Intensive insulin therapy versus conventional glycemic control in patients with acute neurological injury: a prospective controlled trial

OBJECTIVE: To compare intensive insulin therapy to conventional glycemic control in patients with acute neurological injury evaluating neurological outcome and morbimortality. METHOD: Patients with two glycemias above 150 mg/dL 12 hours after admission were randomized to receive intensive insulin therapy (G1) or conventional treatment (G2). We evaluated a subgroup of patients with acute brain injury from July, 2004 to June, 2006. RESULTS: G1 patients (n=31) received 70.5 (45.1-87.5) units of insulin/day while G2 patients (n=19) received 2 (0.6-14.1) units/day (p<0.0001). The median glycemia was comparable in both groups (p=0.16). Hypoglycemia occurred in 2 patients (6.4%) in G1 and in 1 patient (5.8%) in G2 (p=1.0). Mortality in G1 was of 25.8% and of 35.2% in G2 (relative reduction of 27%). Neurological outcome was similar in both groups. CONCLUSION: A less strict intensive insulin therapy can reduce hypoglycemia and still maintain its benefits

Nanostructured interfacial self-assembled peptide-polymer membranes for enhanced mineralization and cell adhesion

This work was supported by national funds through the Portuguese Foundation for Science and Technology (FCT) under the scope of the project PTDC/CTM-BIO/0814/2012 and by the European Regional Development Fund (ERDF) through the Operational Competitiveness Programme “COMPETE” (FCOMP-01-0124-FEDER-028491). J. Borges and R. P. Pirraco gratefully acknowledge funding support from FCT for postdoctoral (SFRH/BPD/103604/2014) and investigator (IF/00347/2015) grants, respectively. Y. Shi acknowledges China Scholarship Council for her PhD scholarship (no. 201307060020). H. S. Azevedo also acknowledges financial support from the EU-funded project “SuprHApolymers” (PCIG14-GA-2013-631871) and A. Mata acknowledges the European Research Council Starting Grant “STROFUNSCAFF” and the Marie Curie Career Integration Grant “BIOMORPH”

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11