Citations

Abstract Part of the substantial unexplained familial aggregation of breast cancer may be due to interactions between common variants, but few studies have had adequate statistical power to detect interactions of realistic magnitude. We aimed to assess all two-way interactions in breast cancer susceptibility between 70 917 single nucleotide polymorphisms (SNPs) selected primarily based on prior evidence of a marginal effect. Thirty-eight international studies contributed data for 46 450 breast cancer cases and 42 461 controls of European origin as part of a multi-consortium project (COGS). First, SNPs were preselected based on evidence (P < 0.01) of a per-allele main effect, and all two-way combinations of those were evaluated by a per-allele (1 d.f.) test for interaction using logistic regression. Second, all 2.5 billion possible two-SNP combinations were evaluated using Boolean operation-based screening and testing, and SNP pairs with the strongest evidence of interaction (P < 10−4) were selected for more careful assessment by logistic regression. Under the first approach, 3277 SNPs were preselected, but an evaluation of all possible two-SNP combinations (1 d.f.) identified no interactions at P < 10−8. Results from the second analytic approach were consistent with those from the first (P > 10−10). In summary, we observed little evidence of two-way SNP interactions in breast cancer susceptibility, despite the large number of SNPs with potential marginal effects considered and the very large sample size. This finding may have important implications for risk prediction, simplifying the modelling required. Further comprehensive, large-scale genome-wide interaction studies may identify novel interacting loci if the inherent logistic and computational challenges can be overcome.

We report a case of an abdominal aortic aneurysm (AAA) that underwent inflammatory transformation which we treated medically with corticosteroids. Medical therapy resulted in resolution of presenting symptoms and observed inflammatory changes. We review the clinical features, associated pathology, diagnostic, and therapeutic options in the management of inflammatory AAA.

Abstract Objective Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. Participants The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. Conclusions Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

Objectives/HypothesisRobotic surgery is increasingly used for a variety of head and neck surgical procedures but has yet to be adapted for routine robotic microlaryngeal surgery (RMLS). Current retractor technology is limited by the following: poor tongue retraction, poor oral commissure retraction, poor larynx visualization, and laryngeal blades that do not take advantage of the robot's ability to operate without line‐of‐site exposure. Additionally, adequate instrumentation for RMLS is lacking.Study DesignFeasibility study.MethodsWe performed a feasibility study of RMLS using a newly designed robotic retractor in a cadaver model with the goal of routinely exposing the glottis. Microlaryngeal instrumentation was also adapted for the da Vinci Surgical Robot effector arms.ResultsRMLS surgery was successfully performed including microflap elevation, anterior commissure surgery, false cordectomy, true cordotomy/cordectomy, and arytenoidectomy. Photographic and video documentation was obtained demonstrating feasibility.ConclusionsWe present a newly designed laryngeal robotic retractor and novel microlaryngeal instrumentation in a cadaveric model. This allows for glottic and anterior commissure exposure, effector arm access to the glottis, and performance of delicate endolaryngeal procedures with the robot. The overall efficacy of our retractor will need to be examined in an in vivo human model.Level of EvidenceNA Laryngoscope, 124:1624–1630, 2014

Objectives/HypothesisMultiple system atrophy (MSA) is a degenerative neurologic disorder that can affect vocal fold mobility. Our aim was to further elucidate the impact of vocal fold motion impairment (VFMI) in MSA.Study DesignRetrospective case series.MethodsWe undertook a retrospective review of all MSA patients reporting voice or respiratory symptoms from 1975 to 2010 at Mayo Clinic Rochester who also received otolaryngologic examination.ResultsThirty‐eight MSA patients demonstrated VFMI. Median duration of vocal or respiratory symptoms prior to diagnosis of MSA was 12.0 months (range, 1–60 months). Stridor was present in 25 (68%) of patients. There was bilateral VFMI in 32 (82.4%) of the patients and isolated VFMI of the left true vocal fold (TVF) in six (17.6%) of the patients. No patients had isolated right VFMI. There was isolated unilateral or bilateral paresis in 21 (55.3%) of the patients and unilateral or bilateral complete paralysis in 15 (39.5%) of the patients. One patient presented with left TVF paralysis and right TVF paresis, whereas one other patient had findings of right TVF paralysis and left TVF paresis comprising the remaining 5.2% of patients with VFMI. The median survival after diagnosis of VFMI was 51.6 months. Unilateral or bilateral TVF paralysis was statistically associated with a decreased overall survival (P = .0384). The presence of stridor was not associated with adverse prognosis.ConclusionsThe increasing severity of VFMI negatively impacts overall survival in patients with MSA. Therefore, otolaryngologic examination is warranted at the time of MSA diagnosis.Level of Evidence4. Laryngoscope, 124:730–735, 2014