Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn’s disease

AIM:To investigate the correlation between rs1568885,rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease(CD).METHODS:One hundred and twenty-six patients diagnosed with CD based on standard clinical,endoscopic,radiological,and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the1st Department of Propaedeutic Surgery.Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0,2,6 and then every 8 wk.Clinical and serological responses were assessed using the HarveyBradshaw Index and serum C-reactive protein(CRP)levels,respectively,and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and non-responders.Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions.χ2test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies.RESULTS:Eighty patients(63.49%)were classified as complete and 32(25.39%)as partial responders to infliximab,while 14(11.11%)were primary non-responders.No correlation was found between response to infliximab and patients’characteristics such as age,gender and disease duration.There was consistency between Harvey-Bradshaw index scores and serum CRP levels.The TT genotype of the rs1568885 polymorphism was significantly related to partial response(P=0.024)and resistance to infliximab(P=0.007)while the AT genotype was more frequent in partial responders(P=0.035)and in primary non-responders(P=0.032).Regarding rs1813443,the CC genotype was found to be associated with partial response(P=0.005)and primary resistance(P=0.002)to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab.CONCLUSION:Based on our results,the rs1568885and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn’s disease.     

Coronary Arteriovenous Fistulae: A Review

Coronary arteriovenous fistulae are a coronary anomaly, presenting in 0.002% of the general population. Their etiology can be congenital or acquired. We present a review of recent literature related to their epidemiology, etiology, pathophysiology, clinical presentation, diagnostic approach, and therapeutic management.     

Fixation of complex proximal humeral fractures in elderly patients with a locking plate: A retrospective analysis of radiographic and clinical outcome and complications

Purpose: The optimal surgical treatment of displaced type B and C fractures of the proximal humerus in the elderly remains controversial. Good clinical results have been reported by plating these fractures as well as a high rate of complications. Our retrospective study aims to evaluate clinical recovery and complications using the S3 locking plate in elderly patients. Methods: Fifty-one patients older than 65 years of age, with a complex proximal humeral fracture type B or C (AO classification system), were included. Patients have been followed up for a minimum of 12 months. We assessed callus formation, radiological results, clinical outcome (according to the Constant Shoulder Score System) and complications. Any difference in the clinical recovery among the 2 types of fracture pattern (B and C) was investigated. Results: The mean time of fracture healing was 12.4 weeks. The mean Constant score at 3, 6 and 12 months was 68, 73 and 75 respectively. No statistically significant difference in the clinical outcome was observed between the B and C fracture patterns (p > 0.05). We noticed an overall of 5 complications (9.8%). There was no need to revision any of the implants. Conclusion: Anatomic reduction and proper plate positioning are essential for minimizing implantrelated complications. In our experience the S3 angular stability system offers a proper osteosyntesis and a good clinical recovery with a low rate of complications.     

Coronary Artery Perforation following PCI: An Interesting Finding into the Pericardial Space

Coronary artery perforation is a known complication of percutaneous coronary intervention and potentially life threatening. Normally, these perforations are small and localized. We report the successful surgical management of a coronary artery perforation following stent insertion with extrusion of an 8-cm endarterectomy length of the circumflex coronary artery with a brief review of the recent literature.     

Ileal Neobladder and Its Variants

Orthotopic neobladder substitution represents an important step in the evolution of urinary diversion. It is now considered the diversion of choice for the majority of patients, both male and female, who undergo cystectomy and is the procedure with which other types of diversion must be compared. Nevertheless, in the preoperative setting, all options for urinary diversion should be explained comprehensibly to the patient, along with the potential short- and long-term risks and the beneficial effects of each type of diversion. With regard to the risk of urethral recurrence, the decision to perform a neobladder ultimately depends on the intraoperative frozen section analysis of the distal urethral margin.Neobladder construction is based on the concept of detubularization and folding to construct a low-pressure reservoir. All parts of the small and large intestine as well as the stomach have been intensely studied for the construction of neobladders. In this respect, there is substantial agreement in the literature that the terminal ileum possesses superior anatomic and functional characteristics.Given the lack of prospective randomized trials, controversies still exist with regard to the technique for preventing reflux in orthotopic substitutes and the superiority of one neobladder technique over others, provided the detubularized intestinal segment is reconfigured to an adequate-sized spherical reservoir.     

Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis.

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.     

Type 1 and type 2 cytokine-producing CD4+ and CD8+ T cells in primary antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis and/or recurrent fetal loss as well as the presence of autoantibodies against epitopes present on phospholipid-binding proteins. The role of cellular immunity in the pathogenesis of the syndrome remains unclear. We studied the cellular phenotype and the production of type 1 [interferon (IFN)-, interleukin (IL)-2] and type 2 (IL-4, IL-10) cytokines by CD4+ and CD8+ T-lymphocyte subsets in 13 patients with untreated primary APS (PAPS) and in 32 healthy controls. The production of cytokines was determined in T cells after a 5-h culture with or without mitogenic stimulation using a flow cytometric method of intracellular cytokine staining. In six of the patients these studies were repeated 6 months later. In PAPS patients we found a reduced percentage of circulating CD4+CD45RA+ and an increased percentage and absolute number of CD8+HLA-DR+ cells. A type 1 response was observed in the patients unstimulated cells, indicated by an increase in IFN--producing CD8+, IL-2-producing CD4+ T cells, and a decrease in IL-4-producing CD4+ and CD8+ T cells. Similar results were obtained in the patients at follow-up. Taken together, these results suggest a chronic in vivo stimulation of CD4+ and CD8+ T cells in PAPS patients exhibiting a type 1 polarization. Changes of cellular immunity may contribute to the pathogenesis of the clinical manifestations of the syndrome and might be proven to be useful targets for therapeutic interventions in the future.