tbuckley/cabot-search huggingface dataset:
Assessment of the Accuracy of Using <i>ICD-9</i> Diagnosis Codes to Identify Pneumonia Etiology in Patients Hospitalized With Pneumonia
Authors: Thomas L. Higgins, Abhishek Deshpande, Marya D. Zilberberg, Peter K. Lindenauer, Peter B. Imrey, Pei-Chun Yu, Sarah D. Haessler, Sandra S. Richter, Michael B. Rothberg
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Administrative databases may offer efficient clinical data collection for studying epidemiology, outcomes, and temporal trends in health care delivery. However, such data have seldom been validated against microbiological laboratory results. <h3>Objective</h3> To assess the validity of<i>International Classification of Diseases, Ninth Revision (ICD-9)</i>organism-specific administrative codes for pneumonia using microbiological data (test results for blood or respiratory culture, urinary antigen, or polymerase chain reaction) as the criterion standard. <h3>Design, Setting, and Participants</h3> Cross-sectional diagnostic accuracy study conducted between February 2017 and June 2019 using data from 178 US hospitals in the Premier Healthcare Database. Patients were aged 18 years or older admitted with pneumonia and discharged between July 1, 2010, and June 30, 2015. Data were analyzed from February 14, 2017, to June 27, 2019. <h3>Exposures</h3> Organism-specific pneumonia identified from<i>ICD-9</i>codes. <h3>Main Outcomes and Measures</h3> Sensitivity, specificity, positive predictive value, and negative predictive value of<i>ICD-9</i>codes using microbiological data as the criterion standard. <h3>Results</h3> Of 161 529 patients meeting inclusion criteria (mean [SD] age, 69.5 [16.2] years; 51.2% women), 35 759 (22.1%) had an identified pathogen.<i>ICD-9</i>–coded organisms and laboratory findings differed notably: for example,<i>ICD-9</i>codes identified only 14.2% and 17.3% of patients with laboratory-detected methicillin-sensitive<i>Staphylococcus aureus</i>and<i>Escherichia coli</i>, respectively. Although specificities and negative predictive values exceeded 95% for all codes, sensitivities ranged downward from 95.9% (95% CI, 95.3%-96.5%) for influenza virus to 14.0% (95% CI, 8.8%-20.8%) for parainfluenza virus, and positive predictive values ranged downward from 91.1% (95% CI, 89.5%-92.6%) for<i>Staphylococcus aureus</i>to 57.1% (95% CI, 39.4%-73.7%) for parainfluenza virus. <h3>Conclusions and Relevance</h3> In this study,<i>ICD-9</i>codes did not reliably capture pneumonia etiology identified by laboratory testing; because of the high specificities of<i>ICD-9</i>codes, however, administrative data may be useful in identifying risk factors for resistant organisms. The low sensitivities of the diagnosis codes may limit the validity of organism-specific pneumonia prevalence estimates derived from administrative data.
Utility of COVID-19 Screening in Cancer Patients
Authors: Lennard Y.W. Lee, Thomas Hill, Oliver Topping, Michael Tilby, Mark Baker, Julian Greig, Lawrence Isherwood, Robert Miller, Yuriy Petrenko, Ruchi Desai, Alice Field, Bethany Kennedy, Shahbano Khan, Alexandra Kountourou, Sandisile Ndlovu, Thomas Starkey, Francesca Storey, Lucy Turner, William Vaughan-Williams, Surrinder Moyler, Helen Preston, Beverley Latty, Sharon Walker, Daniel R. Henderson, Joyce Thompson, Nicola Jones, Qamar Ghafoor, Jenny Pascoe, Sarah Williams, Gary Middleton
Journal: Cancer Cell (2020)
Offline: Preparing for a vaccine against COVID-19
Authors: Richard Horton
Journal: The Lancet (2020)

The results of two randomised trials reported this week in The Lancet give great encouragement to the view that a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be produced within the next 18 months. There are no guarantees. But the evidence is hopeful. Pedro Folegatti and colleagues from The Jenner Institute at the University of Oxford used a chimpanzee adenovirus viral vector expressing SARS-CoV-2 spike protein to create a vaccine given by a single intramuscular injection.
Yeast Cell wall Particle mediated Nanotube-RNA delivery system loaded with miR365 Antagomir for Post-traumatic Osteoarthritis Therapy via Oral Route
Authors: Long Zhang, Hang Peng, Wan Zhang, Yankun Li, Liang Liu, Tongtong Leng
Journal: Theranostics (2020)

Post-traumatic osteoarthritis (PTOA) is an acute injury-induced joint inflammation followed by a gradual degradation of articular cartilage. However, there is no FDA-approved Disease-Modifying Osteoarthritis Drug currently. Although gene therapy with microRNA can improve PTOA progression, there is no effective gene delivery vehicle for orally deliver therapeutics due to the harsh environment of the gastrointestinal tract. In this study, we investigated the effect of yeast cell wall particle (YCWP) mediated nanotube-RNA delivery system on PTOA therapy via oral route. Methods: Nontoxic and degradable AAT and miRNA365 antagomir was self-assembled into miR365 antagomir/AAT (NPs). Then NPs-YCWP oral drug delivery system was constructed by using NPs and non-pathogenic YCWP which can be specifically recognized by macrophages. Moreover, surgical destabilization of the medial meniscus induced PTOA mice model was established to evaluate the therapeutic effect of NPs-YCWP via oral route. Results: Compared with control group, NPs showed higher gene inhibition efficiency both in chondrogenic cell line and primary chondrocytes in vitro. Treatment of macrophages with fluorescently labeled NPs-YCWP, the results showed that NPs-YCWP was successfully engulfed by macrophages and participated in the regulation of gene expression in vitro. Under the protection of YCWP, miR365 antagomir/AAT passes through the gastrointestinal tract without degradation after oral administration. After NPs-YCWP therapy, the results of histological staining, gene and protein expression showed that miR365 antagomir/NPs-YCWP improved the symptom of PTOA. Conclusion: Here, we constructed a biodegradable drug delivery system based on non-pathogenic YCWP and nanotubes, which can be used for PTOA therapy via the oral route. It suggests a new gene therapy strategy with YCWP mediated oral nano drug delivery system may serve as a platform for joint degeneration treatment.
Abstract 10770: A New Phenotype of Superior-type Fast-slow Atrioventricular Nodal Reentrant Tachycardia Mimicking the Slow-fast Type
Authors: Yoshiaki Kaneko, Tadashi Nakajima, Shuntaro Tamura, Hiroshi Hasegawa, Masahiko Kurabayashi
Journal: Circulation (2019)

Introduction: Superior-type fast-slow atrioventricular nodal reentrant tachycardia (sup-F/S-AVNRT) is a rare form of AVNRT that incorporates a fast pathway (FP) as the antegrade limb and a superior...
Acute Myeloid Leukemia (AML) Patients Demonstrate Increased Prevalence of AML-Defining Mutations in Peripheral Blood Years Prior to the Development of Overt Leukemia: A Case-Control Study
Authors: Pinkal Desai, Nuria Mencia-Trinchant, Savenkov Oleksandr, Michael S. Simon, Sangmin Lee, Ellen K Ritchie, Monica L. Guzman, Karla Ballman, Gail J. Roboz, Duane C. Hassane
Journal: Blood (2017)
The C/D box small nucleolar RNA SNORD52 regulated by Upf1 facilitates Hepatocarcinogenesis by stabilizing CDK1
Authors: Cuicui Li, Long Wu, Pengpeng Liu, Kun Li, Zhonglin Zhang, Yueming He, Quanyan Liu, Ping Jiang, Zhiyong Yang, Zhisu Liu, Yufeng Yuan, Lei Chang
Journal: Theranostics (2020)

Rationale: Understanding the roles of small nucleolar RNAs (snoRNAs) in hepatocarcinogenesis will provide new avenues to identify diagnostic and therapeutic targets for hepatocellular carcinoma (HCC). Our previous research confirmed the tumor-suppressive effect of Up-frameshift 1 (Upf1) in HCC. Herein, we examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells. Methods: We examined the expression profiles of snoRNAs regulated by Upf1 in hepatoma cells using RNA-sequencing analysis and then investigated the expression and significance of SNORD52 in HCC tissue and different cell lines. The protumorigenic effects of SNORD52 on HCC cells were confirmed both in vitro and in vivo by gain-of-function and loss-of-function assays. RNA pull-down assays and mass spectrometry were used to identify the RNA-binding protein that binds to SNORD52. Results: Many snoRNAs were identified; one of which, the human C/D box small nucleolar RNA SNORD52, was upregulated in HCC tissues and negatively correlated with Upf1 expression, and patients with higher SNORD52 expression had a poor clinical prognosis. SNORD52 promoted HCC tumorigenesis both in vitro and in vivo. Mechanistically, KEGG analysis showed that SNORD52 upregulated a series of cell cycle genes in HCC cells. We further confirmed that SNORD52 upregulated CDK1 by enhancing the stability of CDK1 proteins and that the function of SNORD52 depends on the presence of CDK1. Conclusion: Overall, the present study indicates that SNORD52 could be a potential biomarker for HCC. Targeting the Upf1/SNORD52/CDK1 pathway might have therapeutic potential for HCC.
Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus — CDC Guidance, United States, 2020
Authors: Anne C. Moorman, Marie A. de Perio, Ronald Goldschmidt, Carolyn Chu, David Kuhar, David K. Henderson, Susanna Naggie, Saleem Kamili, Philip R. Spradling, Stuart C. Gordon, Mark B. Russi, Eyasu H. Teshale
Journal: MMWR Recommendations and Reports (2020)

Exposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be performed as soon as possible (preferably within 48 hours) after the exposure. A source patient refers to any person receiving health care services whose blood or other potentially infectious material is the source of the HCP's exposure. Two options are recommended for testing the source patient. The first option is to test the source patient with a nucleic acid test (NAT) for HCV RNA. This option is preferred, particularly if the source patient is known or suspected to have recent behaviors that increase risk for HCV acquisition (e.g., injection drug use within the previous 4 months) or if risk cannot be reliably assessed. The second option is to test the source patient for antibodies to hepatitis C virus (anti-HCV), then if positive, test for HCV RNA. For HCP, baseline testing for anti-HCV with reflex to a NAT for HCV RNA if positive should be conducted as soon as possible (preferably within 48 hours) after the exposure and may be simultaneous with source-patient testing. If follow-up testing is recommended based on the source patient's status (e.g., HCV RNA positive or anti-HCV positive with unavailable HCV RNA or if the HCV infection status is unknown), HCP should be tested with a NAT for HCV RNA at 3-6 weeks postexposure. If HCV RNA is negative at 3-6 weeks postexposure, a final test for anti-HCV at 4-6 months postexposure is recommended. A source patient or HCP found to be positive for HCV RNA should be referred to care. Postexposure prophylaxis of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids. This guidance was developed based on expert opinion (CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommend Rep 2001;50[No. RR-11]; Supplementary Figure, https://stacks.cdc.gov/view/cdc/90288) and reflects updated guidance from professional organizations that recommend treatment for acute HCV infection. Health care providers can use this guidance to update their procedures for postexposure testing and clinical management of HCP potentially exposed to hepatitis C virus.
Atopic Diseases Are Associated With Development of Inflammatory Bowel Diseases in Korea: A Nationwide Population-based Study
Authors: Hosim Soh, Hyun Jung Lee, Kyungdo Han, Seona Park, Seung Wook Hong, Jung Min Moon, Eun Ae Kang, Jooyoung Lee, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Journal: Clinical Gastroenterology and Hepatology (2020)
Impact of self-imposed prevention measures and short-term government-imposed social distancing on mitigating and delaying a COVID-19 epidemic: A modelling study
Authors: Alexandra Teslya, Thi Mui Pham, Noortje G. Godijk, Mirjam E. Kretzschmar, Martin C. J. Bootsma, Ganna Rozhnova
Journal: PLoS Medicine (2020)

The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every country in the world since it first emerged in China in December 2019. Many countries have implemented social distancing as a measure to "flatten the curve" of the ongoing epidemics. Evaluation of the impact of government-imposed social distancing and of other measures to control further spread of COVID-19 is urgent, especially because of the large societal and economic impact of the former. The aim of this study was to compare the individual and combined effectiveness of self-imposed prevention measures and of short-term government-imposed social distancing in mitigating, delaying, or preventing a COVID-19 epidemic.
Acute Colonic Diverticulitis (Japanese Version)
Authors: Sophia M. Swanson, Lisa L. Strate
Journal: Annals of Internal Medicine (2018)

In the Clinic1 May 2018Acute Colonic Diverticulitis (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREESophia M. Swanson, MD and Lisa L. Strate, MD, MPHSophia M. Swanson, MDFrom the University of Washington School of Medicine, Seattle, Washington. (S.M.S., L.L.S.)Search for more papers by this author and Lisa L. Strate, MD, MPHFrom the University of Washington School of Medicine, Seattle, Washington. (S.M.S., L.L.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201805010_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Acute Colonic Diverticulitis (Swanson SM, Strate LL. Acute Colonic Diverticulitis. Ann Intern Med. 2018;168:ITC65-ITC80. doi:10.7326/AITC201805010). Author, Article, and Disclosure InformationAffiliations: From the University of Washington School of Medicine, Seattle, Washington. (S.M.S., L.L.S.)Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Funding Source: American College of Physicians.Disclosures: Dr. Swanson, ACP Contributing Author, has disclosed no conflicts of interest. Dr. Strate, ACP Contributing Author, reports grants from the National Institutes of Health during the conduct of the study. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0023.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAcute Colonic Diverticulitis Sophia M. Swanson and Lisa L. Strate Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the Clinic 1 May 2018Volume 168, Issue 9Page: JITC65-JITC80 ePublished: 21 July 2020 Issue Published: 1 May 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Trem2 deficiency differentially affects phenotype and transcriptome of human APOE3 and APOE4 mice
Authors: Nicholas F. Fitz, Cody M. Wolfe, Brittany E. Playso, Richard J. Biedrzycki, Yi Lu, Kyong Nyon Nam, Iliya Lefterov, Radosveta Koldamova
Journal: Molecular Neurodegeneration (2020)

Abstract Background Alzheimer’s Disease (AD) is a neurodegenerative disorder influenced by aging and genetic risk factors. The inheritance of APOE ε4 and variants of Triggering Receptor Expressed on Myeloid cells 2 ( TREM2 ) are major genetic risk factors for AD. Recent studies showed that APOE binds to TREM2, thus raising the possibility of an APOE-TREM2 interaction that can modulate AD pathology. Methods The aim of this study was to investigate this interaction using complex AD model mice - a crossbreed of Trem2 ko and APP/PSEN1dE9 mice expressing human APOE3 or APOE4 isoforms (APP/E3 and APP/E4 respectively), and their WT littermates (E3 and E4), and evaluate cognition, steady-state amyloid load, plaque compaction, plaque growth rate, glial response, and brain transcriptome. Results In both, APP/E3 and APP/E4 mice, Trem2 deletion reduced plaque compaction but did not significantly affect steady-state plaque load. Importantly, the lack of TREM2 increased plaque growth that negatively correlated to the diminished microglia barrier, an effect most pronounced at earlier stages of amyloid deposition. We also found that Trem2 deficiency significantly decreased plaque-associated APOE protein in APP/E4 but not in APP/E3 mice in agreement with RNA-seq data. Interestingly, we observed a significant decrease of Apoe mRNA expression in plaque-associated microglia of APP/E4/Trem2 ko vs APP/E4 mice. The absence of TREM2, worsened cognitive performance in APP transgenic mice but not their WT littermates. Gene expression analysis identified Trem2 signature - a cluster of highly connected immune response genes, commonly downregulated as a result of Trem2 deletion in all genotypes including APP and WT littermates. Furthermore, we identified sets of genes that were affected in TREM2- and APOE isoform-dependent manner. Among them were Clec7a and Csf1r upregulated in APP/E4 vs APP/E3 mice, a result further validated by in situ hybridization analysis. In contrast, Tyrobp and several genes involved in the C1Q complement cascade had a higher expression level in APP/E3 versus their APP/E4 counterparts. Conclusions Our data demonstrate that lack of Trem2 differentially impacts the phenotype and brain transcriptome of APP mice expressing human APOE isoforms. The changes probably reflect the different effect of APOE isoforms on amyloid deposition.
Avelumab in Patients With Gestational Trophoblastic Tumors With Resistance to Single-Agent Chemotherapy: Cohort A of the TROPHIMMUN Phase II Trial
Authors: Benoit You, Pierre-Adrien Bolze, Jean-Pierre Lotz, Jérome Massardier, Laurence Gladieff, Florence Joly, Touria Hajri, Delphine Maucort-Boulch, Sylvie Bin, Pascal Rousset, Mojgan Devouassoux-Shisheboran, Adeline Roux, Marine Alves-Ferreira, Daniele Grazziotin-Soares, Carole Langlois-Jacques, Catherine Mercier, Laurent Villeneuve, Gilles Freyer, Francois Golfier
Journal: Journal of Clinical Oncology (2020)

Women with gestational trophoblastic tumors (GTT) resistant to single-agent chemotherapy receive alternative chemotherapy regimens, which, although effective, cause considerable toxicity. All GTT subtypes express programmed death-ligand 1 (PD-L1), and natural killer (NK) cells are involved in trophoblast immunosurveillance. Avelumab (anti-PD-L1) induces NK cell-mediated cytotoxicity. The TROPHIMMUN trial assessed avelumab in women with chemotherapy-resistant GTT.In this phase II multicenter trial (ClinicalTrials.gov identifier: NCT03135769), women with GTT who experienced disease progression after single-agent chemotherapy received avelumab 10 mg/kg intravenously every 2 weeks until human chorionic gonadotropin (hCG) normalization, followed by 3 consolidation cycles. Rate of hCG normalization was the primary endpoint (2-step Simon design).Between December 2016 and September 2018, 15 patients were treated. Median age was 34 years; disease stage was I or III in 53.3% and 46.7% of women, respectively; and International Federation of Gynecology and Obstetrics (FIGO) score was 0-4 in 33.3%, 5-6 in 46.7%, and ≥ 7 in 20% of patients. Prior treatment included methotrexate (100%) and actinomycin D (7%). Median follow-up was 25 months, and median number of avelumab cycles was 8 (range, 2-11). Grade 1-2 treatment-related adverse events occurred in 93% of patients, most commonly (≥ 25%) fatigue (33.3%), nausea/vomiting (33.3%), and infusion-related reaction (26.7%). One patient had grade 3 uterine bleeding (treatment unrelated). Eight patients (53.3%) had hCG normalization after a median of 9 avelumab cycles; none subsequently relapsed. Probability of normalization was not associated with disease stage, FIGO score, or baseline hCG. One patient subsequently had a healthy pregnancy. In avelumab-resistant patients (46.7%), hCG was normalized with actinomycin D (42.3%) or combination chemotherapy/surgery (57.1%).In patients with single-agent chemotherapy-resistant GTT, avelumab had a favorable safety profile and cured approximately 50% of patients. Avelumab could be a new therapeutic option, particularly in patients who would otherwise receive combination chemotherapy.
UK government’s work to tackle health disparities of covid-19
Authors: Kemi Badenoch
Journal: BMJ (2020)

I am writing to provide further detail on the government’s work to tackle the health disparities caused by covid-19, after the recent Public Health England (PHE) review and subsequent stakeholder report.123

I’m glad that a respected specialist publication such as The BMJ is taking the time to cover this important story. I strongly agree with the key point in your editorial that the PHE review doesn’t go far enough, particularly as “no original or secondary data are presented” and “the proposals lack detail.” This is why the prime minister and the health secretary have asked me to take forward further work to ensure everything possible is being done to protect our minority …