Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R2: 53%, P<10−77). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43–0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04–4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.

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BackgroundPrevalence of metabolic syndrome (MS) in obese adolescents has been reported to range between 18–42%, depending on country of origin, thus suggesting an ethnic-based association between obesity and MS.AimThis study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon.Subjects and methodsThe sample included 263 adolescents at 4th and 5th Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X-ray absorptiometry.ResultsAccording to International Diabetes Federation criteria, MS was identified in 21.2% of obese, 3.8% of overweight and 1.2% of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group.ConclusionsMS was identified in a substantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi-component interventions addressing adolescent obesity.

Little research has been done on the current cut-off international normalized ratio (INR) value of 1.5 for patients undergoing surgery. The objectives of this study are to assess the association between INR and postoperative major bleeding and mortality in patients undergoing surgery and to identify an ideal pre-operative INR for surgical patients. We analyzed data from the American College of Surgeons' National Surgical Quality Improvement Program database between 2008 and 2011 (636,231 patients). The primary outcomes were major bleeding and mortality at 30 days postoperatively. Multivariate logistic regression analyses were carried out to assess these associations. Compared to an INR of <1, the adjusted odds ratio (aOR) for major bleeding was 1.22 (95 % CI 1.18-1.25) for INR 1-1.49, 1.48 (95 % CI 1.40-1.56) for INR 1.5-1.9, and 1.49 (95 % CI 1.39-1.60) for INR ≥2. The aOR for mortality at 30 days post-operation compared to INR of <1 was 1.51 (95 % CI 1.41-1.62), 2.31 (95 % CI 2.12-2.52), and 2.81 (95 % CI 2.56-3.10) for INR 1-1.49, 1.5-1.9, and ≥2, respectively. The ideal pre-operative INR value to predict an increased risk for major bleeding was 1.10 and 1.13 for mortality. In conclusion, preoperative INR is significantly and independently associated with postoperative major bleeding and mortality.

Intra-arterial administration of gemcitabine has a major advantage related to reduced toxicity as increasing the dose through this administration route will eventually result in pancreatic cellular drug target delivery prior to systemic availability. Despite the low number of patients recruited, the clinical results are encouraging and this approach should be tested in a randomised study.