tbuckley/cabot-search huggingface dataset:
Scanner colographie et coloscopie: deux moyens d’investigation complémentaires?
Authors: A Badaoui, D Salovic, JF Gallez, N Hachez, A Vanderschuren, J Kirsch, A Nakad
Journal: Endoscopy (2004)

But: La coloscopie et le scanner colographie (SC) nécessitent une préparation lourde. En cas de suspicion de lésion au SC ou de coloscopie incomplète, il faudrait pouvoir réaliser les deux examens en moins de 24 h de manière à profiter d’une préparation commune. Nous avons étudié la faisabilité de cette démarche. Patients et Méthodes: Sur 500 coloscopies et 60 SC adressés sur une période de 6 mois par les médecins généralistes ou spécialistes, 47 patients ont bénéficiédes 2 examens dans les 24 heures, et avec la même préparation. Vingt trois patients (4,6%) avec coloscopies incomplètes ont bénéficié d’un SC en deuxième intention pour: sténoses néoplasiques (3), sigmoïdes non franchissables (5), et dolichocolons (15). Vingt quatre SC (40%) ont nécessité une coloscopie seconde pour: découverte de polypes (16), segments coliques douteux (manques d’expansion) (5) et examens non contributifs (intolérance, résidus.) (3). Résultats: Le deuxième examen était toujours possible et contributif sans avoir recours à une deuxième préparation chez tous les patients. Trois des 16 polypes découverts au SC (qui mesuraient 5, 6, et 14 mm de diamètre) n’ont pas été objectivés à la coloscopie (18,7%). Deux des 5 segments douteux décrits au SC n’étaient pas retrouvés en coloscopie. Les 3 autres correspondaient à une pathologie inflammatoire bénigne. Conclusion: Moyennant une bonne collaboration entre radiologues, endoscopistes et anesthésistes, coloscopie et SC peuvent être complémentaires et réalisables en 24 heures avec une seule préparation. En cas de coloscopie incomplète ou de lésions suspectées au SC, l’association de ces 2 techniques peut augmenter la sensibilité du SC et diminuer la morbidité de la coloscopie.
PTH-018 Learning curve and outcomes of endoscopic submucosal dissection in a uk centre
Authors: PC Boger, J Kelly, P Patel
Journal: Endoscopy (2017)

<h3>Introduction</h3> It can be difficult for Endoscopists in the UK to gain experience in endoscopic submucosal dissection (ESD) partly due to the lack of suitable easier gastric cases, time constraints, and fear of complications. Studies have suggested that 20 colorectal cases in a Western setting may be sufficient to achieve satisfactory outcomes <sup>1</sup>, but the applicability of this to a training model in the UK is unknown. The aim of this study is to report on initial experience and a training model of ESD in a single UK centre. <h3>Method</h3> A total of 34 cases were referred for ESD between May 2013 and January 2017 to the University Hospital Southampton. The authors underwent a structured training schedule; training and practice on <i>ex-vivo</i> pig models followed by training on live pig models with expert tuition (at ASGE institute, Chicago), progressing to human cases in the colon and stomach, utilising knife assisted resection techniques (KAR) when required. The authors employed a local buddy system during cases to share learning, and one author (PB) attended a further upskilling course on live pig models (at ESGE Workshop, Salzburg) after 20 cases. Outcomes were prospectively recorded and the first 20 cases were compared with the subsequent 14 cases. <h3>Results</h3> Indications were suspected early rectal (14/36), sigmoid (1/36) or gastric cancer (4/36), gastric NETs (2/36), scarred colonic adenomas (7 rectal, 1 transverse colon), or adenomas abutting dentate line (5/36). Mean diameter of lesion was 3.5 cm (1–7 cm). Median total procedure time fell between study periods (110 v 90mins, p=NS). R0 resection rates significantly improved after 20 cases from 45% to 85.7% (p=0.016) and use of KAR techniques significantly reduced (65% v 21.4%, p=0.012). R0 resection rates were significantly reduced when KAR was used (43% v 78%, p=0.042). When procedures using KAR were excluded, time/cm<sup>2</sup> fell from 43.8 to 30 mins/cm<sup>2</sup>, p=NS). Perforation was seen in one patient in the first 20 cases (sealed with clips, surgery not required). No significant post procedural bleeding was seen. 30/34 patients have completed 3 month follow up; recurrence was 7.1% after R1% and 0% after R0 en-bloc resection. 1 patient underwent surgery for sm3 disease. <h3>Conclusion</h3> Learning ESD can be achieved safely in the UK using primarily rectal cases. Use of KAR techniques can help operators gain experience of knives but are associated with increased risk of R1 resection. Using our model of training after 20 cases, outcomes including R0 resection and complication rates were comparable with published data <sup>2, 3</sup>. <h3>References</h3> Iacopini F, et al. Gastrointestinal endoscopy2012; 76:1188–96 Probst A, et al. Endoscopy2012; 44: 660–67 Repici, et al. Endosocpy2012; 44: 137–47 <h3>Disclosure of Interest</h3> None Declared
The role of temozolomide (TMZ) in the management of anaplastic astrocytoma (AA): A comparison of survival in the era prior to and following TMZ.
Authors: Inas Abuali, Roy E. Strowd, Yao Lu, Xiaobu Ye, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2015)

2053 Background: Adding TMZ to radiation therapy (RT) is common clinical practice for patients with AAs despite the lack of prospective studies documenting a survival advantage. Two retrospective studies, each with methodologic limitations, provide conflicting advice regarding the optimal treatment strategy. Methods: This single-institution retrospective study was conducted to determine survival trends in patients with AA. All patients > 18 years with newly diagnosed AA treated at Johns Hopkins from 1995-2012 were analyzed. As we incorporated TMZ into high grade glioma treatment regimens in 2004, patients were divided into pre-2004 and post-2004 groups for analysis. Clinical, radiographic, and pathologic data were collected. Results: A total of 196 patients were identified; 74 pre-2004 and 122 post-2004; mean age 47 years (+/-15); 57% male; 87% white, 69% surgical debulking. Baseline prognostic factors did not differ between groups. Chemotherapy was administered to 12% (TMZ = 1, PCV = 2, gliadel = 6) of the pre-2004 patients and 94% (TMZ in all, p < 0.001) of the post-2004 patients. The median OS was 32 months (95%CI 23-43 mo) with the post-2004 group faring better (37 mo, 24-64) than the pre-2004 group (27 mo, 19-40). Multivariate analysis controlling for age, Karnofsky performance status, and extent of resection revealed a 37% reduced risk of death (HR 0.63, 0.44-0.91, p = 0.015) in patients with AA receiving TMZ. Conclusions: This retrospective analysis suggests a significant improvement in the survival of patients with AA receiving TMZ with RT. Until prospective phase III data is available, our findings support the use of TMZ in the management of newly diagnosed AA.
Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial
Authors: Dilan Athauda, Kate Maclagan, Simon S Skene, Martha Bajwa-Joseph, Dawn Letchford, Kashfia Chowdhury, Steve Hibbert, Natalia Budnik, Luca Zampedri, John Dickson, Yazhou Li, Iciar Aviles-Olmos, Thomas T Warner, Patricia Limousin, Andrew J Lees, Nigel H Greig, Susan Tebbs, Thomas Foltynie
Journal: The Lancet (2017)
巨大右冠動脈の急性心筋梗塞に対してパルス注入冠動脈血栓溶解療法(PIT)を施行した1例
Authors: 藤村達大, 橋本弦太, 岡村誉之, 山田寿太郎, 福本優作, 廣高史, 藤井崇史, 松崎益徳
Journal: Circulation (2007)
89Zr-anti-γH2AX-TAT but not 18F-FDG Allows Early Monitoring of Response to Chemotherapy in a Mouse Model of Pancreatic Ductal Adenocarcinoma
Authors: James C. Knight, Michael J. Mosley, Luisa Contreras Bravo, Veerle Kersemans, P. Danny Allen, Somnath Mukherjee, Eric O'Neill, Bart Cornelissen
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Late-stage, unresectable pancreatic ductal adenocarcinoma (PDAC) is largely resistant to chemotherapy and consequently has a very poor 5-year survival rate of &amp;lt;5%. The ability to assess the efficacy of a treatment soon after its initiation would enable rapid switching to potentially more effective therapies if the current treatment is found to be futile. We have evaluated the ability of the PET imaging agent, 89Zr-anti-γH2AX-TAT, to monitor DNA damage in response to fluorouracil (5-FU), gemcitabine, or capecitabine treatment in a mouse model of pancreatic cancer. We have also compared the utility of this approach against the standard clinical PET radiotracer, 18F-FDG. Experimental Design: C57BL/6 mice bearing subcutaneous pancreatic cancer (KPC; B8484) allografts were treated with 5-FU, gemcitabine, or capecitabine. Therapeutic response was monitored by PET and ex vivo biodistribution experiments using either 89Zr-anti-γH2AX-TAT or 18F-FDG as imaging agents. To further examine the effect of therapeutic response upon uptake of these imaging agents, IHC analysis of harvested tumor allograft tissue was also performed. Results: Accumulation of 89Zr-anti-γH2AX-TAT in the tumors of mice that received chemotherapy was higher compared with vehicle-treated mice and was shown to be specifically mediated by γH2AX. In contrast, 18F-FDG did not provide useful indications of therapeutic response. Conclusions: 89Zr-anti-γH2AX-TAT has shown a superior ability to monitor early therapeutic responses to chemotherapy by PET imaging compared with 18F-FDG in an allograft model of PDAC in mice. Clin Cancer Res; 23(21); 6498–504. ©2017 AACR.
長時間作用型ミクロスフェアのin vivo性能を評価するためのケージインプラントシステムの検証【Powered by NICT】
Authors: C Doty Amy, Hirota Keiji, F Olsen Karl, Sakamoto Naoya, Ackermann Rose, R Feng Meihua, Wang Yan, Choi Stephanie, Qu Wen, Schwendeman Anna, P Schwendeman Steven
Journal: Biomaterials (2016)
A third myotomy with peroral endoscopic myotomy after two failed Heller myotomies
Authors: Majidah Bukhari, Yamile Chavez, Yen-I Chen, Olaya Brewer Gutierrez, Mouen Khashab
Journal: Endoscopy (2017)

Heller myotomy is the optimal surgical management for achalasia. Recurrent or persistent symptoms after surgical myotomy can occur in approximately 10 % of patients [1] [2].
Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients
Authors: Myriam Delaunay, Jacques Cadranel, Amélie Lusque, Nicolas Meyer, Valérie Gounant, Denis Moro-Sibilot, Jean-Marie Michot, Judith Raimbourg, Nicolas Girard, Florian Guisier, David Planchard, Anne-Cécile Metivier, Pascale Tomasini, Eric Dansin, Maurice Pérol, Marion Campana, Oliver Gautschi, Martin Früh, Jean-David Fumet, Clarisse Audigier-Valette, Sébastien Couraud, Stéphane Dalle, Marie-Thérèse Leccia, Marion Jaffro, Samia Collot, Grégoire Prévot, Julie Milia, Julien Mazieres
Journal: European Respiratory Journal (2017)

Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event. Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies. We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancer versus melanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%). ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.
Clinical and pathological study on 88 cases of very low-risk gastrointestinal stromal tumors
Authors: Y. Hou, Y. Zhou, S. Lu, Y. Tan
Journal: Journal of Clinical Oncology (2009)

e21521 Tumor size &lt;2 cm and mitotic figures &lt;5 per 50 high-power field are considered as very-low-risk GIST according to the NIH consensus criteria, but this two indices can not guarantee a benign clinical course with prolonged follow-up. We investigate whether there are morphological parameters associating with the biological behavior in the very-low-risk GISTs. 88 tumors met the very-low-risk criteria were enrolled for this study. Among them, 80 patients were followed up ranging from 1 to 16.3 years, 5 patients developed relapse. Microscopically, definite infiltrative growth pattern such as muscularis propria, muscularis mucosa or nerve infiltration were identified in 4 of 5 patients, 3 of the 4 patients experienced multiple recurrences. Infiltrative growth characters became more extensive in recurrent tumors. No infiltrative feature was found in other 83 patients. Microscopic infiltrative growth patterns played an important role in predicting prognosis for the very-low-risk GISTs. No significant financial relationships to disclose.
06.14 Proteasome inhibition with bortezomib in sle promotes therapeutically relevant depletion of short- and long-lived plasma cells but does not prevent their regeneration
Authors: Tobias Alexander, Qingyu Cheng, Jens Klotsche, Bimba Hoyer, Adriano Taddeo, Aderajew Waka, Anja A. Kühl, Gerd R Burmester, Andreas Radbruch, Falk Hiepe
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> We previously identified long-lived plasma cells (PCs) are an essential component of the pathogenic immunologic memory, which is resistant to immunosuppressive and B cell depleting therapies and contributes to the chronicity of SLE. We recently demonstrated that their targeting with the proteasome inhibitor bortezomib resulted in therapeutically relevant plasma cell depletion in refractory cases of SLE. Here we investigated in detail the cellular and serologic responses of bortezomib treatment. <h3>Methods</h3> Eight patients received a median of two 21-day cycles of intravenous bortezomib 1.3mg/m<sup>2</sup> as induction therapy for active SLE. Disease activity was assessed using the SLEDAI-2K score. Serum concentrations of anti-double-stranded DNA (anti-dsDNA), vaccine-induced antibodies and BAFF levels were monitored. Flow cytometry was performed to analyse peripheral blood B cells, T cells and PCs and Siglec-1 expression on monocytes as surrogate marker for type-I interferon (IFN). <h3>Results</h3> Upon proteasome inhibition, serum levels for anti-double-stranded (ds)DNA (~60%) and vaccine-induced antibodies for Measels, Mumps, TT (~30%) significantly declined, complement levels and serum BAFF levels significantly increased and SLEDAI significantly decreased (p=0.014). The level of bone marrow PCs decreased by 50%, affecting both CD19<sup>+</sup> and CD19<sup>-</sup> CD138/CD38 expressing PCs. While number and phenotype of peripheral blood T- and B cells remained unaffected, proteasome inhibition was associated with a significant depletion of HLA-DR<sup>+</sup> (p=0.024), HLA-DR<sup>-</sup> (p=0.038) and IgA<sup>+</sup> (p=0.032) PCs, but their regeneration was fast. Within ten days from the last bortezomib injection, their numbers significantly increased (beta=2.1; 95% CI: 0.5, 3.7; p=0.012), an effect that was more pronounced in HLA-DR<sup>+</sup> short-lived than in HLA-DR<sup>-</sup> long-lived PCs. Overall, the magnitude of increase over time did not significantly decrease. Siglec-1 expression on monocytes significantly declined. <h3>Conclusions</h3> These findings identify proteasome inhibitors as a promising novel treatment option for patients with refractory SLE by targeting short- and long-lived PCs and type I IFN activity. Bortezomib efficiently induces short-term remissions but would require additional B cell directed treatment approaches to inhibit PC regeneration from their precursors for sustained efficacy.
SP0035 Consensus-based recommendations (share) for the management of juvenile scleroderma
Authors: F Zulian
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In 2012, a European initiative called Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile Scleroderma in its two variety, localized scleroderma (JLS) and systemic sclerosis (JSS) is a rare disease within the group of paediatric rheumatic diseases (PRDs) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians9 experience. Consequently, treatment regimens differ throughout Europe. <h3>Objectives</h3> To provide recommendations for diagnosis and treatment of both JLS and JSS. <h3>Methods</h3> Recommendations were developed by an evidence-informed consensus process using the EULAR standard operating procedures. A committee was constituted, consisting of 16 experienced paediatric rheumatologists, mainly from Europe. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using nominal group technique. Recommendations were accepted if &gt;80% agreement was reached. <h3>Results</h3> In total, 1 overarching principle, 17 recommendations on diagnosis and 13 recommendations on therapy were accepted with &gt;80% agreement among experts. Topics covered include assessment of skin and major organ involvement and suggested treatment pathways. <h3>Conclusions</h3> The SHARE initiative aims to identify best practices for treatment of patients suffering from PRD. Within this remit, recommendations for the diagnosis and treatment of JLS and JSS have been formulated by an evidence informed consensus process to produce a standard of care throughout Europe. <h3>Disclosure of Interest</h3> None declared
Recalculating the Costs of Overtriage
Authors: Lauren J. Taylor, Walker A. Julliard, Margaret L. Schwarze
Journal: JAMA Internal Medicine (2017)

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02.28 The role of arginase I in osteoclasts
Authors: Julia S. Brunner, Melanie Hofmann, Victoria Saferding, Andrea Vogel, Birgit Niederreiter, Hannah Paar, Li Chen, Paul Cheng, Gernot Schabbauer, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoclasts are multi-nucleated, bone resorbing cells that derive from the monocyte-macrophage linage. They are further known as the main effector cells for development of age-related osteoporosis and are critically involved in the pathogenesis of rheumatic diseases. Arginase I is classically known as a marker for anti-inflammatory macrophage polarisation, but its importance for osteoclasts and their development has not been characterised. Our aim was therefore to investigate the importance of the enzyme in the context of osteoclastogenesis and osteoclast metabolism. <h3>Materials and methods</h3> We analysed osteoclastogenesis of C57BL/6J wildtype bone marrow cells <i>in vitro</i> in the presence and absence of recombinant Arginase 1 (recARG1). This approach was complemented via qPCR analysis of relevant osteoclast marker genes. We further investigated the effect of recARG1 regarding an <i>in vivo</i> model called serum transfer arthritis, where we treated C57BL/6J wildtype mice with the recombinant enzyme. Disease severity was then assessed using clinical scores and paw histology. <h3>Results</h3> We observed that Arginase 1 was downregulated from the progression of a precursor to a mature osteoclast. When we incubated osteoclast precursors stimulated with RANKL with recARG1, we completely inhibited the generation of osteoclasts. In line, recARG1 could also inhibit the mRNA expression of RANKL-induced osteoclastogenic marker genes such as NFATc1, Cathepsin K and others. Of note, recARG1 did not affect M-CSF-dependent generation of osteoclast precursors. In an <i>in vivo</i> model known as serum transfer arthritis, mice with recARG1 showed reduced signs of disease, assessed by clinical scores (mouse weight, paw swelling and grip strength). This finding was complemented by scoring of paw histological slides. Although synovial inflammation was only numerically reduced, treatment with recARG1 lead to a significant decrease in the numbers of osteoclasts in the inflamed paws. <h3>Conclusions</h3> We propose that the activity of the enzyme Arginase I is critical for the development of osteoclasts from myeloid precursors and hypothesise that administration or recombinant Arginase I might influence development and severity of osteoclast driven diseases.