Significant role of Loss or Reduced BRCA1 gene expression in clinical implication of ovarian cancer

Background: BRCA1 immunohistochemistry (IHC) provides a rapid initial screen to detect BRCA1 dysfunction in ovarian cancer that resulting from genetic alterations. Aim: To assess the expression of BRCA1 protein by IHC analysis among a group of Iraqi ovarian cancer patients to evaluate the patterns of expression and its correlation with the clinicopathological parameters in attempting to evaluate a significance role of BRCA1 gene implication in ovarian cancer. Methods: Forty three paraffin embedded samples of ovarian cancer cases were analyzed for BRCA1dysfunction by IHC analysis. The semi-quantitative approach using modified histochemical score (H-score) was achieved to assess the patterns of BRCA1 gene expression. Results: Complete loss of BRCA1 nuclear expression was detected in 30.2% of the cases while, reduced expression occurred in 46.5% of cases, giving rise to 76.7% of all cases detected with altered BRCA1 nuclear expression. Altered BRCA1 expression was found to be higher in age group ≤ 45 years (78.3%) in comparison with those of ages >45 years. Altered BRCA1 expression was significantly correlated with the high grade and with the unilateral tumor site when compared with the low grade and bilateral tumor site (P≤0.05), and was insignificantly correlated with the high stage ovarian tumors, 11.6% of cases were detected by cytoplasmic BRCA1 expression and no association was found between cytoplasmic expression and tumor grade, stage and tumor site. Conclusion: Altered BRCA1 expression may play a significant role in the progression of ovarian cancer. Recommendation: BRCA1 IHC is a clinically useful approach to detect the BRCA1 dysfunction and the H-score assessment reflects good estimation for BRCA1expression patterns

Accelerated surgery versus standard care in hip fracture (HIP ATTACK) : an international, randomised, controlled trial

Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4\u20139) in the accelerated-surgery group and 24 h (10\u201342) in the standard-care group (p<0\ub70001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0\ub791 (95% CI 0\ub772 to 1\ub714) and absolute risk reduction (ARR) of 1% ( 121 to 3; p=0\ub740). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0\ub797 (0\ub783 to 1\ub713) and an ARR of 1% ( 122 to 4; p=0\ub771). Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Funding: Canadian Institutes of Health Research