tbuckley/cabot-search huggingface dataset:
New Drugs for NASH and HIV Infection: Great Expectations for a Great Need
Authors: Giovanni Guaraldi, James B. Maurice, Catia Marzolini, Kenneth Monteith, Jovana Milic, Emmanuel Tsochatzis, Sanjay Bhagani, Caryn G. Morse, Jennifer C. Price, Patrick Ingiliz, Maud Lemoine, Giada Sebastiani
Journal: Hepatology (2020)

In recent years, there has been an increasing number of clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). People living with human immunodeficiency virus (PLWH) are commonly excluded from these studies, usually due to concerns over drug-drug interactions associated with antiretroviral therapy. The Steatohepatitis in HIV Emerging Research Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of drug-drug interactions between antiretroviral therapy and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL-3196), which are currently in phase 3 trials for the treatment of NASH, are reviewed. A model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subpopulation within studies.
Annals Graphic Medicine - Progress Notes: Coding Humanity
Authors: Michael Natter
Journal: Annals of Internal Medicine (2020)

Web Exclusives18 February 2020Annals Graphic Medicine - Progress Notes: Coding HumanityFREEMichael Natter, MDMichael Natter, MDNYU School of Medicine, New York, New York (M.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G19-0089 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: NYU School of Medicine, New York, New York (M.N.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G19-0002.Author/Illustrator Information: Michael Natter, MD, is a current internal medicine resident at NYU School of Medicine and a graduate of Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia. His artwork is inspired by his medical training, patient encounters, and the human condition. A type 1 diabetic, Dr. Natter views himself as a patient as well as a doctor and plans to pursue a fellowship in endocrinology to help others who also share his disease. You can find more of his illustrations, stories, and comics on Instagram (www.instagram.com/mike.natter) and Twitter (@mike_natter).About Progress Notes: Progress Notes explores the everyday emotional, clinical, humorous, and ethical challenges of the medical residency training process. As implied by the title of the series, these pieces act as a visual bildungsroman, graphically dissecting the subtext of what it means to be a young doctor in today's medical world. Progress Notes appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 February 2020Volume 172, Issue 4Page: W61-W62KeywordsConflicts of interestDisclosureEmotionsEndocrinologyFellowshipsGraduate medical educationResidency ePublished: 18 February 2020 Issue Published: 18 February 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract CS1-1: Origins and Clinical Implications of HER2 Heterogeneity
Authors: A Richardson
Journal: Cancer Research (2020)

Abstract The presentation will describe the types of HER2 heterogeneity and how it is identified pathologically including case examples and molecular studies. The implications for treatment decisions and for its possible role in patient outcomes will also be discussed. Citation Format: A Richardson. Origins and Clinical Implications of HER2 Heterogeneity [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr CS1-1.
Abstract P5-11-20: Efficacy observation of 306 patients with fulvestrant 500mg treatment in hormone-receptor positive HER2 negative metastasis breast cancer, a real world study
Authors: Wen Lei, Huiping Li, Guohong Song, Ruyan Zhang, Ran Ran, Ying Yan
Journal: Cancer Research (2020)

Abstract Background: Fulvestrant 500mg has been proved better efficacy in breast cancer with hormone receptor positive (HR+),and then become an optional strategy for primary or second line treatment of HR+ positive metastasis breast cancer (MBC). Methods: In this real world study, we retrospectively analyzed the patients with HR+ HER 2 negative MBC who received fulvestrant 500mg treatment at Beijing cancer hospital during January 2015 to December 2018. Clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS) and adverse events were investigated. Results: There were 306 patients enrolled, median age was 48.7(range 20-75) years, median line of fulvestrant was 2.11(range 1-6), 68.3%(209/306) patients were involved with visceral metastasis. The CBR was 68.6%, median PFS was 8.41m (95%CI: 7.079m-9.743m, range 0.89m-80.16m). Among the patients received fulvestrant at the first line, the PFS was 10.55m(95%CI:6.46m-14.64m, range 0.92m-34.3m). The median OS hasn’t been obtained. In subgroup analysis, the patients without liver metastasis(12.49m vs. 4.60m, p&amp;lt;0.001), small tumor burden(metastasis number 1-2 vs. 3-4 vs. &amp;gt;4, 12.65m vs. 7.72m vs. 3.98m respectively, p&amp;lt;0.001) and experience no or less line of chemotherapy(none vs. 1-2 lines vs. &amp;gt;2 lines, 14.06m vs. 7.79m vs. 3.52m respectively, p&amp;lt;0.001) for metastatic disease were obtained more benefit from fulvestrant treatment. For patients with visceral metastasis, the patients absence of liver metastasis was corelated with longer PFS 9.27m than 4.60m(p&amp;lt;0.001). There were 20(6.54%) adverse events occurred in 306 patients, 95%(19/20) were grade 1-2. The most common adverse event was oral ulcer, and serious adverse events were observed in 1 patients (0.33%) with pulmonary embolism. Conclusions: Fulvestrant was an effective and safe regimen in endocrine therapy for hormone receptor positive HER2 negative MBC. The patients who were in first line treatment, absence of liver metastasis and small tumor burden might be more benefit from fulvestrant. Corresponding authors: Huiping Li, huipingli2012@hotmail.com; Guohong Song, songguohong918@hotmail.com, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital &amp; Institute, 52 Fucheng Rd, Beijing 100142, China Citation Format: Wen Lei, Huiping Li, Guohong Song, Ruyan Zhang, Ran Ran, Ying Yan. Efficacy observation of 306 patients with fulvestrant 500mg treatment in hormone-receptor positive HER2 negative metastasis breast cancer, a real world study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-20.
Airway Hyperresponsiveness, Inflammation, and Pulmonary Emphysema in Rodent Models Designed to Mimic Exposure to Fuel Oil–Derived Volatile Organic Compounds Encountered during an Experimental Oil Spill
Authors: Óscar Amor-Carro, Kathryn M. White, Rebeca Fraga-Iriso, Luis A. Mariñas-Pardo, Laura Núñez-Naveira, Beatriz Lema-Costa, Marta Villarnovo, Héctor Verea-Hernando, David Ramos-Barbón
Journal: Environmental Health Perspectives (2020)

Background: Fuel oil–derived volatile organic compounds (VOCs) inhalation is associated with accidental marine spills. After the Prestige petroleum tanker sank off northern Spain in 2002 and the Deepwater Horizon oil rig catastrophe in 2009, subjects involved in environmental decontamination showed signs of ongoing or residual lung disease up to 5 y after the exposure. Objectives: We aimed at investigating mechanisms driving persistent respiratory disease by developing an animal model of inhalational exposure to fuel oil–derived VOCs. Methods: Female Wistar and Brown Norway (BN) rats and C57BL mice were exposed to VOCs produced from fuel oil mimicking the Prestige spill. Exposed animals inhaled the VOCs 2 h daily, 5 d per week, for 3 wk. Airway responsiveness to methacholine (MCh) was assessed, and bronchoalveolar lavage (BAL) and lung tissues were analyzed after the exposure and following a 2-wk washout. Results: Consistent with data from human studies, both strains of rats that inhaled fuel oil–derived VOCs developed airway hyperresponsiveness that persisted after the washout period, in the absence of detectable inflammation in any lung compartment. Histopathology and quantitative morphology revealed the development of peripherally distributed pulmonary emphysema, which persisted after the washout period, associated with increased alveolar septal cell apoptosis, microvascular endothelial damage of the lung parenchyma, and inhibited expression of vascular endothelial growth factor (VEGF). Discussion: In this rat model, fuel oil VOCs inhalation elicited alveolar septal cell apoptosis, likely due to DNA damage. In turn, the development of a peculiar pulmonary emphysema pattern altered lung mechanics and caused persistent noninflammatory airway hyperresponsiveness. Such findings suggest to us that humans might also respond to VOCs through physiopathological pathways different from those chiefly involved in typical cigarette smoke–driven emphysema in chronic obstructive pulmonary disease (COPD). If so, this study could form the basis for a novel disease mechanism for lasting respiratory disease following inhalational exposure to catastrophic fuel oil spills. https://doi.org/10.1289/EHP4178
Practices “waste hours” writing labels under new HPV screening system
Authors: Elisabeth Mahase
Journal: BMJ (2020)

General practice staff have been forced to waste hours of clinical time by handwriting labels for HPV cervical screening tests because a new IT system was implemented without the ability to print sticky labels.

The new system was rolled out to coincide with the new HPV primary screening programme and a new pathology and diagnostic service for London’s 1200 general practices.

Since the changes came into effect on 2 December 2019 the service has processed over 100 000 cervical screening tests, potentially equating to thousands of unnecessary hours spent writing out labels that were previously automatically printed.

GPs told The BMJ that the problem stemmed from a lack of consultation on the changes to the cervical screening service and that it could have been avoided with …
Longitudinal Human Antibody Repertoire against Complete Viral Proteome from Ebola Virus Survivor Reveals Protective Sites for Vaccine Design
Authors: Surender Khurana, Supriya Ravichandran, Megan Hahn, Elizabeth M. Coyle, Spencer W. Stonier, Samantha E. Zak, Jason Kindrachuk, Richard T. Davey, John M. Dye, Daniel S. Chertow
Journal: Cell Host & Microbe (2020)
Identification of novel biomarkers for breast cancer, including brca1-associated breast cancer
Authors: M. A. Brown, J. D. French, S. L. Edwards, K. M. Peters, A. Wronski, C. E. Smart, B. L. Brewster, J. E. Wee, N. Waddell, G. D. Francis
Journal: Annals of Oncology (2010)
<i>Kdm6a</i> Deficiency Activates Inflammatory Pathways, Promotes M2 Macrophage Polarization, and Causes Bladder Cancer in Cooperation with <i>p53</i> Dysfunction
Authors: Kohei Kobatake, Ken-ichiro Ikeda, Yuichiro Nakata, Norimasa Yamasaki, Takeshi Ueda, Akinori Kanai, Kazuhiro Sentani, Yasuyuki Sera, Tetsutaro Hayashi, Miho Koizumi, Yoshihiko Miyakawa, Toshiya Inaba, Yusuke Sotomaru, Osamu Kaminuma, Tatsuo Ichinohe, Zen-ichiro Honda, Wataru Yasui, Shigeo Horie, Peter C. Black, Akio Matsubara, Hiroaki Honda
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Epigenetic deregulation is deeply implicated in the pathogenesis of bladder cancer. KDM6A (Lysine (K)-specific demethylase 6A) is a histone modifier frequently mutated in bladder cancer. However, the molecular mechanisms of how KDM6A deficiency contributes to bladder cancer development remains largely unknown. We hypothesized that clarification of the pathogenic mechanisms underlying KDM6A-mutated bladder cancer can help in designing new anticancer therapies. Experimental Design: We generated mice lacking Kdm6a in the urothelium and crossed them with mice heterozygous for p53, whose mutation/deletion significantly overlaps with the KDM6A mutation in muscle-invasive bladder cancer (MIBC). In addition, BBN (N-butyl-N-(4-hydroxybutyl) nitrosamine), a cigarette smoke-like mutagen, was used as a tumor-promoting agent. Isolated urothelia were subjected to phenotypic, pathologic, molecular, and cellular analyses. The clinical relevance of our findings was further analyzed using genomic and clinical data of patients with MIBC. Results: We found that Kdm6a deficiency activated cytokine and chemokine pathways, promoted M2 macrophage polarization, increased cancer stem cells and caused bladder cancer in cooperation with p53 haploinsufficiency. We also found that BBN treatment significantly enhanced the expression of proinflammatory molecules and accelerated disease development. Human bladder cancer samples with decreased KDM6A expression also showed activated proinflammatory pathways. Notably, dual inhibition of IL6 and chemokine (C-C motif) ligand 2, upregulated in response to Kdm6a deficiency, efficiently suppressed Kdm6a-deficient bladder cancer cell growth. Conclusions: Our findings provide insights into multistep carcinogenic processes of bladder cancer and suggest molecular targeted therapeutic approaches for patients with bladder cancer with KDM6A dysfunction.
Cardiac Metastases in Neuroendocrine Tumors
Authors: Stuart Lane Polk, Jaime Montilla-Soler, Kenneth L. Gage, Arthur Parsee, Daniel Jeong
Journal: Clinical Nuclear Medicine (2020)

Neuroendocrine tumor (NET) cardiac metastases can be associated with complications including ventricular outflow obstruction, arrhythmias, heart failure, and cardiac arrest, warranting intervention. Anatomical characterization of these lesions via cardiac magnetic resonance (CMR) is helpful to assess and predict the risk of complications and guide therapy. Images of 2 patients with small bowel NET related cardiac metastases are described on Ga-DOTATATE PET/CT and CMR. The lesions were significantly smaller and more obscure on CMR compared with PET/CT. On CMR, T2-weighted dark blood images and late gadolinium enhancement images offered the most conspicuous detection of the NET myocardial metastases in these cases.
Abstract P6-08-36: Uptake of preventive surgeries in a prospective cohort of BRCA1/2 healthy women
Authors: Priscila Nejo, Catarina Bexiga, S. Fragoso, A Mayer, S Santos, P Louro, A Luis, C Moura, Ana Clara, Fatima Vaz
Journal: Cancer Research (2020)

Abstract PURPOSE Previous studies referred to uptake of preventive surgeries (PS) in BRCA1/2 healthy carriers in ages older than recommended (35yrs). Since our population has a higher prevalence of BRCA2 mutations (usually associated with an older age at Breast Cancer diagnosis) we proposed to study ages and type of preventive surgeries uptaken by BRCA1/2 women included in prospective follow up. PATIENTS AND METHODS Review of all healthy (without a previous cancer diagnosis) BRCA1/2 carriers included in our program from January 2000 to June 2019. Follow-up started after genetic testing. Men were excluded from this analysis. RESULTS A total of 5504 cases (4021 index, 1483 relatives) consented for BRCA1/2 testing. We identified 238 healthy BRCA1/2 carriers (BRCA2:158 (66.4%) vs BRCA1 80 (33.6%). Median age at genetic diagnosis was 38.9 yrs (16-78). With a median follow up of 4yrs, bilateral adnexectomy (BA) was the most frequent PS observed (45 BRCA2 and 28 BRCA1 cases) with 15/45 % and 6/28% undergoing BA and bilateral mastectomy (BM) simultaneously. Bilateral mastectomy was uptaken by 14% BRCA2 women and 10% BRCA1 women. Median ages for PS were: BRCA2-AB: 47,4 (28-71), BRCA1-AB: 46.7 (37-59); BRCA2-BM: 36.6 (31-52) and BRCA1-BM:42.5 (30-55). Isolated BM was observed in 7 BRCA2 cases and 2 BRCA1 cases. Most of women submitted to BA, also underwent total hysterectomy (HT): 65% for BRCA2 and 61% BRCA1. Most cases (88% non-adherent) adhere to radiological surveillance, 111/238 with annual breast S MRI and mammography. All pts submitted to BM are prescribed at least one breast MRI to check for remaining breast tissue. CONCLUSION Our data reveal that even if, in general, BRCA1/2 women uptake preventive surgeries at a later age that recommended, we observed a strong adherence to radiological (most with breast MRI) surveillance. BA is the PS most frequently observed but, surprisingly for healthy women, most cases also underwent TH. BRCA2 healthy women uptaken bilateral mastectomy at an earlier age than BRCA1 women. It´s possible that BRCA1 women, when deciding for BM also decided for BA. Citation Format: Priscila Nejo, Catarina Bexiga, S. Fragoso, A Mayer, S Santos, P Louro, A Luis, C Moura, Ana Clara, Fatima Vaz. Uptake of preventive surgeries in a prospective cohort of BRCA1/2 healthy women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-36.
Role of gastrointestinal endoscopy in the screening of digestive tract cancers in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement
Authors: Adrian Săftoiu, Cesare Hassan, Miguel Areia, Manoop S. Bhutani, Raf Bisschops, Erwan Bories, Irina M. Cazacu, Evelien Dekker, Pierre H. Deprez, Stephen P. Pereira, Carlo Senore, Riccardo Capocaccia, Giulio Antonelli, Jeanin van Hooft, Helmut Messmann, Peter D. Siersema, Mario Dinis-Ribeiro, Thierry Ponchon
Journal: Endoscopy (2020)

Summary of statements In Europe at present, but also in 2040, 1 in 3 cancer-related deaths are expected to be caused by digestive cancers. Endoscopic technologies enable diagnosis, with relatively low invasiveness, of precancerous conditions and early cancers, thereby improving patient survival. Overall, endoscopy capacity must be adjusted to facilitate both effective screening programs and rigorous control of the quality assurance and surveillance systems required. 1 For average-risk populations, ESGE recommends the implementation of organized population-based screening programs for colorectal cancer, based on fecal immunochemical testing (FIT), targeting individuals, irrespective of gender, aged between 50 and 75 years. Depending on local factors, namely the adherence of the target population and availability of endoscopy services, primary screening by colonoscopy or sigmoidoscopy may also be recommendable. 2 In high-risk populations, endoscopic screening for gastric cancer should be considered for individuals aged more than 40 years. Its use in countries/regions with intermediate risk may be considered on the basis of local settings and availability of endoscopic resources. 3 For esophageal and pancreatic cancer, endoscopic screening may be considered only in high-risk individuals: – For squamous cell carcinoma, in those with a personal history of head/neck cancer, achalasia, or previous caustic injury; – For Barrett’s esophagus (BE)-associated adenocarcinoma, in those with long-standing gastroesophageal reflux disease symptoms (i. e., &gt; 5 years) and multiple risk factors (age ≥ 50 years, white race, male sex, obesity, first-degree relative with BE or esophageal adenocarcinoma [EAC]). – For pancreatic cancer screening, endoscopic ultrasound may be used in selected high-risk patients such as those with a strong family history and/or genetic susceptibility.
Dissimilarity of the gut–lung axis and dysbiosis of the lower airways in ventilated preterm infants
Authors: David Gallacher, Emma Mitchell, Dagmar Alber, Richard Wach, Nigel Klein, Julian R. Marchesi, Sailesh Kotecha
Journal: European Respiratory Journal (2020)

Background Chronic lung disease of prematurity (CLD), also called bronchopulmonary dysplasia, is a major consequence of preterm birth, but the role of the microbiome in its development remains unclear. Therefore, we assessed the progression of the bacterial community in ventilated preterm infants over time in the upper and lower airways, and assessed the gut–lung axis by comparing bacterial communities in the upper and lower airways with stool findings. Finally, we assessed whether the bacterial communities were associated with lung inflammation to suggest dysbiosis. Methods We serially sampled multiple anatomical sites including the upper airway (nasopharyngeal aspirates), lower airways (tracheal aspirate fluid and bronchoalveolar lavage fluid) and the gut (stool) of ventilated preterm-born infants. Bacterial DNA load was measured in all samples and sequenced using the V3–V4 region of the 16S rRNA gene. Results From 1102 (539 nasopharyngeal aspirates, 276 tracheal aspirate fluid, 89 bronchoalveolar lavage, 198 stool) samples from 55 preterm infants, 352 (32%) amplified suitably for 16S RNA gene sequencing. Bacterial load was low at birth and quickly increased with time, but was associated with predominant operational taxonomic units (OTUs) in all sample types. There was dissimilarity in bacterial communities between the upper and lower airways and the gut, with a separate dysbiotic inflammatory process occurring in the lower airways of infants. Individual OTUs were associated with increased inflammatory markers. Conclusions Taken together, these findings suggest that targeted treatment of the predominant organisms, including those not routinely treated, such as Ureaplasma spp., may decrease the development of CLD in preterm-born infants.