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Meadows T.A.,Mid Carolina Cardiology | Bhatt D.L.,Brigham and Womens Hospital | Cannon C.P.,Harvard University | Gersh B.J.,Mayo Medical School | And 7 more authors.
Mayo Clinic Proceedings

OBJECTIVE: To determine whether ethnic-specific differences in the prevalence of cardiovascular risk factors and outcomes exist worldwide among individuals with stable arterial disease. PATIENTS AND METHODS: From December 1, 2003, to June 30, 2004, the prospective, observational REduction of Atherothrombosis for Continued Health (REACH) Registry enrolled 49,602 outpatients with coronary artery disease, cerebrovascular disease, and/or peripheral arterial disease from 7 predefined ethnic/racial groups: white, Hispanic, East Asian, South Asian, Other Asian, black, and Other (comprising any race distinct from those specified). The baseline demographic and risk factor profiles, medication use, and 2-year cardiovascular outcomes were assessed among these groups. RESULTS: The prevalence of traditional atherothrombotic risk factors varied significantly among the ethnic/racial groups. The use of medical therapies to reduce risk was comparable among all groups. At 2-year follow-up, the rate of cardiovascular death was significantly higher in blacks (6.1%) compared with all other ethnic/ racial groups (3.9%; P=.01). Cardiovascular death rates were significantly lower in all 3 Asian ethnic/racial groups (overall, 2.1%) compared with the other groups (4.5%; P<.001). CONCLUSION:The REACH Registry, a large international study of individuals with atherothrombotic disease, documents the important ethnic-specific differences in cardiovascular risk factors and variations in cardiovascular mortality that currently exist worldwide. © 2011 Mayo Foundation for Medical Education and Research. Source

Maliniemi P.,University of Helsinki | Hahtola S.,University of Helsinki | Ovaska K.,University of Helsinki | Jeskanen L.,University of Helsinki | And 7 more authors.
Orphanet Journal of Rare Diseases

Background: Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood. Methods: The aim of this study was to unravel molecular pathways critical to the SPTL pathogenesis. Therefore, we analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry. Results: Interestingly, indoleamine 2,3-dioxygenase (IDO-1), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5), were also significantly increased. Confirmed using immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c- CD68- cells but not in CD11c+ dendritic cells in the microenvironment. The proportion of FoxP3+ cells in SPTL exceeded that in the benign panniculitis samples. Conclusions: Our results indicate that the up regulation of the tolerogenic IDO-1 together with the up regulation of IFNG, CXCR3 ligands, and CCL5 are features of SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favorable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma. © 2014 Maliniemi et al.; licensee BioMed Central Ltd. Source

Bernardini G.L.,Albany Medical Center | Schellinger P.D.,Johannes Wesling Klinikum Minden | Abou-Chebl A.,University of Louisville | Cockroft K.,Penn State Hershey Medical Center | And 6 more authors.
Journal of Stroke and Cerebrovascular Diseases

Atrial fibrillation (AF) is a well-established independent risk factor for stroke. We examined cerebral blood flow augmentation in the treatment of acute ischemic stroke (AIS) in patients with AF by performing secondary analysis of data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, a randomized controlled trial evaluating NeuroFlo treatment in stroke patients within 14 hours of symptom onset. We report subgroup analyses of outcomes in SENTIS patients with a history or new diagnosis of AF. Among patients with AF, those treated with NeuroFlo demonstrated significant improvement over those not treated for multiple end points: global efficacy end point (P =.030), modified Rankin Scale (mRS) score 0-2 versus 3-6 (P =.029), and stroke-related mortality (P =.015). There was a significant improvement in global end point for those aged 60 years or older (P =.042) and 80 years or older (P =.017), with a trend toward improvement for age 70 years or older (P =.055), and significant improvement in those who achieved good outcomes (mRS score 0-2 versus 3-6) at age 60 years or older (P =.038), 70 years or older (P =.022), and 80 years or older (P =.008). NeuroFlo treatment in stroke patients with AF resulted in significantly better outcomes compared with nontreated patients with AF. Collateral flow recruitment, maintenance of cerebral blood flow around stroke core, and improvement of penumbral blood flow are potential mechanisms for these improved outcomes. NeuroFlo may represent a valid therapeutic option for patients with AF and AIS, and therefore, future trials of the device are warranted. © 2014 by National Stroke Association. Source

Schellinger P.D.,Johannes Wesling Klinikum Minden | Shuaib A.,University of Alberta | Kohrmann M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Liebeskind D.S.,University of California at Los Angeles | And 8 more authors.
American Journal of Neuroradiology

BACKGROUND AND PURPOSE: The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial showed a trend for reduced all-cause mortality and positive secondary safety end point outcomes. We present further analyses of the mortality and severe disability data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial. MATERIALS AND METHODS: The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke trial was a multicenter, randomized, controlled trial that evaluated the safety and effectiveness of the NeuroFlo catheter in patients with stroke. The current analysis was performed on the as-treated population. All-cause and stroke-related mortality rates at 90 days were compared between groups, and logistic regression models were fit to obtain ORs and 95% CIs for the treated versus not-treated groups. We categorized death-associated serious adverse events as neurologic versus non-neurologic events and performed multiple logistic regression analyses. We analyzed severe disability and mortality by outcomes of the mRS. Patient allocation was gathered by use of a poststudy survey. RESULTS: All-cause mortality trended in favor of treated patients (11.5% versus 16.1%; P = .079) and stroke-related mortality was significantly reduced in treated patients (7.5% versus 14.2%; P = .009). Logistic regression analysis for freedom from stroke-related mortality favored treatment (OR, 2.41; 95% CI, 1.22, 4.77; P = .012). Treated patients had numerically fewer neurologic causes of stroke-related deaths (52.9% versus 73.0%; P = .214). Among the 90-day survivors, nominally fewer treated patients were severely disabled (mRS 5) (5.6% versus 7.5%; OR, 1.72; 95% CI, 0.72, 4.14; P = .223). Differences in allocation of care did not account for the reduced mortality rates. CONCLUSIONS: There were consistent reductions in all-cause and stroke-related mortality in the NeuroFlo-treated patients. This reduction in mortality did not result in an increase in severe disability. Source

Saeger W.,University of Hamburg | Honegger J.,University of Tubingen | Theodoropoulou M.,Max Planck Institute of Psychiatry | Knappe U.J.,Johannes Wesling Klinikum Minden | And 3 more authors.
Endocrine Pathology

WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately. © 2016 Springer Science+Business Media New York Source

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