Genetic Variants in FBN-1 and Risk for Thoracic Aortic Aneurysm and Dissection.

OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS: The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD

Treatment of pediatric extra-axial sinogenic infection: case series and literature review

PURPOSE: Analyze the clinical presentation, microbiology, outcomes, and medical and surgical treatment strategies of intracranial extension of sinogenic infection in pediatric patients. METHODS: A retrospective, single-center study of patients \u3c 18 years of age, presenting with intracranial extension of bacterial sinogenic infections requiring surgical intervention over a 5-year period, was conducted. Electronic medical records were reviewed for age, sex, primary symptoms, duration of symptoms, presence of sinusitis at initial presentation, microorganisms isolated, mode of surgery, timing of surgery, length of stay, and neurologic sequelae. RESULTS: Seventeen patients were identified; mean age was 10 years with 82.3% male predominance. Average duration of illness prior to presentation was 9.8 days, with 64.7% of patients displaying disease progression while on oral antibiotics prior to presentation. Sinusitis and intracranial extension were present in all patients upon admission. Simultaneous endoscopic endonasal drainage and craniotomy were performed on 70.5% of the patients, with the remaining 29.5% undergoing endonasal drainage only. Of the patients who underwent simultaneous endoscopic endonasal drainage and craniotomy, 17.6% required repeat craniotomy and 5.8% required repeat sinus surgery. The most commonly isolated organisms were S. intermedius (52.9%), S. anginosus (23.5%), and S. pyogenes (17.6%). All patients were treated postoperatively antibiotic on average 4-6 weeks. Frequently occurring long-lasting complications included seizures (29.4%) and focal motor deficits (17.6%); learning disability, anxiety disorders, impaired cognition, and sensory deficits occurred less frequently. CONCLUSION: In the case of intracranial extension of bacterial sinogenic infection, early identification and surgical treatment are crucial to avoid neurological sequelae

Association of two SNPs in <i>FBN-1</i> with Non-dissecting Thoracic Aortic Aneurysm.

<p>*Adjusted for sex and study center.</p>†<p>Adjusted for sex, study center, age, hypertension, and smoking.</p

Characteristics of Dissection, Non-dissecting Aneurysm Cases, and Controls.

<p>*P value for Dissection cases vs. controls;</p>†<p>P value for Non-dissecting aneurysm cases vs. controls.</p><p>Data presented as mean ± standard deviation for age and as a number (%) of subjects for other variables.</p><p><i>P</i> values are from Fisher exact test, except those for age, which are from the Wilcoxon rank sum test.</p

Association of the SNPs in <i>FBN-1</i> with Thoracic Aortic Dissection or Aneurysm.

<p>*Adjusted for sex and study center.</p>†<p>Adjusted for sex, study center, age, hypertension, and smoking.</p

Association of two SNPs in <i>FBN-1</i> with Thoracic Aortic Dissection.

<p>*Adjusted for sex and study center.</p>†<p>Adjusted for sex, study center, age, hypertension, and smoking.</p