Objective-To examine CD11c, a ␤ 2 -integrin, on adipose tissue (AT) leukocytes and blood monocytes and its role in diet-induced obesity. Methods and Results-High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blood by flow cytometry, RNase protection assay, quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. Obese C57BL/6 mice had increased CD11c in AT and blood compared with lean controls. CD11c messenger RNA positively correlated with monocyte chemoattractant protein 1 in human visceral AT. Obese humans with metabolic syndrome had a higher CD11c level on blood monocytes compared with lean humans. Low-fat diet-induced weight loss reduced blood monocyte CD11c in obese mice and humans. Mouse and human monocyte CD11c levels and mouse AT CD11c messenger RNA correlated with insulin resistance. CD11c deficiency in mice did not alter weight gain but decreased inflammation, evidenced by a lower T-cell number and reduced levels of major histocompatibility complex class II, C-C chemokine ligand 2 (CCL5), CCL4, and interferon ␥ in AT, and ameliorated insulin resistance and glucose intolerance associated with diet-induced obesity. Conclusions-Diet-induced obesity increased CD11c in both AT and blood in mice and humans. CD11c plays an important role in T-cell accumulation and activation in AT, and contributes to insulin resistance associated with obesity. Key Words: inflammation Ⅲ obesity O besity increases the risk for type 2 diabetes and cardiovascular disease. Chronic inflammation, which occurs in obesity, has been acknowledged as an important link between obesity and the development of diabetes and cardiovascular disease. Adipose tissue (AT) synthesizes and secretes proinflammatory substances, such as cytokines, which are upregulated in obesity and may play important roles in mediating obesity-linked insulin resistance. 1 Chemokines, which contribute to inflammation because of their active properties for leukocyte trafficking and activation, have also been shown to be expressed by AT and increased in obesity. 2,3 Along with the increased levels of chemokines, such as monocyte chemoattractant protein (MCP) 1, or CCL2, and regulated on activation, normal T-cell expressed and secreted (RANTES), or CCL5, leukocytes, including macrophages and T cells, are increased in AT in obesity, and increased leukocytes in AT may contribute to obesity-linked metabolic abnormalities. 2,4 -7 Initial studies used CD11b and/or F4/80 to define total macrophages in AT. 4,5 Using mice fed a high-fat diet (HFD) for 3 weeks, we first reported a significant increase in CD11cϩ cells in AT. 8 Subsequently, other investigators reported an accumulation of F4/80 ϩ CD11c ϩ leukocytes in the AT of obese mice. 9,10 CD11c ϩ leukocytes in the AT of obese mice show proinflammatory characteristics of classically activated macrophages (M1) 9,10 and were demonstrated to play an important role in obesity-linked AT inflam...

IMPORTANCE Stress cardiac magnetic resonance imaging (CMR) is not widely used in current clinical practice, and its ability to predict patient mortality is unknown. OBJECTIVE To determine whether stress CMR is associated with patient mortality. DESIGN, SETTING, AND PARTICIPANTS Real-world evidence from consecutive clinically ordered CMR examinations. Multicenter study of patients undergoing clinical evaluation of myocardial ischemia. Patients with known or suspected coronary artery disease (CAD) underwent clinical vasodilator stress CMR at 7 different hospitals. An automated process collected data from the finalized clinical reports, deidentified and aggregated the data, and assessed mortality using the US Social Security Death Index. MAIN OUTCOMES AND MEASURES All-cause patient mortality. RESULTS Of the 9151 patients, the median (interquartile range) patient age was 63 (51-70) years, 55% were men, and the median (interquartile range) body mass index was 29 (25-33) (calculated as weight in kilograms divided by height in meters squared). The multicenter automated process yielded 9151 consecutive patients undergoing stress CMR, with 48 615 patient-years of follow-up. Of these patients, 4408 had a normal stress CMR examination, 4743 had an abnormal examination, and 1517 died during a median follow-up time of 5.0 years. Using multivariable analysis, addition of stress CMR improved prediction of mortality in 2 different risk models (model 1 hazard ratio [HR], 1.83; 95% CI, 1.63-2.06; P < .001; model 2: HR, 1.80; 95% CI, 1.60-2.03; P < .001) and also improved risk reclassification (net improvement: 11.4%; 95% CI, 7.3-13.6; P < .001). After adjustment for patient age, sex, and cardiac risk factors, Kaplan-Meier survival analysis showed a strong association between an abnormal stress CMR and mortality in all patients (

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Background: An accurate subtype classification of acute ischemic stroke is important in clinical practice as it can greatly influence patient care in terms of acute management and devising secondary stroke prevention strategies. Approximately, one third of ischemic strokes are cryptogenic despite a comprehensive workup. Diagnostic workup for detecting cardioaortic sources of cerebral embolism commonly includes transthoracic echocardiography (TTE). However, TTE has a limited diagnostic power to detect some of the cardioaortic abnormalities and additional imaging modalities are often needed to accurately assess such abnormalities. Purpose: We evaluated the feasibility of cardiovascular magnetic resonance (CMR) imaging to detect the cardioaortic sources of ischemic stroke. Methods: A total of 106 patients were included, of which 85 had an ischemic stroke and 21 had a transient ischemic attack (TIA). Routine diagnostic workup (RDW) included brain diffusion-weighted image MRI, telemetry, magnetic resonance angiography/CT angiography of head and neck, carotid duplex ultrasonography, laboratory studies and TTE. Patients additionally underwent CMR. Subtype assignment was performed in accordance with the Stop Stroke Study of the Trial of Org 10172 in Acute Stroke Treatment classification system by a stroke neurologist after reviewing the admission notes and diagnostic test results. A second subtype classification was assigned with an additional criterion defined based on delayed enhancement (DE)-CMR findings. Additionally, the presence of non-coronary artery disease (CAD) scarring was assessed in ischemic stroke patients and compared with the TIA patients as the control group. Results: RDW detected cardioaortic embolism (CAE) stroke in 32 (37.6%) patients and cryptogenic stroke in 23 patients (27.1%). Addition of CMR resulted in a 26.1% reduction in the rate of cryptogenic strokes (6 patients). Furthermore, DE-CMR findings allowed for reclassification of three additional cryptogenic subtypes, resulting in a 39.1% reduction of cryptogenic stroke rate. Non-CAD scarring was detected in 13 (15.3%) stroke patients as opposed to only 1 (4.8%) TIA patient. Conclusions: CMR is a valuable tool for the detection of CAE sources in patients with cryptogenic ischemic stroke and provides clinicians with a unique set of information that may substantially change the long-term management of these patients. DE-CMR also detects non-CAD scarring, which may indicate a predisposition to ischemic stroke. Further studies with larger samples and long-term follow-up are needed to further evaluate the clinical significance of our findings.

Introduction: Although current guidelines recommend withholding statins in perioperative patients, little information is available on whether perioperative statin use increases risk for postoperative renal failure. Aims: We examined the relation between preoperative statin therapy and postoperative risk for renal insufficiency in patients undergoing cardiac surgery. Methods: Retrospective cohort review from the Texas Heart Institute research database was performed. Patients were divided into two groups: those who received preoperative statins and those who did not. Primary outcome was the development of postoperative renal insufficiency (requiring dialysis or not). Outcomes were assessed in the entire cohort and in subgroups undergoing isolated coronary artery bypass grafting (CABG), isolated valve surgery, or combined CABG and valve surgery. Results: Of 3001 patients, 56% received preoperative statins. In multivariate logistic regression analysis, preoperative statins were associated with significant reductions in risk for postoperative renal insufficiency in the entire cohort (odds ratio [OR] = 0.60, 95% confidence interval [CI] 0.38-0.95) and in patients undergoing isolated CABG (OR = 0.34, 95% CI 0.17-0.68). In patients undergoing isolated valve surgery (OR = 1.35, 95% CI 0.61-2.96) or combined CABG and valve surgery (OR = 1.39, 95% CI 0.48-3.99), preoperative statins were not associated with decreased incidence of postoperative renal insufficiency. Age >65 years, preoperative renal insufficiency, history of congestive heart failure, preoperative intra-aortic balloon pump insertion, and total cardiopulmonary bypass time >80 min were also independent predictors associated with increased risk for postoperative renal insufficiency. Conclusions: Preoperative statin therapy was associated with decreased incidence of postoperative renal insufficiency in patients undergoing cardiac surgeries, particularly in patients undergoing isolated CABG.