The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value <25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA <4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA >10 mm2 (P <.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (<4 mm2, 4-8 mm2, >8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was <1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation

Predictors and clinical significance of progression or regression of asymptomatic carotid stenosis

OBJECTIVE: To determine baseline clinical and ultrasonographic plaque factors predictive of progression or regression of asymptomatic carotid stenosis and the predictive value of changes in stenosis severity on risk of first ipsilateral cerebral or retinal ischemic events (including stroke). METHODS: A total of 1121 patients with asymptomatic carotid stenosis of 50% to 99% in relation to the bulb diameter (European Carotid Surgery Trial [ECST] method) underwent six monthly clinical assessments and carotid duplexes for up to 8 years (mean follow-up, 4 years). Progression or regression was considered present if there was a change of at least one grade higher or lower, respectively, persisting for at least two consecutive examinations. RESULTS: Regression occurred in 43 (3.8%), no change in 856 (76.4%), and progression in 222 (19.8%) patients. Younger age, high grades of stenosis, absence of discrete white areas in the plaque, and taking lipid lowering therapy were independent baseline predictors of increased incidence of regression. High serum creatinine, male gender, not taking lipid lowering therapy, low grades of stenosis, and increased plaque area were independent baseline predictors of progression. One hundred and thirty first ipsilateral cerebral or retinal ischemic events, including 59 strokes, occurred. Forty (67.8%) of the strokes occurred in patients whose stenosis was unchanged, 19 (32.2%) in those with progression, and zero in those with regression. For the entire cohort, the 8-year cumulative ipsilateral cerebral ischemic stroke rate was zero in patients with regression, 9% if the stenosis was unchanged, and 16% if there was progression (average annual stroke rates of 0%, 1.1%, and 2.0%, respectively; log-rank, P = .05; relative risk in patients with progression, 1.92; 95% confidence interval, 1.14-3.25). For patients with baseline stenosis 70% to 99% in relation to the distal internal carotid (North American Symptomatic Carotid Endarterectomy Trial [NASCET] method), in the absence of progression (n = 349), the 8-year cumulative ipsilateral cerebral ischemic stroke rate was 12%. In the presence of progression (n = 77), it was 21% (average annual stroke rates of 1.5% and 2.6%, respectively; log-rank, P = .34). Only nine (30%) of the 30 strokes occurred in the progression group. CONCLUSIONS: Progressive asymptomatic carotid stenosis identified a subgroup with about twice the risk of ipsilateral stroke compared with those without progression. However, the clinical value of screening for progression simply for selecting patients for carotid procedures is limited because of the low frequency of progression and its relatively low associated stroke rate. The cost effectiveness of screening for change in stenosis severity to better direct current optimal medical treatment needs testing

Mortality from esophagectomy for esophageal cancer across low, middle, and high-income countries: An international cohort study.

BACKGROUND No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer. METHOD This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI). RESULTS Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI: 0.54-1.32, p = 0.5), compared to HIC. CONCLUSION Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)