tbuckley/cabot-search huggingface dataset:
PTH-003 Endobarrier®: a safe and effective novel treatment for obesity and type 2 diabetes?
Authors: A Mohanaruban, N Patel, H Ashrafian, K Stoenchev, C Le Roux, N Penney, J Kelly, J Byrne, J Hopkins, J Mason, J Teare
Journal: Endoscopy (2017)

<h3>Introduction</h3> Obesity is a modern pandemic. One of the major complications of obesity is the development of diabetes which leads to considerable mortality, morbidity and enormous health care costs.<sup>1</sup> The EndoBarrier is an endoscopically implantable duodenal-jejunal sleeve bypass (DJSB); anchored in the duodenum, preventing ingested food from coming into contact with the proximal intestine and induces weight loss and improvement in glycaemic control. The aim of this prospective study was to assess the safety and efficacy of the EndoBarrier in obese patients with type 2 diabetes. <h3>Method</h3> This was a non-randomised study conducted at three investigational sites (Southampton, London, and Manchester) over an 18 month period with clinical and biochemical assessments carried out at 3 monthly intervals. The device was implanted for 12 months with 6 months follow up. All patients were obese with poorly controlled diabetes. Adverse events were recorded and statistical analysis was performed. <h3>Results</h3> A total of 45 subjects were enrolled into the study At 12 months following implant: 1) HbA1c significantly reduced from baseline at 0.8% below the mean at baseline (95% CI 0.1–1.6; p&lt;0.05). 2) Mean weight loss was 15 kg (95% CI 0.62–29.38; p&lt;0.05) 3) BMI was reduced by 4.9kg/m<sup>2</sup> (95% CI 1.1–8.7; p&lt;0.005). 14 patients withdrew from the study, 6 required premature EndoBarrier removal. Of these, only 2 patients presented with device related complications (device migration and gastrointestinal bleeding), the others withdrew due to unrelated medical adverse events. <h3>Conclusion</h3> The EndoBarrier appears to be a safe and effective treatment strategy in those who are overweight and have poor glycaemic control despite medical therapy, or in those who are eligible but decline bariatric surgery. Larger randomised controlled trials with longer follow-up periods post-explant of the device need to be performed to investigate the device's effects on long term glycaemic control and weight. <h3>Reference</h3> Control C. f. D. &amp; Prevention. Prevalence of overweight and obesity among adults with diagnosed diabetes-United States, 1988–1994 and 1999–2002. MMWR. Morbidity and mortality weekly report2004;53:1066. <h3>Disclosure of Interest</h3> None Declared
Reactive oxygen species-responsive polymeric nanoparticles for alleviating sepsis-induced acute liver injury in mice
Authors: Gan Chen, Hongzhang Deng, Xiang Song, Mingzi Lu, Lian Zhao, Sha Xia, Guoxing You, Jingxiang Zhao, Yulong Zhang, Anjie Dong, Hong Zhou
Journal: Biomaterials (2017)
THE TRANSLATION OF SPORTS INJURY PREVENTION AND SAFETY PROMOTION KNOWLEDGE: INSIGHTS FROM KEY ORGANISATIONS
Authors: Sheree Bekker, Penny Paliadelis, Caroline Finch
Journal: British Journal of Sports Medicine (2017)

Background A recognised research-to-practice gap exists in the field of sports injury prevention and safety promotion. The role of key organisations in increasing the relevancy, accessibility, and legitimacy of injury prevention and safety promotion research knowledge for sport settings remains under-explored. Objective This study sought to provide new insight into the knowledge translation activities undertaken by a set of key organisations that work to ‘bridge the gap’ between research and practice in sport settings. Design Semi-structured face-to-face interviews about organisational processes of knowledge translation were undertaken with representatives from five key organisations. Setting The National Guidance for Australian Football Partnerships and Safety (NoGAPS) project provided a clear and purposeful context for this study. Participants The participants in this study were the self-nominated representatives from the following NoGAPS partnership organisations: 1) Australian Football League, 2) Victorian Health Promotion Foundation, 3) JLT Sport as a division of Jardine Lloyd Thompson Australia Pty Ltd, 4) Sport and Recreation Victoria, and 5) Sports Medicine Australia. Main Outcome Measurements A qualitative descriptive methodology was used to analyse participants' descriptions of knowledge translation activities undertaken at their respective organisations. Results Several knowledge translation processes and considerations emerged around three key themes: 1) identifying a need for knowledge translation, 2) developing and disseminating resources, and 3) barriers and enablers to knowledge translation. Conclusions This study provides new insight into knowledge translation processes that key organisations undertake when developing and disseminating injury prevention and safety promotion resources for sport settings. The role these organisations play in increasing the relevancy, accessibility, and legitimacy of research knowledge through the development of useful injury prevention and safety promotion resources is key to influencing policy and practice in sport settings.
How Dangerous Is Hyperkalemia?
Authors: John R. Montford, Stuart Linas
Journal: Journal of the American Society of Nephrology (2017)

Hyperkalemia is a potentially life-threatening electrolyte disorder appreciated with greater frequency in patients with renal disease, heart failure, and with use of certain medications such as renin angiotensin aldosterone inhibitors. The traditional views that hyperkalemia can be reliably diagnosed by electrocardiogram and that particular levels of hyperkalemia confer cardiotoxic risk have been challenged by several reports of patients with atypic presentations. Epidemiologic data demonstrate strong associations of morbidity and mortality in patients with hyperkalemia but these associations appear disconnected in certain patient populations and in differing clinical presentations. Physiologic adaptation, structural cardiac disease, medication use, and degree of concurrent illness might predispose certain patients presenting with hyperkalemia to a lower or higher threshold for toxicity. These factors are often overlooked; yet data suggest that the clinical context in which hyperkalemia develops is at least as important as the degree of hyperkalemia is in determining patient outcome. This review summarizes the clinical data linking hyperkalemia with poor outcomes and discusses how the efficacy of certain treatments might depend on the clinical presentation.
THE EPIDEMIOLOGY OF US HIGH SCHOOL FOOTBALL (SOCCER) INJURIES, 2005–06 THROUGH 2013–14
Authors: Morteza Khodaee, Dustin W Currie, Irfan Asif, R. Dawn Comstock
Journal: British Journal of Sports Medicine (2017)

Background Despite the worldwide popularity of football, research on epidemiology of high school injury is sparse. Objective To describe high school football injury rates and patterns by type of athletic exposure and gender. Design This descriptive epidemiologic study used retrospective analysis of high school sports injury data from a multi-year US surveillance program capturing data from a large national cohort of schools. Setting Annually, this prospective surveillance study recruits 100 US high schools with National Athletic Trainers' Association affiliated, athletic trainers to report exposure and injury data for athletes participating in school-sanctioned high school sports. Participants Student football players from these nationally representative high schools from 2005–06 through 2013–14. Assessment of Risk Factors Independent variables included gender, mechanism of injury, playing position, and field location. Main Outcome Measurements Rates and patterns of football-related injuries. Results Overall 6154 football injuries occurred during 2,985,991 athlete exposures (AEs); injury rate of 2.06 per 1000 AEs. This corresponded to a national estimate of 3,381,189 US high school football-related injuries. Injury rates were higher in girls (2.33) than boys (1.83) (RR=1.27, 95% CI 1.21–1.34). Player-player contact more commonly resulted in competition injuries (injury proportion ratio [IPR]=2.87; 95% CI 2.57–3.21), while noncontact mechanisms were more common among practice injuries (IPR=2.10; 95% CI 1.86–2.38). Most injuries occurred to midfielders (37.6%), followed by forwards (28.9%), and defenders (23.6%).. The most common activities leading to injuries were general play (24%), defending (13%), and chasing a loose ball (11%). Injury patterns were similar between genders with respect to position played and location on the field at the time of injury. Conclusions High school football injury rates vary by gender and type of exposure while injury patterns are more similar across genders. These findings should drive additional research into development, implementation, and evaluation of targeted injury prevention efforts.
08.14 IL-23 receptor signalling is critical in normal bone remodelling and influences osteoclast activity in vitro and t cell-driven inflammatory bone damage in vivo
Authors: Wida Razawy, Patrick S Asmawidjaja, Adriana MC Mus, Marijke Schreuders-Koedam, Marlieke Molendijk, Mohamed Oukka, Vijay K Kuchroo, Bram CJ van der Eerden, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The interleukin (IL)−23/IL-17A immune pathway is critical for the development of autoimmune arthritis. Moreover, systemic exposure of IL-23 induced chronic arthritis, increased osteoclast differentiation and systemic bone loss in mice. However, the role of IL-23 on normal and pathologic bone remodelling is not fully elucidated. We studied the role of IL-23R signalling on normal bone phenotype and bone damage during a T cell-mediated inflammatory arthritis <i>in vivo</i> and osteoclast differentiation and activity <i>in vitro.</i> <h3>Materials and methods</h3> For antigen-induced arthritis (AIA), WT and IL-23R<sup>GFP+/GFP+</sup> (IL-23R<sup>/-</sup>) mice were immunised with methylated bovine serum albumin (mBSA) in supplemented Complete Freund’s Adjuvant. After 7 days mice were injected in the knee joints with mBSA. Mice were macroscopically scored at given time points and knees were used for histological analysis. Naïve WT and IL-23R<sup>/-</sup> bone marrow cells (BM) were cultured towards osteoclasts with MCSF, RANKL and +/- IL-23 and assessed for tartrate-resistant acid phosphatase (TRAP) staining, qPCRs and bone resorption. Femurs were used for MicroCT analysis and three-point bending test. <h3>Results</h3> During AIA the onset of disease was not prevented in IL-23R<sup>-/-</sup> mice. However, the progression of arthritis was diminished, resulting in significantly less disease. Histological analysis revealed significantly less inflammation-mediated bone damage in knees of IL-23R<sup>/-</sup> versus WT mice. <i>In vitro</i>, IL-23 had no direct effect on the number of TRAP<sup>+</sup> cells, but increased bone resorption by osteoclasts. Interestingly, microCT data revealed a low bone mass phenotype in IL-23R<sup>-/-</sup> mice, with lower trabecular bone volume fraction, thickness and number as well as lower cortical volume and thickness. Preliminary three-point bending data show significantly reduced maximum force in IL-23RKO femurs. <h3>Conclusions</h3> <i>In vitro</i>, IL-23 is involved in the activation of osteoclasts. Whereas T cell-driven inflammatory bone erosion is IL-23R signalling mediated, during normal bone remodelling IL-23R signalling is important for the maintenance of bone mass.
AMETROPIA, VISUAL DEFICITS AND MOTOR PERFORMANCE IN SCHOOL SPORTS
Authors: Gernot Jendrusch, Vanessa Oertzen-Hagemann, Petra Platen
Journal: British Journal of Sports Medicine (2017)

Background In childhood/puberty essential physical and school developments take place. Poor eyesight in this phase represents a handicap, as is known. Concluding, the basic correlation between a good eyesight and a safe, successful engaging in sports activities, as well as a motor development are documented through numerous studies. A database concerning the topic “Ametropia in school and its consequences on motor abilities” does not yet exist. Design Against this background a study at 17 elementary and 6 high schools concerning ametropia in school sports, together with a simultaneous survey of motor abilities has been carried out. Participants were tested with eight tests to assess a motor fitness profile involving strength, endurance, coordination and flexibility. In parallel, various tests to detect ametropia have been carried out (visual-acuity-test, auto-refraction, stereoacuity- and contrast-sensitivity-test). Participants A total of 1.222 children (52.2% male; 47.8% female) at the age of 5–18 participated in the test (age: 8.9±1.7 years). Results A synoptic view of the visual test results showed that 25.4% of the children were classified as ametropic (needing correction). This means, a defective vision/ametropia has been discovered for the first time, or else they participated in school sports without actually needed visual aids, or rather, with insufficient correction. The children with ametropia attained significantly worse overall results in the motor performance test than the ones without defective vision (2p&lt;0.05). 38.3% of the pupils with ametropia achieved results below or far below average in the motor performance test (emmetropic students: 12.1%). The coordination test balancing backwards showed analog results. Conclusions The high rate of ametropia and the correlation between eyesight in deficit and weaknesses in motor performance shows that regular visual tests are necessary in order to enable the detection and correction of deficits early. Simple screening tests should be implemented in the everyday school (sport) life.
Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis
Authors: Rudi Alberts, Elisabeth M G de Vries, Elizabeth C Goode, Xiaojun Jiang, Fotis Sampaziotis, Krista Rombouts, Katrin Böttcher, Trine Folseraas, Tobias J Weismüller, Andrew L Mason, Weiwei Wang, Graeme Alexander, Domenico Alvaro, Annika Bergquist, Niklas K Björkström, Ulrich Beuers, Einar Björnsson, Kirsten Muri Boberg, Christopher L Bowlus, Maria C Bragazzi, Marco Carbone, Olivier Chazouillères, Angela Cheung, Georgios Dalekos, John Eaton, Bertus Eksteen, David Ellinghaus, Martti Färkkilä, Eleonora A M Festen, Annarosa Floreani, Irene Franceschet, Daniel Nils Gotthardt, Gideon M Hirschfield, Bart van Hoek, Kristian Holm, Simon Hohenester, Johannes Roksund Hov, Floris Imhann, Pietro Invernizzi, Brian D Juran, Henrike Lenzen, Wolfgang Lieb, Jimmy Z Liu, Hanns-Ulrich Marschall, Marco Marzioni, Espen Melum, Piotr Milkiewicz, Tobias Müller, Albert Pares, Christian Rupp, Christian Rust, Richard N Sandford, Christoph Schramm, Stefan Schreiber, Erik Schrumpf, Mark S Silverberg, Brijesh Srivastava, Martina Sterneck, Andreas Teufel, Ludovic Vallier, Joanne Verheij, Arnau Vich Vila, Boudewijn de Vries, Kalliopi Zachou, Roger W Chapman, Michael P Manns, Massimo Pinzani, Simon M Rushbrook, Konstantinos N Lazaridis, Andre Franke, Carl A Anderson, Tom H Karlsen, Cyriel Y Ponsioen, Rinse K Weersma
Journal: Gut (2017)

Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07×10 –9 ). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3 , we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.
02.42 Description of a series of patients with psoriatic arthritis treatment with biological therapy
Authors: Raquel Hernández, Julia Uceda, Carmen Almeida, Jose L. Marenco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Introduction</h3> Psoriatic arthritis (PSA) is a chronic inflammatory joint disease associated with the presence of cutaneous psoriasis. <h3>Objective</h3> The main aim was to describe the characteristics of a series of patients from the southern hospital area of Seville (Hospital Virgen de Valme) with PSA diagnosis in treatment with biological therapies (TB) <h3>Material and methods</h3> Retrospective observational study of 25 patients diagnosed with APS with peripheral affection according to CASPAR criteria, in treatment with TB registered in the database of the UGC of Rheumatology of the hospital Virgen de Valme. Description of baseline sociodemographic characteristics, age, sex, APs form, cutaneous involvement, and indicated biological therapies. <h3>Results</h3> A total of 25 patients have been reviewed. Of these, 68% were men, compared to 32% women. The mean age at present is 48 years, and the mean age at diagnosis is 37 years. Or this 92% has cutaneous involvement and 12% of nail involvement. The clinical profiles were : 40% has polyarticular afecction, 36% oligoarticular, 12% axial, 8% axial and peripheral, and 4% involvement of the distal interphalangeal. WE don´t have a mutilante form. The TB most used as first line of treatment was Etanercept in 36%, followed by Infliximab in 32%, and Adalimumab (16%). In the 2nd line of treatment, we again find Etanercept as the most used drug followed by Adalimumab, which was the most used also in 3rd line. Exceptionally, we observed a single patient with highly refractory psoriatic arthritis treated with Abatacept in the fourth line and currently being treated with Ustekinumab in the 5th line. (After 6 months of treatment it has a NAT=0 and NAD=0 and a cutaneous involvement with a BSA &lt;3%) Finally we found the 84% of the patients were responders to the 1 st biological therapy measured by a DAS28 &lt;2.6 (almost remission) or, failing that, a DAS28 &lt;3.2 (low activity) and/or an MAE. <h3>Conclusion</h3> In our sample we found a predominance of male involvement in the most aggressive forms. Peripheral involvement is the most frequent, coinciding with the patterns described in the literature and most of the patients had cutaneous symptoms. TB in general is effective in archieved high response rates after the first biological in real clinical practice conditions. Finally, the newly accepted therapies, anti-IL 17 and IL 12–23 drugs extend the therapeutic arsenal with data on efficacy and safety in real clinical practice.
Differential Toxicity in Patients with and without DNA Repair Mutations: Phase I Study of Carboplatin and Talazoparib in Advanced Solid Tumors
Authors: Mallika S. Dhawan, Imke H. Bartelink, Rahul Raj Aggarwal, Jim Leng, Jenna Z. Zhang, Nela Pawlowska, Manuela Terranova-Barberio, Jennifer A. Grabowsky, Andrew Gewitz, Amy J. Chien, Mark Moasser, Robin K. Kelley, Tayeba Maktabi, Scott Thomas, Pamela N. Munster
Journal: Clinical Cancer Research (2017)

Purpose: The PARP inhibitor (PARPi) talazoparib may potentiate activity of chemotherapy and toxicity in cells vulnerable to DNA damage.Experimental Design: This phase I study evaluated the safety, tolerability, pharmacokinetics, and efficacy of talazoparib and carboplatin. Pharmacokinetic modeling explored associations between DNA vulnerability and hematologic toxicity.Results: Twenty-four patients (eight males; 16 females) with solid tumors were enrolled in four cohorts at 0.75 and 1 mg daily talazoparib and weekly carboplatin (AUC 1 and 1.5, every 2 weeks or every 3 weeks), including 14 patients (58%) with prior platinum treatment. Dose-limiting toxicities included grade 3 fatigue and grade 4 thrombocytopenia; the MTD was not reached. Grade 3/4 toxicities included fatigue (13%), neutropenia (63%), thrombocytopenia (29%), and anemia (38%). After cycle 2's dose, delays/reductions were required in all patients. One complete and two partial responses occurred in germline BRCA1/2 (gBRCA1/2) patients. Four patients showed stable disease beyond 4 months, three of which had known mutations in DNA repair pathways. Pharmacokinetic toxicity modeling suggests that after three cycles of carboplatin AUC 1.5 every 3 weeks and talazoparib 1 mg daily, neutrophil counts decreased 78% [confidence interval (CI), 87-68] from baseline in gBRCA carriers and 63% (CI, 72-55) in noncarriers (P < 0.001). Pharmacokinetic toxicity modeling suggests an intermittent, pulse dosing schedule of PARP inhibition, differentiated by gBRCA mutation status, may improve the benefit/risk ratio of combination therapy.Conclusions: Carboplatin and talazoparib showed efficacy in DNA damage mutation carriers, but hematologic toxicity was more pronounced in gBRCA carriers. Carboplatin is best combined with intermittent talazoparib dosing differentiated by germline and somatic DNA damage mutation carriers. Clin Cancer Res; 23(21); 6400-10. ©2017 AACR.
Acquired anhidrosis associated with systemic sarcoidosis: quantification of nerve fibres around eccrine glands by confocal microscopy
Authors: M. Nishida, T. Namiki, Y. Sone, T. Hashimoto, S. Tokoro, T. Hanafusa, H. Yokozeki
Journal: British Journal of Dermatology (2017)

Neurological disorders can cause hypohidrosis and/or anhidrosis by disturbing either the central or the peripheral nervous systems.1-3 Although a syringotropic variant of cutaneous sarcoidosis causes dysfunction of sweating, systemic sarcoidosis rarely causes hypohidrosis or anhidrosis.4,5 Here we present a novel case of an acquired anhidrosis in a patient with systemic sarcoidosis. Furthermore, we developed a novel methodology to quantify nerve fibers around eccrine glands using confocal microscopy and found that nerve fibers around eccrine glands in anhidrotic areas are significantly decreased compared to hidrotic areas.

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