Outpatient management of cholesteatoma with canal wall reconstruction tympanomastoidectomy

Objectives The postoperative wound infection rate for canal wall reconstruction (CWR) tympanomastoidectomy with mastoid obliteration in the treatment of chronic otitis media with cholesteatoma has been reported to be 3.6%. Postoperative administration of 24–48 hours of intravenous antibiotics has been recommended. We aim to determine the infection rate of CWR with postoperative outpatient oral antibiotics. Study Design Institutional review board—approved retrospective case review. Setting Tertiary referral center. Patients: Retrospective review of consecutive patients who underwent CWR tympanomastoidectomy with mastoid obliteration at a single institution from 2014 to 2016. Main Outcome Measure: Patient characteristics (age, sex) were calculated. Rate of postoperative complications and infections within 1 month of surgery were calculated. Comparison to previous published infection rates with postoperative intravenous antibiotics. Results 51 patients underwent CWR followed by outpatient oral antibiotics with a mean age of 25.9 years (16 patients were less than 10 years old). There were no postoperative wound infections. Outpatient antibiotics showed non-inferiority to IV antibiotic historic controls (0% vs. 3.6%; 95% confidence interval [CI], 0–6.09%; p = 0.03). One patient had small postoperative wound dehiscence with CSF leak that was managed conservatively. One patient developed Clostridium difficile colitis on postoperative day 2. Conclusions The infection rate after CWR tympanomastoidectomy with use of outpatient antibiotics is low and is non-inferior to a historic cohort treated with inpatient intravenous antibiotics. A larger randomized controlled trial is warranted. Level of Evidence 4

A proteasome-resistant fragment of NIK mediates oncogenic NF-κB signaling in schwannomas

Schwannomas are common, highly morbid and medically untreatable tumors that can arise in patients with germ line as well as somatic mutations in neurofibromatosis type 2 (NF2). These mutations most commonly result in the loss of function of the NF2-encoded protein, Merlin. Little is known about how Merlin functions endogenously as a tumor suppressor and how its loss leads to oncogenic transformation in Schwann cells (SCs). Here, we identify nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-inducing kinase (NIK) as a potential drug target driving NF-κB signaling and Merlin-deficient schwannoma genesis. Using a genomic approach to profile aberrant tumor signaling pathways, we describe multiple upregulated NF-κB signaling elements in human and murine schwannomas, leading us to identify a caspase-cleaved, proteasome-resistant NIK kinase domain fragment that amplifies pathogenic NF-κB signaling. Lentiviral-mediated transduction of this NIK fragment into normal SCs promotes proliferation, survival, and adhesion while inducing schwannoma formation in a novel in vivo orthotopic transplant model. Furthermore, we describe an NF-κB-potentiated hepatocyte growth factor (HGF) to MET proto-oncogene receptor tyrosine kinase (c-Met) autocrine feed-forward loop promoting SC proliferation. These innovative studies identify a novel signaling axis underlying schwannoma formation, revealing new and potentially druggable schwannoma vulnerabilities with future therapeutic potential

Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2

Mutations in the tumor suppressor gene NF2 lead to Neurofibromatosis type 2 (NF2), a tumor predisposition syndrome characterized by the development of schwannomas, including bilateral vestibular schwannomas with complete penetrance. Recent work has implicated the importance of COX-2 in schwannoma growth. Using a genetically engineered murine model of NF2, we demonstrate that selective inhibition of COX-2 with celecoxib fails to prevent the spontaneous development of schwannomas or sensorineural hearing loss in vivo, despite elevated expression levels of COX-2 in Nf2-deficient tumor tissue. These results suggest that COX-2 is nonessential to schwannomagenesis and that the proposed tumor suppressive effects of NSAIDs on schwannomas may occur through COX-2 independent mechanisms

Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays

Objective To compare differences in audiologic outcomes between slim modiolar electrode (SME) CI532 and slim lateral wall electrode (SLW) CI522 cochlear implant recipients. Study Design Retrospective cohort study. Setting Tertiary academic hospital. Methods Comparison of postoperative AzBio sentence scores in quiet (percentage correct) in adult cochlear implant recipients with SME or SLW matched for preoperative AzBio sentence scores in quiet and aided and unaided pure tone average. Results Patients with SLW (n = 52) and patients with SME (n = 37) had a similar mean (SD) age (62.0 [18.2] vs 62.6 [14.6] years, respectively), mean preoperative aided pure tone average (55.9 [20.4] vs 58.1 [16.4] dB; P = .59), and mean AzBio score (percentage correct, 11.1% [13.3%] vs 8.0% [11.5%]; P = .25). At last follow-up (SLW vs SME, 9.0 [2.9] vs 9.9 [2.6] months), postoperative mean AzBio scores in quiet were not significantly different (percentage correct, 70.8% [21.3%] vs 65.6% [24.5%]; P = .29), and data log usage was similar (12.9 [4.0] vs 11.3 [4.1] hours; P = .07). In patients with preoperative AzBio <10% correct, the 6-month mean AzBio scores were significantly better with SLW than SME (percentage correct, 70.6% [22.9%] vs 53.9% [30.3%]; P = .02). The intraoperative tip rollover rate was 8% for SME and 0% for SLW. Conclusions Cochlear implantation with SLW and SME provides comparable improvement in audiologic functioning. SME does not exhibit superior speech recognition outcomes when compared with SLW

American Society of Hematology 2019 guidelines for management of venous thromboembolism : prevention of venous thromboembolism in surgical hospitalized patients

Background: Venous thromboembolism (VTE) is a common source of perioperative morbidity and mortality. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about preventing VTE in patients undergoing surgery. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic reviews. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 30 recommendations, including for major surgery in general (n = 8), orthopedic surgery (n = 7), major general surgery (n = 3), major neurosurgical procedures (n = 2), urological surgery (n = 4), cardiac surgery and major vascular surgery (n = 2), major trauma (n = 2), and major gynecological surgery (n = 2). Conclusions: For patients undergoing major surgery in general, the panel made conditional recommendations for mechanical prophylaxis over no prophylaxis, for pneumatic compression prophylaxis over graduated compression stockings, and against inferior vena cava filters. In patients undergoing total hip or total knee arthroplasty, conditional recommendations included using either aspirin or anticoagulants, as well as for a direct oral anticoagulant over low-molecular-weight heparin (LMWH). For major general surgery, the panel suggested pharmacological prophylaxis over no prophylaxis, using LMWH or unfractionated heparin. For major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, the panel suggested against pharmacological prophylaxis. For major trauma surgery or major gynecological surgery, the panel suggested pharmacological prophylaxis over no prophylaxis.Peer reviewe

Challenges and Opportunities in the Hydrologic Sciences

This is the Table of Contents and Introduction of a Report published as Hornberger, G. M., E. Bernhardt, W. E. Dietrich, D. Entekhabi, G. E. Fogg, E. Foufoula-Georgiou, W. J. Gutowski, W. B. Lyons, K. W. Potter, S. W. Tyler, H. J. Vaux, C. J. Vorosmarty, C. Welty, C. A. Woodhouse, C. Zheng, Challenges and Opportunities in the Hydrologic Sciences. 2012: Water Science and Technology Board, Division on Earth and Life Studies, National Academy of Sciences, Washington, DC. 173 pp. Posted with permission.</p

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.Cancer Research UK Clinician Scientist Fellowship C53779/A20097 (M.L.B), Leukaemia Foundation Australia Senior Fellowship and Howard Hughes Medical Institute International Research Scholarship 55008729 (M.A.D), Peter and Julie Alston Centenary fellowship (K.D.S.), Wellcome Trust Principal Research Fellowship 101835/Z/13/Z (P.J.L), Peter MacCallum Postgraduate Scholarship (C.E.S), NHMRC Postgraduate Scholarship (K.L.C.), Maddie Riewoldt's Vision 064728 (Y-C.C), Victorian Cancer Agency (E.Y.N.L), CSL Centenary fellowship (S-J.D), National Breast Cancer Foundation Fellowship ECF-17-005 (P.A.B.), Addenbrooke’s Charitable Trust and NIHR Cambridge BRC (M.L.B., P.J.L), NHMRC grant 1085015, 1106444 (M.A.D) and 1128984 (M.A.D, S-J.D)

Meals in western eating and drinking

Meals are a way of organizing eating into events that have a particular structure and form, and they play an indisputable and even self-evident role within the rhythms and routines of everyday life. In late modern societies, concern about the fate of meals has arisen in both public and academic discourse. It has been suggested that eating is characterized today by individualization, destructuration, and informalization and that communal meals are increasingly being replaced by snacks and solitary eating. This chapter focuses on meals in today’s affluent societies and reflects on why meals are considered important, how meals are defined, and what material elements and social dimensions they contain. It looks at how societal and cultural changes and ecological concerns may influence the organization and future of meals, and it suggests that the content of meals will change in response to the need to diminish the ecological burden of food production and consumption. In particular, plant-based options will at least partly need to replace meat and other animal-based foods. However, there is no reason to expect that the meal as a social institution will break down. Despite the fact that not all meals are characterized by conviviality and companionship, they continue to serve as a significant arena of human sociability and togetherness. Sharing food is, after all, an essential part of being human.Non peer reviewe