CHADS2 and CHA2DS2-VASc scores as predictors of platelet reactivity in acute coronary syndrome

BackgroundPlatelet function testing (PFT) in patients treated with P2Y₁₂ inhibitors has been widely evaluated for the prediction of stent thrombosis, myocardial infarction, and bleeding events following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). Thus, PFT-guided treatment could positively affect patient outcomes. Data regarding clinical parameters for predicting platelet reactivity in ACS patients are limited. Therefore, our study aims to evaluate CHADS2 and CHA2DS2-VASc scores as predictors for platelet reactivity in ACS patients.MethodsTwo hundred and ninety-one consecutive patients who underwent PCI and were treated with aspirin and clopidogrel due to ACS were tested for their CHADS2, CHA2DS2-VASc scores and platelet reactivity using adenosine diphosphate (ADP)-induced aggregation (conventional aggregometry). Patients were classified into groups according to their CHADS2 and CHA2DS2-VASc scores. Low-risk group (0–1 score) for CHADS2 and CHA2DS2-VASc scores and high-risk group (2–6, 2–9) for CHADS2 and CHA2DS2-VASc scores, respectively. Furthermore, platelet reactivity in each group were compared (low CHADS2 group vs high CHADS2 group, and low CHA2DS2-VASc vs high CHA2DS2-VASc). Platelet reactivity was defined as low platelet reactivity (<19 U), optimal platelet reactivity [(OPR); 19–46 U], and high on-treatment platelet reactivity [(HPR); >46 U]. Thereafter receiver operating characteristic curve analysis was conducted to verify whether CHADS2 and CHA2DS2-VASc scores could predict platelet reactivity.ResultsLow CHADS2 and CHA2DS2-VASc scores were significantly correlated with lower mean platelet ADP-induced aggregation as compared with high CHADS2 and CHA2DS2-VASc scores [45.5 U (± 16) vs. 54.8 U (±15) and 44.2 U (±16) vs. 51.0 U (±17), respectively, p = 0.01 for both].ConclusionIn ACS patients treated with clopidogrel following PCI, high CHADS2 and CHA2DS2-VASc scores correlated with HPR and lower scores correlated with OPR. Further studies are needed to evaluate our findings’ clinical implications.     

Angioplasty Guidewire Velocity: A New Simple Method to Calculate Absolute Coronary Blood Velocity and Flow

The Thrombolysis In Myocardial Infarction (TIMI) frame count is a relative index of coronary flow that measures time by counting the number of frames required for dye to travel from the ostium to a standardized coronary landmark in a cineangiogram filmed at a known speed (frames/s). We describe a new method to measure distance along arteries so that absolute velocity (length ÷ time) and absolute flow (area × velocity) may be calculated in patients undergoing percutaneous transluminal coronary angiography (PTCA). After PTCA, the guidewire tip is placed at the coronary landmark and a Kelly clamp is placed on the guidewire where it exits the Y-adapter. The guidewire tip is then withdrawn to the catheter tip and a second Kelly clamp is placed on the wire where it exits the Y-adapter. The distance between the 2 Kelly clamps outside the body is the distance between the catheter tip and the anatomic landmark inside the body. Velocity (cm/s) may be calculated as this distance (cm) ÷ TIMI frame count (frames) × film frame speed (frames/s). Flow (ml/s) may be calculated by multiplying this velocity (cm/s) and the mean cross-sectional lumen area (cm²) along the length of the artery to the TIMI landmark. In 30 patients, velocity increased from 13.9 ± 8.5 cm/s before to 22.8 ± 9.3 cm/s after PTCA (p <0.001). Despite TIMI grade 3 flow both before and after PTCA in 18 patients, velocity actually increased 38%, from 17.0 ± 5.4 to 23.5 ± 9.0 cm/s (p = 0.01). For all 30 patients, flow doubled from 0.6 ± 0.4 ml/s before to 1.2 ± 0.6 ml/s after PTCA (p <0.001). In the 18 patients with TIMI grade 3 flow both before and after PTCA, flow increased 86%, from 0.7 ± 0.3 to 1.3 ± 0.6 ml/s (p = 0.001). Distance along coronary arteries (length) can be simply measured using a PTCA guidewire. This length may be combined with the TIMI frame count to calculate measures of absolute velocity and flow that are sensitive to changes in perfusion. TIMI grade 3 flow is composed of a range of velocities and flows.     

Vitamin D deficiency in children with bronchial asthma in southern Jordan: a cross-sectional study

ObjectivesTo assess serum 25-hydroxycholecalciferol (25-OH vitamin D) levels in Jordanian children with bronchial asthma, and to examine correlations between 25-OH vitamin D levels and asthma severity and control.MethodsA cross-sectional study was conducted at the Paediatric Chest Clinic, Al-Karak Governmental Hospital, Southern Jordan, between May 2015 and February 2016. Serum 25-hydroxyvitamin D level was determined in children aged 1–14 years diagnosed with bronchial asthma (6–14 years) or recurrent wheezing episodes (<6 years). Asthma severity was determined based on the Global Initiative for Asthma assessment, the Asthma Control Test, and the Childhood Asthma Control Test. Demographic and clinical characteristics were compared between patients with low and normal 25-OH vitamin D levels, and correlations between asthma severity and 25-OH vitamin D level were assessed.ResultsOut of 98 included children, 25-OH vitamin D levels were deficient and insufficient in 41 (41.8%) and 34 (34.7%) children, respectively. Only 23 (23.5%) had sufficient 25-OH vitamin D levels. A significant correlation was found between severity of asthma symptoms and 25-OH vitamin D deficiency.Conclusion25-OH vitamin D deficiency is highly prevalent in Jordanian children with bronchial asthma and correlates significantly with asthma severity.     

Staphylococcus aureus: the search for novel targets

In the UK, 20,000 cases of Staphylococcus aureus bacteraemia are reported each year, half of which are antibiotic resistant and approximately 4% are fatal, exemplifying a worldwide phenomenon of tremendous economic and human impact. Novel treatments and prophylaxis are urgently required to combat such a serious threat. A common goal in the postgenomic era is to identify new targets for drug intervention (using small molecules) and immunologicals. Several promising cellular targets are now being developed in the quest to control such a life-threatening pathogen.     

Histologically benign intraventricular meningioma with concurrent pulmonary metastasis: case report and review of the literature

Only 1-2% of all meningiomas are intraventricular in location. Metastasis from a histologically "benign" meningioma is a rare, but well-documented event. However, there are only four reported cases in the literature of metastatic spread from a purely intraventricular meningioma. The tumors in these reports had a frankly malignant histology or were associated with surgical manipulation and recurrence of the primary lesion. In this report, the authors present a rare case of the concurrent presentation of a histologically benign intraventricular meningioma and a solitary lung lesion which proved to be metastatic meningioma.     

Double-Blind,Randomized Study Evaluating the Glycemic and Anti-inflammatory Effects of Subcutaneous LY2189102, a Neutralizing IL-1β Antibody,in Patients With Type 2 Diabetes

OBJECTIVE

Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1β antibody, in T2DM patients.

RESEARCH DESIGN AND METHODS

Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications.

RESULTS

LY2189102 reduced HbA_1c at 12 weeks (adjusted mean differences versus placebo: −0.27, −0.38 and −0.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated.

CONCLUSIONS

Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA_1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM.Type 2 diabetes occurs when pancreatic β-cell function fails to compensate for insulin resistance (1,2). As the duration of diabetes increases, β-cell function progressively deteriorates, partly as a result of apoptotic cell death (3–5). Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity, supporting the notion that inflammation plays a key role in aggravating or even causing type 2 diabetes specifically or the metabolic syndrome generally (6). Interleukin (IL)-1β is an inflammatory mediator that may contribute to this pathophysiology. IL-1β expression has been observed in β-cells of patients with type 2 diabetes (7). Moreover, production and secretion of IL-1β from β-cells is induced by high glucose levels and inhibits the function and promotes the apoptosis of β-cells (7–10). The IL-1 receptor antagonist (IL-1ra) protects human β-cells from glucose-induced functional impairment (7) and apoptosis, and its expression is decreased in patients with type 2 diabetes (11).The hypothesis that blocking IL-1β activity could be therapeutic in type 2 diabetes was tested clinically with anakinra, a recombinant IL-1ra (12,13). Results from a proof-of-concept study indicated that anakinra modestly improved hemoglobin A_1c (HbA_1c) relative to placebo, reduced circulating inflammatory cytokines, and showed signs of improved β-cell secretory function after 13 weeks of daily subcutaneous dosing (13). Nine months after treatment completion, anakinra-treated patients continued to have improved proinsulin/insulin ratios and reduced inflammatory cytokines; anakinra responders required less exogenous insulin than did nonresponders (14). Clinical evaluation of a neutralizing IL-1β monoclonal antibody (XOMA 052) in type 2 diabetic patients showed similar results. XOMA 052 improved HbA_1c relative to placebo after a single intravenous infusion and after repeated subcutaneous dosing; improvements in fasting blood glucose and insulin sensitivity after subcutaneous dosing were also noted (15).Typically only a small percentage of cytokine receptors require engagement to activate downstream signaling pathways, and cytokines are typically labile proteins expressed at low concentrations. Because anakinra binds to the IL-1 receptor and has a short half-life (4–6 h) (16), it is unclear whether the modest nature of the response in type 2 diabetes was related to compound-specific properties or a reflection of the role of this cytokine pathway in the disease pathogenesis. Although XOMA 052 binds and neutralizes IL-1β directly and has a longer half-life, it was dosed in a limited number of subjects and for short duration. Further evaluation of the intervention in the IL-1β pathway in diabetes would help determine whether this approach could be a successful therapy.LY2189102 (LY) is a humanized monoclonal antibody (IgG4) that binds to IL-1β with high affinity (2.8 pmol/L) and neutralizes its activity. Previous clinical studies have evaluated its safety and pharmacokinetics, as well as its effects on signs and symptoms of rheumatoid arthritis ({"type":"clinical-trial","attrs":{"text":"NCT00380744","term_id":"NCT00380744"}}NCT00380744). This phase II study aimed to evaluate the efficacy, safety, and tolerability of LY in type 2 patients with diabetes treated with diet and exercise, with or without approved antidiabetic medications.