Mid-esophagus unresectable cancer treated with a low cost stent. First experience

<p>Abstract</p> <p>Background</p> <p>In the cancer of the esophagus, with recent technologic advances, self-expanding metal stents (SEMS) are at the forefront of the armamentarium for re-establishing luminal patency. Weighed against the numerous advantages of stents are the import conditions and the cost. In light of this, we tested new low cost prostheses having the basic needs and characteristics to aim a significant benefit to poor people having advanced esophageal cancer, in a Brazilian regional public hospital.</p> <p>Methods</p> <p>This initial experience included fifteen patients (eleven men and four women, 55 ± 6.17 years old), presenting esophageal cancer, located at the medium third of the thoracic esophagus, extending for 5.5-8 cm long, not suitable for surgical procedure because they had been staged on fourth grade of the disease, two of them having fistula communicating esophagus to respiratory tree. The stents were placed under endoscopic and fluoroscopic guidance, after attempting an esophageal dilatation. An appropriate covered stent was then deployed, twelve of 10 cm and three of 13 cm in length. A chest X-ray was done 2 h after the procedure and a barium swallow was performed within 12 hours. Seven days and monthly until complete a six month follow-up after the procedure the patients were questioned about presence of pain, regurgitation, heartburn, cough, and their alimentary behavior.</p> <p>Results</p> <p>There were no severe complications and transient mild chest pain resolved until the seventh day after the stent deployment. Chest X-ray demonstrated expansion of the stent in all patients. In 2 cases of fistula, a barium swallow showed its complete sealing. The completion of the proposed follow-up was not achieved in three cases, limited by the patient's death until the third month, due to cancer progression. Recurrent dysphagia to paste food accounted for by tumor overgrowth proximal or distal to the stent and stent migration were not observed in the series.</p> <p>Conclusions</p> <p>The new low cost endoprostheses is effective and forthcoming increased experience and prospective trials including questionnaires to analyze quality of life will allow for more informed decisions tailoring to a particular patient situation or to unexpected complications.</p

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Alk-1-ene Polymerization in the Presence of a Monocyclopentadienyl Zirconium(IV) Acetamidinate Catalyst: Microstructural and Mechanistic Insights

uitably activated, (Cp*){N(tBu)C(Me)N(Et)}ZrMe 2 is known to initiate the 'living' and isotacticselective polymerization of alk-1-enes, and it can be used to synthesize block copolymers and stereoblock polymers. We report a full molecular kinetic investigation of propene, but-1-ene,and hex-1-ene polymerization with a MAOactivated catalyst system. By combining NMR microstructural polymer analysis with QM modeling of the active species, the complicated regio- and stereochemistry of the polyinsertion process, as well as the active chain-transfer pathways, are investigated. The perspectives and limitations of this catalyst for application in (stereo)block polymerizations are discussed

Mechanism of mitoribosomal small subunit biogenesis and preinitiation

Mitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. (1)) outcompetes RBFA to complete the assembly with the SSU-mS37-mtIF3 complex(2) that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome