Recombinant activated factor VII for postoperative hemorrhage following repair of acute type A aortic dissection.

BACKGROUND: Perioperative hemorrhage in the repair of acute type A aortic dissection increases morbidity, mortality, and costs of treatment. Recombinant activated factor VII (rFVIIa) mitigates intractable blood loss in surgery. By enhancing thrombin generation on activated platelet surfaces and activating thrombin-activatable fibrinolysis inhibitor and factor XIII, rFVIIa promotes platelet aggregation and fibrin plug formation at the site of endothelial injury. We report outcomes for type A aortic dissection patients treated postoperatively with rFVIIa for life-threatening hemorrhage. METHODS: Patients' charts were reviewed to gather demographic, procedural, and laboratory data as well as information regarding clinical outcomes and blood product use. RESULTS: Nine patients with acute type A aortic dissection received rFVIIa in the perioperative period. In the 6 hour period after rFVIIa treatment, transfusion of blood products was reduced. The international normalized ratio decreased after treatment (1.6 versus 0.9, P < .01). One patient experienced perioperative stroke. CONCLUSIONS: In patients with acute type A aortic dissections who have life-threatening bleeding, early administration of rFVIIa may safely normalize coagulation variables, decrease transfusion requirements, and enhance hemostasis.

Clinical outcomes of stenting for colorectal obstruction at a tertiary centre.

PURPOSE: Self-expandable metal stents (SEMS) have been used to manage large bowel obstruction as a palliative treatment or to initially decompress the colon as a bridge to definitive surgery. Our goal was to review clinical outcomes in patients undergoing placement of a SEMS for colorectal obstruction at a tertiary care hospital. METHODS: A retrospective review was done of patients undergoing placement of a colorectal SEMS at a single centre between August 2005 and March 2011 for obstructing lesions. Outcomes identified included clinical relief of obstruction, successful bridging to surgery or palliation, and stent-related complications. RESULTS: SEMS were placed in a total of 58 patients. The intent of stenting was to bridge to definitive surgery in 11 patients and palliation in 47 patients. Stent placement was clinically successful in relieving obstruction without early complication in 45 (78%) patients. Of the patients intended to bridge to surgery, 7/11 (64%) were successfully bridged to surgery. One patient suffered a perforation, two failed to relieve obstruction, and one re-obstructed. Of the patients stented for palliation, 32/47 (68%) were successfully palliated at a mean follow-up of 7.5 months. Five patients had perforations, six re-obstructed, two had stent migration, and two failed to relieve obstruction. The overall rates for perforation, re-obstruction, and stent migration were 10, 12, and 7%, respectively. CONCLUSION: SEMS placement as a bridge to surgery and for palliation of colorectal obstruction is associated with moderate rates of clinical success but a high rate of perforation.

Association of NPAS3 exonic variation with schizophrenia.

BACKGROUND: We previously identified the neuronal PAS3 (NPAS3) gene as a candidate gene for schizophrenia. A mother and daughter, both with schizophrenia, were carriers of a translocation, t(9;14)(q34;q13), that disrupts the NPAS3 gene. The gene is located at 14q13, a region implicated in schizophrenia and bipolar disorder in various linkage studies. NPAS3 belongs to the basic helix-loop-helix Per-Arnt-Sim (bHLH-PAS) transcription factor family, involved in diverse processes including the regulation of cell differentiation and circadian rhythms, and the development and function of the nervous system. METHODS: The 12 exons encoding NPAS3 were sequenced in DNA from individuals with schizophrenia. NPAS3 variants were identified in exons 6 and 12, initially in 12 patients only. These two exons were then sequenced in 83 patients and 83 controls. RESULTS AND CONCLUSION: Three common variants of NPAS3, also found in controls, showed a positive association with schizophrenia (NM_001164749: rs12434716, c.1654G>C, p=0.009; rs10141940, c.2208C>T, p=0.01; rs10142034, c.2262C>G, p=0.01). The c.1654G>C variant, results in an p.Ala552Pro change and may affect NPAS3 protein function directly. Alternatively, the three SNPs may affect the splicing of NPAS3 transcripts, as they are each located within putative exonic splicing enhancer (ESE) motifs (ESEFinder). A c.726C>T variant, identified in three patients, is located in an ESE element and is predicted to reduce the function of the motif. Other variants, identified in controls, included c.2089G>A (p.Gly697Ser) and c.2097T>C. Our identification of potentially defective NPAS3 variants supports recent studies that implicate perturbations in NPAS3 pathways in impaired neurogenesis and psychosis.