A case of aspirin-resistance probably related to glycemic excursion

Diabetes is characterised by development of specific microvascular complications and by a high incidence of accelerated atherosclerosis. Several Authors demonstrated that post-prandial hyperglycaemia is certainly an independent risk factor of vascular complications in type 2 diabetes. The endothelial dysfunction, the oxidative stress, the post-prandial hyperglycaemia and the haemostatic and thrombotic parameters alterations are the principal causes for the cardiovascular risk increase in diabetic patient. For this reason many studies on anti-platelet therapy have been made in order to reduce thrombotic complication of diabetes mellitus. However, data suggest that the clinical efficacy of low-dose aspirin in patients with diabetes is substantially lower than in individuals without diabetes. Indeed, several evidences support the hypothesis that diabetes might represent a case of “aspirin resistance”

Negative Emotions in Skin Disorders: A Systematic Review

The main purpose of this study is to describe how negative emotions were investigated in the sphere of dermatological diseases, in order (1) to summarize literature trends about skin disorders and emotions, (2) to highlight any imbalances between the most studied and neglected emotions, (3) and to offer directions for future research. A computerized literature search provided 41 relevant and potentially eligible studies. Results showed that the study of emotions in skin disease is limited to Sadness/depression and Fear/anxiety. The emotions of Anger and Disgust have been poorly explored in empirical studies, despite they could be theoretically considered a vulnerability factor for the development of skin disorders and the dermatological extreme consequences, as negative emotionality toward self and the pathological skin condition. The bibliometric qualitative analysis with VOSViewer software revealed that the majority of the studies have been focused on the relationships between vitiligo and Sadness/depression, dermatitis and Fear/anxiety, psoriasis, and Anger, suggesting the need of future research exploring Disgust and, in general, a wider emotional spectrum

Cardiac Resynchronization Therapy Outcomes in Type 2 Diabetic Patients: Role of MicroRNA Changes

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two growing and related diseases in general population and particularly in elderly people. In selected patients affected by HF and severe dysfunction of left ventricle ejection fraction (LVEF), with left bundle brunch block, the cardiac resynchronization therapy with a defibrillator (CRT) is the treatment of choice to improve symptoms, NYHA class, and quality of life. CRT effects are related to alterations in genes and microRNAs (miRs) expression, which regulate cardiac processes involved in cardiac apoptosis, cardiac fibrosis, cardiac hypertrophy and angiogenesis, and membrane channel ionic currents. Different studies have shown a different prognosis in T2DM patients and T2DM elderly patients treated by CRT-D. We reviewed the literature data on CRT-D effect on adult and elderly patients with T2DM as compared with nondiabetic patients

Serum CD26 levels in patients with gastric cancer: a novel potential diagnostic marker

Background: CD26 is an ectoenzyme with dipeptidyl peptidase 4 (DPP4) activity expressed on a variety of cell types. Considering that serum CD26 levels have been previously associated with different cancers, we examined the potential diagnostic value of serum CD26 levels in gastric cancer.Methods: Soluble serum CD26 levels were measured in pre and postoperative serum samples of 30 patients with gastric cancer and in 24 healthy donors by a specific ELISA kit.Results: We found significantly lower serum CD26 levels in patients with gastric cancer (557.7 +/- 118.3 pg/mL) compared with healthy donors (703.4 +/- 170.3 pg/mL). Moreover patients with HER2 positive tumors had significantly lower CD26 serum levels (511.8 +/- 84.8 pg/mL) compared with HER2 negative tumors (619.1 +/- 109.9 pg/mL, p = 0.006). A binary logistic model having gastric cancer as the dependent variable while age, gender, CEA, CA19.9 and CD26 levels as covariates, showed that CD26 serum levels were independently associated with gastric cancer presence. Indeed after 3 months from surgery serum CD26 levels significantly increased (700.1 +/- 119.9 pg/mL vs 557.7 +/- 118.3 pg/ml) in all patients (t = -4.454, p < 0.0001).Conclusions: This is a preliminary study showing that the measurement of serum CD26 levels could represent an early detection marker for gastric cancer

Bariatric Surgery Reduces Oxidative Stress by Blunting 24-h Acute Glucose Fluctuations in Type 2 Diabetic Obese Patients

OBJECTIVE - We evaluated the efficacy of malabsorptive bariatric surgery on daily blood glucose fluctuations and oxidative stress in type 2 diabetic obese patients. RESEARCH DESIGN AND METHODS - The 48-h continuous subcutaneous glucose monitoring was assessed in type 2 diabetic patients before and 1 month after biliopancreatic diversion (BPD) (n = 36), or after diet-induced equivalent weight loss (n = 20). The mean amplitude of glycemic excursions and oxidative stress (nitrotyrosine) were evaluated during continuous subcutaneous glucose monitoring. During a standardized meal, glucagon-like peptide (GLP)-1, glucagon, and insulin were measured. RESULTS - Fasting and postprandial glucose decreased equally in surgical and diet groups. A marked increase in GLP-1 occurred during the interprandial period in surgical patients toward the diet group (P < 0.01). Glucagon was more suppressed during the interprandial period in surgical patients compared with the diet group (P < 0.01). Mean amplitude of glycemic excursions and nitrotyrosine levels decreased more after BPD than after diet (P < 0.01). CONCLUSIONS - Oxidative stress reduction after biliopancreatic diversion seems to be related to the regulation of glucose fluctuations resulting from intestinal bypass. © 2010 by the American Diabetes Association

Neurovascular coupling in patients with type 2 diabetes mellitus

Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 +/- 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 +/- 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer's disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology

Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients

ObjectivesThis study evaluated whether subclinical episodes of atrial fibrillation (AF) were associated with an increased risk of silent cerebral infarct (SCI) and stroke in diabetic patients younger than 60 years who did not have other clinical evidence of AF and cerebrovascular disease at baseline.BackgroundIn type 2 diabetic patients, one-fourth of strokes are of unknown cause, and subclinical episodes of AF may be a common etiologic factor.MethodsA total of 464 type 2 diabetic patients younger than 60 years were included in a longitudinal observational study and matched to patients without diabetes. Patients underwent 48-h electrocardiographic Holter monitoring quarterly to detect brief subclinical episodes of AF (duration of AF <48 h) and were followed up for 37 months. The outcomes were SCI, assessed by magnetic resonance imaging of the brain, and stroke events during the follow-up period.ResultsThe prevalence of subclinical episodes of AF was significantly greater among patients with diabetes compared with matched healthy subjects (11% vs. 1.6%, p < 0.0001). During an average duration of 37 months, 43 stroke events occurred in the diabetic population and no events occurred in healthy subjects. Diabetic patients with silent episodes of AF (n = 176) had a higher baseline prevalence of SCI (61% vs. 29%; p < 0.01) and a higher number of stroke events (17.3% vs. 5.9%; p < 0.01) during the follow-up period than the other patients (n = 288). An episode of silent AF was an independent determinant of SCI (odds ratio: 4.441; p < 0.001; confidence interval: 2.42 to 8.16) and an independent predictor of the occurrence of stroke in diabetic patients (hazard ratio: 4.6; p < 0.01; confidence interval: 2.7 to 9.1).ConclusionsSubclinical episodes of AF occurred frequently in type 2 diabetic patients and were associated with a significantly increased risk of SCI and stroke

Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i

The Role of Basic Symptoms and Aberrant Salience in Borderline Personality Disorder

Background: The prevalence of pre-psychotic symptoms and aberrant salience in BPD has not been systematically studied. The present study aims to investigate the intensity, frequency and correlation between basic symptoms, aberrant salience and borderline personality traits, in subjects that have not yet developed a frank psychotic episode.  Methods: Twenty-eight subjects, 8 males and 20 females, aged between 24 and 55 years (M = 41.36 ± 9.9) has been individually tested throughout the Frankfurt Complaint Questionnaire (FBF), the Aberrant Salience Inventory (ASI) and the Personality Inventory for the DSM-5- Adult (PID-5).  Results: Findings showed that 85.7% of the sample (n = 24) reported significant scores of the aberrant salience traits, which in turn were correlated to basic symptoms. Furthermore, emerged several correlations between pre-psychotic symptoms and PID-5 personality dimensions not only with Negative Affectivity and Detachment but also with Psychoticism. Conclusions: This study highlights the phenomenological continuity between the borderline personality traits and the attenuated manifestation of the psychotic disease

An Update on the Current and Emerging Use of Thiazolidinediones for Type 2 Diabetes

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists ("glitazones") are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies