SYNTAX Score and Outcomes of Coronary Revascularization in Diabetic Patients

Purpose of Review

This review describes the dynamic relationship between diabetes mellitus (DM) and coronary artery disease (CAD) with respect to different revascularization strategies and how angiographic tools such as the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score can supplement clinical decision-making.

Recent Findings

The SYNTAX score characterizes the anatomical extent of CAD in terms of the number of lesions, functional importance, and complexity. Studies not limited to patients with DM suggest that percutaneous coronary intervention (PCI) is a reasonable alternative to coronary artery bypass grafting (CABG) in patients with low-medium SYNTAX scores, while patients with high SYNTAX scores should be revascularized with CABG if operable. Similar findings were also observed for diabetes patients with multivessel disease in retrospective pooled analysis. The SYNTAX II score combines anatomical and clinical risk to improve upon the decision regarding the optimal revascularization strategy. The SYNTAX II score can be applied to patients with DM.

Summary

The SYNTAX scores provide guidance to clinicians faced with determining the optimal revascularization strategy in patients with DM and advanced CAD. Using a heart team approach, the information can be considered along with other factors that influence PCI or CABG risk.

     

Increased levels of interleukin-10 and IgG3 are hallmarks of Indian post-kala-azar dermal leishmaniasis

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL), an established sequela of visceral leishmaniasis (VL), is proposed to facilitate anthroponotic transmission of VL, especially during interepidemic periods. Immunopathological mechanisms responsible for Indian PKDL are still poorly defined. METHODS: Our study attempted to characterize the immune profiles of patients with PKDL or VL relative to that of healthy control subjects by immunophenotyping, intracellular cytokine staining of peripheral blood mononuclear cells, and enzyme-linked immunosorbent assay for serum cytokines and immunoglobulin G (IgG) subclasses. RESULTS: Patients with PKDL had significantly raised percentages of peripheral CD3+CD8+ cells compared with control subjects, a difference that persisted after cure. Patients with PKDL showed an intact response to phytohemagglutinin, with the percentages of lymphocytes expressing interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10 being comparable to those in control subjects. Patients with VL had decreased IFN-gamma and IL-2 expression, which was restored after cure, and increased IL-10 expression, which persisted after cure. In their response to Leishmania donovani antigen, patients with PKDL showed a 9.6-fold increase in the percentage of IL-10-expressing CD3+CD8+ lymphocytes compared with control subjects, and this percentage decreased with treatment. Patients with PKDL had raised levels of IgG3 and IgG1 (surrogate markers for IL-10), concomitant with increased serum levels of IL-10. CONCLUSIONS: IL-10-producing CD3+CD8+ lymphocytes are important protagonists in the immunopathogenesis of Indian PKDL.     

Evaluation of area-based collagen scoring by nonlinear microscopy in chronic hepatitis C-induced liver fibrosis

In this paper we analyze a fibrosis scoring method based on measurement of the fibrillar collagen area from second harmonic generation (SHG) microscopy images of unstained histological slices from human liver biopsies. The study is conducted on a cohort of one hundred chronic hepatitis C patients with intermediate to strong Metavir and Ishak stages of liver fibrosis. We highlight a key parameter of our scoring method to discriminate between high and low fibrosis stages. Moreover, according to the intensity histograms of the SHG images and simple mathematical arguments, we show that our area-based method is equivalent to an intensity-based method, despite saturation of the images. Finally we propose an improvement of our scoring method using very simple image processing tools.OCIS codes: (180.4315) Nonlinear microscopy, (170.1610) Clinical applications, (170.3880) Medical and biological imaging, (170.4580) Optical diagnostics for medicine, (110.2960) Image analysis     

Gene control of tyrosine kinase TIE2 and vascular manifestations of infections

Ligands of the endothelial-enriched tunica interna endothelial cell kinase 2 (Tie2) are markedly imbalanced in severe infections associated with vascular leakage, yet regulation of the receptor itself has been understudied in this context. Here, we show that TIE2 gene expression may constitute a novel vascular barrier control mechanism in diverse infections. Tie2 expression declined rapidly in wide-ranging models of leak-associated infections, including anthrax, influenza, malaria, and sepsis. Forced Tie2 suppression sufficed to attenuate barrier function and sensitize endothelium to permeability mediators. Rapid reduction of pulmonary Tie2 in otherwise healthy animals attenuated downstream kinase signaling to the barrier effector vascular endothelial (VE)-cadherin and induced vascular leakage. Compared with wild-type littermates, mice possessing one allele of Tie2 suffered more severe vascular leakage and higher mortality in two different sepsis models. Common genetic variants that influence TIE2 expression were then sought in the HapMap3 cohort. Remarkably, each of the three strongest predicted cis-acting SNPs in HapMap3 was also associated with the risk of acute respiratory distress syndrome (ARDS) in an intensive care unit cohort of 1,614 subjects. The haplotype associated with the highest TIE2 expression conferred a 28% reduction in the risk of ARDS independent of other major clinical variables, including disease severity. In contrast, the most common haplotype was associated with both the lowest TIE2 expression and 31% higher ARDS risk. Together, the results implicate common genetic variation at the TIE2 locus as a determinant of vascular leak-related clinical outcomes from common infections, suggesting new tools to identify individuals at unusual risk for deleterious complications of infection.Among vascular-enriched receptor tyrosine kinases, Tie2 is unusual in at least two functional aspects. First, Tie2 phosphorylation is tightly controlled by the interplay of several proteins: a paralogous receptor, Tie1; a tyrosine phosphatase, vascular endothelial-protein tyrosine phosphatase (VE-PTP); and two secreted ligands, angiopoietin (Angpt)-1 and Angpt-2, the latter of which can act as an agonist, partial agonist, or antagonist depending upon context (1–6). Second, unlike classic growth factor receptors, Tie2 is heavily expressed and phosphorylated throughout the quiescent adult vasculature (7), suggesting that Tie2 signaling has one or more roles in vascular maintenance.Based largely on Angpt-1 overexpression studies, Tie2 has been implicated in vascular barrier defense (8, 9). However, adult-specific deletion of Angpt-1 does not appear to trigger vascular leakage (10). Moreover, Angpt-1 has repeatedly been ascribed functions that are independent of Tie2 (11–13). Finally, observational studies in humans suffering clinical manifestations of vascular leakage have consistently shown a marked imbalance in Tie2 ligands tilting in favor of Angpt-2 (reviewed in 14). Although decreased Tie2 activity has been inferred from these reports, the role of TIE2 gene expression has not been directly queried experimentally or in clinical settings.This question is important not only for understanding control mechanisms of the circulatory system but also to guide the development of strategies to predict, stratify, and treat patients affected by acute vascular leakage. If tonic Tie2 signaling is indeed necessary for vascular barrier maintenance, then reducing the pool of receptors could constitute a ligand-independent means to attenuate barrier-protective signaling in the endothelium. We therefore hypothesized that the level of Tie2 expression modulates the sensitivity of blood vessels, and thereby the entire organism, to noxious stimuli. Cellular, rodent, and human genetics studies were undertaken to test this concept.     

Behavioral and electrophysiological responses of Aedes albopictus to certain acids and alcohols present in human skin emanations

Human skin emanations attract hungry female mosquitoes toward their host for blood feeding. In this study, we report the flight orientation and electroantennogram response of Aedes albopictus females to certain unsaturated acids and alcohols found in human skin. In the Y-tube olfactometer, odors of lactic acid and 2-methyl-3-pentanol attracted 54–65 % of Ae. albopictus females at all doses in a dose-dependent manner. However, at the highest dose (10^?2 g), the acids repelled 40–45 % females. Attractancy (ca. 62–68 %) at lower doses and repellency (ca. 30–45 %) at higher doses were recorded for 3-methyl-3-pentanol and 1-octen-3-ol, while 5-hexen-1-ol, cis-2-hexen-1-ol, and trans 2-hexen-1-ol odor repelled ca. 55–65 % of Ae. albopictus females at all doses. Antenna of female Ae. albopictus exhibited a dose-dependent EAG response up to 10^?3 g of l-lactic acid, trans-2-methyl-2-pentenoic acid, 2-octenoic acid, trans-2-hexen-1-ol and 1-octen-3-ol stimulations; however, the highest dose (10^?2 g) caused a little decline in the EAG response. EAG response of 9–10-fold was elicited by lactic acid, 2-octenoic acid, trans-2-hexenoic acid, and 3-methyl-3-pentanol, while cis-2-hexen-1-ol and trans-2-methyl pentenoic acid elicited 1–5-fold responses compared to solvent control. A blend of attractive compounds could be utilized in odor-baited trap for surveillance and repellent molecules with suitable formulation could be used to reduce the biting menace of mosquitoes.     

Risk of Colorectal Adenomas in Women with Prior Breast Cancer

Background and Aims

Longer life expectancy in patients with prior breast cancer may increase their risk of developing other primary cancers, including colorectal cancer (CRC). Whether the risk of developing CRC in this patient population is higher in comparison to those with no prior cancer remains unclear. The purpose of this study was to compare the prevalence of colorectal adenomas and any CRC in breast cancer survivors with those who have no history of prior cancer and assess any difference with use of antiestrogen therapy.

Methods

We compared the prevalence of colorectal cancer and adenomas in breast cancer survivors with that of a group of matched controls. Eligible survivors were ??85?years of age; had initially been diagnosed with stage 0, I, II, or III breast cancer; had completed all cancer treatments with the exception of adjuvant antiestrogen therapy; and had no evidence of recurrence on follow-up. We used the screening colonoscopy database at our institution to identify age-, sex-, and race-matched controls with no history of cancer.

Results

We identified 302 study-eligible breast cancer survivors and 302 matched controls. No colorectal cancers were found in either group. Forty-one breast cancer survivors and 30 controls had tubular adenomas; four survivors and three controls had villous adenoma; and eight survivors and ten controls had advanced adenoma. Multivariate regression analysis revealed that adjuvant antiestrogen therapy was not significantly associated with an increased risk of advanced adenoma.

Conclusions

The prevalence of colorectal adenomas in breast cancer survivors and controls was similar. Breast cancer survivors, including those receiving adjuvant antiestrogen therapies may follow the colorectal screening guidelines used for average-risk population.     

Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial fibrillation or heart failure

Dronedarone is a benzofuran derivative approved by the Food and Drug Administration to decrease the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) and associated cardiovascular risk factors who are in sinus rhythm or will undergo cardioversion. There has been recent evidence to suggest that dronedarone may not have a favorable safety profile. We decided to evaluate all available evidence on the cardiovascular safety of this drug. A systematic search was made of the PubMed, CENTRAL, and EMBASE databases for randomized controlled trials from 1966 through 2011 comparing dronedarone to comparators in AF/heart failure. Intervention was dronedarone for AF for some studies and heart failure for others. Comparators included standard medical therapy and/or placebo and amiodarone for 1 study. Outcomes assessed were all-cause mortality, cardiovascular mortality, ventricular arrhythmias, embolic events, acute coronary syndrome, heart failure exacerbations, and hospitalization rates in the intervention versus comparator group at the end of ≥ 3 months of follow up with abstraction of data by 1 author. Seven randomized controlled trials were included in our analysis. Dronedarone use was associated with a trend toward worse all-cause and cardiovascular mortalities and increased heart failure exacerbations. It also showed numerically higher event rates for all other outcome events except acute coronary syndrome. Our pooled analysis showed increased all-cause and cardiovascular mortalities and increased heart failure exacerbations with use of dronedarone across a wide spectrum of populations. In conclusion, we recommend exercising caution using dronedarone, especially in patients with cardiovascular risk factors.