Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. A genome-wide survey of 114 TOF patients and their unaffected parents identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. A second, independent TOF cohort (n = 398) was then examined for additional CNVs at these loci. In 1% (5/512, p = 0.0002, OR = 22.3) of non-syndromic sporadic TOF cases we identified CNVs at chromosome 1q21.1. Recurrent CNVs were also identified at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single TOF case occurred at six loci, two that encode known (NOTCH1, JAG1) disease genes. Our data predicts that at least 10% (4.5–15.5, 95% CI) of sporadic, non-syndromic TOF reflects de novo CNVs and implicates mutations within these loci as etiologic in other cases of TOF.

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The majority of patients with acute type B dissection will fail medical therapy over time as evidenced by a 6-year intervention-free survival of 41%. Patients who underwent any aortic intervention had a significant survival advantage over those who were treated with medical management alone. Further study is necessary to determine who will benefit most from early intervention.

There has been a significant increase in the use of TEVAR for management of diseases of the DTA. TEVAR offers a significant perioperative survival advantage when compared with OPEN regardless of the indication for repair. However, in the Medicare population, the 5-year survival is similar between the 2 cohorts.

Small SAAs (≤25 mm) are not prone to significant expansion and do not require frequent surveillance imaging. Imaging every 3 years for small SAAs is adequate. Aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach.

The methylenetetrahydrofolate reductase (MTHFR) gene is a polymorphic gene involved in folate metabolism, DNA biosynthesis, methylation and genomic integrity in actively dividing cells. The MTHFR C677T and A1298C polymorphisms are likely to play an important role in the susceptibility to breast cancer. In this case-control study, we examined the role of MTHFR C677T and A1298C polymorphisms in breast cancer patients. We genotyped 118 premenopausal women with sporadic breast cancer and 193 controls, using a PCR-RFLP method. The allele frequencies of the MTHFR 677T were 31.36% in the breast cancer cases and 28.76% in the controls. The allele frequencies of the MTHFR 1298C were 37.29% in the breast cancer subjects and 31.35% in the controls. Frequencies of MTHFR C677C, C677T and T677T were 50.8, 33.9 and 14.4% in the breast cancer patients and 48.7, 45.1 and 6.2% in the controls, respectively. The results of a χ² analysis indicated that the MTHFR 677T allele was significantly distributed (χ² = 7.234; p = 0.027). Likewise, the MTHFR T677T genotype showed a 2.5-fold increased risk for breast cancer and the C1298C genotype showed a 1.9-fold increased risk for breast cancer. In the compound genotypes, T677T/A1298A and C677C/C1298C showed a 4.472- and a 2.301-fold increased risk for breast cancer (OR = 4.472, p = 0.001, and OR = 2.301, p = 0.024), respectively. In conclusion, our data suggest that the MTHFR 677T, 1298C alleles, T677T, C1298C genotypes, and C677C/C1298C and T677T/A1298A compound genotypes are genetic risk factors for premenopausal women with sporadic breast cancer.

Background Patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms can exhibit variations in sac behavior ranging from complete regression to expansion. We evaluated the impact of sac behavior at 1-year follow-up on late survival. Methods We used the Vascular Study Group of New England (VSGNE) registry from 2003 to 2011 to identify EVAR patients with 1-year computed tomography follow-up. Aneurysm sac enlargement $5 mm (sac expansion) and decrease ≥5 mm (sac regression) were defied per Society for Vascular Surgery guidelines. Predictors of change in sac diameter and impact of sac behavior on long-term mortality were assessed by multivariable methods. Results Of 2437 patients who underwent EVAR, 1802 (74%) had complete 1-year follow-up data and were included in the study. At 1 year, 162 (9%) experienced sac expansion, 709 (39%) had a stable sac, and 931 (52%) experienced sac regression. Sac expansion was associated with preoperative renal insufficiency (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.5–8.0; P < .01), urgent repair (OR, 2.7; 95% CI, 1.4–5.1; P < .01), hypogastric coverage (OR, 1.7; 95% CI, 1.1–2.7; P = .02), and type I/III (OR, 16.8; 95% CI, 7.3–39.0; P < .001) or type II (OR, 2.9; 95% CI, 2.0–4.3; P < .001) endoleak at follow-up, and sac expansion was inversely associated with smoking (OR, 0.6; 95% CI, 0.4–0.96; P = .03) and baseline aneurysm diameter (OR, 0.7; 95% CI, 0.6–0.9; P < .001). Sac regression (vs expansion or stable sac) was associated with female gender (OR, 1.8; 95% CI, 1.4–2.4; P < .001) and larger baseline aneurysm diameter (OR, 1.4; 95% CI, 1.2–1.5; P < .001) and inversely associated with type I/III (OR, 0.2; 95% CI, 0.1–0.5; P < .01) or type II endoleak at follow-up (OR, 0.2; 95% CI, 0.2–0.3; P < .001). After risk-adjusted Cox regression, sac expansion was independently associated with late mortality (hazard ratio, 1.5; 95% CI, 1.1–2.0; P = .01), even with adjustment for reinterventions and endoleak during follow-up. Sac regression was associated with lower late mortality (hazard ratio, 0.6; 95% CI, 0.5–0.7; P < .001). Long-term survival was lower (log-rank, P < .001) in patients with sac expansion (98% 1-year and 68% 5-year survival) compared with all others (99% 1-year and 83% 5-year survival). Conclusions These data suggest that an abdominal aortic aneurysm sac diameter increase of at least 5 mm at 1 year, although infrequent, is independently associated with late mortality regardless of the presence or absence of endoleak and warrants close observation and perhaps early intervention.

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