Perturbational phenotyping of human blood cells reveals genetically determined latent traits associated with subsets of common diseases.

Although genome-wide association studies (GWAS) have successfully linked genetic risk loci to various disorders, identifying underlying cellular biological mechanisms remains challenging due to the complex nature of common diseases. We established a framework using human peripheral blood cells, physical, chemical and pharmacological perturbations, and flow cytometry-based functional readouts to reveal latent cellular processes and performed GWAS based on these evoked traits in up to 2,600 individuals. We identified 119 genomic loci implicating 96 genes associated with these cellular responses and discovered associations between evoked blood phenotypes and subsets of common diseases. We found a population of pro-inflammatory anti-apoptotic neutrophils prevalent in individuals with specific subsets of cardiometabolic disease. Multigenic models based on this trait predicted the risk of developing chronic kidney disease in type 2 diabetes patients. By expanding the phenotypic space for human genetic studies, we could identify variants associated with large effect response differences, stratify patients and efficiently characterize the underlying biology.

Durable Results with In Situ Graft Repair of Ruptured Salmonella Aneurysm in a Patient with Autoimmune Deficiency Syndrome.

We describe a case of a 42-year-old male patient with advanced autoimmune deficiency syndrome (AIDS) (CD4 count of 16 cells/mm3) found to have a ruptured infected infrarenal aortic aneurysm. Emergent in situ repair was performed with a Hemashield Dacron graft (Boston Scientific, Natick, MA). Aortic tissue cultures grew group D Salmonella. Patient was placed initially on intravenous ciprofloxacin followed by lifelong oral levofloxacin and trimethoprim. Over 2 years following repair, he remains asymptomatic, with repair intact and no recurrent infection. This case is the first reported successful long-term repair of a ruptured salmonella infected abdominal aortic aneurysm in the setting of advanced AIDS.

Predictive models for mortality after ruptured aortic aneurysm repair do not predict futility and are not useful for clinical decision making.

OBJECTIVE: The clinical decision-making utility of scoring algorithms for predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains unknown. We sought to determine the clinical utility of the algorithms compared with our clinical decision making and outcomes for management of rAAA during a 10-year period. METHODS: Patients admitted with a diagnosis rAAA at a large university hospital were identified from 2005 to 2014. The Glasgow Aneurysm Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score, University of Washington Ruptured Aneurysm Score, Vascular Study Group of New England rAAA Risk Score, and the Artificial Neural Network Score were analyzed for accuracy in predicting mortality. Among patients quantified into the highest-risk group (predicted mortality >80%-85%), we compared the predicted with the actual outcome to determine how well these scores predicted futility. RESULTS: The cohort comprised 64 patients. Of those, 24 (38%) underwent open repair, 36 (56%) underwent endovascular repair, and 4 (6%) received only comfort care. Overall mortality was 30% (open repair, 26%; endovascular repair, 24%; no repair, 100%). As assessed by the scoring systems, 5% to 35% of patients were categorized as high-mortality risk. Intersystem agreement was poor, with κ values ranging from 0.06 to 0.79. Actual mortality was lower than the predicted mortality (50%-70% vs 78%-100%) for all scoring systems, with each scoring system overestimating mortality by 10% to 50%. Mortality rates for patients not designated into the high-risk cohort were dramatically lower, ranging from 7% to 29%. Futility, defined as 100% mortality, was predicted in five of 63 patients with the Hardman Index and in two of 63 of the University of Washington score. Of these, surgery was not offered to one of five and one of two patients, respectively. If one of these two models were used to withhold operative intervention, the mortality of these patients would have been 100%. The actual mortality for these patients was 60% and 50%, respectively. CONCLUSIONS: Clinical algorithms for predicting mortality after rAAA were not useful for predicting futility. Most patients with rAAA were not classified in the highest-risk group by the clinical decision models. Among patients identified as highest risk, predicted mortality was overestimated compared with actual mortality. The data from this study support the limited value to surgeons of the currently published algorithms.

Novel Approach to a Giant External Iliac Vein Aneurysm Secondary to Posttraumatic Femoral Arteriovenous Fistula.

We describe a case of a 55-year-old male with a remote history of a gunshot wound to the left thigh who presented with a 1-year history of worsening high-output congestive heart failure, left lower extremity edema, and left lower abdominal discomfort. Diagnostic evaluation included a computed tomographic angiography (CTA) that demonstrated a fistulous communication between the left superficial femoral artery (SFA) and vein (SFV) as well as a 7.2-cm external iliac vein aneurysm. Given his symptomatology, an endovascular repair of his AVF was recommended, followed by antithrombotic therapy for his aneurysm. Three-month postoperative CTA confirmed AVF exclusion as well as a significant decrease in maximal diameter of the left external iliac vein aneurysm now measuring 24 mm. This case is the first reported successful mid-term repair of a iliac venous aneurysm in the setting of a traumatic arteriovenous fistula using an endovascular approach.