Rapamycin inhibits oral cancer cell growth by promoting oxidative stress and suppressing ERK1/2, NF-κB and beta-catenin pathways.

Treatment of oral cancer is based exclusively on surgery combined with or without chemotherapy. However, it has several side effects. Targeting a new, more effective therapy has become an urgent matter.

Diagnostic Accuracy of Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer.

Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND.

Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure.

Anethole induces anti-oral cancer activity by triggering apoptosis, autophagy and oxidative stress and by modulation of multiple signaling pathways.

Oral cancer is one of the major public health problems. The aim of this study was to evaluate the effects of anethole, 1-methoxy-4-[(E)-1-propenyl]-benzene, on growth and apoptosis of oral tumor cells, and to identify the signaling pathways involved in its interaction with these cancer cells. Cancer gingival cells (Ca9-22) were treated with different concentrations of anethole.

The curcumin analog (PAC) suppressed cell survival and induced apoptosis and autophagy in oral cancer cells.

PAC (3,5-Bis (4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone), a novel bioactive curcumin analog, has been reported to have anticancer properties against various tumors. However, the anti-cancer effects of PAC on oral cavity squamous cell carcinoma were not studied yet. Our aim is to investigate the anti-oral cancer properties of PAC in vitro, and determine the molecular mechanisms underlying these effects.

TUmor-volume to breast-volume RAtio for improving COSmetic results in breast cancer patients (TURACOS); a randomized controlled trial.

Background: Cosmetic result following breast conserving surgery (BCS) for cancer influences quality of life and psychosocial functioning in breast cancer patients. A preoperative prediction of expected cosmetic result following BCS is not (yet) standard clinical practice and therefore the choice for either mastectomy or BCS is still subjective. Recently, we showed that tumour volume to breast volume ratio as well as tumour location in the breast are independent predictors of superior cosmetic result following BCS.

Comparing GPS, Log, Survey, and Accelerometry to Measure Physical Activity.

Objectives: We explored how objectively measured global positioning system (GPS) and accelerometer data match with travel logs and questionnaires in predicting trip duration and physical activity (PA).

Methods: 99 participants wore GPS devices and accelerometers, and recorded all trips in a log for 5 consecutive days. Participants also completed a self-administered questionnaire on PA and travel behaviors.

Validation of Six Nomograms for Predicting Non-sentinel Lymph Node Metastases in a Dutch Breast Cancer Population.

Background: The usefulness of axillary lymph node dissection (ALND) in patients with positive sentinel nodes (SN) is still an ongoing debate. Several nomograms have been developed for predicting non-sentinel lymph node metastases (NSLNM). We validated six nomograms using data from 10 years of breast cancer surgery in our hospital.

The influence of mechanical bowel preparation on long-term survival in patients surgically treated for colorectal cancer.

Background: In this study, we evaluated long-term survival in patients treated with and without mechanical bowel preparation (MBP) before colorectal surgery for cancer.

Methods: Long-term outcome of patients of 2 main participating hospitals in a prior multicenter randomized trial comparing clinical outcome of MBP versus no MBP was reviewed. Primary endpoint was cancer-related mortality and secondary endpoint was all-cause mortality.

A prospective validation study of sentinel lymph node biopsy in multicentric breast cancer: SMMaC trial.

Background: Multicentric breast cancer is often considered a contra-indication for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false negative rate. To assess SLN feasibility and accuracy in multicentric breast cancer, the multi-institutional SMMaC trial was conducted.

Methods: In this study 30 patients with multicentric breast cancer and a clinically negative axilla were prospectively included.

Dynamic TIMI risk score for STEMI.

Background: Although there are multiple methods of risk stratification for ST-elevation myocardial infarction (STEMI), this study presents a prospectively validated method for reclassification of patients based on in-hospital events. A dynamic risk score provides an initial risk stratification and reassessment at discharge.

Methods And Results: The dynamic TIMI risk score for STEMI was derived in ExTRACT-TIMI 25 and validated in TRITON-TIMI 38.

A practical mortality risk score for emergent colectomy.

Background: Critically ill patients requiring emergent colectomy have significant mortality risk.

Objective: A national administrative database was used to compose a simple scoring scheme for predicting in-hospital mortality risk.

Design: The 2007 to 2009 Nationwide Inpatient Sample was queried to identify patients requiring nonelective colectomy.

A systems approach to designing effective clinical trials using simulations.

Background: Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit in comparison with standard clinical therapy. This study demonstrates a computational framework to systematically evaluate preclinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes.

Methods And Results: We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs.

Efficacy of 'radioguided occult lesion localisation' (ROLL) versus 'wire-guided localisation' (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial.

For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.

The influence of mechanical bowel preparation in elective colorectal surgery for diverticulitis.

Background: Mechanical bowel preparation (MBP) has been shown to have no influence on the incidence of anastomotic leakage in overall colorectal surgery. The role of MBP in elective surgery in combination with an inflammatory component such as diverticulitis is yet unclear. This study evaluates the effects of MBP on anastomotic leakage and other septic complications in 190 patients who underwent elective surgery for colonic diverticulitis.

Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease.

Context: Variants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clopidogrel.

Objective: To test whether higher doses (up to 300 mg daily) improve the response to clopidogrel in the setting of loss-of-function CYP2C19 genotypes.

Design, Setting, And Patients: ELEVATE-TIMI 56 was a multicenter, randomized, double-blind trial that enrolled and genotyped 333 patients with cardiovascular disease across 32 sites from October 2010 until September 2011.

Changes in physical activity and travel behaviors in residents of a mixed-use development.

Background: Mixed-use developments may be especially promising settings for encouraging walking and other types of physical activity.

Purpose: This study examined the physical activity and travel behaviors of individuals before and after they relocated to Atlantic Station, a mixed-use redevelopment community in metropolitan Atlanta.

Methods: A survey study was conducted to compare the behaviors, experiences, and attitudes of Atlantic Station residents before and after moving to a mixed-use neighborhood.

Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy.

Background: Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs.

Methods: A variety of platelet function results was analyzed from 2 large cohorts of patients undergoing coronary intervention after loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg (n = 87).

Evaluation of morbidity and mortality after anastomotic leakage following elective colorectal surgery in patients treated with or without mechanical bowel preparation.

Background: A previous multicenter randomized trial demonstrated that mechanical bowel preparation (MBP) does not guard against anastomotic leakage in elective colorectal surgery. The aim of this complementary study was to evaluate the effects of MBP on morbidity and mortality after anastomotic leakage in elective colorectal surgery.

Methods: A subgroup analysis was performed of a randomized trial comparing the incidence of anastomotic leakage and septic complications with and without MBP in patients undergoing elective colorectal surgery.

Predictors of bleeding and time dependence of association of bleeding with mortality: insights from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38).

Background: The balance between benefit (ischemia protection) and risk (bleeding) is a key consideration in choosing the intensity of antiplatelet therapy for patients with acute coronary syndromes. The goals of this analysis were to identify baseline characteristics that independently predict bleeding and to determine how bleeding events impact the subsequent mortality in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel--Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38).

Methods And Results: Multivariable Cox regression analyses adjusted for treatment, baseline, and procedural variables were used to determine the predictors for serious (TIMI major or minor) bleeding.

Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of Thrombin–Acute Coronary Syndromes Trial.

Background: Atopaxar (E5555) is a reversible protease-activated receptor-1 thrombin receptor antagonist that interferes with platelet signaling. The primary objective of the Lessons From Antagonizing the Cellular Effects of Thrombin-Acute Coronary Syndromes (LANCELOT—ACS) trial was to evaluate the safety and tolerability of atopaxar in patients with ACS.

Methods And Results: Six hundred and three subjects were randomized within 72 hours of non-ST-elevation ACS to 1 of 3 doses of atopaxar (400-mg loading dose followed by 50, 100, or 200 mg daily) or matching placebo.

Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of Thrombin–Coronary Artery Disease Trial.

Background: Thrombin is a key mediator of platelet activation. Atopaxar is a reversible protease-activated receptor-1 antagonist that interferes with thrombin-mediated platelet effects. The phase II Lessons From Antagonizing the Cellular Effect of Thrombin-Coronary Artery Disease (LANCELOT-CAD) trial examined the safety and tolerability of prolonged therapy with atopaxar in subjects with CAD.

Evaluation of NT-proBNP and high sensitivity C-reactive protein for predicting cardiovascular risk in patients with arthritis taking longterm nonsteroidal antiinflammatory drugs.

Objective: Patients with arthritis frequently are at increased risk for future cardiovascular (CV) events. We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflammatory drugs (NSAID).

Methods: We evaluated 2-year CV outcomes in a prospective, nested biomarker study among patients (N = 6273) with rheumatoid arthritis and osteoarthritis treated with NSAID in the MEDAL (Multinational Etoricoxib and Diclofenac Arthritis Long-term) trial.

Metabolic effects of a late hypotensive insult combined with reduced intracranial compliance following traumatic brain injury in the rat.

Introduction: Traumatic brain injury makes the brain vulnerable to secondary insults. Post-traumatic alterations in intracranial dynamics, such as reduced intracranial compliance (IC), are thought to further potentiate the effects of secondary insults. Reduced IC combined with intracranial volume insults leads to metabolic disturbances in a rat model.

Clopidogrel with or without omeprazole in coronary artery disease.

Background: Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel.

Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis.

Context: Clinicians and trialists have difficulty with identifying which patients are highest risk for cardiovascular events. Prior ischemic events, polyvascular disease, and diabetes mellitus have all been identified as predictors of ischemic events, but their comparative contributions to future risk remain unclear.

Objective: To categorize the risk of cardiovascular events in stable outpatients with various initial manifestations of atherothrombosis using simple clinical descriptors.