tbuckley/cabot-search huggingface dataset:
Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study
Authors: Elizabeth Crellin, Kathryn E Mansfield, Clémence Leyrat, Dorothea Nitsch, Ian J Douglas, Adrian Root, Elizabeth Williamson, Liam Smeeth, Laurie A Tomlinson
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population. <h3>Design</h3> Cohort study. <h3>Setting</h3> UK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. <h3>Participants</h3> Adults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015. <h3>Main outcome measures</h3> The outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics. <h3>Results</h3> Among a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury. <h3>Conclusion</h3> Trimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.
Biomarkers for In Vivo Assessment of Transporter Function
Authors: Fabian Müller, Ashish Sharma, Jörg König, Martin F. Fromm
Journal: Pharmacological Reviews (2018)

Drug-drug interactions are a major concern not only during clinical practice, but also in drug development. Due to limitations of in vitro-in vivo predictions of transporter-mediated drug-drug interactions, multiple clinical Phase I drug-drug interaction studies may become necessary for a new molecular entity to assess potential drug interaction liabilities. This is a resource-intensive process and exposes study participants, who frequently are healthy volunteers without benefit from study treatment, to the potential risks of a new drug in development. Therefore, there is currently a major interest in new approaches for better prediction of transporter-mediated drug-drug interactions. In particular, researchers in the field attempt to identify endogenous compounds as biomarkers for transporter function, such as hexadecanedioate, tetradecanedioate, coproporphyrins I and III, or glycochenodeoxycholate sulfate for hepatic uptake via organic anion transporting polypeptide 1B or N1-methylnicotinamide for multidrug and toxin extrusion protein-mediated renal secretion. We summarize in this review the currently proposed biomarkers and potential limitations of the substances identified to date. Moreover, we suggest criteria based on current experiences, which may be used to assess the suitability of a biomarker for transporter function. Finally, further alternatives and supplemental approaches to classic drug-drug interaction studies are discussed.
La papille diverticulaire est elle un faceur d'echec du catheterisme de la voie biliaire principale dans la pathologie lithiasique?
Authors: F Bouhamou, H Seddik, A Aomari, S Morabit, S Jamal, H Boutallaka, K Loubaris, R Berraida, I El Koti, S Sentissi, A Benkirane
Journal: Endoscopy (2018)

Les diverticules duodénaux sont fréquents (6 à 20%). Ces derniers peuvent constituer une difficulté au cathétérisme de la VBP et sont plus fréquents en cas de lithiase biliaire associée.
Ben Barres: neuroscientist and fighter for diversity
Authors: Bob Roehr
Journal: BMJ (2018)

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Credit: Stanford University

Achieving excellence in a single aspect of life is difficult, doing so in two is phenomenal. Ben Barres was a phenomenon; the “godfather” who largely created the modern neurobiology specialism of glial research, and who was equally prominent for championing equality for minorities, particularly women, in the sciences.

Barres’s unique journey began as one of fraternal twin girls in postwar middle class suburban New Jersey. She was named Barbara and grew up a tomboy who took an early interest in science and decided in eighth grade that she would go to the Massachusetts Institute of Technology.

MIT was a nearly all male place in those days. Barres was given early acceptance and a scholarship, but not an easy road towards graduation in 1976. “I was the only person in a large class of nearly all men to solve a hard maths problem, only to be told by the professor that my boyfriend must have solved it for me,” Barres would later write.

Medical school at Dartmouth led to a residency in clinical neurology at Cornell, where the fascination with glia took hold. Barres felt the need for further study and turned to Harvard for a PhD in …
Alternative macrophages in atherosclerosis: not always protective!
Authors: Benoit Pourcet, Bart Staels
Journal: Journal of Clinical Investigation (2018)

Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.
Vitamins A, C and E and lactulose in the prevention of recurrence of adenomatous polyps: preliminary results of a controlled study
Authors: Maurizio Ponz De Leon, Luca Roncucci, P. Di Donato, M. Perini, A. Antonioli, A. Ferrari, B. Paris, S. Svanoni, M. Girola
Journal: Gut (1989)
IL-17C/IL-17 Receptor E Signaling in CD4+ T Cells Promotes TH17 Cell-Driven Glomerular Inflammation
Authors: Sonja Krohn, Jasper F. Nies, Sonja Kapffer, Tilman Schmidt, Jan-Hendrik Riedel, Anna Kaffke, Anett Peters, Alina Borchers, Oliver M. Steinmetz, Christian F. Krebs, Jan-Eric Turner, Silke R. Brix, Hans-Joachim Paust, Rolf A. K. Stahl, Ulf Panzer
Journal: Journal of the American Society of Nephrology (2018)

The IL-17 cytokine family and the cognate receptors thereof have a unique role in organ-specific autoimmunity. Most studies have focused on the founding member of the IL-17 family, IL-17A, as the central mediator of diseases. Indeed, although pathogenic functions have been ascribed to IL-17A and IL-17F in the context of immune-mediated glomerular diseases, the specific functions of the other IL-17 family members in immunity and inflammatory kidney diseases is largely unknown. Here, we report that compared with healthy controls, patients with acute Anti-neutrophil cytoplasmatic antibody (ANCA)-associated crescentic glomerulonephritis (GN) had significantly elevated serum levels of IL-17C (but not IL-17A, F, or E). In mouse models of crescentic GN (nephrotoxic nephritis) and pristane-induced lupus nephritis, deficiency in IL-17C significantly ameliorated the course of GN in terms of renal tissue injury and kidney function. Deficiency of the unique IL-17C receptor IL-17 receptor E (IL-17RE) provided similar protection against crescentic GN. These protective effects associated with a reduced T H 17 response. Bone marrow transplantation experiments revealed that IL-17C is produced by tissue-resident cells, but not by lymphocytes. Finally, IL-17RE was highly expressed by CD4 + T H 17 cells, and loss of this expression prevented the T H 17 responses and subsequent tissue injury in crescentic GN. Our findings indicate that IL-17C promotes T H 17 cell responses and immune-mediated kidney disease via IL-17RE expressed on CD4 + T H 17 cells. Targeting the IL-17C/IL-17RE pathway may present an intriguing therapeutic strategy for T H 17-induced autoimmune disorders.
Gros calculs de la voie biliaire principale: Résultats du traitement endoscopique
Authors: S Jardak, M Medhioub, S Ben Amor, L Hamzaoui, K Amal, MM Azouz
Journal: Endoscopy (2018)

La lithiase de la voie biliaire principale (LVBP) constitue une des principales indications de la sphinctérotomie endoscopique (SE). Les résultats de ce traitement, souvent satisfaisants, peuvent cependant être limités par certains facteurs notamment la taille des calculs. Le but de ce travail est d'évaluer l'efficacité et les complications du traitement endoscopique en cas de gros calculs de la voie biliaire principale.
In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites
Authors: Nil Gural, Liliana Mancio-Silva, Alex B. Miller, Ani Galstian, Vincent L. Butty, Stuart S. Levine, Rapatbhorn Patrapuvich, Salil P. Desai, Sebastian A. Mikolajczak, Stefan H.I. Kappe, Heather E. Fleming, Sandra March, Jetsumon Sattabongkot, Sangeeta N. Bhatia
Journal: Cell Host & Microbe (2018)

The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood-stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs). MPCCs feature key aspects of P. vivax biology, including establishment of persistent small forms and growing schizonts, merosome release, and subsequent infection of reticulocytes. We find that the small forms exhibit previously described hallmarks of hypnozoites, and we pilot MPCCs as a tool for testing candidate anti-hypnozoite drugs. Finally, we employ a hybrid capture strategy and RNA sequencing to describe the hypnozoite transcriptome and gain insight into its biology.
Résection endoscopique transpariétale avec un bistouri (ESD) versus Full Thickness Resection Device (FTRD): quelle technique utilisée?
Authors: MA Guillaumot, Y Le Baleur, J Jacques, S Koch, S Leblanc, G Rahmi, V Lepilliez, J Rivory, M Pioche, F Prat, S Chaussade
Journal: Endoscopy (2018)

Dans les situations ou la dissection sous muqueuse endoscopique (ESD) n'est pas réalisable (fibrose sous-muqueuse cicatricielle ou associée à certaines tumeur, infiltration carcinomateuse sous muqueuse, lésions sous muqueuses....), de nouvelles techniques de résection colo-rectale transpariétale per endoscopique sont en cours d'évaluation afin d'éviter le recours systématique à la chirurgie. La résection transpariétale par le système FTRD est la technique la plus fréquemment utilisée. La résection transparietale endoscopique par bistouri est une technique en cours d'évaluation. L'objectif de ce travail rétrospectif et multicentrique est de comparer la faisabilité, l'efficacité et la morbidité de la résection trans-pariétale avec le système FTRD avec les résections trans-pariétales endoscopiques avec un bistouri effectuées par des gastroentérologues.
E-cigarette vapour enhances pneumococcal adherence to airway epithelial cells
Authors: Lisa Miyashita, Reetika Suri, Emma Dearing, Ian Mudway, Rosamund E Dove, Daniel R. Neill, Richard Van Zyl-Smit, Aras Kadioglu, Jonathan Grigg
Journal: European Respiratory Journal (2018)

E-cigarette vapour contains free radicals with the potential to induce oxidative stress. Since oxidative stress in airway cells increases platelet-activating factor receptor (PAFR) expression, and PAFR is co-opted by pneumococci to adhere to host cells, we hypothesised that E-cigarette vapour increases pneumococcal adhesion to airway cells.Nasal epithelial PAFR was assessed in non-vaping controls, and in adults before and after 5 min of vaping. We determined the effect of vapour on oxidative stress-induced, PAFR-dependent pneumococcal adhesion to airway epithelial cells in vitro, and on pneumococcal colonisation in the mouse nasopharynx. Elemental analysis of vapour was done by mass spectrometry, and oxidative potential of vapour assessed by antioxidant depletion in vitroThere was no difference in baseline nasal epithelial PAFR expression between vapers (n=11) and controls (n=6). Vaping increased nasal PAFR expression. Nicotine-containing and nicotine-free E-cigarette vapour increased pneumococcal adhesion to airway cells in vitro Vapour-stimulated adhesion in vitro was attenuated by the PAFR blocker CV3988. Nicotine-containing E-cigarette vapour increased mouse nasal PAFR expression, and nasopharyngeal pneumococcal colonisation. Vapour contained redox-active metals, had considerable oxidative activity, and adhesion was attenuated by the antioxidant N-acetyl cysteine.This study suggests that E-cigarette vapour has the potential to increase susceptibility to pneumococcal infection.
Evaluation de l'efficacité du traitement endoscopique des fistules post sleeve gastrectomie en fonction de leur type radiologique
Authors: A Sportes, G Airinei, C Pratico, JJ Raynaud, G Donatelli, JM Sabaté, R Benamouzig
Journal: Endoscopy (2018)

Les fistules sont la principale complication de la sleeve gastrectomie (SG). Plusieurs types de fistules sont distingués en fonction de leur communication à un abcès et/ou d'une atteinte sus-diaphragmatique (Type I à III). Le drainage interne avec pose de prothèse double queue de cochon par voie endoscopique (DIE) a montré des résultats encourageant. Les résultats de cette thérapeutique en fonction du type de fistule n'ont pas, à notre connaissance, été encore évalués. L'originalité de cette étude repose sur l'évaluation de l'efficacité du DIE en fonction du type de fistule.
Abstract 20645: Lamin A/C Aggregation is a Major Factor Underlying Skeletal and Cardiac Muscle Laminopathies
Authors: Corey L Anderson, Timothy C Routes, Timothy J Kamp
Journal: Circulation (2016)

Background: LMNA encodes lamin A/C, which are comprised of an N-terminal head domain, a central rod consisting of four coiled-coil domains (CCD 1A, 1B, 2A, and 2B) and a C-terminal immunoglobulin-l...
Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
Authors: Nimitha R Mathew, Francis Baumgartner, Lukas Braun, David O'Sullivan, Simone Thomas, Miguel Waterhouse, Tony A Müller, Kathrin Hanke, Sanaz Taromi, Petya Apostolova, Anna L Illert, Wolfgang Melchinger, Sandra Duquesne, Annette Schmitt-Graeff, Lena Osswald, Kai-Li Yan, Arnim Weber, Sonia Tugues, Sabine Spath, Dietmar Pfeifer, Marie Follo, Rainer Claus, Michael Lübbert, Christoph Rummelt, Hartmut Bertz, Ralph Wäsch, Johanna Haag, Andrea Schmidts, Michael Schultheiss, Dominik Bettinger, Robert Thimme, Evelyn Ullrich, Yakup Tanriver, Giang Lam Vuong, Renate Arnold, Philipp Hemmati, Dominik Wolf, Markus Ditschkowski, Cordula Jilg, Konrad Wilhelm, Christian Leiber, Sabine Gerull, Jörg Halter, Claudia Lengerke, Thomas Pabst, Thomas Schroeder, Guido Kobbe, Wolf Rösler, Soroush Doostkam, Stephan Meckel, Kathleen Stabla, Stephan K Metzelder, Sebastian Halbach, Tilman Brummer, Zehan Hu, Joern Dengjel, Björn Hackanson, Christoph Schmid, Udo Holtick, Christof Scheid, Alexandros Spyridonidis, Friedrich Stölzel, Rainer Ordemann, Lutz P Müller, Flore Sicre-de-Fontbrune, Gabriele Ihorst, Jürgen Kuball, Jan E Ehlert, Daniel Feger, Eva-Maria Wagner, Jean-Yves Cahn, Jacqueline Schnell, Florian Kuchenbauer, Donald Bunjes, Ronjon Chakraverty, Simon Richardson, Saar Gill, Nicolaus Kröger, Francis Ayuk, Luca Vago, Fabio Ciceri, Antonia M Müller, Takeshi Kondo, Takanori Teshima, Susan Klaeger, Bernhard Kuster, Dennis (Dong Hwan) Kim, Daniel Weisdorf, Walter van der Velden, Daniela Dörfel, Wolfgang Bethge, Inken Hilgendorf, Andreas Hochhaus, Geoffroy Andrieux, Melanie Börries, Hauke Busch, John Magenau, Pavan Reddy, Myriam Labopin, Joseph H Antin, Andrea S Henden, Geoffrey R Hill, Glen A Kennedy, Merav Bar, Anita Sarma, Donal McLornan, Ghulam Mufti, Betul Oran, Katayoun Rezvani, Omid Shah, Robert S Negrin, Arnon Nagler, Marco Prinz, Andreas Burchert, Andreas Neubauer, Dietrich Beelen, Andreas Mackensen, Nikolas von Bubnoff, Wolfgang Herr, Burkhard Becher, Gerard Socié, Michael A Caligiuri, Eliana Ruggiero, Chiara Bonini, Georg Häcker, Justus Duyster, Jürgen Finke, Erika Pearce, Bruce R Blazar, Robert Zeiser
Journal: Nature Medicine (2018)
Doctors can stop ventilating 11 month old boy brain damaged at birth
Authors: Clare Dyer
Journal: BMJ (2018)

The parents of an 11 month old boy who was severely brain damaged during his birth have lost a legal battle to keep him alive.1

At the High Court in London, Mr Justice MacDonald ruled that it was no longer in Isaiah Haastrup’s best interests to give him life sustaining treatment. He declared that doctors treating him at Kings College Hospital in London could stop providing him with ventilation, and that he should have only palliative care.

Isaiah was born at Kings by emergency caesarean after his mother’s uterus ruptured. He was found in her abdominal cavity. One expert in the case told the court that he was …
TC-325 (HEMOSPRAY™) vs. traitement classique dans la prise en charge des hémorragies digestives hautes ou basses d'origine tumorale: un essai clinique randomisé
Authors: YI Chen, M Bardou, Y Lu, J Wyse, G White, M Martel, A Barkun
Journal: Endoscopy (2018)

La prise en charge habituelle (PECH) de l'hémorragie gastro-intestinale (HGI) d'origine tumorale, incluant les approches endoscopiques, radiologiques, chirurgicales et radio-thérapiques traditionnelles, a une efficacité hémostatique limitée. Le TC-325 est une nouvelle poudre hémostatique endoscopique qui s'est révélée prometteuse dans la gestion de ces patients. Cette étude avait comme objectif d'évaluer les stratégies de recrutement et de conception opérationnelle d'étude pour un essai clinique plus large, tout en permettant d'obtenir des estimations ponctuelles valides sur l'efficacité de TC-325 par rapport à PECH, pour l'hémostase initiale et les taux de récidive précoce dans l'HGI maligne. Cet essai pilote n'a pas été dimensionné pour démontrer une différence entre les prises en charge car il n'existe pas à ce jour de données comparatives de haut qualité publiées.
Right Ventricular Function in Aortic Stenosis: Early Marker of Decompensation and Left Ventricular Recovery
Authors: M Rigolli, S Sivalokanathan, S Bull, R S Wijesurendra, R Ariga, M Loudon, J M Francis, T D Karamitsos, S Neubauer, M Mahmod, S G Myerson
Journal: Circulation (2017)
Clip-fixed endoloop: an efficacious new method for mucosal defect closure
Authors: Tatsuma Nomura, Makoto Kobayashi, Takaaki Morikawa, Noriyuki Horiki
Journal: Endoscopy (2018)

Endoloop suturing of a mucosal defect using a two-channel scope has been shown to be efficacious [1] [2]. Recently, methods of simple, useful endoloop suturing with a single-channel scope have also been reported [3] [4]. However, fixing the first clip to determine the position of the endoloop is cumbersome. We have developed a new and efficient suturing method, the clip-fixed endoloop, that fixes the endoloop to the clip in advance.
Prevention of vaccine-matched and mismatched influenza in children aged 6–35 months: a multinational randomised trial across five influenza seasons
Authors: Carine Claeys, Khalequ Zaman, Ghassan Dbaibo, Ping Li, Allen Izu, Pope Kosalaraksa, Luis Rivera, Beatriz Acosta, Maria Luisa Arroba Basanta, Asma Aziz, Miguel Angel Cabanero, Vijayalakshmi Chandrashekaran, Bartholomew Corsaro, Luis Cousin, Adolfo Diaz, Javier Diez-Domingo, Ener Cagri Dinleyici, Saul N Faust, Damien Friel, Jose Garcia-Sicilia, Grace D Gomez-Go, Maria Liza Antoinette Gonzales, Stephen M Hughes, Teresa Jackowska, Shashi Kant, Marilla Lucero, Ludovic Malvaux, Josep Mares Bermudez, Federico Martinon-Torres, Mariano Miranda, May Montellano, Maria Amor Peix Sambola, Roman Prymula, Thanyawee Puthanakit, Renata Ruzkova, Iwona Sadowska-Krawczenko, Ignacio Salamanca de la Cueva, Etienne Sokal, Jyoti Soni, Henryk Szymanski, Angels Ulied, Anne Schuind, Varsha K Jain, Bruce L Innis, Beatriz Acostas, Arshad Amanullah, Miguel Ariza, Maria Luisa Arroba Basanta, Asma Aziz, Milagros Bautista, Ashish Bavdekar, Bhavesh Bodalia, Lulu C Bravo, Jerzy Brzostek, Miguel Angel Cabanero, Ian Caldwell, Alfonso Carmona, Vijayalakshmi Chandrashekaran, Carine Claeys, Bartholomew Corsaro, Luis Cousin, Jasur Danier, Ghassan Dbaibo, Ana Isabel Diaz Cirujano, Adolfo Diaz, Javier Diez-Domingo, Ener Cagri Dinleyici, Martine Docx, Daniel Drazan, Saul N Faust, Andrzej Galaj, Fermin Garcia Rodriguez, Jose Garcia-Sicilia, Maria Liza Antoinette Gonzales, Grace D Gomez-Go, Trevor Gooding, Mustafa Hacimustafaoglu, Paul Heath, Paul Heaton, Stephen M Hughes, Bruce L Innis, Allen Izu, Teresa Jackowska, Varsha K Jain, Shashi Kant, Pope Kosalaraksa, Sanjay Lalwani, Jennifer Langlands, Ping Li, Karl Logghe, Marilla Lucero, Ludovic Malvaux, Jolanta Mantyka, Josep Mares Bermudez, Federico Martinon-Torres, Damien McNally, Edyta Miszczak-Kowalska, May Montellano, Maria Amor Peix Sambola, Roman Prymula, Thanyawee Puthanakit, Luis Rivera, Simon Royal, Renata Ruzkova, Benjamin Sablan, Iwona Sadowska-Krawczenko, Ignacio Salamanca de la Cueva, Anne Schuind, Matthew Snape, Jyoti Soni, Richard Tomlinson, Angels Ulied, Marc Verghote, Andre Vertruyen, Marie Wheeler, Khalequ Zaman
Journal: The Lancet Child & Adolescent Health (2018)