Oral antiplatelet therapy in diabetes mellitus and the role of prasugrel: an overview

Diabetics have a prothrombotic state that includes increased platelet reactivity. This contributes to the less favorable clinical outcomes observed in diabetics experiencing acute coronary syndromes as well as stable coronary artery disease. Many diabetics are relatively resistant to or have insufficient response to several antithrombotic agents. In the setting of percutaneous coronary intervention, hyporesponsiveness to clopidogrel is particularly common among diabetics. Several strategies have been examined to further enhance the benefits of oral antiplatelet therapy in diabetics. These include increasing the dose of clopidogrel, triple antiplatelet therapy with cilostazol, and new agents such as prasugrel. The large TRITON TIMI 38 randomized trial compared clopidogrel to prasugrel in the setting of percutaneous coronary intervention for acute coronary syndromes. The diabetic subgroup (n = 3146) experienced considerable incremental benefit with a 4.8% reduction in cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke at 15-month follow-up with prasugrel treatment. Among diabetics on insulin this combined endpoint was reduced by 7.9% at 15 months. Major bleeding was not increased in the diabetic subgroup. This confirms the general hypothesis that more potent oral antiplatelet therapy can partially overcome the prothrombotic milieu and safely improve important clinical outcomes in diabetics

Successful enteral nutrition in the treatment of esophagojejunal fistula after total gastrectomy in gastric cancer patients

<p>Abstract</p> <p>Background</p> <p>Esophagojejunal fistula is a serious complication after total gastrectomy in gastric cancer patients. This study describes the successful conservative management in 3 gastric cancer patients with esophagojejunal fistula after total gastrectomy using total enteral nutrition.</p> <p>Methods</p> <p>Between January 2004 to December 2008, 588 consecutive patients with a proven diagnosis of gastric cancer were taken to the operation room to try a curative treatment. Of these, 173 underwent total gastrectomy, 9 of them had esophagojejunal fistula (5.2%). In three selected patients a trans-anastomotic naso-enteral feeding tube was placed under fluoroscopic vision when the fistula was clinically detected and a complete polymeric enteral formula was used.</p> <p>Results</p> <p>The complete closing of the esophagojejunal fistula was obtained in day 8, 14 and 25 respectively.</p> <p>Conclusion</p> <p>In some selected cases it is possible to make a successful enteral nutrition using a feeding tube distal to the leak area inserted with the help of fluoroscopic vision. The specialized management of a gastric surgery unit and nutritional therapy unit are highlighted.</p

Lawsonia intracellularis exploits β-catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation

Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of β-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE

Clinical nutrition and human rights. An international position paper

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition

Heme- and nonheme-iron absorption and iron status 12 mo after sleeve gastrectomy and Roux-en-Y gastric bypass in morbidly obese women

Background: The effect of bariatric surgery on iron absorption is only partially known. Objective: The objective was to study the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) on heme- and nonheme-iron absorption and iron status. Design: Fifty-eight menstruating women were enrolled in this prospective study [mean (±SD) age: 35.9 ± 9.1 y; weight: 101.7 ± 13.5 kg; BMI (in kg/m2): 39.9 ± 4.4]. Anthropometric, body-composition, dietary, and hematologic indexes and heme- and nonheme-iron absorption - using a standardized meal containing 3 mg Fe - were determined before and 12 mo after surgery. Forty-three subjects completed the 12-mo follow-up. Iron supplements were strictly controlled. Results: Heme-iron absorption was 23.9% before and 6.2% 12 mo after surgery (P &lt; 0.0001). Nonheme-iron absorption decreased from 11.1% to 4.7% (P &lt; 0.0001). No differences were observed by type of surgery. Iron intakes from all sources of supplements were 27.9 ± 6.2 mg/d in the SG