Circulating Tumor Cells in Patients Undergoing Surgery for Primary Breast Cancer: Preliminary Results of a Pilot Study

Introduction  Circulating tumor cells (CTCs) have recently been shown to be an independent predictor of progression-free and overall survival in patients undergoing treatment for metastatic breast cancer. This study evaluates the presence and significance of CTCs in patient undergoing surgical resection of clinically localized primary breast cancer. Methods  Patients undergoing surgery for clinically localized primary breast cancer were enrolled into a prospective study. Thirty milliliters of blood was drawn and studied using the CellSearch assay. Results  Forty-one patients were enrolled at a single tertiary referral center. Ten patients (24.4%) had detectable CTCs preoperatively (PreOp). Nine (30%) patients were found to have CTCs postoperatively (PostOp). Overall, 16 (39%) were found to have CTCs either PreOp or PostOp. Hormone-negative patients were significantly more likely to have CTCs than hormone-positive patients. No other pathologic factor was predictive of the presence of CTCs. Conclusion  CTCs are detectable and quantifiable in breast surgery patients. CTCs were more likely to be found in hormone receptor negative patients. Further study will allow correlation with other pathological variables and clinical outcome.     

Natural polyphenols and cardioprotection

With more than 8000 polyphenols found in food (mainly, wine, tea, coffee, cocoa, vegetables and cereals), many epidemiological studies suggest that the intake of polyphenol-rich foods has a beneficial effect on a large number of cardiovascular risk factors, such as high blood pressure, high blood cholesterol, obesity, diabetes and smoking. The mechanisms involved in the cardioprotective effects of polyphenols are numerous and include antioxidant, vasodilator, anti-inflammatory, anti-fibrotic, antiapoptotic and metabolic. Most importantly, recent experimental data demonstrate that polyphenols can exert its cardioprotective effect via the activation of several powerful prosurvival cellular pathways that involve metabolic intermediates, microRNAs, sirtuins and mediators of the recently described reperfusion injury salvage kinases (RISK) and survivor activating factor enhancement (SAFE) pathways.     

Keap1 perceives stress via three sensors for the endogenous signaling molecules nitric oxide, zinc, and alkenals

Recognition and repair of cellular damage is crucial if organisms are to survive harmful environmental conditions. In mammals, the Keap1 protein orchestrates this response, but how it perceives adverse circumstances is not fully understood. Herein, we implicate NO, Zn(2+), and alkenals, endogenously occurring chemicals whose concentrations increase during stress, in this process. By combining molecular modeling with phylogenetic, chemical, and functional analyses, we show that Keap1 directly recognizes NO, Zn(2+), and alkenals through three distinct sensors. The C288 alkenal sensor is of ancient origin, having evolved in a common ancestor of bilaterans. The Zn(2+) sensor minimally comprises H225, C226, and C613. The most recent sensor, the NO sensor, emerged coincident with an expansion of the NOS gene family in vertebrates. It comprises a cluster of basic amino acids (H129, K131, R135, K150, and H154) that facilitate S-nitrosation of C151. Taken together, our data suggest that Keap1 is a specialized sensor that quantifies stress by monitoring the intracellular concentrations of NO, Zn(2+), and alkenals, which collectively serve as second messengers that may signify danger and/or damage.     

Measuring clinically significant chemotherapy-related toxicities using Medicare claims from Cancer and Leukemia Group B (CALGB) trial participants

BACKGROUND: Because the elderly are underrepresented on clinical trials, physicians have few sources of information to estimate the risks (ie, toxicities) and benefits of chemotherapy administration to the elderly. OBJECTIVE: Our goal was to determine whether the standard measures of toxicity used in clinical trials could be captured from observational Medicare claims data. METHODS: We identified 175 elderly clinical trial patients treated on 2 Cancer and Leukemia Group B (CALGB) trials (9344, adjuvant breast study and 9730, advanced lung cancer study) and merged participants' CALGB data with their Medicare data. From CALGB data, we identified the most frequent Extended Clinical Toxicity Critieria grade III/IV toxicities. We reviewed diagnostic and procedure codes from Medicare manuals, developed algorithms to measure the toxicities, and then finalized the algorithms after empiric review of patients' codes. We compared results of Medicare algorithms to gold standard CALGB toxicity information to calculate test characteristics. RESULTS: CALGB data documented that 15 grade III/IV chemotherapy-related toxicities occurred in > or =3% of the 175 patients: white blood cell, hemoglobin, platelets, anorexia, nausea, vomiting, diarrhea, stomatitis, sensory neuropathy, motor neuropathy, motor or sensory neuropathy, dyspnea, hyperglycemia, infection, and malaise. Vomiting was the only toxicity identified by the Medicare-based algorithm with a sensitivity, specificity, and area under the receiver operator curve of > or =80%. CONCLUSIONS: The results of this preliminary study suggest that Medicare diagnostic and procedure codes may be of only limited value in measuring clinically significant chemotherapy-related toxicities in elderly Medicare beneficiaries. Future research includes confirming these findings in a larger and more diverse sample.     

Local versus systemic mechanisms underlying supervised exercise training for intermittent claudication

The mechanisms by which exercise training improves intermittent claudication remain unclear. In this article, the effects of local and systemic physiological factors on improved exercise tolerance after a supervised exercise program in claudicants are investigated. A total of 60 patients were randomized to 3 months of supervised exercise followed by 3 months of unsupervised exercise, or to exercise advice alone (control). Supervised exercise increased both pain-free and maximal walking distances. Heart rate during submaximal exercise and resting mean arterial pressure were lower after supervised exercise at 6 months. Serum lactate at maximum claudication increased significantly after 3 months in the supervised exercise group but this change had resolved by 6 months. Symptomatic improvement was accompanied by modest reductions in mean arterial pressure and submaximal heart rate on exercise. Increased serum lactate at maximum claudication subsequently declined despite continued improvement in walking distance, suggesting local adaptations to improve efficiency of muscle oxygen delivery and/or utilization.     

Current debate on the use of antibiotic prophylaxis for caesarean section

Caesarean delivery is frequently complicated by surgical site infections, endometritis and urinary tract infection. Most surgical site infections occur after discharge from the hospital, and are increasingly being used as performance indicators. Worldwide, the rate of caesarean delivery is increasing. Evidence-based guidelines recommended the use of prophylactic antibiotics before surgical incision. An exception is made for caesarean delivery, where narrow-range antibiotics are administered after umbilical cord clamping because of putative neonatal benefit. However, recent evidence supports the use of pre-incision, broad-spectrum antibiotics, which result in a lower rate of maternal morbidity with no disadvantage to the neonate.     

Pearls for aesthetic reconstruction of cleft lip and nose defects

Mastery of the anatomy and embryology of the normal and cleft upper lip, primary palate, and secondary palate is an essential foundation for grasping techniques in aesthetic reconstruction of cleft lip defects. The surgical goals in repairing cleft lip deformities are to address the deficiencies of the cleft lip defect, restore static and dynamic anatomy, reshape the cleft nasal deformity, and leave a natural-appearing scar that mimics the contours of the philtral components. An additional goal is to improve skeletal alignment and retention of teeth in the vicinity of the alveolar cleft. There are advantages and disadvantages inherit in all repair techniques. However, there are principles that can be universally applied and that will improve the success of most approaches. Certain steps deserve special attention to detail, which provide for enhanced results in lip repair. In addition, the pearls for aesthetic reconstruction of cleft lip and nose defects outlined within this article--attention to scars and surface detail, utilizing the orthopedic forces of the orbicularis pull to achieve improved alveolar alignment, the importance of mucosal detail, and attention to the cleft nasal defect--will help to improve results and reduce secondary defects.