronary Intervention in Bifurcation Lesions Using Machine Learning Algorithms

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74–0.83) in the overall population, 0.74 (0.62–0.85) at internal validation and 0.71 (0.62–0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance

Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD.In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer.These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology