TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Although the echolucent plaque in carotid stenosis is associated with future ischemic stroke, the predictive value of echogenicity in small and medium size carotid plaques on vascular events has not been thoroughly examined. Thus, we prospectively tested the hypothesis that plaque echogenicity of carotid atheroma can predict the future total cardiovascular events in patients with vascular risk factors.', 'Ultrasound assessment of carotid intima-media complex thickness (IMT) and plaque echogenicity using integrated backscatter (IBS) analysis was performed in 596 patients aged 40 or more, with any history of vascular events or with at least 1 risk factor, who were enrolled between 2001 and 2006 in the Osaka Follow-up Study for Carotid Atherosclerosis, part 2 (OSACA2). We followed the incidence of total cardiovascular events including cerebrovascular events, coronary heart disease (CHD), and peripheral artery disease (PAD) for 6.4 years. We divided the patients into two groups according to the IBS index above (echorich plaques) and under (echolucent plaque) the median value, and calculated the hazard ratios (HR) of the echolucent group compared with the echogenic group in the risk of cardiovascular events.', 'Among 596 patients, carotid stenosis was found only in 87 patients. During the follow-up period, we observed 121 cardiovascular events including 63 cerebrovascular events, 45 CHD cases, and 13 PAD cases. The patients with incident cardiovascular events had larger plaque thickness and lower IBS index than those without incident vascular events. The relative risk of vascular events for echolucent versus echorich plaques was 1.45 (95% confidence interval [CI] 0.99-2.13, p = 0.058) after adjustment for risk factors and plaque thickness. In patients with plaque size above the median value (>2.1 mm), the relative risk of vascular events for echolucent plaques was 1.72 (95% CI 1.06-2.85, p = 0.029), but this association was not observed in patients with plaque size <2.0 mm.\Question: Does echogenicity of medium-to-large carotid plaques predict future vascular events?

SOLUTION: The association between echogenicity of carotid plaque and incident vascular events is dependent on the plaque size. Echolucent medium-to-large plaques, but not small plaques, are associated with the risk of future total cardiovascular events. This finding suggests that measurement of echolucency in medium-to-large carotid plaques may improve selection of patients at high risk for total vascular events.

PROBLEM: Context: Trauma centers are currently benchmarked on mortality outcomes alone. However, pay-for-performance measures may financially penalize centers based on complications. Our objective was to determine whether the results would be similar to the current standard method of mortality-based benchmarking if trauma centers were profiled on complications.', 'We analyzed data from the National Trauma Data Bank from 2007 to 2010. Patients 16 years or older with blunt or penetrating injuries and an Injury Severity Score (ISS) of 9 or higher were included. Risk-adjusted observed-to-expected (O/E) mortality ratios for each center were generated and used to rank each facility as high, average, or low performing. We similarly ranked facilities on O/E morbidity ratios defined as occurrence of any major complication. Concordance between hospital performance rankings was evaluated using a weighted κ statistic. Correlation between morbidity- and mortality-based O/E ratios was assessed using Pearson coefficients. Sensitivity analyses were performed to mitigate the competing risk of death for the morbidity analyses.', 'A total of 449,743 patients from 248 facilities were analyzed. The unadjusted morbidity and mortality rates were 10.0% and 6.9%, respectively. No correlation was found between morbidity- and mortality-based O/E ratios (r = -0.01). Only 40% of the centers had similar performance rankings for both mortality and morbidity. Of the 31 high performers for mortality, only 11 centers were also high performers for morbidity. A total of 78 centers were ranked as average, and 11 ranked as low performers on both outcomes. Comparison of hospital performance status using mortality and morbidity outcomes demonstrated poor concordance (weighted κ = 0.03, p = 0.22).\Question: Does benchmarking trauma centers on mortality alone reflect quality of care : implications for pay-for-performance?

SOLUTION: Mortality-based external benchmarking does not identify centers with high complication rates. This creates a dichotomy between current trauma center profiling standards and measures used for pay-for-performance. A benchmarking mechanism that reflects all measures of quality is needed.

PROBLEM: Context: Endothelin receptor antagonists improve pulmonary arterial hypertension (PAH). Mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2) predispose to PAH. Here, we sought to determine whether there might exist interactions between these 2 signaling pathways and their effect on the acquisition of the altered phenotype of pulmonary artery smooth muscle cells (PA-SMCs) observed in PAH.', 'Expression of BMPR2, of the BMP agonist BMP4, and of the BMP antagonists gremlin1 and gremlin2 was evaluated in lungs and in PA-SMCs from 6 PAH patients and 14 controls treated with endothelin-1. Endothelin-1 pre-treated PA-SMCs were assessed for proliferation, apoptosis, and downstream signaling activation of Smad1/5/8 and p38 mitogen-activated protein kinase (p38(MAPK)) after BMP2 treatment.', 'In PA-SMCs from PAH patients, expression of BMPR2 and BMP4 decreased, whereas expression of gremlin1 and gremlin2 increased compared with controls. Treatment of control PA-SMCs with endothelin-1 induced a dose-dependent increase in gremlin1 and gremlin2, whereas BMPR2 and BMP4 expression decreased, reaching similar levels as those observed in PAH cells. In control PA-SMCs, endothelin-1 pre-treatment reduced inhibitor of DNA binding 1 (Id1) expression and Smad1/5/8 activation induced by BMP2, whereas it enhanced p38(MAPK) activation. Moreover, BMP2 decreased serum-induced proliferation and increased the pro-apoptotic Bax/Bcl-2 ratio. These effects were attenuated by endothelin-1 pre-treatment. Endothelin-1 did not alter BMPR2 signaling in PA-SMCs from PAH patients.\Question: Does endothelin-Bone morphogenetic protein type 2 receptor interaction induce pulmonary artery smooth muscle cell hyperplasia in pulmonary arterial hypertension?

SOLUTION:
Endothelin-1 downregulates canonical BMPR2 signaling. This is related to decreased BMPR2 and increased anti-BMP gremlin expression associated with increased activation of p38(MAPK) and results in PA-SMC proliferation.