tbuckley/cabot-search huggingface dataset:
02.26 Increased expression of s100a9 regulates pain response during experimentally induced acute synovitis
Authors: Edwin JW Geven, Esmeralda N. Blaney Davidson, Elly L. Vitters, Annet W. Sloetjes, Birgitte Walgreen, Arjen B. Blom, Peter L. E. M. van Lent
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Synovitis-associated pain is an important aspect of arthritis pathology. Inflammatory mediators released by the synovium have been implicated in the regulation of pain, including S100A8 and S100A9, which may act via stimulation of TLR4 on the nerve endings in the synovium. In this study we investigated the role of S100A9 in the pain response after induction of an acute synovitis using streptococcal cell walls (SCW) as a trigger, comparing S100A9<sup>-/-</sup> mice and their WT controls. <h3>Materials and methods</h3> Acute synovitis was induced by a single i.a. SCW injection in the knee joint of C57Bl6 (WT) and S100A9<sup>-/-</sup> mice. Serum S100A8/A9 levels were investigated by ELISA and S100A8 and S100A9 expression in synovium by immunohistochemistry. Joint swelling and cell influx was assessed by <sup>99m</sup>Tc accumulation and histology, respectively. Pain response was investigated by Incapacitance Tester (weight bearing), Catwalk (gait analysis) and von Frey's filaments (mechanical allodynia). Gene expression of neuron activation markers in dorsal root ganglia (DRG) were determined by q-PCR. <h3>Results</h3> A single i.a. SCW injection resulted in increased synovial expression of S100A8 and S100A9 as well as significant increased serum S100A8/A9 levels (2.6-fold, p&lt;0.001) 1 day p.i.. These increased levels however, did not contribute to the development of inflammation since joint swelling and cell influx were similar in both mice strains. WT mice showed a significant decrease in percentage of weight bearing on the SCW hindpaw (28%, p&lt;0.001) 1 day p.i., while S100A9<sup>-/-</sup> mice showed no reduction. In line with that, gait analysis showed that the stand-phase of the unaffected paws was significantly increased in WT mice 1 day p.i., but not in S100A9<sup>-/-</sup> mice. No difference in mechanical allodynia was observed, both mouse strains showed a similar reduction of paw withdrawal threshold. Gene expression of neuron activation markers NAV1.7, ATF3 and GAP43 in DRG were significantly increased in SCW injected WT mice 1 day p.i (p=0.022, 0.004 and 0.030, respectively) but not in S100A9<sup>-/-</sup> mice. <h3>Conclusions</h3> These findings show that S100A9, which is released from the synovium upon inflammation, is an important mediator of pain response in the knee during the acute phase of inflammation.
INJURY MECHANISMS OF THE KOREA LADIES PROFESSIONAL GOLFERS, 2015 SEASON PROSPECTIVE STUDY
Authors: Young Moo Na, Young Jae Cho, Hee Seong Jung, Sae Yong Lee
Journal: British Journal of Sports Medicine (2017)

Background Epidemiological study analyzing golf specific injury mechanism has not been conducted in women's professional level golf. Objective To analyze the golf specific injury mechanisms of Korean ladies Professional Golfers in different tour levels of play (ie, Division I, II and III tour). Design Prospective epidemiological study. Setting Using Yonsei Institute of Sports Science and Exercise Medicine Injury Surveillance System (YISSEM ISS) questionnaire survey division I, II and III tour Korean women professional golfers were participated in this study. Patients (or Participants) A total of 388 professional golfers in the 2015 KLPGA tour were recruited. Interventions (or Assessment of Risk Factors) Injuries sustained as a professional golfer. Main Outcome Measurements Time of injury, basic injury mechanism, when and where the injury occurred, amount of golf swing training per day and ground status while injured. A chi-square and logistic regression analysis were conducted to evaluate the golf-related injury mechanisms and any possible risk factors. Results The injury rate was greater in the morning practice (34%) than afternoon (14%) or evening (4%) practice (P&lt;0.05). A total range of 69 to 74% of all injury occurred during golf swing. The injury was most likely to occur during downswing specifically at ball impact (I:42%, II:37%, III:46%) followed by the follow-through (I:17%, II:19%, III:15%). Swing on the bad grass was 101.80 times more likely to result in injury (OR=101.80, CI 9.28–1116.43) and golfers are 58.7 times more likely to get injured during golf swing (OR=58.7, CI 9.23–373.76). Conclusions Golfers are more prone to have injury when practicing golf swing during downswing on the bad grass condition in the morning. It was surprising result that environmental factors which can be quite easily modified results in various types of golf injuries. Before starting golf swing, golfers should check environmental factors to prevent golf injury.
Efficacy and safety data from patients with advanced squamous NSCLC and brain metastases participating in the nivolumab Expanded Access Programme (EAP) in Italy
Authors: P. Bidoli, R. Chiari, A. Catino, F. Grossi, C. Noberasco, F. Gelsomino, M. Gilli, C. Proto, H.J. Soto Parra, M.R. Migliorino, L. Bonomi, D. Tassinari, A. Frassoldati, V. Albanese, G.M. Fadda, F. Cognetti, F. de galitiis, G. Finocchiaro, A. Delmonte
Journal: Annals of Oncology (2016)
Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): High Efficacy of High Dose Chemotherapy and Autologous Stem Cell Transplantation (HDC auto-SCT). A Study of the Lymphoma Working Party (LWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Saad Akhtar, Silvia Montoto, Ariane Boumendil, Luca Castagna, Herve Finel, Tamas Masszi, Pavel Jindra, Damir Nemet, Herrad Baurmann, Yves Beguin, Felicetto Ferrara, Saveria Capria, Ram Malladi, Jose M Moraleda, Gilles Salles, Adrian Bloor, Julia Meissner, Anna Sureda, Peter Dreger
Journal: Blood (2016)
The PKA pathway plays a role in mediating trans-10, cis-12 conjugated linoleic acid-induced apoptosis in mouse mammary tumor cells
Authors: Yung-Chun Hsu, Lihui Ou, Xiaojing Meng, Margot Ip
Journal: Cancer Research (2008)

1253   Conjugated linoleic acid (CLA) has attracted attention for its anti-carcinogenic and anti-obesity properties. In several animal models, including breast, prostate, skin, and colon cancers, CLA has been shown to reduce tumor incidence and inhibit tumor growth. The pro-apoptotic ability of CLA partially accounts for its anti-carcinogenic effect; however, the precise mechanism remains elusive. We have previously shown that after 3 days of treatment, trans-10, cis-12 CLA induced apoptosis of p53-mutant mouse mammary tumor cells (TM4t) in a concentration-dependent manner. CLA-treated cells released cytochrome c within 24h, followed by the cleavage of PARP, and caspases 3 and 9 at ~ 48h. The objective of the current study was to investigate biochemical pathways mediating the apoptotic effect of t10,c12-CLA in TM4t cells. We found that 40μM CLA activated cyclic-AMP-dependent protein kinase A (PKA), as indicated by enhanced phosphorylation of the PKA substrate, cyclic AMP response element binding protein (CREB). Concurrently, expression of the pro-apoptotic protein Bim was increased ~3 and 7 fold at 48 and 72h respectively at the same CLA concentration. Bim has been shown to activate Bax and promote its translocation to mitochondria to induce the release of cytochrome c; its expression has been shown by others to be enhanced by cyclic AMP through PKA. To evaluate the functional significance of the CLA-induced increase in PKA activity, TM4t cells were treated with 10μM of the PKA inhibitor H-89. H-89 repressed CLA-induced CREB phosphorylation and Bim expression. In addition, cleavage of PARP, caspase 3 and caspase 9 were also significantly reduced at 48 and 72h in cells concurrently treated with H-89 and CLA compared to those treated with CLA alone. These findings suggest that the PKA pathway may play a role in mediating CLA-induced apoptosis through Bim activation. Supported by NCI CA61763.
Relationship of lymphocyte and eosinophil counts and immune-related adverse events in recipients of programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.
Authors: Adam Diehl, Mark Yarchoan, Ting Yang, Blake Scott, Burles Avner Johnson, Alexander Hopkins, Nilofer Saba Azad, Elizabeth M. Jaffee, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2017)

e14586 Background: Inhibition of the PD-1 checkpoint can cause immune activation in non-target tissues, resulting in immune-related adverse events (irAE) in up to 50% of patients. Biomarkers that are associated with irAEs in patients treated with PD-1 inhibitors may have implications for patient selection and clinical management. Methods: We performed an IRB-approved retrospective chart review of adult solid tumor patients treated with nivolumab or pembrolizumab at a single institution from January 2015 until November 2016. Patients were excluded if concurrently receiving investigational therapies, or on unreported clinical trials. Data were collected on treatment history, leukocyte counts, and irAE, defined as adverse events with a potential immunologic basis with grading performed using CTCAE v.4.0. Results: 172 patients were included (lung n = 54; melanoma n = 61; kidney n = 25; esophageal n = 12; bladder n = 8; other tumors n = 12) with median age 67. 18% were treated with concurrent ipilimumab. 31% experienced an adverse event of any grade with a mean time to develop an irAE of 3.5 months. Of those with an irAE, 85% required treatment, 68% were grade ≥ 2, 32% were grade 3 or 4 and 35% required therapy discontinuation due to the irAE. In univariate analysis, a higher ALC at both the start of therapy and at 1 month was associated with increased risk of an irAE of grade ≥ 2 (p &lt; 0.05). A higher absolute lymphocyte count (ALC) or higher absolute eosinophil count (AEC) at 1 month into therapy was associated with increased risk of all irAE (p &lt; 0.05) as well as irAE requiring treatment (p &lt; 0.05). In addition, in a multivariate regression analysis including age, race, tumor type, prior chemotherapy, prior radiation, and concurrent ipilimumab therapy, an ALC &gt; 2000 at the start of therapy was a significant predictor of irAE of grade ≥ 2 (p &lt; 0.05 and OR 2.0), as was an ALC &gt; 2000 at 1 month into therapy (p &lt; 0.05 and OR 1.86). Conclusions: These results suggest that high lymphocyte and eosinophil counts early in the course of anti-PD1 therapy may be associated with a higher risk for clinically significant irAE.
Novel lumen-apposing stent to treat benign esophageal stricture
Authors: Antonino Granata, Michele Amata, Dario Ligresti, Ilaria Tarantino, Luca Barresi, Mario Traina
Journal: Endoscopy (2017)

A 58-year-old patient underwent an esophageal epiphrenic diverticulum resection with a video thoracoscopic approach. The surgery was complicated by an esophageal pleural fistula, which was successfully treated using a fully covered self-expandable metal stent.
05.01 Protein profiling in plasma reveals molecular subgroups in systemic lupus erythematosus
Authors: Helena Idborg, Arash Zandian, Cecilia Hellström, Cecilia Mattsson, Claudia Fredolini, Mathias Uhlén, Jochen M Schwenk, Burcu Ayoglu, Maja Neiman, Iva Gunnarsson, Elisabet Svenungsson, Per-Johan Jakobsson, Peter Nilsson
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> Systemic Lupus Erythematosus (SLE) is a heterogeneous systemic autoimmune disease that is currently lacking specific diagnostic biomarkers. The diversity within the patients might obstruct clinical trials and could reflect differences in underlying pathogenesis. Our objective was to identify protein profiles that could be used for diagnosis and to identify molecular subgroups within SLE for patient stratification subjected to different treatment. <h3>Method</h3> In a cross-sectional study we performed protein profiling of 695 plasma samples from SLE patients and matched controls. This was achieved by utilising an antibody suspension bead array targeting 367 proteins. T-test and ROC analysis was performed to identify differences in the protein profiles between SLE and controls. Unsupervised K-means clustering was performed to identify data-driven SLE subgroups. <h3>Results</h3> We report that the novel proteins MMP1, SELE, and S100A12 can distinguish between SLE patients and controls with an area under curve of 0.80 in a ROC analysis. In addition, 28 proteins were found to show differences (corrected p-value&lt;0.05) between SLE patients and controls. By unsupervised clustering we identified an IRF5, NOS3 and CLDN8-driven subgroup, an ARID2 and SELE-driven subgroup and one subgroup characterised by low SLC22A2 levels. <h3>Conclusion</h3> We have identified potential biomarkers of SLE that may be used to improve the diagnosis of SLE patients. Our suggested panel of biomarkers needs to be validated in an additional SLE cohort and also in relation to other systemic autoimmune diseases before it can be used as a diagnostic test. We have also identified subgroups characterised by different molecular patterns, indicating underlying pathogenic differences. These patient groups might benefit from different treatment strategies. Our work adds new information to today's view of classifying the heterogeneous subgroups within SLE and the importance of personalised medicine.
Response to DAA therapy in the NHS England Early Access Programme for rare HCV subtypes from low and middle income countries
Authors: Ana da Silva Filipe, Vattipally Sreenu, Joseph Hughes, Elihu Aranday-Cortes, William L. Irving, Graham R. Foster, Kosh Agarwal, William Rosenberg, Douglas Macdonald, Paul Richardson, Mark A. Aldersley, Martin Wiselka, Andrew Ustianowski, John McLauchlan, Emma C. Thomson
Journal: Journal of Hepatology (2017)
Effects of Rare and Common Blood Pressure Gene Variants on Essential Hypertension
Authors: Khanh-Dung H. Nguyen, Vasyl Pihur, Santhi K. Ganesh, Ankit Rakha, Richard S. Cooper, Steven C. Hunt, Barry I. Freedman, Joe Coresh, W.H. Linda Kao, Alanna C. Morrison, Eric Boerwinkle, Georg B. Ehret, Aravinda Chakravarti
Journal: Circulation Research (2012)

Hypertension affects ≈30% of adults in industrialized countries and is the major risk factor for cardiovascular disease.
Whole-blood RNA transcript-based models can predict clinical response in two large independent clinical studies of patients with advanced melanoma treated with the checkpoint inhibitor, tremelimumab
Authors: Philip Friedlander, Karl Wassmann, Alan M. Christenfeld, David Fisher, Chrisann Kyi, John M. Kirkwood, Nina Bhardwaj, William K. Oh
Journal: Journal for ImmunoTherapy of Cancer (2017)

Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions.Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset). A central panel of radiologists determined objective response using RECIST criteria. Gene expression for 169 mRNA transcripts was measured using quantitative PCR. A 15-gene pre-treatment response-predictive classifier model was identified. An independent population (N = 150) of refractory melanoma patients receiving tremelimumab after chemotherapy enrolled in a worldwide phase II study (validation dataset). The classifier model, using the same genes, coefficients and constants for objective response and one-year survival after treatment, was applied to the validation dataset.A 15-gene pre-treatment classifier model (containing ADAM17, CDK2, CDKN2A, DPP4, ERBB2, HLA-DRA, ICOS, ITGA4, LARGE, MYC, NAB2, NRAS, RHOC, TGFB1, and TIMP1) achieved an area under the curve (AUC) of 0.86 (95% confidence interval 0.81 to 0.91, p < 0.0001) for objective response and 0.6 (95% confidence interval 0.54 to 0.67, p = 0.0066) for one-year survival in the discovery set. This model was validated in the validation set with AUCs of 0.62 (95% confidence interval 0.54 to 0.70 p = 0.0455) for objective response and 0.68 for one-year survival (95% confidence interval 0.59 to 0.75 p = 0.0002).To our knowledge, this is the largest blood-based biomarker study of a checkpoint inhibitor, tremelimumab, which demonstrates a validated pre-treatment mRNA classifier model that predicts clinical response. The data suggest that the model captures a biological signature representative of genes needed for a robust anti-cancer immune response. It also identifies non-responders to tremelimumab at baseline prior to treatment.
Features of Autoimmune Pancreatitis Associated With Inflammatory Bowel Diseases
Authors: Diane Lorenzo, Frédérique Maire, Carmen Stefanescu, Jean-Marc Gornet, Philippe Seksik, Mélanie Serrero, Barbara Bournet, Philippe Marteau, Aurelien Amiot, David Laharie, Caroline Trang, Benoit Coffin, Guy Bellaiche, Guillaume Cadiot, Catherine Reenaers, Antoine Racine, Stephanie Viennot, Arnaud Pauwels, Guillaume Bouguen, Guillaume Savoye, Anne-Laure Pelletier, Guillaume Pineton de Chambrun, Pierre Lahmek, Stéphane Nahon, Vered Abitbol, Vered Abitbol, Matthieu Allez, Aurelien Amiot, Marc Barthet, Laurent Beaugerie, Guy Bellaiche, Guillaume Bouguen, Yoram Bouhnik, Arnaud Bourreille, Barbara Bournet, Gaëlle Brillault, Louis Buscail, Guillaume Cadiot, Franck Carbonnel, Stanislas Chaussade, Benoit Coffin, Jacques Cosnes, Violette Delrieu, Patricia Détré, Jean-Marc Gornet, Jean-Charles Grimaud, Laure Jerber, David Laharie, Pierre Lahmek, Philippe Levy, Edouard Louis, Diane Lorenzo, Frédérique Maire, Philippe Marteau, Jacques Moreau, Stéphane Nahon, Thierry Paupard, Arnaud Pauwels, Anne-Laure Pelletier, Guillaume Pineton de Chambrun, Antoine Racine, Vinciane Rebours, Catherine Reenaers, Philippe Ruszniewski, Guillaume Savoye, Philippe Seksik, Mélanie Sererro, Marion Simon, Harry Sokol, Carmen Stefanescu, Gilles Tordjman, Caroline Trang, Stephanie Viennot
Journal: Clinical Gastroenterology and Hepatology (2017)
Financial toxicity of cancer treatment at a large academic cancer center.
Authors: Divya Ahuja Parikh, Krunal Amin, Evan Thomas Hall, Manali I. Patel
Journal: Journal of Clinical Oncology (2017)

e18323 Background: Many studies have shown that patients with cancer are at higher risk of financial difficulty than those without cancer. Given the rising cost of cancer therapy it is important to study the financial distress associated with cancer care. Therefore, we assessed patient reported financial toxicity at a large tertiary academic cancer institute. Methods: From July 2014 to August 2014, we asked 300 patients at the Stanford Cancer Center to participate in an 11-item questionnaire about costs incurred with cancer care. We calculated patient-reported financial toxicity using the COST score, validated at the University of Chicago (scores range from 0-44 with higher values indicating higher financial burden). We obtained demographic information including sex (male or female), education level (high school or less, associates/bachelors degree, or masters/professional degree), race (white or non-white) and annual household income ( &lt; $49,999, $50,000-$99,999, or &gt; $100,000) and used multivariable logistic regression to analyze the association between demographic factors and COST score. Results: Out of the 300 patients approached 254 patients (84.7%) participated in the survey. Nearly half (46%) responded that they “worry about the financial problems in the future as a result of illness or treatment“ quite a bit (4) or very much (5). More than half (52%) reported “I feel I have no choice about the amount of money I spend on care” quite a bit (4) or very much (5). Of patients without missing data (n = 184, 61.3%), the mean COST score was 21 (range 2-41). There were no significant differences in COST score by sex, education level, or race. However, there was a significant difference in COST score by annual household income with a higher degree of financial burden in the lowest income group (OR = 1.04, CI = 0.69-1.38, p &lt; 0.001). Conclusions: Financial toxicity is an unmet concern among patients in our single institution study, with increased burden expressed by those in lower income groups. Our results demonstrate that financial toxicity is a critical concern despite our limited sample. Multicenter studies should be conducted to better characterize the risk factors and serve as a basis for interventions for patients at risk for financial toxicity.
Traitement des gros adénomes colorectaux: endoscopie versus chirurgie
Authors: A Ledit, O Towa, D Frohnmuller, P Chiappa, J Bottlaender, AM Weiss, A Peter, D Maguin, B Denis
Journal: Endoscopy (2004)

Introduction: Le champ de la résection endoscopique (RE) s’est étendu aux gros adénomes de taille ³ 2 cm. La part résiduelle de la résection chirurgicale (RC) n’est pas connue. But: déterminer les parts respectives de la RE et de la RC dans le traitement des gros adénomes colorectaux. Patients et Méthodes: Etude rétrospective de tous les gros adénomes colorectaux de taille ³ 2 cm réséqués dans un centre hospitalier du 1/1/2001 au 31/8/2003. Résultats: 101 gros adénomes étaient réséqués chez 58 hommes et 34 femmes. Soixante sept patients bénéficiaient d’une RE et 25 d’une RC. La RE était réalisée par mucosectomie dans 46% des cas. Une endoloop était utilisée dans 10% des cas. Douze pour cent des RC étaient réalisées par voie transanale, 12% par coelioscopie et 76% par laparotomie. Quatre vingt quatre pour cent des RC comportaient une colectomie. Les principales caractéristiques des 2 groupes figurent dans le tableau ci-dessous. Le type histologique et le degré de dysplasie étaient comparables dans les 2 groupes. Dans le groupe RE survenaient une perforation et une hémorragie traitées chirurgicalement et l’un d’eux décédait à J33 de complications post opératoires. Aucune complication ne survenait dans le groupe RC. Deux patients du groupe RE bénéficiaient d’une RC secondaire en raison d’un adénocarcinome invasif. Un contrôle endoscopique était réalisé chez 22 patients du groupe RE après un délai moyen de 6,5 mois. Cinq récidives étaient diagnostiquées: 3 bénéficiaient d’une RE itérative et 2 d’une RC. Au total, 6 patients du groupe RE ont donc du être opérés secondairement. Quatre vingt quatre pour cent des patients dont la coloscopie était réalisée par un endoscopiste expert ont pu bénéficier d’une RE. Sur 11 patients confiés en deuxième recours à un endoscopiste expert, 81% ont pu bénéficier d’une RE. Cinquante deux pour cent des RC n’avaient pas eu de tentative de RE par un endoscopiste expert. Les échecs de RE étaient dus dans 80% des cas à la taille de l’adénome (Tableau 1). Conclusion: 1) Malgré les progrès de l’endoscopie, un patient sur 3 porteurs d’un gros adénome est opéré. 2) Le recours à un endoscopiste expert permet de diminuer le taux de RC à moins de 20% au prix d’une morbidité acceptable. 3) Le recours à la RC est lié à la taille, à la forme sessile ou plane et à la topographie droite des adénomes ainsi qu’à l’absence de recours à un endoscopiste expert.
Case 67-1963
Authors: Richard A. Field, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of Case First admission. A sixty-two-year-old man entered the hospital because of dyspnea and pain in the chest.The patient had been well until one month previously, when he was awakened by a pressing substernal pain that was accompanied by dyspnea and relieved by sitting or by walking around. Nocturia began to occur three or four times nightly. A physician told him that he had asthma and prescribed a pink liquid, which was without benefit. The nocturnal chest pain and dyspnea persisted, and he began to experience dyspnea on climbing one flight of stairs. There was no edema, exertional . . .