Can medical therapy mimic the clinical efficacy or physiological effects of bariatric surgery?

The number of bariatric surgical procedures performed has increased dramatically. This review discusses the clinical and physiological changes, and in particular, the mechanisms behind weight loss and glycaemic improvements, observed following the gastric bypass, sleeve gastrectomy and gastric banding bariatric procedures. The review then examines how close we are to mimicking the clinical or physiological effects of surgery through less invasive and safer modern interventions that are currently available for clinical use. These include dietary interventions, orlistat, lorcaserin, phentermine/topiramate, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, pramlintide, dapagliflozin, the duodenal–jejunal bypass liner, gastric pacemakers and gastric balloons. We conclude that, based on the most recent trials, we cannot fully mimic the clinical or physiological effects of surgery; however, we are getting closer. A ‘medical bypass' may not be as far in the future as we previously thought, as the physician's armamentarium against obesity and type 2 diabetes has recently got stronger through the use of specific dietary modifications, novel medical devices and pharmacotherapy. Novel therapeutic targets include not only appetite but also taste/food preferences, energy expenditure, gut microbiota, bile acid signalling, inflammation, preservation of β-cell function and hepatic glucose output, among others. Although there are no magic bullets, an integrated multimodal approach may yield success. Non-surgical interventions that mimic the metabolic benefits of bariatric surgery, with a reduced morbidity and mortality burden, remain tenable alternatives for patients and health-care professionals

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Safety and effectiveness of bariatric surgery: Roux-en-Y gastric bypass is superior to gastric banding in the management of morbidly obese patients

<p>Abstract</p> <p>Background</p> <p>The use of bariatric surgery in the management of morbid obesity is rapidly increasing. The two most frequently performed procedures are laparoscopic Roux-en-Y bypass and laparoscopic gastric banding. The objective of this short overview is to provide a critical appraisal of the most relevant scientific evidence comparing laparoscopic gastric banding versus laparoscopic Roux-en-Y bypass in the treatment of morbidly obese patients.</p> <p>Results and discussion</p> <p>There is mounting and convincing evidence that laparoscopic gastric banding is suboptimal at best in the management of morbid obesity. Although short-term morbidity is low and hospital length of stay is short, the rates of long-term complications and band removals are high, and failure to lose weight after laparoscopic gastric banding is prevalent.</p> <p>Conclusion</p> <p>The placement of a gastric band appears to be a disservice to many morbidly obese patients and therefore, in the current culture of evidence based medicine, the prevalent use of laparoscopic gastric banding can no longer be justified. Based on the current scientific literature, the laparoscopic gastric bypass should be considered the treatment of choice in the management of morbidly obese patients.</p

Low-frequency variants in HMGA1 are not associated with type 2 diabetes risk.

It has recently been suggested that the low-frequency c.136-14_136-13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136-14_136-13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136-14_136-13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease

Comparison between observed children's tooth brushing habits and those reported by mothers

<p>Abstract</p> <p>Background</p> <p>Information bias can occur in epidemiological studies and compromise scientific outcomes, especially when evaluating information given by a patient regarding their own health. The oral habits of children reported by their mothers are commonly used to evaluate tooth brushing practices and to estimate fluoride intake by children. The aim of the present study was to compare observed tooth-brushing habits of young children using fluoridated toothpaste with those reported by mothers.</p> <p>Methods</p> <p>A sample of 201 mothers and their children (aged 24-48 months) from Montes Claros, Brazil, took part in a cross-sectional study. At day-care centres, the mothers answered a self-administered questionnaire on their child's tooth-brushing habits. The structured questionnaire had six items with two to three possible answers. An appointment was then made with each mother/child pair at day-care centres. The participants were asked to demonstrate the tooth-brushing practice as usually performed at home. A trained examiner observed and documented the procedure. Observed tooth brushing and that reported by mothers were compared for overall agreement using Cohen's Kappa coefficient and the McNemar test.</p> <p>Results</p> <p>Cohen's Kappa values comparing mothers' reports and tooth brushing observed by the examiner ranged from poor-to-good (0.00-0.75). There were statistically significant differences between observed tooth brushing habits and those reported by mothers (p < 0.001). When observed by the examiner, the frequencies of dentifrice dispersed on all bristles (35.9%), children who brushed their teeth alone (33.8%) and those who did not rinse their mouths during brushing (42.0%) were higher than those reported by the mothers (12.1%, 18.9% and 6.5%, respectively; p < 0.001).</p> <p>Conclusions</p> <p>In general, there was low agreement between observed tooth brushing and mothers' reports. Moreover, the different methods of estimation resulted in differences in the frequencies of tooth brushing habits, indicative of reporting bias. Data regarding children's tooth-brushing habits as reported by mothers should be considered with caution in epidemiological surveys on fluoridated dentifrice use and the risk of dental fluorosis.</p

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m−2, intravenous bolus) followed by docetaxel (60, 75 or 85 mg m−2, 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m−2 with cyclophosphamide 600 mg m−2, the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22–61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m−2 in combination with cyclophosphamide 600 mg m−2 every three weeks for phase II evaluation