Context Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. Objective To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. Design, Setting, and Participants Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level ≤10 mg/dL) aged 19 to 55 years and of African descent (n=149) or community controls (Hb AA and normal hemoglobin level) (n=47). Participants were stratified on age, sex, and education. Main Outcome Measures The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. Results The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, −5.50; 95% confidence interval {CI}, −9.55 to −1.44]; P =.008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, −5.19; 95% CI, −9.24 to −1.13]; P =.01), working memory (90.75 vs 95.25 [mean difference, −4.50; 95% CI, −8.55 to −0.45]; P =.03), processing speed (86.50 vs 97.95 [mean difference, −11.46; 95% CI, −15.51 to −7.40]; P <.001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. Conclusion Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.

The present study and a review of the literature suggest that obesity and duration of surgery are the most important predictors of mediastinitis. Furthermore, although the early increase in mortality has been well described, the present study documents for the first time that mediastinitis has a significant negative influence on long-term survival independent of the patient's preoperative condition.

Observational assessments reveal that stable chest pain patients who undergo a more aggressive diagnostic strategy have higher diagnostic costs and greater rates of intervention and follow-up costs. Cost differences may reflect a diminished necessity for resource consumption for patients with normal test results.

Adults with Sickle Cell Disease (SCD) experience multiple disease-related complications, but few studies have examined relationships between these events and health-related quality of life (HRQOL). We determined the number and type of previous or co-occurring SCD related complications and their reported HRQOL in a cohort of 1046 adults from the Comprehensive Sickle Cell Centers (CSCC). Participants had a median age of 28.0 years (48% male, 73% SS or Sβ0 thalassemia) and had experienced several SCD-related complications (mean 3.8 ± 2.0), which were influenced by age, gender and hemoglobinopathy type (p<0.0001). In multivariate models, increasing age reduced all SF-36 scales scores (p<0.05) except mental health, while female gender additionally diminished physical function and vitality scale scores (p< 0.01). Of possible complications, only vaso-occlusive crisis, asthma, or avascular necrosis diminished SF-36 scale scores. Chronic antidepressants usage predominantly diminished scores on bodily pain, vitality, social functioning, emotional role, and mental health scales, while chronic opioid usage diminished all scale scores (p<0.01). Our study documents substantial impairment of HRQOL in adults with SCD that was influenced by only a few of many possible medical complications. It suggests that more effective treatments of persistent pain and depression would provide the largest HRQOL benefit.

Background-Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined. Methods and Results-A logistic regression model was used to predict significant (Ն75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (PϽ0.0001) and severe (PϽ0.0001) coronary artery disease. For low-risk patients (score Նϩ5), 60% had no coronary stenosis Ն75% and 16% had single-vessel Ն75% stenosis. By comparison, 74% of high-risk patients (score ϽϪ11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (PϽ0.0001). Conclusions-The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease. (Circulation. 1998;98:1622-1630.)

The purpose of this study was to evaluate long-term survival benefits of bypass surgery and angioplasty versus medical therapy in 9263 patients at Duke University Medical Center between 1984 and 1990 with coronary artery disease confirmed by cardiac catheterization to involve one, two, or three vessels. Clinical data were prospectively entered into an established cardiovascular database, and annual follow-up was 97% complete for a mean interval of 5.3 years and a maximal interval of 10 years. Outcomes were analyzed with the Coronary Artery Surgery Study "method A" to define patient groups treated by medicine (n = 2449), angioplasty (n = 2924), or bypass surgery (n = 3890). Differences among treatment groups in baseline characteristics were adjusted by Cox proportional hazard models. The anatomic severity of coronary artery stenosis best defined survival benefit from bypass surgery and angioplasty versus medical treatment. One or both interventional treatments provided better long-term survival than did medical treatment for all levels of disease severity. All patients with single-vessel disease, except those with at least 95% proximal left anterior descending stenosis, benefited from angioplasty versus bypass. All patients with three-vessel disease and those two-vessel patients with > or = 95% proximal left anterior descending stenosis benefited from bypass surgery versus angioplasty. All other patients with two-vessel disease and those with > or = 95% proximal left anterior descending stenosis only had similar survival with either interventional treatment. The absolute survival benefit was greatest for patients with severe three-vessel disease treated with bypass surgery.

• Children with SCA and stroke show severe parenchymal and vascular abnormalities that can be assessed using a vasculopathy grading scale. • Results from the SWiTCHTrial support concerns about ineffectiveness of transfusion therapy in preventing cerebrovascular injury progression.The Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial compared standard (transfusions/chelation) to alternative (hydroxyurea/phlebotomy) treatment to prevent recurrent stroke and manage iron overload in children chronically transfused over 7 years before enrollment. Standardized brain magnetic resonance imaging/magnetic resonance angiography (MRA) and transcranial Doppler (TCD) exams were performed at entry and exit, with a central blinded review. A novel MRA vasculopathy grading scale demonstrated frequent severe baseline left/right vessel stenosis (53%/41% ‡Grade 4); 31% had no vessel stenosis on either side. Baseline parenchymal injury was prevalent (85%/79% subcortical, 53%/37% cortical, 50%/35% subcortical and cortical). Most children had low or uninterpretable baseline middle cerebral artery TCD velocities, which were associated with worse stenoses (incidence risk ratio [IRR] 5 5.1, P £ .0001 and IRR 5 4.1, P < .0001) than normal velocities; only 2% to 12% had any conditional/abnormal velocity. Patients with adjudicated stroke (7) and transient ischemic attacks (19 in 11 standard/8 alternative arm subjects) had substantial parenchymal injury/vessel stenosis. At exit, 1 child (alternative arm) had a new silent infarct, and another had worse stenosis. SWiTCH neuroimaging data document severe parenchymal and vascular abnormalities in children with SCA and stroke and support concerns about chronic transfusions lacking effectiveness for preventing progressive cerebrovascular injury. The novel SWiTCH vasculopathy grading scale warrants validation testing and consideration for use in future clinical trials. This trial was registered at www.clinicaltrials.gov as #NCT00122980. (Blood. 2014;124(6):891-898)

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA).Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group. We hypothesized that individuals with SCA would exhibit reductions in frontal lobe cortex thickness and reduced basal ganglia and thalamus volumes compared with HCs and that these structural brain abnormalities would be associated with measures of cognitive functioning (Wechsler Adult Intelligence Scale, 3rd edition). Results: