Patients with atrial fibrillation undergoing total joint arthroplasty increase hospital burden.

BACKGROUND: More than 3 million people in the United States have atrial fibrillation, most of whom are being managed with anticoagulation therapy for life. The goal of the present study was to examine the effect of chronic anticoagulation therapy on patients with atrial fibrillation who undergo total joint arthroplasty. METHODS: We retrospectively reviewed all patients undergoing aseptic primary or revision total joint arthroplasty at our facility from March 2007 to August 2011. One hundred and sixty-one patients with atrial fibrillation (Group A) were compared with 161 matched controls (Group B). A total of 112 hips and 210 knees underwent 239 primary arthroplasties and eighty-three revisions. The groups were compared with use of conditional logistic regression (with matching on the basis of the involved joint [hip or knee], type of procedure [revision or primary], age, and sex) with regard to the length of hospital stay, postoperative hemoglobin levels, transfusion requirements, and readmissions. RESULTS: The preoperative length of stay (1.7 versus 0.2 days; p \u3c 0.0001), postoperative length of stay (4.6 versus 3.2 days; p = 0.0002), and total length of stay (6.3 versus 3.4 days; p \u3c 0.0001) were significantly longer for patients with atrial fibrillation (Group A). Hemoglobin levels were lower (but not significantly so) for Group A at baseline (13.1 versus 13.8 mg/dL), on Postoperative Day 2 (10.1 versus 10.6 mg/dL), on Postoperative Day 3 (9.8 versus 10.2 mg/dL), on Postoperative Day 4 (9.6 versus 10.1 mg/dL), on Postoperative Day 5 (9.7 versus 9.9 mg/dL), and at discharge (9.9 versus 10.3 mg/dL). Group A had a significantly higher prevalence of blood transfusion (15.5% versus 3.7%; p = 0.0005) and periprosthetic joint infection (5.6% versus 0.62%; p = 0.0196). A diagnosis of atrial fibrillation (odds ratio, 4.09; 95% confidence interval, 2.05 to 8.18; p \u3c 0.0001) significantly increased the odds of total joint arthroplasty complication and the need for hospital readmission. CONCLUSIONS: Patients with preoperative atrial fibrillation undergoing total joint arthroplasty had an increased length of hospital stay, increased transfusion requirements, and an increased risk of periprosthetic joint infection and unplanned hospital readmission

Number of Unfavorable Intermediate‐Risk Factors Predicts Pathologic Upstaging and Prostate Cancer‐Specific Mortality Following Radical Prostatectomy: Results From the SEARCH Database

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135480/1/pros23255.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135480/2/pros23255_am.pd

Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139104/1/pros23436_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139104/2/pros23436.pd

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs

The TESS-Keck Survey. XI. Mass Measurements for Four Transiting sub-Neptunes orbiting K dwarf TOI-1246

Multi-planet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V=11.6, K=9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31 d, 5.90 d, 18.66 d, and 37.92 d. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97±0.06 R⊕,2.47±0.08 R⊕,3.46±0.09 R⊕, 3.72±0.16 R⊕), and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1±1.1M⊕, 8.8±1.2M⊕, 5.3±1.7M⊕, 14.8±2.3M⊕). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (Pe/Pd=2.03) and exhibit transit timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only six systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70±0.24 to 3.21±0.44g/cm3, implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 ± 3.6 M⊕. This planet candidate is exterior to TOI-1246 e with a candidate period of 93.8 d, and we discuss the implications if it is confirmed to be planetary in nature