Brachial Artery Constriction during Brachial Artery Reactivity Testing Predicts Major Adverse Clinical Outcomes in Women with Suspected Myocardial Ischemia: Results from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study

Background:Limited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia.Objectives:To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC.Methods:We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure.Results:BA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors.Conclusions:BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women. © 2013 Sedlak et al

Hemoglobin level is an independent predictor for adverse cardiovascular outcomes in women undergoing evaluation for chest pain Results from the National Heart, Lung, and Blood Institute women's ischemia syndrome evaluation study

AbstractObjectivesThis study was designed to investigate the relationship between hemoglobin level (Hgb) and adverse cardiovascular outcomes in women with suspected ischemia.BackgroundLow Hgb levels correlate with increased cardiovascular morbidity and mortality in patients presenting with acute myocardial infarction (MI) or congestive heart failure (CHF). However, the prognostic significance of Hgb in women with suspected ischemia is unclear.MethodsAs part of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE), we prospectively studied 936 women referred for coronary angiography to evaluate suspected ischemia. We compared Hgb levels with cardiovascular risk factors, core lab interpreted angiograms, inflammatory markers, and adverse cardiovascular outcomes.ResultsOf women enrolled, 864 (mean age 58.4 ±11.6 years) had complete Hgb, angiogram, and follow-up (mean 3.3 ± 1.7 years) data. The mean Hgb was 12.9 g/dl (range 7.7 to 16.4 g/dl) and 184 women (21%) were anemic (Hgb <12 g/dl). Anemic women had higher creatinine and were more likely to be nonwhite and have a history of diabetes, hypertension, and CHF (p < 0.05). However, we found no difference in EF or severity of coronary artery disease. Anemic women had a higher risk of death from any cause (10.3% vs. 5.4%; p = 0.02) and total adverse outcomes (26% vs. 16%, p < 0.01). In a multivariable model, decreasing Hgb was associated with significantly higher risk of adverse outcomes (hazard ratio = 1.20, p = 0.002). Also, anemic women had shorter survival time free of adverse outcome (p < 0.001).ConclusionsOur findings extend previous reports, linking lower hemoglobin levels with higher risk for adverse cardiovascular outcomes, to women evaluated for suspected ischemia in the absence of acute MI or CHF

Acute myeloid leukemia patients’ clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts

In translational research described, we investigated biomarker expression by flow cytometry for MDM2 antagonist clinical response association in relapsed/refractory AML patients treated with idasanutlin-based therapy (Clinicaltrials.gov identifier: NCT01773408)

Lower extremity compartment syndrome in the acute care surgery paradigm: safety lessons learned

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer:A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.</p

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Glycophenotypic Alterations Induced by Pteridium aquilinum in Mice Gastric Mucosa: Synergistic Effect with Helicobacter pylori Infection

The bracken fern Pteridium aquilinum is a plant known to be carcinogenic to animals. Epidemiological studies have shown an association between bracken fern exposure and gastric cancer development in humans. The biological effects of exposure to this plant within the gastric carcinogenesis process are not fully understood. In the present work, effects in the gastric mucosa of mice treated with Pteridium aquilinum were evaluated, as well as molecular mechanisms underlying the synergistic role with Helicobacter pylori infection. Our results showed that exposure to Pteridium aquilinum induces histomorphological modifications including increased expression of acidic glycoconjugates in the gastric mucosa. The transcriptome analysis of gastric mucosa showed that upon exposure to Pteridium aquilinum several glycosyltransferase genes were differently expressed, including Galntl4, C1galt1 and St3gal2, that are mainly involved in the biosynthesis of simple mucin-type carbohydrate antigens. Concomitant treatment with Pteridium aquilinum and infection with Helicobacter pylori also resulted in differently expressed glycosyltransferase genes underlying the biosynthesis of terminal sialylated Lewis antigens, including Sialyl-Lewisx. These results disclose the molecular basis for the altered pattern of glycan structures observed in the mice gastric mucosa. The gene transcription alterations and the induced glycophenotypic changes observed in the gastric mucosa contribute for the understanding of the molecular mechanisms underlying the role of Pteridium aquilinum in the gastric carcinogenesis process