Citations

Abstract Rapid development of next generation sequencing technology has enabled the identification of genomic alterations from short sequencing reads. There are a number of software pipelines available for calling single nucleotide variants from genomic DNA but, no comprehensive pipelines to identify, annotate and prioritize expressed SNVs (eSNVs) from non-directional paired-end RNA-Seq data. We have developed the eSNV-Detect, a novel computational system, which utilizes data from multiple aligners to call, even at low read depths, and rank variants from RNA-Seq. Multi-platform comparisons with the eSNV-Detect variant candidates were performed. The method was first applied to RNA-Seq from a lymphoblastoid cell-line, achieving 99.7% precision and 91.0% sensitivity in the expressed SNPs for the matching HumanOmni2.5 BeadChip data. Comparison of RNA-Seq eSNV candidates from 25 ER+ breast tumors from The Cancer Genome Atlas (TCGA) project with whole exome coding data showed 90.6–96.8% precision and 91.6–95.7% sensitivity. Contrasting single-cell mRNA-Seq variants with matching traditional multicellular RNA-Seq data for the MD-MB231 breast cancer cell-line delineated variant heterogeneity among the single-cells. Further, Sanger sequencing validation was performed for an ER+ breast tumor with paired normal adjacent tissue validating 29 out of 31 candidate eSNVs. The source code and user manuals of the eSNV-Detect pipeline for Sun Grid Engine and virtual machine are available at http://bioinformaticstools.mayo.edu/research/esnv-detect/.

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic “starfield” pattern on MRI. This “starfield” MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high‐grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long‐term quality of life in patients following esophagectomy.

BackgroundDevice infection is associated with increased mortality in patients receiving cardiovascular implantable electronic device (CIED) therapy. However, long‐term mortality associated with CIED infections has not been systematically analyzed in larger studies. This study sought to determine the long‐term mortality associated with CIED infection in a large cohort of Medicare beneficiaries.MethodsWe used a retrospective study design to analyze 3‐year mortality in 200,219 Medicare fee‐for‐service patients admitted for CIED generator implantation, replacement, or revision between January 1, 2007 and December 31, 2007. Multivariate analysis adjusting for age, sex, race, and 28 comorbidities was performed to determine the relative risk (RR) of death in the 12 quarters following CIED infection.ResultsPatients with CIED infection, compared to device recipients without infection, had increased mortality that persisted for at least 3 years after the admission quarter for all device types: pacemakers (PMs: 53.8% vs 33%; P < 0.001), implantable cardioverter defibrillator (ICD: 47.7% vs 31.6%; P < 0.001), and cardiac resynchronization therapy‐defibrillator (CRT‐D: 50.8% vs 36.5%; P < 0.001). After adjusting for patient demographics and comorbidities, significantly increased RR of death following CIED infection persisted for at least 3 years following PM infection, and for at least 2 years with single‐ and dual‐chamber ICD infection.ConclusionsCIED recipients who develop device infection have increased, device‐dependent, long‐term mortality even after successful treatment of infection. The etiology of this persistent increased risk of death associated with CIED infection is unknown and merits further investigation.

HCV-specific neutralizing antibodies protect humanized mice from challenge and suppress established infections.

Purpose The purpose of this study was to investigate the influence of multiple demographic and radiographic findings on the size of labral tears identified at the time of hip arthroscopy. Methods Data were prospectively collected for patients treated with arthroscopic labral repair or debridement from February 2008 to August 2011. Preoperative radiographic and demographic data were collected for 392 patients during the study period. Exclusion criteria included revision surgery and previous hip conditions. An anteroposterior pelvic view, 45° Dunn view, and false‐profile view were used to measure Tönnis grade, neck‐shaft angle, alpha angle, lateral center edge angle (LCEA), anterior center edge angle (ACEA), acetabular inclination, and the extent of crossover sign when present. At the time of surgery, labral tear size and location were documented for all patients, using traditional acetabular clock face nomenclature for sizing. A multiple linear regression analysis was then performed to assess the correlation of radiographic and demographic findings with the size of the labral tear. Results Regression analysis displayed statistical significance for sex ( P < .0001), age ( P < .0001), and alpha angle ( P = .005) with labral tear size. For female patients, Tönnis grade ( P = .0004) and neck‐shaft angle ( P = .004) correlated with labral tear size. This model accounted for only 26% of variation in labral tear size. Conclusions Preoperative risk factors for the extent of labral tear size are male sex, increasing age, and increasing alpha angle. Labral tears were larger in female patients with higher Tönnis grades and lower neck‐shaft angles. Measurements of acetabular coverage and version showed no correlation with labral tear size. The majority of labral tear size variation was not accounted for in this model. Level of Evidence Level IV, therapeutic case series.

SummaryDickkopf‐1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti‐DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma‐related bone disease and as an agent with potential anti‐myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose‐limiting toxicity (DLT) of escalating doses in combination with anti‐myeloma therapy and zoledronic acid. Twenty‐eight patients were enrolled and received BHQ880 at doses of 3–40 mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal‐related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti‐myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.