tbuckley/cabot-search huggingface dataset:
Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN)
Authors: Nicola Dalbeth, Thomas Bardin, Michael Doherty, Frédéric Lioté, Pascal Richette, Kenneth G. Saag, Alexander K. So, Lisa K. Stamp, Hyon K. Choi, Robert Terkeltaub
Journal: Nature Reviews Rheumatology (2017)

In this Consensus Statement, an expert panel compares and contrasts recommendations for the management of gout produced by rheumatology organizations and the American College of Physicians (ACP), and present the G-CAN position on the ACP guideline. In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future.
Minimally invasive and endoscopic versus open necrosectomy for necrotising pancreatitis: a pooled analysis of individual data for 1980 patients
Authors: Sandra van Brunschot, Robbert A Hollemans, Olaf J Bakker, Marc G Besselink, Todd H Baron, Hans G Beger, Marja A Boermeester, Thomas L Bollen, Marco J Bruno, Ross Carter, Jeremy J French, Djalma Coelho, Björn Dahl, Marcel G Dijkgraaf, Nilesh Doctor, Peter J Fagenholz, Gyula Farkas, Carlos Fernandez del Castillo, Paul Fockens, Martin L Freeman, Timothy B Gardner, Harry van Goor, Hein G Gooszen, Gerjon Hannink, Rajiv Lochan, Colin J McKay, John P Neoptolemos, Atilla Oláh, Rowan W Parks, Miroslav P Peev, Michael Raraty, Bettina Rau, Thomas Rösch, Maroeska Rovers, Hans Seifert, Ajith K Siriwardena, Karen D Horvath, Hjalmar C van Santvoort
Journal: Gut (2017)

<h3>Objective</h3> Minimally invasive surgical necrosectomy and endoscopic necrosectomy, compared with open necrosectomy, might improve outcomes in necrotising pancreatitis, especially in critically ill patients. Evidence from large comparative studies is lacking. <h3>Design</h3> We combined original and newly collected data from 15 published and unpublished patient cohorts (51 hospitals; 8 countries) on pancreatic necrosectomy for necrotising pancreatitis. Death rates were compared in patients undergoing open necrosectomy versus minimally invasive surgical or endoscopic necrosectomy. To adjust for confounding and to study effect modification by clinical severity, we performed two types of analyses: logistic multivariable regression and propensity score matching with stratification according to predicted risk of death at baseline (low: &lt;5%; intermediate: ≥5% to &lt;15%; high: ≥15% to &lt;35%; and very high: ≥35%). <h3>Results</h3> Among 1980 patients with necrotising pancreatitis, 1167 underwent open necrosectomy and 813 underwent minimally invasive surgical (n=467) or endoscopic (n=346) necrosectomy. There was a lower risk of death for minimally invasive surgical necrosectomy (OR, 0.53; 95% CI 0.34 to 0.84; p=0.006) and endoscopic necrosectomy (OR, 0.20; 95% CI 0.06 to 0.63; p=0.006). After propensity score matching with risk stratification, minimally invasive surgical necrosectomy remained associated with a lower risk of death than open necrosectomy in the very high-risk group (42/111 vs 59/111; risk ratio, 0.70; 95% CI 0.52 to 0.95; p=0.02). Endoscopic necrosectomy was associated with a lower risk of death than open necrosectomy in the high-risk group (3/40 vs 12/40; risk ratio, 0.27; 95% CI 0.08 to 0.88; p=0.03) and in the very high-risk group (12/57 vs 28/57; risk ratio, 0.43; 95% CI 0.24 to 0.77; p=0.005). <h3>Conclusion</h3> In high-risk patients with necrotising pancreatitis, minimally invasive surgical and endoscopic necrosectomy are associated with reduced death rates compared with open necrosectomy.
French comment on article Efficacy of segmental re-examination of proximal colon for adenoma detection during colonoscopy: a randomized controlled trial1 Efficacité d’un ré-examen segmentaire du colon proximal pour la détection d’adénome en coloscopie: un essai randomisé contrôlé
Journal: Endoscopy (2017)

Quel est le meilleur moyen d’améliorer son taux de détection d’adénome (TDA), en particulier au sein du colon proximal (en amont de l’angle gauche) et par la même occasion diminuer le risque de cancer d’intervalle pour ses patients?
Macrophage-derived IL-10 mediates mucosal repair by epithelial WISP-1 signaling
Authors: Miguel Quiros, Hikaru Nishio, Philipp A. Neumann, Dorothee Siuda, Jennifer C. Brazil, Veronica Azcutia, Roland Hilgarth, Monique N. O’Leary, Vicky Garcia-Hernandez, Giovanna Leoni, Mingli Feng, Gabriela Bernal, Holly Williams, Priya H. Dedhia, Christian Gerner-Smidt, Jason Spence, Charles A. Parkos, Timothy L. Denning, Asma Nusrat
Journal: Journal of Clinical Investigation (2017)

In response to injury, epithelial cells migrate and proliferate to cover denuded mucosal surfaces and repair the barrier defect. This process is orchestrated by dynamic crosstalk between immune cells and the epithelium; however, the mechanisms involved remain incompletely understood. Here, we report that IL-10 was rapidly induced following intestinal mucosal injury and was required for optimal intestinal mucosal wound closure. Conditional deletion of IL-10 specifically in CD11c-expressing cells in vivo implicated macrophages as a critical innate immune contributor to IL-10-induced wound closure. Consistent with these findings, wound closure in T cell- and B cell-deficient Rag1-/- mice was unimpaired, demonstrating that adaptive immune cells are not absolutely required for this process. Further, following mucosal injury, macrophage-derived IL-10 resulted in epithelial cAMP response element-binding protein (CREB) activation and subsequent synthesis and secretion of the pro-repair WNT1-inducible signaling protein 1 (WISP-1). WISP-1 induced epithelial cell proliferation and wound closure by activating epithelial pro-proliferative pathways. These findings define the involvement of macrophages in regulating an IL-10/CREB/WISP-1 signaling axis, with broad implications in linking innate immune activation to mucosal wound repair.
Early seasonal influenza vaccination and delayed influenza peaks – A possible cause of end-of-season outbreaks
Authors: Julian W. Tang, Juliette Mutuyimana, Kah Wee Teo, Sarah Lea, Monica Galiano, Angie Lackenby, Bernadette Donaghy, Janice Blount, Joanna Ellis, Simon Range
Journal: Journal of Infection (2017)
OC-013 The national early warning score (news) accurately discriminates the risk of serious in-hospital adverse outcomes in patients with liver disease
Authors: T Hydes, P Meredith, P Schmidt, G Smith, D Prytherch, R Aspinall
Journal: Gut (2017)

Introduction  Patients with liver disease who develop decompensation are at high risk of multiple organ dysfunction and death. The National Early Warning Score (NEWS), launched in the United Kingdom by the Royal College of Physicians, identifies adult inpatients at risk of deterioration. However, it includes physiological parameters that may be disturbed in cirrhosis, potentially reducing its accuracy. Therefore, we studied the performance of NEWS in acute and chronic liver diseases using a hospital dataset of over 3.5 million clinical observations.  Method  In a major acute hospital serving a catchment of 650,000, for all adult admissions between 2010 and 2014, the performance of NEWS was compared in patients: (i) assigned ICD-10 codes for primary and non-primary liver disease, and for patients without liver disease; (ii) assigned ICD-10 liver-related codes, subdivided clinically, e.g. acute (alcohol), acute (other), chronic non-cirrhotic and cirrhotic; and (iii) with liver disease grouped by Summary Hospital-level Mortality Indicator (SHMI) diagnoses for alcohol-related and other liver diseases. We compared the ability of NEWS and 34 other EWS to discriminate 24 hour mortality, cardiac arrest or unanticipated ICU admission using area under the receiver operating characteristics (AUROC) curve and by EWS efficiency curves.  Results  During the study period 773 patients and 2525 patients were discharged with primary and non-primary diagnoses of liver disease. NEWS attained AUROC [CI] values of 0.873 [0.860–0.886], 0.898 [0.891–0.905] and 0.879 [0.877–0.881] for patients with primary, non-primary and no diagnoses of liver disease, respectively. Performance was significantly higher in patients with acute alcohol induced liver injury (AUROC [CI] 0.927 [0.912–0.941]) and although it was slightly lower in patients with cirrhosis, efficiency values remained relevant (AUROC [CI] 0.824 [0.797–0.850]). Similar results were seen for division by SHMI groups. NEWS outperformed all other EWS systems for patients with a primary or non-primary diagnosis of liver disease.  Conclusion  NEWS accurately discriminates patients at risk of death, ICU admission or cardiac arrest within a 24 hour period for a range of liver-related diagnoses. Its widespread use provides a ready-made, easy-to-use option for identifying patients with liver disease who require early assessment and intervention, without the need to modify parameters, weightings or escalation criteria.  Disclosure of Interest  None Declared
NBEAL2 is required for neutrophil and NK cell function and pathogen defense
Authors: John M. Sowerby, David C. Thomas, Simon Clare, Marion Espéli, Jose A. Guerrero, Kim Hoenderdos, Katherine Harcourt, Morgan Marsden, Juneid Abdul-Karim, Mathew Clement, Robin Antrobus, Yagnesh Umrania, Philippa R. Barton, Shaun M. Flint, Jatinder K. Juss, Alison M. Condliffe, Paul A. Lyons, Ian R. Humphreys, Edwin R. Chilvers, Willem H. Ouwehand, Gordon Dougan, Kenneth G.C. Smith
Journal: Journal of Clinical Investigation (2017)

Mutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by a lack of α granules in platelets. The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS. We therefore investigated the role of NBEAL2 in immunity by analyzing the phenotype of Nbeal2-deficient mice. We found profound abnormalities in the Nbeal2-deficient immune system, particularly in the function of neutrophils and NK cells. Phenotyping of Nbeal2-deficient neutrophils showed a severe reduction in granule contents across all granule subsets. Despite this, Nbeal2-deficient neutrophils had an enhanced phagocyte respiratory burst relative to Nbeal2-expressing neutrophils. This respiratory burst was associated with increased expression of cytosolic components of the NADPH oxidase complex. Nbeal2-deficient NK cells were also dysfunctional and showed reduced degranulation. These abnormalities were associated with increased susceptibility to both bacterial (Staphylococcus aureus) and viral (murine CMV) infection in vivo. These results define an essential role for NBEAL2 in mammalian immunity.
Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials
Journal: BMJ (2017)

Abstract Objective To synthesise the evidence on the overall and differential effects of interventions based on diet and physical activity during pregnancy, primarily on gestational weight gain and maternal and offspring composite outcomes, according to women’s body mass index, age, parity, ethnicity, and pre-existing medical condition; and secondarily on individual complications. Design Systematic review and meta-analysis of individual participant data (IPD). Data sources Major electronic databases from inception to February 2017 without language restrictions. Eligibility criteria for selecting studies Randomised trials on diet and physical activity based interventions in pregnancy. Data synthesis Statistical models accounted for clustering of participants within trials and heterogeneity across trials leading to summary mean differences or odds ratios with 95% confidence intervals for the effects overall, and in subgroups (interactions). Results IPD were obtained from 36 randomised trials (12 526 women). Less weight gain occurred in the intervention group than control group (mean difference −0.70 kg, 95% confidence interval −0.92 to −0.48 kg, I 2 =14.1%; 33 studies, 9320 women). Although summary effect estimates favoured the intervention, the reductions in maternal (odds ratio 0.90, 95% confidence interval 0.79 to 1.03, I 2 =26.7%; 24 studies, 8852 women) and offspring (0.94, 0.83 to 1.08, I 2 =0%; 18 studies, 7981 women) composite outcomes were not statistically significant. No evidence was found of differential intervention effects across subgroups, for either gestational weight gain or composite outcomes. There was strong evidence that interventions reduced the odds of caesarean section (0.91, 0.83 to 0.99, I 2 =0%; 32 studies, 11 410 women), but not for other individual complications in IPD meta-analysis. When IPD were supplemented with study level data from studies that did not provide IPD, the overall effect was similar, with stronger evidence of benefit for gestational diabetes (0.76, 0.65 to 0.89, I 2 =36.8%; 59 studies, 16 885 women). Conclusion Diet and physical activity based interventions during pregnancy reduce gestational weight gain and lower the odds of caesarean section. There is no evidence that effects differ across subgroups of women.
HLA-DQ:gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge
Authors: Vikas K Sarna, Gry I Skodje, Henrik M Reims, Louise F Risnes, Shiva Dahal-Koirala, Ludvig M Sollid, Knut E A Lundin
Journal: Gut (2017)

Initiation of a gluten-free diet without proper diagnostic work-up of coeliac disease is a frequent and demanding problem. Recent diagnostic guidelines suggest a gluten challenge of at least 14 days followed by duodenal biopsy in such patients. The rate of false-negative outcome of this approach remains unclear. We studied responses to 14-day gluten challenge in subjects with treated coeliac disease.We challenged 20 subjects with biopsy-verified coeliac disease, all in confirmed mucosal remission, for 14 days with 5.7 grams per oral gluten daily. Duodenal biopsies were collected. Blood was analysed by multiplex assay for cytokine detection, and by flow cytometry using HLA-DQ:gluten tetramers.Nineteen participants completed the challenge. Villous blunting appeared at end of challenge in 5 of 19 subjects. Villous height to crypt depth ratio reduced with at least 0.4 concomitantly with an increase in intraepithelial lymphocyte count of at least 50% in 9 of 19 subjects. Interleukin-8 plasma concentration increased by more than 100% after 4 hours in 7 of 19 subjects. Frequency of blood CD4+ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells increased by more than 100% on day 6 in 12 of 15 evaluated participants.A 14-day gluten challenge was not enough to establish significant mucosal architectural changes in majority of patients with coeliac disease (sensitivity ≈25%-50%). Increase in CD4+ effector-memory gut-homing HLA-DQ:gluten tetramer-binding T cells in blood 6 days after gluten challenge is a more sensitive and less invasive biomarker that should be validated in a larger study.NCT02464150.
Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Sung-Bae Kim, Rebecca Dent, Seock-Ah Im, Marc Espié, Sibel Blau, Antoinette R Tan, Steven J Isakoff, Mafalda Oliveira, Cristina Saura, Matthew J Wongchenko, Amy V Kapp, Wai Y Chan, Stina M Singel, Daniel J Maslyar, José Baselga, Sung-Bae Kim, Keun Seok Lee, Seock-Ah Im, Marc Espié, Hwei-Chung Wang, Sibel Blau, Rebecca Dent, Antoinette Tan, Joo Hyuk Sohn, Michelino De Laurentiis, Laura Garcia Estevez, Chiun-Sheng Huang, Gilles Romieu, Michel Velez, Rafael Villanueva, Pier Franco Conte, Shaker Dakhil, Marc Debled, Antonio Gonzalez Martin, Sara Hurvitz, Jee Hyun Kim, Christelle Levy, Mafalda Oliveira, Pedro Sanchez Rovira, Jae Hong Seo, Vicente Valero, Gregory Vidal, Andrea Wong, Mary Ann K Allison, Robert Figlin, David Chan, Shin-Cheh Chen, Yen-Hsun Chen, Melody Cobleigh, Filippo De Braud, Luc Dirix, Vincent Hansen, Anne Hardy Bessard, Nicholas Iannotti, Steven Isakoff, William Lawler, Alvaro Montaño, Mohamad Salkini, Leonard Seigel
Journal: The Lancet Oncology (2017)
AB0040 Immune modulatory effects of mesenchymal stem cell to mononuclear cells from patients with active adult onset still's disease
Authors: IW Sohn, H-J Jeong, GY Ahn, MJ Kim, H Kim, S Kang, DH Yoo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adult onset Still9s disease (AOSD) is an inflammatory disorder of unknown etiology, which is accompanied by increased levels of serum pro-inflammatory cytokine. Mesenchymal stem cells (MSCs) have immunomodulatory capacities and might be a promising therapeutic option in the treatment of refractory autoimmune diseases. Both cell-to-cell contact and the release of soluble factors mediate immune modulatory functions of MSCs. <h3>Objectives</h3> We aimed to determine if MSCs could modulate serum cytokine level in patients with active untreated AOSD, either through paracrine secretion or via direct contacts with the MSCs. <h3>Methods</h3> Human peripheral blood mononuclear cells (hPBMCs) from 6 patients with active AOSD were co-cultured for 72 hours with human MSCs (hMSCs at a ratio of 10 to 1). We compared the cytokine levels before and after direct or indirect (transwell cultures) exposition to activated mononuclear cells (LPS, 10ng/ml) or T cell-inducing conditions (anti-CD3 [5 μg/ml], anti-CD28 [5 μg/ml], recombinant human IL-2 [5 ng/ml]). Cytokine levels were detected by multiplex cytokine detection kit by flow cytometry, or ELISA with culture supernatant. In vitro platform for studying the effects of MSCs on individual cytokines, the Wilcoxon signed-rank test was employed for comparison of serum cytokine levels. <h3>Results</h3> Treatment of mononuclear cells with hMSCs resulted in significant reduction of mean TNF-α level (mean 463.4 pg/ml vs 137.8 pg/ml, p&lt;0.05) and IL-1 β (mean 1887.1 pg/ml vs 1127.9 pg/ml, p&lt;0.05). When the hMSCs were present during the T-cell differentiation, there was a significant decrease in the mean secreted TNF-α (mean 10953.5 pg/ml vs 454.9 pg/ml, p&lt;0.05), IFN-γ (mean 14301.0 pg/ml vs 5090.4 pg/ml, p&lt;0.05) and sIL-2 receptor (mean 3550.8 pg/ml vs 2506.4 pg/ml, p&lt;0.05). On the contrary, level of TGF-β was significantly increased (mean 4088.8 pg/ml vs 5104.8 pg/ml, p&lt;0.05). But, there was a significant increase in the amount of IL-6 (mean 2215.5 pg/ml vs 25130.6 pg/ml, p&lt;0.05) and IL-17 α (mean 1357.0 pg/ml vs 2453.6 pg/ml, p&lt;0.05). Two chamber experiments also showed similar pattern of cytokine modulation. <h3>Conclusions</h3> This preliminary experiment demonstrated that MSCs can modulate cyokine profiles of AOSD mononuclear cells by decreasing pro-inflammatory cytokines, and increasing anti-inflammatory cytokine such as TGF-β. However, up-regulation of IL-6 and IL-17 might be a hurdle to overvome in the clinical application of MSCs in AOSD patients. <h3>References</h3> Serum cytokine profiles in patients with Adult onset Still9s disease. J Rheumatol. 2003 Nov;30(11):2422–7. Human mesenchymal stem cells modulated allogeneic immune cell responses. Blood. 2005 Feb 15;105(4):1815–22. Epub 2004 Oct 19. <h3>Acknowledgements</h3> none. <h3>Disclosure of Interest</h3> None declared
Incidence and Outcomes of Infectious and Noninfectious Endophthalmitis after Intravitreal Injections for Age-Related Macular Degeneration
Authors: Vincent Daien, Vuong Nguyen, Rohan W. Essex, Nigel Morlet, Daniel Barthelmes, Mark C. Gillies, M. Gillies, Adrian Hunt, R. Essex, C. Dayajeewa, A. Hunyor, S. Fraser-Bell, C. Younan, A. Fung, R. Guymer, D. Louis, J. Arnold, D. Chan, H. Cass, A. Harper, J. O’Day, M. Daniell, A. Field, L.P. Chow, D. Barthelmes, A. Cohn, S. Young, S. Lal, R. Ferrier, R. Barnes, A. Thompson, A. Vincent, L. Manning, S. Lake, R. Phillips, M. Perks, J.Y. Chen, J. Landers, None Niladri, Gayatri Banerjee, B. Swamy, P. Windle, A. Dunlop, K.C. Tang, I. McLean, A. Amini, Adrian Hunt, G. Clark, I. McAllister, F. Chen, D. Squirrell, C. Ng, P. Hinchcliffe, R. Barry, J. Ah-Chan, H. Steiner, M. Morgan, C. Thompson, J. Game, N. Murray
Journal: Ophthalmology (2017)
HELMET FIT IN YOUTH ICE HOCKEY
Authors: Declan Patton, Shelby Blackmore, Brent Hagel, Carolyn Emery
Journal: British Journal of Sports Medicine (2017)

Background Appropriate helmet fit is thought to contribute to the protective effect of helmets in reducing the risk of concussion in sports. Only one previous study has evaluated helmet fit in youth ice hockey; however, inter-rater reliability was not assessed. Objective To evaluate helmet fit in youth ice hockey players and assess inter-rater reliability of helmet fit criteria. Design Self-report and observational evaluations. Setting 2016 Hockey Calgary Summer Day Camps. Participants Canadian youth (11–18 years) ice hockey players. Methods Helmet fit criteria were developed from previously published ice hockey, skiing, snowboarding and motorcycle helmet fit criteria. A total of 60 players underwent self-report and observational helmet fit evaluations by two independent assessors. Inter-rater reliability was assessed using descriptive statistics and Cohen's kappa coefficient. Results Most players rated helmet fit (90%) and comfort (87%) as ‘excellent’ or ‘good’. Most helmets (93%) and cages (84%) displayed the Canadian Standards Association (CSA) sticker or stamp. Only 23% of players satisfied all helmet fit criteria for both assessors; however, 70% of players failed three or fewer criteria across the evaluations of both assessors. The most commonly failed helmet fit criterion was ‘crown of helmet is 1–2 fingers above eyebrows’, which was failed by 22% of players. For inter-rater reliability, the most commonly disputed helmet fit criterion was ‘helmet does not cover eyes when pressing down’, which was disagreed upon by the assessors for 33% of players; however, all other criteria were agreed upon for over 80% of players. Substantial agreement (K&gt;0.8) was found for 19% of helmet fit criteria, whereas 50% of criteria had little agreement beyond chance (K&lt;0.2). Conclusions The majority of youth ice hockey players did not satisfy all helmet fit criteria for both assessors. The association between helmet fit and concussion needs to be investigated.