tbuckley/cabot-search huggingface dataset:
Tuberculosis Screening, Testing, and Treatment of U.S. Health Care Personnel: Recommendations from the National Tuberculosis Controllers Association and CDC, 2019
Authors: Lynn E. Sosa, Gibril J. Njie, Mark N. Lobato, Sapna Bamrah Morris, William Buchta, Megan L. Casey, Neela D. Goswami, MaryAnn Gruden, Bobbi Jo Hurst, Amera R. Khan, David T. Kuhar, David M. Lewinsohn, Trini A. Mathew, Gerald H. Mazurek, Randall Reves, Lisa Paulos, Wendy Thanassi, Lorna Will, Robert Belknap
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

The 2005 CDC guidelines for preventing Mycobacterium tuberculosis transmission in health care settings include recommendations for baseline tuberculosis (TB) screening of all U.S. health care personnel and annual testing for health care personnel working in medium-risk settings or settings with potential for ongoing transmission (1). Using evidence from a systematic review conducted by a National Tuberculosis Controllers Association (NTCA)-CDC work group, and following methods adapted from the Guide to Community Preventive Services (2,3), the 2005 CDC recommendations for testing U.S. health care personnel have been updated and now include 1) TB screening with an individual risk assessment and symptom evaluation at baseline (preplacement); 2) TB testing with an interferon-gamma release assay (IGRA) or a tuberculin skin test (TST) for persons without documented prior TB disease or latent TB infection (LTBI); 3) no routine serial TB testing at any interval after baseline in the absence of a known exposure or ongoing transmission; 4) encouragement of treatment for all health care personnel with untreated LTBI, unless treatment is contraindicated; 5) annual symptom screening for health care personnel with untreated LTBI; and 6) annual TB education of all health care personnel.
Existe-il des facteurs prédictifs de la présence d'un adénome avancé?
Authors: A Nakhli, R Ennaifer, N Hemdani, B Bouchabou, H Ben Romdhane, H Ben Nejma
Journal: Endoscopy (2019)

Un adénome avancé se définit comme un adénome dont la taille est ≥10 mm ou avec une dysplasie de haut grade ou un contingent villeux > 25%. Il est à haut risque d'évolution vers un cancer colorectal (CCR) et de ce fait constitue la principale cible du dépistage du CCR. L'objectif de notre étude était de rechercher les facteurs prédictifs de présence d'un adénome avancé afin d'optimiser la stratégie de dépistage.
Abstract 15140: VEGFR2 Blockade in Murine Vein Grafts Reduces Intraplaque Hemorrhage due to Enhanced Plaque Neovessel Maturation
Authors: Margreet R de Vries, Erna A Peters, Jaap F Hamming, MarieJosé T Goumans, Paul H Quax
Journal: Circulation (2015)

Introduction: Vein graft patency rates are poor due to the development of extensive neointimal thickening, atherosclerosis and lesion instability. We have previously shown that murine vein graft lesions exhibit leaky neovessels and that intraplaque hemorrhage induces lesion growth. Immature plaque neovessels contribute to atherosclerotic plaque instability by leakage of erythrocytes and leukocytes (intraplaque haemorrhage) in the plaque. Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), together with the angiopoietin (Ang)-Tie2 system, regulates the maturation of neovessels. Hypothesis: VEGFR2 blockade induces plaque neovessel maturation resulting in reduced intraplaque hemorrhage and plaque instability. Methods: Donor caval veins were engrafted in carotid arteries of recipient hypercholesterolemic ApoE3*Leiden mice (n=14/group). Mice were treated at day 14, 17, 21 and 25 with VEGFR2 blocking antibodies (DC101) or control IgG antibodies. At day 28 vein grafts were harvested for histological and RNA analysis. Results: Morphometric analysis revealed a striking 50% decrease in vein graft segments that expressed intraplaque hemorrhage in the DC101 treated group. This was accompanied by a significant 25-fold decrease in extravasated erythrocytes. DC101 treatment resulted in a decrease in VEGF expression whereas VEGFR1 and VEGFR2 expression was comparable between the two groups. Connexin 37 and 43 expression was also comparable between the groups, indicating that gap junctions were not affected upon DC101 treatment. However, lesions that exhibit intraplaque hemorrhage showed a strong increase in destabilizing Ang-2. The vein graft lesion area was significantly reduced in the DC101 group, which was accompanied by an increased plaque stability phenotype as a result of a significant reduction in macrophage content and increases in smooth muscle cells and collagen content. Conclusions: Blockade of VEGFR2 leads to reduced intraplaque hemorrhage, decreased vein graft lesion area and increased plaque stability as a result of increased neovessel maturation. This identifies plaque neovascularization as an attractive target for the treatment of unstable atherosclerotic diseases.
NOT A SHOT IN THE DARK; THE IRISH EXPERIENCE OF EUS GUIDED GALLBLADDER DRAINAGE WITH THE HOT AXIOS STENT
Authors: P Maheshwari, C Moran, M Farman, S Kumar, G Harewood, S Sengupta, D Cheriyan
Journal: Endoscopy (2019)

The management of gallbladder disease is particularly challenging in patients who are elderly or poor surgical candidates. Current standard of care for acute cholecystitis in this cohort involves antibiotics and possible percutaneous drainage via interventional radiology. External drains are uncomfortable, may dislodge, and can result in delayed hospital discharge or re-admission. We report the first 10 cases in Ireland of EUS guided placement of a lumen apposing metal stent between the gallbladder and stomach or duodenum using the hot AXIOS system.
Secondary mechanisms of anti-HER2 resistance in breast cancer: NF1 as an actionable target
Authors: B.A. Duso, C. Poletti, G. Curigliano, P.G. Pelicci, L. Mazzarella
Journal: Annals of Oncology (2019)

Background: HER2-targeting agents are standard of care for the treatment of HER2+ breast cancer (BC), but resistance inevitably occurs and the underlying molecular mechanisms remain poorly characterized. The comparison between mutational profiles of primary (treatment-naïve) and metastatic (who will mostly have received multiple courses of HER2-targeting agents) tumors can inform the search for resistance-inducing genetic alterations to be modeled in vitro and in vivo. Methods: We analyzed the mutational spectrum of metastatic vs primary HER2+ BC by retrieving data from ERBB2-amplified cases in the MSKCC-IMPACT and the TCGA datasets, containing almost exclusively samples from metastatic sites and primary tumors, respectively. Multiple in vitro (HER2+ cell lines with stable RNA interference of candidate genes, 2D- and 3D-culturing) and in vivo models (NOD-SCID xenografts and the MMTV-neu transgenic mice) are used for validation. Results: Mutations in NF1, TSC2 and HER2 were significantly enriched in metastatic cases. All are plausible mediators of resistance, being associated with signalling pathways downstream of HER2 or the HER2 receptor itself. NF1 in particular is a tumor suppressor gene which encodes a RAS-GTPase that negatively regulates Ras/MEK/ERK and PI3K/AKT/mTOR pathways. NF1 alterations were the most significant (Odds Ratio 11.7, p = 0.00018, FDR=0.23) and the most prevalent in metastatic cases (∼10%). As NF1 mutations lead to protein loss of function, we modeled their effect in vitro by RNA interference and found that it induces an increase in mTOR activation. Stably-interfered HER2+ cell lines will be used to explore synergistic drug combinations in vitro and in vivo. Conclusions: We provide proof of concept that secondary resistance to anti-HER2 agents can be mapped to specific genetic alterations in a sizeable fraction of patients. Ongoing efforts are aimed at investigating if NF1 loss instructs HER2+ BC with a metastasis-promoting phenotype as well as metabolic and transcriptional changes. Legal entity responsible for the study: European Institute of Oncology. Funding: Fondazione IEO-CCM University of Milan. Disclosure: G. Curigliano: Advisor: Roche, Pfizer, Novartis, Lilly. All other authors have declared no conflicts of interest.
Germline PALB2 heterozygous mutations in breast cancers: Haploinsufficiency paradigm
Authors: Q. Ouyang, Z.-Y. Hu, L. Liu, J. Gao, H. Wu, J. Lu, N. Xie, C. Tian, Z. Liu, Y. Xu
Journal: Annals of Oncology (2019)

Background: PALB2 loss-of-function (Lof) mutation strongly suggests it as a tumor suppressor in familial breast cancer (BC). In Knudson's hypothesis, mutation in both alleles is required for a single functional tumor suppressor to sufficiently cause malignant phenotype. But, some reports suggest the inhibition of one copy of PALB2 can lead to malignant phenotype (haploinsufficiency). Methods: 143 familial BC patients were enrolled. All the cases were assessed by Familial Cancer specialists and determined to be eligible for clinical genetic testing. Tumors and blood specimens were obtained and subjected to the whole-exome or big-panel gene sequencing. Both germline and somatic mutations were analyzed. Somatic mutation of PALB2 in local and public cancer database were analyzed, too. Results: In both the public and our local database, the somatic PALB2 mutation rate is 0.8%∼1.6%, much less than the germline mutation rate of 4.03%∼4.8%, in sporadic BC samples. In recruited 143 familial BC patients, ten (6.99%) had mono-allelic PALB2 germline mutations. The hotspots were c.1057A[3>2] and c.3114-1G>A. Other mutations included c.389delA, c.2068C>T, c.2167_2168delAT, c.2629delT and c.2968G>T. All were high risk stop gain, frameshift or splicing mutations, leading to truncated protein. Out of the ten patients, only one had accompanied somatic PALB2 mutation, one had accompanied germline BRCA1 heterozygous mutation, and three patients had other accompanied somatic gene mutations (eg. TP53, PIK3CA, etc). For the rest four patients, the germline PALB2 mutation was the only DNA hit, conforming to the haploinsufficient hypothesis; their germline PALB2 mutations concentrated in EX5 to EX9 regions, which were the key functional regions to binding to MRG15 and RAD51. The mono-allelic mutation caused a low expression level and severely functional damages, explaining their dominant pathological clinical phenotypes. Conclusions: Many familial breast cancer patients with mono-allelic germline PALB2 mutations had the single DNA hit, suggesting a haploinsufficiency theory. The mutations concentrated in EX5-EX9, the MRG15 and RAD51-binding region, resulting in severe functional defects and breast cancer phenotype. Legal entity responsible for the study: Hunan Provincial Cancer Hospital and Geneplus Beijing Institute. Funding: Hunan Provincial Key Research Prokect (2018SK2124, Quchang Ouyang). Disclosure: All authors have declared no conflicts of interest.
Faisabilité du drainage biliaire sous écho-endoscopie des sténoses hilaires malignes non opérables
Authors: J Winkler, F Caillol, E Bories, JP Ratone, C Pesenti, A Debourdeau, C Decoster, M Pizzicannella, M Giovannini
Journal: Endoscopy (2019)

L'objectif du drainage biliaire des sténoses hilaires malignes est d'obtenir un pourcentage maximal de foie drainé puisque celui-ci est corrélé à la survie (1). Cependant le choix des techniques n'est pas standardisé et dans nombres de cas une approche multimodale est nécessaire. Le développement des techniques de drainage guidé par écho-endoscopie a permis d'offrir de nouvelles perspectives.
HYBRID-APC FOR THE ENDOSCOPIC ERADICATION OF DYSPLASTIC BARRETT'S ESOPHAGUS IN A LOW PREVALENCE COUNTRY: LONG-TERM RESULTS OF THE TREATMENT AFTER THE ONSITE TRAINING
Authors: S Kashin, N Vidyaeva, R Kuvaev, E Kraynova, H Manner
Journal: Endoscopy (2019)

This study was undertaken to evaluate the efficacy and safety of Hybrid-APC for the treatment of dysplastic BE in a low prevalence country after the onsite training.
Bipolar and psychotic disorders in elite athletes: a narrative review
Authors: Alan Currie, Paul Gorczynski, Simon M Rice, Rosemary Purcell, R Hamish McAllister-Williams, Mary E Hitchcock, Brian Hainline, Claudia L Reardon
Journal: British Journal of Sports Medicine (2019)

Bipolar and psychotic disorders are relatively common and likely to have a significant impact on quality of life and functioning which, in the context of elite sport, includes a potential negative impact on sporting performance. For this narrative review article, the literature on bipolar and psychotic disorders in elite athletes was comprehensively searched, and little empirical research was found. A diagnosis of bipolar or psychotic disorders may be challenging in elite athletes because of complicating factors related to the modifying role of exercise and potential precipitating impact of substance use. Medications used to treat bipolar and psychotic disorders may have side effects particularly problematic for elite athletes. Future research should be tailored to the specific characteristics and needs of elite athletes and to the sporting context in which the disorders may arise. Specifically, further research is needed on the prevalence and incidence of these conditions in elite athletes and the impact of both the disorders and their treatments on sporting performance.
Role of B7H3/IL-33 Signaling in Pulmonary Fibrosis–induced Profibrogenic Alterations in Bone Marrow
Authors: Taku Nakashima, Tianju Liu, Biao Hu, Zhe Wu, Matthew Ullenbruch, Keitaro Omori, Lin Ding, Noboru Hattori, Sem H. Phan
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

The impact of lung insult on the bone marrow (BM) and subsequent disease is unknown.
YIELD OF FLEXIBLE SIGMOIDOSCOPY-BASED SCREENING FOR COLORECTAL NEOPLASIA IN GREEK AVERAGE-RISK INDIVIDUALS: IMPACT OF SERRATED POLYPS
Authors: V Papastergiou, N Mathou, A Giannakopoulos, A Evgenidi, E Schoretsanitis, D Apessou, M Lenas, K Paraskeva
Journal: Endoscopy (2019)

Flexible sigmoidoscopy (FS) is an attractive screening modality, being less invasive and costly compared to full colonoscopy. We investigated the yield of FS with respect to advanced colorectal neoplasia (ACN) detection and identified factors correlating with ACN missed by FS-based screening.
Liposomal Alpha-Galactosylceramide Ameliorates Graft-Versus-Host Disease with Remaining Intensified GVL Gained By Dose-Reduction of Posttransplant Cyclophosphamaide after Haploidentical HSCT
Authors: Makoto Nakamura, Ken-ichi Matsuoka, Yusuke Meguri, Shuntaro Ikegawa, Hiroyuki Sugiura, Yasuhisa Sando, Miki Iwamoto, Takeru Asano, Yasuyuki Ishii, Yoshinobu Maeda
Journal: Blood (2017)
ENDOSCOPIC PALLIATION OF HILAR COLANGIOCARCINOMA – USEFULNESS OF SELECTIVE OCCLUSION OF ONE INTRAHEPATIC DUCT
Authors: J Fernandes, M Moreira, T Araújo, H Ribeiro, S Giestas, F Lucas, D Libânio, J Ramada, D Martinez-Ares, M Certo, J Canena, L Lopes
Journal: Endoscopy (2019)

ERCP with stent placement for palliative biliary drainage is a common strategy used in the management of patients with unresectable hilar cholangiocarcinomas (HC).
CAUSTIC INGESTION: PREDICTORS OF CLINICAL AND ENDOSCOPIC SEVERITY
Authors: S Santos, V Borges, G Simões, M Rocha, V Gamelas, DF Carvalho, J Saiote, J Esteves, J Coimbra
Journal: Endoscopy (2019)

Ingestion of caustic substances in adulthood carries a risk of necrosis and perforation of the digestive system, which may cause important morbidity and even mortality. We intended to study the relevance of clinical factors in the prediction of severity of caustic injury.
Tissue-Resident Group 2 Innate Lymphoid Cells Differentiate by Layered Ontogeny and In Situ Perinatal Priming
Authors: Christoph Schneider, Jinwoo Lee, Satoshi Koga, Roberto R. Ricardo-Gonzalez, Jesse C. Nussbaum, Lucas K. Smith, Saul A. Villeda, Hong-Erh Liang, Richard M. Locksley
Journal: Immunity (2019)
Clinical Features and Risk Factors of Post-Engraftment Bloodstream Infection in Allogeneic HCT
Authors: Tatsuya Suwabe, Kyoko Fuse, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko
Journal: Blood (2018)
Capsule endoscopy aiding diagnosis of a rare condition – Whipple’s disease
Authors: Carolina Olano, Rodrigo Dorelo, Martin Oricchio, Daniela Mendez, Adrian Canavesi, Cristian Pitetta
Journal: Endoscopy (2019)

A 62-year-old man presented with diarrhea (5 motions/day) that had lasted for 3 months. He had no abdominal pain and no fever, but stated a weight loss without anorexia of 7 kg over 4 months. Physical examination showed normal findings except for cutaneous-mucosal pallor. Laboratory tests revealed anemia, hypoalbuminemia, and decreased prothrombin time. Colonoscopy showed normal appearances. Upper gastrointestinal (GI) endoscopy revealed edema and multiple erosions of the bulb and the second portion of the duodenum ([Fig. 1]). Histological investigation revealed hyperplasia of Brunner glands.
Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components
Authors: Cathy Lordan, Dinesh Thapa, R. Paul Ross, Paul D. Cotter
Journal: Gut Microbes (2019)

The human intestinal commensal microbiota and associated metabolic products have long been regarded as contributors to host health. As the identity and activities of the various members of this community have become clearer, newly identified health-associated bacteria, such as Faecalibacterium prausnitzii, Akkermansia muciniphila, Ruminococcus bromii and Roseburia species, have emerged. Notably, the abundance of many of these bacteria is inversely correlated to several disease states. While technological and regulatory hurdles may limit the use of strains from these taxa as probiotics, it should be possible to utilize prebiotics and other dietary components to selectively enhance their growth in situ. Dietary components of potential relevance include well-established prebiotics, such as galacto-oligosaccharides, fructo-oligosaccharides and inulin, while other putative prebiotics, such as other oligosaccharides, polyphenols, resistant starch, algae and seaweed as well as host gut metabolites such as lactate and acetate, may also be applied with the aim of selectively and/or differentially affecting the beneficial bacterial community within the gastrointestinal environment. The present review provides an overview of the dietary components that could be applied in this manner.
EUS-GUIDED DRAINAGE OF PERIPANCREATIC FLUID COLLECTIONS BY LUMEN-APPOSING METAL STENTS VERSUS SELF-EXPANDING METAL STENTS VERSUS PLASTIC STENTS: SINGLE CENTER EXPERIENCE OVER 6 YEARS
Authors: M Drepper, E Pérez-Cuadrado-Robles, PH Deprez
Journal: Endoscopy (2019)

Comparing outcome after peripancreatic fluid collection (PFC) drainage by plastic double pigtail stents versus self-expanding metal stents (SEMS) versus the recently developed lumen-apposing metal stents (LAMS).
Establishing outcome measures in early knee osteoarthritis
Authors: Carolyn A. Emery, Jackie L. Whittaker, Armaghan Mahmoudian, L. Stefan Lohmander, Ewa M. Roos, Kim L. Bennell, Clodagh M. Toomey, Raylene A. Reimer, Dylan Thompson, Janet L. Ronsky, Gregor Kuntze, David G. Lloyd, Thomas Andriacchi, Martin Englund, Virginia B. Kraus, Elena Losina, Sita Bierma-Zeinstra, Jos Runhaar, George Peat, Frank P. Luyten, Lynn Snyder-Mackler, May Arna Risberg, Ali Mobasheri, Ali Guermazi, David J. Hunter, Nigel K. Arden
Journal: Nature Reviews Rheumatology (2019)
THE ROLE OF CAPSULE ENTEROSCOPY IN COELIAC DISEASE: RESULTS OF A PROSPECTIVE STUDY IN A TERTIARY REFERRAL CENTER
Authors: L Elli, B Marinoni, M Topa, L Roncoroni, M Vecchi
Journal: Endoscopy (2019)

Coeliac disease (CD) is a chronic enteropathy, rarely complicated with refractory disease (RCD type1, 2) and malignancies. Capsule enteroscopy (CE) is a useful tool to evaluate patients with persistence or recurrence of symptoms despite an ongoing gluten free diet (GFD). The aim of this study was to evaluate the diagnostic performance of CE in detecting CD-related complications.
Abstract 3476: Intermittent anti-androgen monotherapy: a possible treatment for androgen receptor-overexpressing prostate cancer
Authors: Tim Oliver, Dan Berney, Greg Shaw
Journal: Cancer Research (2015)

Abstract A case report of a Gleason 4+4 patient who self-medicated on intermittent flutamide with 14 cycles of 3 months on 3 months off, surviving at 14 years.cast doubt on conventional wisdom that intermittently androgen blockade should include an LHRH blocking agent. Anti-androgen(aa) monotherapy was thought to be dangerous as on treatment testosterone rises. It was speculated that he had been Testosterone(T) deficient at diagnosis as in many patients with high grade tumours and had benefited from the blocking action of the aa to control tumour expansion while allowing the off period to allow T to differentiate the tumour possibly by suppressing an over expressed androgen receptor. Following this case others already on AA continuously were recruited to our then ongoing phase 1/2 study of intermittent hormone therapy(Lane 2004). This abstract records their outcome and compares it with those treated with conventional GNRH monotherapy or maximum androgen blockade Results: Between 1997 and 2007 111 patients sort advice about intermittent hormone therapy having started on some form of endocrine treatment. 46 MO patients received GNRH regime and 33 receive aa monotherapy (M0 = 31). Provided PSA was below 4 they were eligible for entry. Median pre-treatment PSA was 22 (range 0.4-237) compared to 22 (range 3.7-402) in MO GNRH groups. Over all survival was 87% ,at 5 year and 78% at 8 years and continuing to respond on protocol 66% at 5 yrs, 57% at 8 compared to 77/56% at 5 and 54/41% at 8 years in M0 GNRH treated group Conclusion: Non-randomised selection in this cohort makes it difficult to draw strong conclusions. As overall survival is significantly better than with GNRH regimens, an exploratory randomised phase 2 trial comparing GNRH against aa monotherapy in patients presenting with over expression of androgen receptor and below normal age-corrected serum testosterone is under consideration Citation Format: Tim Oliver, Dan Berney, Greg Shaw. Intermittent anti-androgen monotherapy: a possible treatment for androgen receptor-overexpressing prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3476. doi:10.1158/1538-7445.AM2015-3476