Citations

AbstractBackgroundThe aim of the present study was to obtain data regarding the timing of anticoagulation resumption in patients with spontaneous rectus sheath hematomas (RSH).Patients and methodsThe study is based on review of patients receiving anticoagulation medication who were diagnosed with a spontaneous RSH (traumatic and iatrogenic excluded) between 14 July 1997 and 17 March 2012.ResultsThere were 156 patients (37 % male; aged 73 ± 13 years) with an average body mass index of 29 ± 7 (procedure group 28 ± 6). Anticoagulants included coumadin (64 %), intravenous heparin (21 %), aspirin (8 %), and others (7 %). An intervention was needed in 29 (19 %) of the patients (5 % operative; 16 % embolization). Sixty‐two percent of patients had their anticoagulation restarted during their hospitalization, with a median re‐initiation time of 4 days after RSH diagnosis (range 2–8 days). Timing of anticoagulant resumption did not differ regardless of the need for intervention (3 vs. 4 days). The complication rate was 19 % (42 % in the procedure group, none specific to the procedure), with the most common being acute renal failure (n = 8; 5 %), death (n = 8; 5 %), and thrombotic events (n = 5; 3 %). After resumption of anticoagulation, two patients suffered enlargement of their RSH, both 2 days after resumption.ConclusionsIntervention to control hemorrhage was unnecessary in the majority of patients with RSH. In those with resumption of anticoagulation, the majority of patients were safely restarted by day 4. Even though complications secondary to anticoagulation were few, thrombotic complications outnumbered bleeding complications, suggesting that anticoagulation was withheld for too long after RSH diagnosis.

Abstract Background: Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model. Methods: Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review. Results: The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37–0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2. Conclusions: Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type. Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.

DBC1 (deleted in breast cancer-1) is a nuclear protein that regulates cellular metabolism. Since alteration in cellular metabolism have been proposed to be the emerging ‘hallmark’ of cancer, it is possible that DBC1 may be implicated in the regulation of cancer cell energy metabolism. However, at this point any role of DBC1 in cancer is only speculative. In this review, we will discuss the new developments in DBC1 research, its molecular structure, regulatory roles and implication in metabolism, aging and cancer.

PAKs (p21-activated kinases) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of LIMK (Lin-11/Isl-1/Mec-3 kinase). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1). Phosphorylation of PAK4 at Ser99 also mediates binding to 14-3-3 protein, and is required for the formation of a PAK4–LIMK–PKD1 complex that regulates cofilin activity and directed cell migration.

Abstract The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Abstract Background: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN). Methods: Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months. Results: Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC. Conclusions: SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival. Impact: SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC. Cancer Epidemiol Biomarkers Prev; 22(10); 1730–5. ©2013 AACR.