Citations

Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P =1.6×10 −6 ), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P =0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratio PRS , 1.26 [95% CI, 1.18–1.36]; P PRS =2.7×10 −11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratio PRS+family history+smoking , 1.24 [95% CI, 1.14–1.35]; P PRS =1.27×10 −6 ). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

Background: When revision elbow arthroplasty is required in the presence of structural proximal ulnar bone loss and triceps insufficiency, structural ulnar bone-grafting and triceps reconstruction are both required to reconstruct the skeleton and to restore active extension. We have developed a technique utilizing a structural proximal ulnar allograft with its attached triceps as an allograft-prosthetic composite (APC) to provide reconstruction of the proximal ulnar bone and deficient extensor mechanism with the same allograft. Methods: Between 2010 and 2017, the senior author performed 10 revision elbow arthroplasties using a proximal ulnar allograft with its intact triceps tendon allograft. The allograft ulna was combined with an ulnar component in an APC fashion, whereas the remaining triceps was repaired to the triceps allograft. Indications for a revision surgical procedure included aseptic loosening in 4 elbows, periprosthetic ulnar fracture with component loosening in 2 elbows, and the second stage of a 2-stage reimplantation in 4 elbows. Two elbows also required humeral APCs due to associated structural humeral bone loss. Postoperatively, all elbows were immobilized in extension for 6 weeks. The mean follow-up time was 45 months (range, 24 to 76 months). Results: Revision elbow arthroplasty resulted in pain improvement in all elbows in a 10-point visual analog scale. The mean flexion-extension arc was 95°, the mean Mayo Elbow Performance Score was 76 points (range, 45 to 95 points), and the mean triceps strength score was 4. There were 6 reoperations: 3 for humeral loosening, 1 for deep infection, 1 for fracture of the ulnar allograft, and 1 for wound debridement and closure. For the 8 elbows with an intact ulnar reconstruction, no ulnar components were radiographically loose, and the ulnar graft was considered radiographically intact and healed in 8 elbows. Conclusions: Reconstruction of the proximal part of the ulna and triceps in failed elbow arthroplasties with structural ulnar bone loss can be effectively accomplished using a structural proximal ulnar allograft as an APC with the preserved triceps tendon for the extensor mechanism reconstruction, but the procedure is associated with an expected high reoperation rate, as is the case in complex revision elbow arthroplasty. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. Methods In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. Results GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. Conclusions GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.

Background: Antifibrinolytic medications, such as tranexamic acid, have recently garnered increased attention. Despite its ability to mitigate intraoperative blood loss and need for blood transfusion, there remains a paucity of research in breast reconstruction. The authors investigate whether intravenous tranexamic acid safely reduces the risk of hematoma following implant-based breast reconstruction. Methods: A single-center retrospective cohort study was performed to analyze all consecutive patients undergoing immediate two-stage implant-based breast reconstruction following mastectomy between 2015 and 2016. The incidence of postoperative hematomas and thromboembolic events among all patients was reviewed. The patients in the intervention group received 1000 mg of intravenous tranexamic acid before mastectomy incision and 1000 mg at the conclusion of the procedure. Fisher’s exact test and the Mann-Whitney-Wilcoxon test were used. Multivariate logistic regression models were performed to study the impact of intravenous tranexamic acid after adjusting for possible confounders. Results: A total of 868 consecutive breast reconstructions (499 women) were reviewed. Overall, 116 patients (217 breasts) received intravenous tranexamic acid, whereas 383 patients (651 breasts) did not. Patient characteristics and comorbidities were similar between the two the groups. Patients who received tranexamic acid were less likely to develop hematomas [n = 1 (0.46 percent)] than patients who did not [n = 19 (2.9 percent)] after controlling for age, hypertension, and type of reconstruction (prepectoral and subpectoral) (p = 0.018). Adverse effects of intravenous tranexamic acid, including thromboembolic phenomena were not observed. Multivariate analysis demonstrated that age and hypertension independently increase risk for hematoma. Conclusions: Intravenous tranexamic acid safely reduces risk of hematoma in implant-based breast reconstruction. Further prospective randomized studies are warranted to further corroborate these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Abstract Defining patient-to-patient similarity is essential for the development of precision medicine in clinical care and research. Conceptually, the identification of similar patient cohorts appears straightforward; however, universally accepted definitions remain elusive. Simultaneously, an explosion of vendors and published algorithms have emerged and all provide varied levels of functionality in identifying patient similarity categories. To provide clarity and a common framework for patient similarity, a workshop at the American Medical Informatics Association 2019 Annual Meeting was convened. This workshop included invited discussants from academics, the biotechnology industry, the FDA, and private practice oncology groups. Drawing from a broad range of backgrounds, workshop participants were able to coalesce around 4 major patient similarity classes: (1) feature, (2) outcome, (3) exposure, and (4) mixed-class. This perspective expands into these 4 subtypes more critically and offers the medical informatics community a means of communicating their work on this important topic.