tbuckley/cabot-search huggingface dataset:
Résultats de la prise en charge endoscopique de l'ulcère gastroduodénal hémorragique: une série de 125 patients
Authors: I Jemni, HL Mohamed, F Aissaoui, S Ben Amor, M Zakhama, A Guediche, W Bouhlel, W Ben Mansour, BC Nabil, L Safer
Journal: Endoscopy (2019)

Les ulcères gastroduodénaux hémorragiques sont la principale cause d'hémorragie digestive haute. Bien qu'une diminution des hospitalisations pour ulcère gastroduodénal soit observée depuis quelques années, la mortalité reste stable entre 2,5 et 5,8%. Les objectifs du traitement endoscopique sont de faire cesser l'hémorragie et de diminuer le risque de récidive hémorragique et d'intervention chirurgicale à visée hémostatique et de réduire la mortalité.
Meta-analysis of Opioids for Chronic Pain—Reply
Authors: Jason W. Busse, Li Wang, Gordon H. Guyatt
Journal: JAMA (2019)

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A Critical Assessment of the Linear No-Threshold Hypothesis
Authors: Jeffry A. Siegel, Antone L. Brooks, Darrell R. Fisher, Pat B. Zanzonico, Mohan Doss, Michael K. O'Connor, Edward B. Silberstein, James S. Welsh, Bennett S. Greenspan
Journal: Clinical Nuclear Medicine (2019)

Abstract The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.
Clinical practice guidelines for laboratory diagnosis of epidermolysis bullosa
Authors: C. Has, L. Liu, M.C. Bolling, A.V. Charlesworth, M. El Hachem, M.J. Escámez, I. Fuentes, S. Büchel, R. Hiremagalore, G. Pohla‐Gubo, P.C. Akker, K. Wertheim‐Tysarowska, G. Zambruno
Journal: British Journal of Dermatology (2019)

Linked Comment:Uitto. Br J Dermatol 2020; 182:526–527. Plain language summary available online
Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis via synergistic upregulation of ALAS1 expression
Authors: Cai-Ping Chen, Kun Chen, Zhiqi Feng, Xiaoan Wen, Hongbin Sun
Journal: Acta Pharmaceutica Sinica B (2019)

Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. In vitro studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down ALAS1 significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors.
Phase III study of [fam-] trastuzumab deruxtecan (DS-8201a) vs T-DM1 for HER2-positive breast cancer
Authors: S. Verma, J. Shahidi, C. Lee, K. Wang, J. Cortes
Journal: Annals of Oncology (2019)

Background: [Fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate (ADC) with a humanized HER2 antibody, topoisomerase I inhibitor payload, and cleavable peptide-based linker. In an ongoing phase 1 trial, [fam-] trastuzumab deruxtecan had a manageable safety profile and promising antitumor activity in HER2+ breast cancer (BC) previously treated with T-DM1 (confirmed objective response rate (ORR) of 54.5%; April 2018 data cutoff). The pivotal, phase 2 DESTINY-Breast01 trial in this population is ongoing. Trial design: This multicenter, open-label, phase 3 trial will assess the efficacy and safety of [fam-] trastuzumab deruxtecan vs T-DM1 in subjects with HER2 + (IHC 3+ or IHC 2+/ISH+; confirmed by centralized testing) unresectable and/or metastatic BC previously treated with trastuzumab and a taxane (NCT03529110, DESTINY-Breast03). Subjects who previously received a HER2-targeted ADC are excluded. Approximately 500 eligible subjects will be randomized (1:1) to receive [fam-] trastuzumab deruxtecan (5.4 mg/kg) or T-DM1 (3.6 mg/kg) IV once every 3 weeks. Randomization will be stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. For subjects randomized to T-DM1, treatment will be in accordance with the approved label. The primary efficacy endpoint is progression-free survival (PFS) based on blinded, independent central review using RECIST v1.1 criteria. Secondary efficacy endpoints include overall survival (OS), ORR, duration of response, clinical benefit rate, and PFS based on investigator assessment. Safety and health-related quality of life will also be assessed. The primary analysis for PFS will be performed when approximately 331 PFS events are observed. This will provide 90% power to detect a hazard ratio of 0.70 for PFS with a 1-sided alpha of 0.025, assuming a median PFS with T-DM1 of 9.6 months and that PFS follows an exponential distribution. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or study closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all randomized subjects receiving ≥1 dose of study treatment. Editorial acknowledgement: Marie-Louise Ricketts, PhD; and Stefan Kolata, PhD of AlphaBioCom, LLC. Clinical trial identification: NCT03529110; release date May 18, 2018. Legal entity responsible for the study: Daiichi Sankyo, Inc., Basking Ridge, NJ, USA. Funding: Daiichi Sankyo, Inc., Basking Ridge, NJ, USA. Disclosure: S. Verma: Consulting fees: Amgen, AstraZeneca, Eli Lilly, Novartis, Daiichi Sankyo, Roche, Seattle Genetics. J. Shahidi, C. Lee, K. Wang: Salaried employee: Daiichi Sankyo, Inc. J. Cortes: Consulting fees: Roche, Celgene, AstraZeneca, Cellestia Biotech, Biothera, Merus, Seattle Genetics; Fees for non-CME services: Roche, Novartis, Eisai, Celgene, Pfizer.
Pragmatic considerations for fostering reproducible research in artificial intelligence
Authors: Rickey E. Carter, Zachi I. Attia, Francisco Lopez-Jimenez, Paul A. Friedman
Journal: npj Digital Medicine (2019)

Abstract Artificial intelligence and deep learning methods hold great promise in the medical sciences in areas such as enhanced tumor identification from radiographic images, and natural language processing to extract complex information from electronic health records. Scientific review of AI algorithms has involved reproducibility, in which investigators share protocols, raw data, and programming codes. Within the realm of medicine, reproducibility introduces important challenges, including risk to patient privacy, challenges in reproducing results, and questions regarding ownership and financial value of large medical datasets. Scientific review, however, mandates some form of resolution of these inherent conflicts. We propose several approaches to permit scientific review while maintaining patient privacy and data confidentiality.
Partha Kar: Our responsibility to the next generation
Authors: Partha Kar
Journal: BMJ (2019)

A fundamental problem with the NHS and its workforce issues sometimes tends to be us—the workforce itself. We can all make small changes that add up to making a big difference. Yet we shy away from them because we think they’re too inconsequential, we’re too beaten down by the process, or because, frankly, we don’t care enough.

A classic example of this has been how doctors have looked after the next generation of the workforce. This issue of pastoral care often comes up when junior colleagues talk about not having leave requests granted, even for special occasions such as weddings. When these issues arise I wonder: …
A RHABDOID CAVITATED JEJUNAL ADENOCARCINOMA DIAGNOSED BY DOUBLE-BALLOON ASSISTED ENTEROSCOPY
Authors: A Pérez Fernandez, E Pérez-Cuadrado-Robles, J Francisco Sánchez Melgarejo, JM Rubio Mateos, M José Sánchez Fernandez, P Esteban Delgado, JL Rodrigo Agudo, E Pérez-Cuadrado Martínez
Journal: Endoscopy (2019)

The rhabdoid phenotypic characteristic in digestive tumors is exceptional. In the jejunum, the primitive undifferentiated adenocarcinoma rarely grows up to invade other organs and appears as a cavitated mass.
Smooth muscle cells-derived CXCL10 prevents endothelial healing through PI3Kγ-dependent T cells response
Authors: Adrien Lupieri, Natalia F Smirnova, Romain Solinhac, Nicole Malet, Mehdi Benamar, Abdel Saoudi, Icia Santos-Zas, Lynda Zeboudj, Hafid Ait-Oufella, Emilio Hirsch, Paul Ohayon, Thibault Lhermusier, Didier Carrié, Jean-François Arnal, Damien Ramel, Stephanie Gayral, Muriel Laffargue
Journal: Cardiovascular Research (2019)

Defects in efficient endothelial healing have been associated with complication of atherosclerosis such as post-angioplasty neoatherosclerosis and plaque erosion leading to thrombus formation. However, current preventive strategies do not consider re-endothelialization in their design. Here, we investigate mechanisms linking immune processes and defect in re-endothelialization. We especially evaluate if targeting phosphoinositide 3-kinase γ immune processes could restore endothelial healing and identify immune mediators responsible for these defects.Using in vivo model of endovascular injury, we showed that both ubiquitous genetic inactivation of PI3Kγ and hematopoietic cell-specific PI3Kγ deletion improved re-endothelialization and that CD4+ T-cell population drives this effect. Accordingly, absence of PI3Kγ activity correlates with a decrease in local IFNγ secretion and its downstream interferon-inducible chemokine CXCL10. CXCL10 neutralization promoted re-endothelialization in vivo as the same level than those observed in absence of PI3Kγ suggesting a role of CXCL10 in re-endothelialization defect. Using a new established ex vivo model of carotid re-endothelialization, we showed that blocking CXCL10 restore the IFNγ-induced inhibition of endothelial healing and identify smooth muscle cells as the source of CXCL10 secretion in response to Th1 cytokine.Altogether, these findings expose an unforeseen cellular cross-talk within the arterial wall whereby a PI3Kγ-dependent T-cell response leads to CXCL10 production by smooth muscle cells which in turn inhibits endothelial healing. Therefore, both PI3Kγ and the IFNγ/CXCL10 axis provide novel strategies to promote endothelial healing.
Immunometabolism orchestrates training of innate immunity in atherosclerosis
Authors: Julia van Tuijl, Leo A B Joosten, Mihai G Netea, Siroon Bekkering, Niels P Riksen
Journal: Cardiovascular Research (2019)

Abstract Atherosclerosis is characterized by a persistent, low-grade inflammation of the arterial wall. Monocytes and monocyte-derived macrophages play a pivotal role in the various stages of atherosclerosis. In the past few years, metabolic reprogramming has been identified as an important controller of myeloid cell activation status. In addition, metabolic and epigenetic reprogramming are key regulatory mechanisms of trained immunity, which denotes the non-specific innate immune memory that can develop after brief stimulation of monocytes with microbial or non-microbial stimuli. In this review, we build the case that metabolic reprogramming of monocytes and macrophages, and trained immunity in particular, contribute to the pathophysiology of atherosclerosis. We discuss the specific metabolic adaptations, including changes in glycolysis, oxidative phosphorylation, and cholesterol metabolism, that have been reported in atherogenic milieus in vitro and in vivo. In addition, we will focus on the role of these metabolic pathways in the development of trained immunity.
HOW ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTROINTESTINAL LESIONS IS BEING IMPLEMENTED? RESULTS OF AN INTERNATIONAL SURVEY
Authors: M Araújo-Martins, P Pimentel-Nunes, D Libânio, M Borges-Canha, M Dinis-Ribeiro
Journal: Endoscopy (2019)

Superficial gastrointestinal (GI) neoplasms can be treated with endoscopic mucosal resection (EMR) and/or endoscopic submucosal dissection (ESD). These techniques are widely used in Eastern countries but experience is more limited in West. In 2010, our group found that ESD was performed only at few centers, with most endoscopists performing a low number of procedures. The aim of this study was to evaluate the current implementation of ESD in Western countries.
Short regimen of rituximab plus lenalidomide in follicular lymphoma patients in need of first-line therapy
Authors: Emanuele Zucca, Stephanie Rondeau, Anna Vanazzi, Bjørn Østenstad, Ulrich J. M. Mey, Daniel Rauch, Björn E. Wahlin, Felicitas Hitz, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J. M. Ferreri, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stefan Dirnhofer, Stefanie Hayoz, Hanne Hawle, Simona Berardi Vilei, Michele Ghielmini, Eva Kimby
Journal: Blood (2019)
Major Adverse Events With Percutaneous Left Atrial Appendage Closure in Patients With Atrial Fibrillation
Authors: Laurent Fauchier, Alexandre Cinaud, François Brigadeau, Antoine Lepillier, Bertrand Pierre, Daniel Gras, Jacques Mansourati, Jean Claude Deharo, Gilles Montalescot, Pascal Defaye
Journal: Journal of the American College of Cardiology (2019)
Dennis Thornton Price
Authors: Gill Price
Journal: BMJ (2019)

Dennis Thornton Price was born in Leeds on 24 May 1930, the eldest child of Kitty and Stanley Price, a couple from Croydon who had four children. During the war he spent three of his formative childhood years away from home, evacuated to a school at Fairbourne near Aberystwyth.

After two years’ national service in the Royal Engineers, he went on to study chemistry at Merton College, Oxford, specialising in the chemistry of osmosis. During this period, he brought a decommissioned army Land Rover and made an ambitious overland trip through postwar Europe and on to Greece, with his brother and two friends.

After graduating in 1953, he went to work for …
ERCP IN BILIARY STONES DISEASE: WHAT RESULTS FOR ELDERLY PATIENTS?
Authors: S Mrabti, H Seddik, H Boutallaka, A Sair, I El koti, S Sentissi, A Benkirane
Journal: Endoscopy (2019)

The aim is to evaluate the indications and safety of ERCP in elderly subjects, and to compare the results with younger patients.
Traitement des métastases pancréatiques d'origine rénale par radiofréquence sous écho-endoscopie: Faisabilité et résultats préliminaires
Authors: B Chanez, G Gravis, J Walz, G Pignot, S brunelle, J Thomassin, N Salem, E Bories, JP Ratone, C Pesenti, F Caillol, M Giovannini
Journal: Endoscopy (2019)

Les métastases pancréatiques dans la prise en charge de l'adénocarcinome rénal sont rares mais associées à u bon prognostic nécessitant un traitement s'intégrant dans une prise en charge à long terme. La prise en charge classique peut-être soit chirurgical, soit médicamenteux par inhibiteur de la tyrosine kinase. L'ablation de ces métastases par radiofréquence (RFA) est une thérapeutique nouvelle prometteuse décrite dans la prise en charge des tumeurs endocrines, des adénocarcinomes pancréatiques primitifs et des tumeurs kystiques pancréatiques. Nous rapportons ici notre expérience dans la prise en charge des métastases pancréatiques d'origine rénale.
FEASIBILITY OF NEW BILIARY AND PANCREATIC BIODEGRADABLE STENT PLACEMENT: INTERIM ANALYSIS OF AN ONGOING SINGLE-CENTER, PROSPECTIVE, PILOT STUDY
Authors: A Anderloni, A Fugazza, L Maroni, R Maselli, V Ormando, F D'Amico, S Carrara, B Mangiavillano, PD Omodei, P Preatoni, L Lamonaca, A Cappello, G Pellegatta, A Repici
Journal: Endoscopy (2019)

New biliary and pancreatic biodegradable stents (BS) have been developed for endoscopic use. Stents are provided in different sizes and polymeric mixtures allowing 3 expected rates of biodegradation: slow (11 weeks), medium (20 days) and fast (12 days). Aim of the study was to evaluate biodegradation time, safety, technical success of implantation of newly available BS.
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) TUBE HOME REPLACEMENT – PROSPECTIVE EVALUATION OF A STANDARDIZED PROTOCOL
Authors: A Lisotti, E Teci, A Calì, C Calvanese, MC D'Ercole, S Guglielmo, M Serrani, A Cominardi, G Mangano, P Fusaroli
Journal: Endoscopy (2019)

Percutaneous endoscopic gastrostomy (PEG) are the main route for enteral nutrition (EN) improving patients' survival and QoL. PEG tube exchange management is still debated. Since the introduction of a gastroenterological home-care service in our territory, our Unit drew and adopted a tube exchange protocol. We prospectively evaluated safety and efficacy of this protocol at patient domicile.
WHAT IS THE OPTIMAL DOSE OF PROTON PUMP INHIBITOR AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GASTRIC EPITHELIAL NEOPLASM?
Authors: JY Jang, JJ Kim
Journal: Endoscopy (2019)

Endoscopic submucosal dissection (ESD) has become a widely accepted for the en bloc resection of large superficial tumors in the gastrointestinal tract. ESD is less invasive when compared to surgery but complications such as bleeding, perforation and pain can be associated. Proton pump inhibitor (PPI) is frequently used to prevent post ESD bleeding but unlike the bleeding from peptic ulcers, proper dosing for post ESD period is still questionable. We can speculate that high dose PPI infusion would be more effective to ameliorate the post ESD pain. Therefore, this study was conducted to find out optimal dose of PPI in terms of minimizing complications after ESD.
ENDOSCOPIC REMOVAL OF A MIGRATED ENDOSCOPIC DUODENOJEJUNAL BYPASS (ENDOBARRIER) WHICH HAD EMBEDDED ITS BARBWIRES INTO THE ANGLE OF TREITZ
Authors: A Martinez-Alcala, PT Kroener, MA D'Assuncao, S Peter, K Mönkemüller
Journal: Endoscopy (2019)

A 56-year-old patient with obesity (BMI 55) underwent placement of a duodenojejunal bypass (Endobarrier). Nine months after the procedure he presented complaining of severe abdominal pain and hematemesis.
Payments From Pharmaceutical Companies to Authors Involved in the Valsartan Scandal in Japan
Authors: Toyoaki Sawano, Akihiko Ozaki, Hiroaki Saito, Yuki Shimada, Tetsuya Tanimoto
Journal: JAMA Network Open (2019)

Financial relationships between pharmaceutical companies and physicians can bias the conduct, findings, and reporting of clinical trials. In Japan, the valsartan scandal was a significant event: all 5 key articles on the valsartan clinical trials were retracted after the revelation of data falsification. Consequently, the Japan Pharmaceutical Manufacturers Association issued transparency guidelines, and pharmaceutical payments have been publicly disclosed since 2013. However, the distribution of payments from pharmaceutical companies among authors involved in the valsartan scandal after its revelation has not been studied to date.
ENDOSCOPIC ULTRASOUND GUIDED LEFT LOBE LIVER LESIONS BIOPSY (EUS-LLB) WITH ATYPICAL MALIGNANCIES, AN ALTERNATIVE APPROACH TO RADIOLOGICAL IMAGE GUIDED BIOPSY
Authors: A Urrehman
Journal: Endoscopy (2019)

EUS is gaining attraction as an alternative method of biopsy. It offers a more targeted approach for focal lesions in liver especially those areas which are accessible via EUS-guided method.
Correction: A novel human <i>IL2RB</i> mutation results in T and NK cell–driven immune dysregulation
Authors: Isabel Z. Fernandez, Ryan M. Baxter, Josselyn E. Garcia-Perez, Elena Vendrame, Thanmayi Ranganath, Daniel S. Kong, Karl Lundquist, Tom Nguyen, Sidney Ogolla, Jennifer Black, Csaba Galambos, James C. Gumbart, Noor Dawany, Judith R. Kelsen, Edwin F. de Zoeten, Ralph Quinones, Hesham Eissa, Michael R. Verneris, Kathleen E. Sullivan, Rosemary Rochford, Catherine A. Blish, Ross M. Kedl, Cullen M. Dutmer, Elena W.Y. Hsieh
Journal: The Journal of Experimental Medicine (2019)

S2 G, the plot for healthy pediatric (H.Ped) #1 CD4 + T cells