tbuckley/cabot-search huggingface dataset:
POSSIBLE STRENGTH DEFICIT IN SHOULDER ROTATION FOR HYPERMOBILE SWIMMERS
Authors: Behnam Liaghat, Aki Salo, Birgit Juul-Kristensen
Journal: British Journal of Sports Medicine (2017)

Background Generalised Joint Hypermobility (GJH) is considered an intrinsic risk factor for shoulder injuries and has a high prevalence in swimmers. Objective The aim of this study was to investigate the influence of GJH on shoulder muscle strength, muscle activity and muscle fatigue during shoulder rotation movement simulating swimming strokes. Design Cross-sectional study. Setting Youth elite sports. Patients (or Participants) 19 elite swimmers with GJH (Beighton's score ≥5 and hypermobile shoulder) were compared to 19 sex- and age-matched control swimmers (Beighton's score ≤3 and no shoulder hypermobility), all 13–17 years. Interventions (or Assessment of Risk Factors) Concentric isokinetic performance in medial rotation (35 ° ) and lateral rotation (60 ° ) was measured at velocities of 60 ° /s (5 repetitions) and 180 ° /s (10 repetitions). Muscle activity during isokinetic testing was measured with surface electromyography from upper trapezius, lower trapezius, serratus anterior, infraspinatus and pectoralis major. Main Outcome Measurements Peak torque (Nm/BW), total work (J/BW), electromyographic muscle activity (%MVC), and isokinetic and electromyographic fatigue development. Results In medial rotation at 60 ° /s, there was a significantly lower (14%) total work compared with controls (2.80 vs. 3.26 J/BW; p=0.049), and a tendency to significantly lower peak torque for the GJH group (0.48 vs. 0.55 Nm/BW; p=0.057). There were no group differences in medial rotation at 180 ° /s, or in lateral rotation at both velocities. Muscle activity was non-significantly lower in serratus anterior (range: 27–33%) and pectoralis major (range: 19–26%) in the GJH group in medial rotation. Fatigue development did not differ between groups. Conclusions Young elite swimmers with GJH displayed decreased medial rotation endurance and strength, which may be potential intrinsic risk factor for development of non-traumatic shoulder injury. These swimmers may benefit from medial rotation endurance and strengthening programs; however, further research is warranted to understand the consequences of such deficits and the corresponding preventive concepts.
Long-term results of a phase 2 study of rituximab and bendamustine for mucosa-associated lymphoid tissue lymphoma
Authors: Antonio Salar, Eva Domingo-Domenech, Carlos Panizo, Concepción Nicolás, Joan Bargay, Ana Muntañola, Miguel Canales, José Luis Bello, Juan Manuel Sancho, José Francisco Tomás, María José Rodríguez, Javier Peñalver, Carlos Grande, José Javier Sánchez-Blanco, Luis Palomera, Reyes Arranz, Eulogio Conde, Mar García, Juan Fernando García, Dolores Caballero, Carlos Montalbán
Journal: Blood (2017)
WEEKLY ANKLE LUNGE TEST SCREENING MIGHT HELP PREVENT ANKLE INJURIES
Authors: Mati Arend, Maarja Kalev, Jarek Mäestu
Journal: British Journal of Sports Medicine (2017)

Background Research has shown that almost 80% of injuries in track and field athletes affect the lower limb. Therefore, it is important to regularly monitor the condition of athlete's musculoskeletal system to prevent injuries. Simplified measurement of ankle dorsiflexion (DF) with ALT has shown to predict injuries to the lower limb. Objective To prevent ankle injuries through weekly monitoring of Ankle Lunge Test (ALT). Design A case series study of weekly ALT screening and injury registration during the 15 week training period. Participants were blinded to the results. Testing was carried out by one physiotherapist following athletes' rest day during the same time period of the day. Setting University of Tartu Academic Sports Club, Track and field team. Patients (or Participants) Seven male (age 21.4±1.0 years; height 184.4±5.5 cm; weight 79.7±6.2 kg; training experience 6.9±3.2 years) and five female (age 22.2±1.3 years; height 171.6±10.7 cm; weight 60.2±6.3 kg; training experience 8.6±3.3 years) semiprofessional track and field athletes. Interventions (or Assessment of Risk Factors) ALT was measured as a distance from the great toe to the wall (nearest 0.1 cm on a tape measure). Main Outcome Measurements Variance of weekly ALT measurements compared to standard deviation of the same test and registered injuries. Results Five athletes (42% of the cohort) suffered an injury to the ankle area. Statistically significant (p&lt;0.05) differences in mean ankle DF was found in four athletes. Also, ankle DF measurements were outside an average standard deviation in four athletes (80% of the ankle injury cohort) prior to the injury. Conclusions Comparing the weekly ALT results to the standard deviation of the previous average values may predict the athletes at increased risk of ankle overuse injuries. This may give valuable information to medical staff to regularly assess the athlete before increasing training load or intensity to keep the athlete injury free.
Expansion of Treatment for Hepatitis C Virus Infection by Task Shifting to Community-Based Nonspecialist Providers
Authors: Sarah Kattakuzhy, Chloe Gross, Benjamin Emmanuel, Gebeyehu Teferi, Veronica Jenkins, Rachel Silk, Elizabeth Akoth, Aurielle Thomas, Charisse Ahmed, Michelle Espinosa, Angie Price, Elana Rosenthal, Lydia Tang, Eleanor Wilson, Soren Bentzen, Henry Masur, Shyam Kottilil
Journal: Annals of Internal Medicine (2017)

Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection has resulted in high rates of disease cure; however, not enough specialists currently are available to provide care.
Abstract P051: Induction of Cardiac Nitrosative Stress and Cell Death by Chronic Alcohol Consumption in an Angiotensin II-, PKC-, and NOX-Dependent Manner
Authors: Yi Tan, Zhanxiang Zhou Zhou, Lu Cai
Journal: Circulation Research (2011)

Alcohol induced cardiac cell death is causative of cardiomyopathy, but the mechanisms responsible for alcoholic cardiac cell death remain largely unknown. We hypothesize that alcohol-induced Ang II plays a critical role in cardiac nitrosative stress, cell death and cardiomyopathy. To test this hypothesis, male C57BL/6 mice were pair-fed an alcohol or isocaloric maltose dextrin liquid diet for 2 months. Alcohol feeding caused significant cardiac cell death and nitrosative damage (shown by TUNEL positive cells, caspase-3 activation and protein nitration) and cardiac remodeling (shown by hypertrophy and fibrosis) along with increases in serum Ang II and cardiac AT1 expression. Mechanistic study in which cardiac H9c2 cells were treated with 100–400 mM alcohol for 24h revealed that alcohol exposure induced cell death, nitrosative damage and fibrosis, along with NADPH oxidase p47 phox (NOX) activation in a dose-dependent manner. Pre-treatment of alcohol-treated cells with NOX inhibitor (apycinin), peroxynitrite scavenger (urate), NOS inhibitor (L-NAME) and superoxide dismutase mimic (MnTMPyP) significantly abolished alcohol induced cell death. Furthermore, exposure to alcohol significantly up-regulated the expression of angiotensin II (Ang II) and its type 1 receptor (AT1) in these cultured cardiac cells. Either PKCα/β1 inhibitor or AT1 blocker completely prevented alcoholic NOX activation, and AT1 blocker inhibited the expression of PKCβ1, implying that alcoholic NOX activation is dependent of PKCα/β1 activation via AT1. To validate the in vitro findings, alcohol-fed and pair-fed mice were treated with MnTMPyP (5 mg/Kg) daily for 2 months, which did not change blood pressure, alcohol-induced cardiac PKC and NOX activation, but significantly prevented alcohol-induced cardiac nitrosative damage and cell death, along with a prevention of cardiac fibrosis and dysfunction. These results suggest that alcohol-induced cardiac cell death is mediated by up-regulated Ang II that via AT1 induces PKCα/β1-dependent NOX activation. The cardiac cell death plays a critical role in the development of alcoholic cardiomyopathy.
08.49 Efficacy of an intensive 24-week physiotherapy programme in scleroderma patients – preliminary data from a single-centre controlled study
Authors: Maja Spiritovic, Hana Smucrova, Sabina Oreska, Hana Storkanova, Petr Cesak, Adela Rathouska, Olga Ruzickova, Herman Mann, Karel Pavelka, Ladislav Senolt, Jiri Vencovsky, Radim Becvar, Michal Tomcik
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Involvement of skin and musculoskeletal system in systemic sclerosis (SSc) leads to loss of function, disability and reduced quality of life. Data on efficacy of non-pharmacologic care in SSc is very limited due to variety in studied interventions/outcomes. <h3>Objectives and methods</h3> To address the limitations of existing studies, and evaluate the effect of a controlled, long-term (24-week intervention, 24-week follow-up), intensive (1 hour physiotherapy +0.5 hour occupational therapy twice weekly, and home-exercise for 0.5 hour 5x weekly), tailored physiotherapy program on function/impairment of hands/face, and quality of life/disability in cohorts with a substantial number of SSc patients. All patients fulfilled ACR/EULAR 2013 criteria, had skin involvement of hands/mouth, and were consecutively recruited between 2014–2016. At months 0,3,6,12 all patients were assessed by a physician (physical history, mRSS, EUSTAR SSc activity score, Medsger severity score), and a physiotherapist blinded to intervention [validated measurements (dFTP-delta finger to palm, inter-incisor/inter-lip distance, grip strength using Baseline dynamometer ); tests (HAMIS-Hand Mobility In Scleroderma)], patients filled out PRO questionnaires (CHFS-Cochin Hand Function Scale, MHISS-Mouth Handicap In SSc Scale, HAQ, SHAQ, SF-36) and provided blood for routine laboratory analysis and biobanking. Normality of data was tested and inter-group analysis performed with 2-way ANOVA and intra-group analysis by Friedmann's test with Dunn's post hoc test. <h3>Results</h3> 25 SSc patients (22 female/3 male, 14 lcSSc/11dcSSc, median of age 54.0 and disease duration 7.0 years, mRSS 12) were recruited into the intervention group (IG) and 29 patients into CG (25 female/4 male, 16 lcSSc/13 dcSSc, median of age 49.0 and disease duration 5.0 years, mRSS 11). Compared to observed statistically significant deterioration in CG over the period of m0-m6, we found statistically significant improvement in dFTP, grip strength, HAMIS, inter-incisor and inter-lip distance. Only numerical improvement in IG compared to numerical deterioration in CG, which have not reached statistical significance, were observed in patient reported outcomes (CHFS, MHISS, HAQ, SHAQ, SF-36). <h3>Conclusions</h3> Our physiotherapy program not only prevented the natural course of progressive deterioration of function of hands/mouth (observed in CG), but led to a significant improvement in monitored parameters, which was clinically meaningful in a substantial proportion of patients. <h3>Acknowledgement</h3> Supported by AZV-16–33574A.
Survival and phenotypic responses of fully activated human hepatic stellate cells to superoxide and TNF: critical role of generation rate and Bcl-2 levels
Authors: E Novo, F Marra, E Zamara, Bonzo Valfrè di, S Cannito, A Mazzocca, A Caligiuri, S Colombatto, R Autelli, M Pinzani, M. Parola
Journal: Hepatology (2005)
Pratique de l’endoscopie pour l’exploration du reflux gastro-ésophagien: observatoire national réalisé auprès de Gastro-entérologues du secteur libéral
Authors: J Escourrou, J Corallo, A Caekaert, P Barthelemy
Journal: Endoscopy (2004)

Introduction: Le but de cet observatoire a été d’évaluer le motif, le mode deréalisation, les résultats de l’endoscopie oeso-gastro-duodénale (EOGD) dans la prise en charge du reflux gastro-ésophagien (RGO) auprès de Gastro-Entérologues (GE) exerçant en secteur libéral. Patients et Méthodes: L’observatoire transversal mis en place en France en octobre 2002, a impliqué 480 GE du secteur libéral qui devaient recruter 4 patients (Pts) adultes présentant des symptômes typiques ou non de RGO pour lesquels une EOGD était réalisée ou programmée le jour de la consultation. Résultats: Mille sept cent soixante-dix-sept Pts (âge: 52 ± 16 ans, 54% hommes, BMI: 25,5, tabac: 18,5%) ont été inclus. Ils étaient adressés par le médecin généraliste (MG) (62%), un spécialiste (8%) ou consultaient en accès direct (30%). Le RGO était connu pour 65% des Pts et, dans ce cas, la médiane d’ancienneté du RGO était de 3 ans. Le diagnostic initial avait été posé par le MG (57%), le GE (40%), autre (3%). Lors de la consultation du jour, les symptômes de pyrosis, de douleurs épigastriques, de régurgitations acides, de dysphagie étaient présents dans respectivement 77%, 52%, 47%, 10% des cas; 74% des Pts avaient des symptômes quotidiens. Cinquante pour cent des Pts étaient traités et 24% suivaient des règles hygiéno-diététiques. Les motifs de l’EOGD était: endoscopie initiale (73%), modification des symptômes (14%), contrôle de cicatrisation (6%), signes extra-digestifs (4%), surveillance d’un endobrachy-ésophage (EBO, 3%). L’EOGD était réalisée sans anesthésie générale (AG), avec AG ou sédation, dans respectivement 56%, 36%, 8% des cas. L’ EOGD montrait des érosions chez 54% des Pts (classification de Los Angeles A: 48%, B: 37%, C: 11%, D: 4%), une hernie hiatale (53%), un EBO (7%), une sténose (2%), un adénocarcinome (0,5%, n = 9). Des biopsies ont été réalisées chez 506 Pts (29%) pour recherche de H. pylori (n = 352, 70%) et EBO (n = 89, 17,6%). La recherche de H. pylori. était positive dans 30% des cas. Les biopsies sur EBO ont montré une dysplasie dans 9% (n = 8) des cas. A l’issue de la consultation, 87% des Pts recevaient un traitement (83% IPP, 8% prokinétique, 7% anti-acide). Le retentissement du RGO sur la qualité de vie était moyenne à forte pour 89% des Pts. Quatre-vingt-six pour cent des Pts étaient satisfaits de leur prise en charge, mais pour 55% des GE, le RGO pourrait être mieux contrôlé. Conclusion: Dans la prise en charge du RGO au sein d’une population consultant un GE, l’EOGD était principalement motivée pour le diagnostic initial, et dans plus de la moitié des cas, une oesophagite était diagnostiquée. Quand l’EBO était biopsié, une dysplasie était retrouvée dans 9% des cas.
NHS decision to deny drug to boy with severe autism was “fundamentally flawed”
Authors: Clare Dyer
Journal: BMJ (2017)

A High Court judge has quashed a “fundamentally flawed” decision by the NHS to refuse funding for a “life changing” drug for a 7 year old boy with severe autism and phenylketonuria (PKU).

Mrs Justice Andrews said that NHS England had made “error upon error” in the steps it took in deciding not to fund sapropterin dihydrochloride (Kuvan) for the boy, “SB,” who displays violent and challenging behaviour and whose autism makes the usual dietary treatment for PKU hard to manage.

The judge quashed that decision, taken last December, and has sent the case back for reconsideration. But she warned against “raising hopes too high,” noting that it was still open to the panel to use its …
Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials
Authors: Arjun Lakshman, Jithma P. Abeykoon, Shaji K. Kumar, S. Vincent Rajkumar, David Dingli, Francis K. Buadi, Wilson I. Gonsalves, Nelson Leung, Angela Dispenzieri, Taxiarchis V. Kourelis, Ronald S. Go, Martha Q. Lacy, Miriam A. Hobbs, Yi Lin, Rahma Warsame, John Lust, Amie L. Fonder, Yi L. Hwa, Suzanne R. Hayman, Stephen J. Russell, Robert A. Kyle, Morie A. Gertz, Prashant Kapoor
Journal: American Journal of Hematology (2017)

Outside of clinical trials, experience with daratumumab-based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43-93) years. High-risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1-14) and time to first DCT from diagnosis was 4.3 years (range, 0.4-13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty-two (41%), 34 (27%), 23 (18%), and 17 (14%) received DPd, DRd, DVd and "other" DCTs, respectively. Overall response rate was 47%. Median follow-up was 5.5 months (95% CI, 4.2-6.1). Median progression-free survival (PFS) was 5.5 months (95% CI, 4.2-7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta-refractory MM (n = 8) vs quadruple refractory MM (n = 18) and others (n = 100) (2.2 [95% CI, 1-2.4] vs 3.1 [95% CI, 2.1-NR] vs 5.9 [95% CI, 5.0-NR]; P < .001); those who were refractory to ≥1 agents used in the DCT vs others (4.9 [95% CI, 3.1-6.0] vs 8.2 [95% CI, 4.6-NR]; P = .02); and those who received >2 prior therapies vs others (5.0 months [95% CI, 3.7-5.9] vs NR [95% CI, NR-NR]; P = .002). Non-hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pretreated patients are lower than those reported in clinical trials.
ALTERATIONS IN REDOX HOMEOSTASIS IN ELITE ENDURANCE ATHLETES DIAGNOSED WITH UNEXPLAINED UNDER-PERFORMANCE SYNDROME (OVERTRAINING SYNDROME)
Authors: Nathan Lewis, John Rogers, Colin Towey, Glyn Howatson, Brian Moore, Charlie Pedlar
Journal: British Journal of Sports Medicine (2017)

Background Alterations in redox homeostasis (ARH) have been implicated in the pathophysiology of Unexplained Under-Performance Syndrome (UUPS). No studies have investigated alterations in ARH in elite athletes with UUPS. Objective To investigate concentrations of antioxidant nutrients and enzymes in world-class endurance athletes diagnosed with UUPS. Design Prospective observational case-control study. Setting UUPS was diagnosed by a sports medicine physician and referred to sports science and nutrition science practitioners for an exercise test, blood work, nutritional history, and an interview involving a questionnaire. Control athletes were required, not to have suffered with any fatigue associated training restrictions for the past four years (Olympic cycle); and tested in the competitive season to ensure performing successfully. Patients (or Participants) Elite endurance athletes from Track &amp; Field and Triathlon (n=16, of which 9 were UUPS and 7 were controls). The athletes were competing at national and international standard, including World and European Championship, Commonwealth and Olympic Games medallists. Main Outcome Measurements Redox biomarkers (α- and β-carotene, lutein, α- and γ-tocopherol, red blood cell superoxide dismutase, total glutathione, and co-enzyme Q10) were measured at rest. Results Resting hydroperoxides (FORT) were significantly higher in controls vs. UUPS athletes (1.40±0.12 vs. 1.89±0.20 mmolŸL −1 H 2 O 2 ; p&lt;0.001, g =2.87). Controls had higher concentrations of total carotenoids (1.49±.052 µmol•L −1 vs. 3.16±1.07 µmol•L −1 , p=0.006, g=2.07) and α-tocopherol than UUPS athletes (22.78±8.54 µmol•L −1 vs. 31.71±5.80 µmol•L −1 , p=0.039, g =1.19). No between-group differences were identified for RBC GSH, SOD, co-enzyme Q10 and γ-tocopherol. Conclusions UUPS athletes have lower concentrations of antioxidant nutrients than healthy elite athletes. We speculate that the measurement of antioxidant nutrients and subsequent dietary interventions may reduce the risk of UUPS in elite endurance athletes.
Safety and Efficacy of 6-thioguanine as a Second-line Treatment for Autoimmune Hepatitis
Authors: Clémence Legué, Ludivine Legros, Solène Kammerer-Jacquet, Caroline Jézequel, Pauline Houssel-Debry, Thomas Uguen, Caroline Le Lan, Anne Guillygomarc’h, Romain Moirand, Bruno Turlin, Dominique Guyader, Edouard Bardou-Jacquet
Journal: Clinical Gastroenterology and Hepatology (2017)
02.35 Time of flight mass cytometry (cytof) and rna sequencing interrogation of ‘pathogenic’ gm-csf lymphocytes in human spondyloarthritis
Authors: Hussein Al-Mossawi, Anna Ridley, Jelle de Wit, Ariane Hammitzsch, Liye Chen, Paul Bowness
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Immunological, genetic and therapeutic studies have implicated T lymphocytes in the pathogenesis of Spondyloarthritis (SpA). GM-CSF is emerging as a cytokine that marks out pathogenic T lymphocytes. Inhibition of this cytokine pathway in the SKG mouse model of SpA leads to improvement of joint scores. <h3>Methods</h3> Matched blood (PBMC) and synovial fluid (SFMC) from patients with SpA was studied <i>ex-vivo</i> using a 40 colour surface and intracellular CyTOF panel. CyTOF findings were validated by flow cytometry in a cohort of patients with SpA, rheumatoid arthritis (RA) controls and healthy donors. CyTOF data was analysed by multi-dimensional viSNE mapping in order to understand the heterogeneity of the synovial fluid inflammatory response. Novel triple cytokine capture was used to purify GM-CSF producing lymphocytes to high purity and RNA sequencing used to interrogate their transcriptional profile. <h3>Results</h3> CyTOF revealed <i>ex-vivo</i> GM-CSF production from multiple lymphoid cell lineages, with CD4 and CD8 cells the main producers in PBMC and SFMC. GM-CSF production overlaps with multiple other cytokines including IL-17A, IFN- and TNF-. 43% (SEM 3.98) of all GM-CSF producing cells in SpA PBMC were CD4 cells. The percentage of CD4 cells producing GM-CSF was significantly increased in SpA PBMC <i>ex-vivo</i> compared to healthy controls (mean 7.73% vs 4.96% n=38, p&lt;0.005). The mean percentage of GM-CSF-positive CD4 cells from <i>ex-vivo</i> SFMCs was 32.2%, and was significantly higher compared to matched PBMC (n=5, p=0.005). RNA sequencing of capture-sorted GM-CSF-positive human CD4 cells showed a unique transcriptional profile and validated key genes previously shown to drive pathogenicity in mouse models of type-17 immune-mediated disease. <h3>Conclusions</h3> The synovial fluid of patients with SpA shows an expanded GM-CSF signature. This corresponds with an expansion of GM-CSF producing T lymphocytes in the peripheral blood of patients with SpA compared to controls. Human GM-CSF-positive CD4 cells have a unique 'pathogenic' transcriptional profile.