tbuckley/cabot-search huggingface dataset:
AB0730 Comparison of a single-centre idiopathic inflammatory myopathy cohort from argentina with the euromyositis international registry
Authors: A.S. Braillard Poccard, R. Gomez, M. Pino, M. Garcia Carrasco, D. Dubinsky
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The idiopathic inflammatory myopathies (IIM) are rare systemic autoinmune diseases that affect the muscle and other organs. Ttraditionally, IIM encompasses polymyositis (PM) and dermatomyositis (DM), but progressively inclusion body myositis (IBM), Immune-mediated necrotising myopathy (IMNM), the antisynthetase syndrome (ASS) and connective tissue diseases-ovler myositis (CTD-OM) have been recognised within the IIM spectrum <h3>Objectives</h3> To compare the clinical characteristics and treatment in a IIM cohort from an Argentinian universitary hospital with the international IIM cohort EUROMYOSITIS <h3>Methods</h3> Descriptive, retrospective study. IIM patients defined by expert opinion followed in our centre between <sup>October 2007</sup> and October 2017 were included. ASS was defined by the presence of arthritis, raynaud's phenomenon, mechanic hands, elevated CK, muscle weakness, interstitial lung disease and/or presence of antisynthetase antibodies and, as in EUROMYOSITIS, patients with IIM with positive antisynthetase antibodies were reclassified as ASS. CTD-OM was defined as patients with IIM fulfilling classification criteria for other CTD. Demographic data, accumulated clinical features, time interval between disease onset and diagnosis, IIM subtype, treatment and presence of neoplasm were evaluated. Ethnicity was defined using the same classification as in EUROMYOSITIS <h3>Results</h3> 58 patients were included: DM 24, PM 4, ASS 10, CTD-OM 20. 89.6% Hispanic, mean age 48.4±15.2 years, median time interval between disease onset and diagnosis 5 months (IQR 2–11 months), been higher in AAS (8.5 months, IQR 1.5–18.2 months). 6,89% (4/58) patients presented associated neoplasm, 3 with DM and 1 with CTD-OM. Table 1 shows the demographic and clinical features of our IIM cohort and EUROMYOSITIS. Table 2 shows treatments received in our cohort and EUROMYOSITIS. <h3>Conclusions</h3> DM was the most frecuent IIM subtype in both cohorts. In our group, CTD-OM was second and ASS was third. Muscle weakness was found less frecuently in our DM and AAS than reported in EUROMYOSITIS. However, calcinosis was more frecuent. This could be explained by our mostly Hispanic population and/or by frecuent Systemic Sclerosis overlap in our patients. It's important to remark that the ethnic variety defined as Hispanic in EUROMYOSITS has a complex composition in Latin America, due to interbreeding. No difference was found in therms of most frecuent treatments between both cohorts. However, use of IVIg was more frecuent in our patients. To our knowledge, this is the first comparative report of an argentinian single-centre IIM cohort and an international multi-centre cohort <h3>Disclosure of Interest</h3> None declared
New modified hook device for endoloop closure of the mucosal defect after gastric endoscopic submucosal dissection
Authors: Tatsuma Nomura, Akira Kamei, Shinya Sugimoto, Takaaki Morikawa, Jun Oyamda
Journal: Endoscopy (2018)

Closing the submucosal defect after gastric endoscopic submucosal dissection (ESD) may reduce postoperative adverse events [1]. In recent years, various methods for mucosal closure after gastric ESD have been developed [2] [3]. However, gastric mucosal defect closure is difficult as the submucosa and muscularis are thicker than in other parts of the digestive tract. Recently, mucosal defect closure using an endoloop was reported [4]. However, it is not common in Japan, and it is difficult to grasp and tighten the length of the endoloop because it is not fixed. Therefore, we developed a new and modified hook device for endoloop closure to grasp the endoloop tail.
Very poor long‐term survival in past and more recent studies for relapsed AML patients: The ECOG‐ACRIN experience
Authors: Chezi Ganzel, Zhuoxin Sun, Larry D. Cripe, Hugo F. Fernandez, Dan Douer, Jacob M. Rowe, Elisabeth M. Paietta, Rhett Ketterling, Michael J. O'Connell, Peter H. Wiernik, John M. Bennett, Mark R. Litzow, Selina M. Luger, Hillard M. Lazarus, Martin S. Tallman
Journal: American Journal of Hematology (2018)

This study examines the long-term OS of relapsed AML patients who were enrolled to 9 successive ECOG-ACRIN trials for newly diagnosed AML, during 1984-2008. The objectives were to examine whether there is a trend of improvement in the survival of relapsed AML patients in the more recent studies and to search for prognostic factors that are associated with long-term OS after relapse. A total of 3012 patients were enrolled, 1779 (59.1%) achieved CR1 and of these, 58.9% relapsed. The median follow-up was 9.7 years. The median OS from relapse was 0.5 years and the 5-year OS was 10 (±1)%. These results were similar even for the most recent studies. A multivariate model showed that age, cytogenetics at diagnosis, duration of CR1 and undergoing allogeneic transplantation were significantly associated with OS from relapse. Even among patients who relapsed with better prognostic factors; age < 40 and CR1 > 12 months, there was no significant OS difference between the studies. In conclusion, this large cohort appears to confirm that the survival of AML patients postrelapse continues to be dismal and has not improved during the past quarter of a century.
Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial
Authors: Stuart A Taylor, Susan Mallett, Gauraang Bhatnagar, Rachel Baldwin-Cleland, Stuart Bloom, Arun Gupta, Peter J Hamlin, Ailsa L Hart, Antony Higginson, Ilan Jacobs, Sara McCartney, Anne Miles, Charles D Murray, Andrew A Plumb, Richard C Pollok, Shonit Punwani, Laura Quinn, Manuel Rodriguez-Justo, Zainib Shabir, Andrew Slater, Damian Tolan, Simon Travis, Alastair Windsor, Peter Wylie, Ian Zealley, Steve Halligan, Jade Dyer, Pranitha Veeramalla, Sue Tebbs, Steve Hibbert, Richard Ellis, Fergus Thursby-Pelham, Richard Beable, Nicola Gibbons, Claire Ward, Anthony O'Connor, Hannah Lambie, Rachel Hyland, Nigel Scott, Roger Lapham, Doris Quartey, Deborah Scrimshaw, Helen Bungay, Maggie Betts, Simona Fourie, Niall Power, Rajapandian Ilangovan, Uday Patel, Evgenia Mainta, Phillip Lung, Ian Johnston, Mani Naghibi, Morgan Moorghen, Adriana Martinez, Francois Porte, Christopher Alexakis, James Pilcher, Anisur Rahman, Jonny Vlahos, Rebecca Greenhalgh, Anita Wale, Teresita Beeston, Wivijin Piga, Joey Clemente, Farooq Rahman, Simona de Caro, Shameer Mehta, Roser Vega, Roman Jastrub, Harbir Sidhu, Hameed Rafiee, Mairead Tennent, Caron Innes, Craig Mowat, Gillian Duncan, Steve Morris
Journal: The Lancet. Gastroenterology & hepatology (2018)

Magnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue.
SAT0501 Early versus late-onset systemic sclerosis: are there clinical and immunological differences?
Authors: M. Luís, F. Costa, A. Carmo, J. Ferreira, T. Santiago, R. Cunha, M.J. Salvador, J. da Silva
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The clinical course of Systemic Sclerosis (SSc) depends on subtype, organ involvement and age. Peak age at onset of SSc is between 30 and 50 years, although SSc may also start in both young and elderly patients. Few data have been reported on patients suffering from late-onset SSc. <h3>Objectives</h3> To characterise clinical and immunological features of early and late-onset SSc in a tertiary referral hospital. <h3>Methods</h3> We analysed data from 178 patients followed at our SSc clinic. All the patients fulfilled the ACR/<sup>EULAR 2013</sup> classification criteria for SSc or the LeRoy's criteria for the classification of early SSc. Based on the mean of age of onset of the whole series (50±15 years), ages extremes were defined as younger than 35 versus older than 65 years of age at onset. Disease characteristics as well as clinical and immunological features were evaluated. <h3>Results</h3> The early and the late-onset groups included 35 and 31 patients, respectively. Patients' current mean age was 42.8±14.1 vs. 75.8±6.2 with a mean disease duration of 14.5±14.7 vs. 4.3±4.6 years. The most common first manifestation of disease was Raynaud phenomena followed by arthritis/inflammatory arthralgia, in both groups. However, the time between clinical onset and SSc diagnosis was higher in the late-onset group (p=0.034). A higher number of diffuse and pre-SS was observed in the early group but this difference didn't prove statistically significant. There was a higher prevalence of centromere antibodies in the late-onset group (p=0.001). Clinical manifestations and target-organ damage didn't differ between groups, except for a higher prevalence of heart conduction abnormalities in the late-onset group (p=0.02). In multivariate analyses, age alone (OR=1.04; 95% CI 1.0, 1.1), but not disease duration (OR=0.99; 95% CI 0.9–1.0), was an independent predictor for the presence of heart conduction abnormalities. <h3>Conclusions</h3> In line with findings from other studies, late-onset SSc shows a distinct clinical and immunological presentation. The present study confirms that late-onset is associated with longer diagnostic delay, positive centromere and heart conduction abnormalities. These observations may be due to age and potential age-associated confounders, rather than the disease itself. Knowledge of these different characteristics can help to improve the management of the disease. <h3>References</h3> [1] Alba M, et al. Early-versus Late-Onset Systemic Sclerosis. Medicine2014;93(2):73–81. [2] Hugle T, et al. Late-onset systemic sclerosis – a systemic survey of the EULAR scleroderma trials and research group database. Rheumatology (Oxford)2010;50(1):161–5. [3] Manno R, et al. Late-Age Onset Scleroderma. J. Rheumatol2011;38(7):1317–1325. <h3>Disclosure of Interest</h3> None declared
AB0309 Need to a walk to the complete remission; foot and/or ankle arthritis impede complete remission in rheumatoid arthritis –part 1, cross-sectional study from korean college of rheumatology biologics (KOBIO) registry
Authors: S.H. Chang, S.W. Lee, M.I. Kang, H.W. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To determine the prevalence of foot synovitis, and the most stringent disease activity index reflecting complete remission among patients with rheumatoid arthritis in Korea. <h3>Methods</h3> We conducted a cross-sectional study using data from the Korean College of Rheumatology BIOlogics (KOBIO) registry. Foot arthritis defined as having one or more tender or swollen joints in ankle and/or 1st to 5th metatarsal joints. Functional status and disease activity evaluated by the routine assessment of patient index data3 (RAPID3), the disease activity score 28 ESR (DAS28), the simplified disease activity index (SDAI), the clinical disease activity index (CDAI), and the ACR/EULAR Boolean criteria. <h3>Results</h3> Baseline data of 2046 patients were analysed. Patients with foot arthritis showed significantly younger age at the diagnosis, longer disease, duration, higher DAS-28/SDAI/CDAI/RAPID-3, lower rate of ACR/EULAR Boolean criteria remission, use of higher dose of glucocorticoid, and higher rate of bone erosion not only on foot but also hand X-rays. Among those patients, 174 patients (8.5%) were in DAS 28 clinical remission. Twenty-one of 174 patients (12.1%) had foot arthritis, who showed higher swollen and tender joint count, RAPID-3 score, and patients’ global assessment but not physicians’ global assessment than those without foot arthritis. Among patients with foot arthritis, rate of complete remission was the highest in patients with CDAI (66.7%). <h3>Conclusions</h3> In patients with rheumatoid arthritis, foot and/or ankle arthritis is associated with high disease activity, not achieving complete remission despite of various clinical remission criteria and discordance between patients’ and physicians’ global assessment. <h3>Disclosure of Interest</h3> None declared
Response to: ‘Association between use of non-steroidal anti-inflammatory drugs and risk of myocardial infarction in patients with spondyloarthritis and osteoarthritis’
Authors: Maureen Dubreuil, Qiong Louie-Gao, Christine Peloquin, Hyon K Choi, Yuqing Zhang, Tuhina Neogi
Journal: Annals of the Rheumatic Diseases (2018)

We wish to thank Zhou and colleagues for their letter.1 As outlined in the published paper,2 the myocardial infarction (MI) case definition was based on the diagnosis being recorded as a MI Read code in The Health Improvement Network (THIN), a validated means of identifying MI in pharmacoepidemiological studies.3 Because THIN is based on general practitioner’s coded records, the …
Advances in Immunotherapy for Metastatic Merkel Cell Carcinoma: A Clinician's Guide
Authors: Kelly G. Paulson, Shailender Bhatia
Journal: Journal of the National Comprehensive Cancer Network (2018)

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer. The clinical impact of MCC has been increasing due to steadily rising incidence rates. Since 2001, more than 24,000 cases of MCC have been reported to the US National Program of Cancer Registries database, and in 2018, more than 2,500 incident cases are expected. MCC is highly aggressive, and one-third of patients will either present with or develop metastatic disease. Outcomes in patients with metastatic MCC have historically been poor; median time to progression with cytotoxic chemotherapy is only 3 months. MCC has long been appreciated to be immunogenic, with reports of spontaneous regression and responsiveness to immunotherapy. However, the mechanisms of this immunogenicity have only been understood over the past decade, with approximately 80% of cases in the United States associated with the Merkel cell polyomavirus (MCPyV) and expression of viral antigens (virus-positive [VP] MCC), and the remaining 20% of cases caused by UV radiation–induced damage leading to a high mutational burden and expression of neoantigens (virus-negative [VN] MCC). These insights have led to multiple successful trials of immunotherapies for MCC. PD-1 axis checkpoint inhibitors are now regarded as the preferred frontline systemic therapy in eligible patients (including both VP- and VN-MCC), with impressive frequency, durability, and depth of objective responses, which compare favorably to those of most solid tumors. This article reviews the safety and efficacy data from the key clinical trials of immune checkpoint inhibitors for metastatic MCC, and discusses several issues relevant to the clinical use of these agents. Finally, emerging immunotherapies for MCC, including cellular therapies and adjuvant systemic therapies, are reviewed.
THU0257 Associations between trabecular bone score and vertebral fractures in patients with axial spondyloarthritis
Authors: H.R. Kim, Y.S. Hong, K.Y. Kang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The bone tissue directly exposed to inflammation in axSpA is the trabecular bone of the vertebrae, and consequently, vertebral osteoporosis and resorption of trabecular bone are increased in axial spondyloarthritis. The trabecular bone score (TBS) is a novel tool used to evaluate bone microarchitecture. AxSpA patients showed poor bone quality compared with matched controls. <h3>Objectives</h3> This study aims to compare TBS between axSpA patients with and without vertebral fractures and investigate associations between TBS and vertebral fractures. <h3>Methods</h3> Two hundred and fifty-five patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. TBS and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Vertebral fracture of the thoracic and lumbar spine was defined according to the Genant criteria. Osteoporosis risk factors, inflammatory markers, disease activity scores, and spinal structural damage were also assessed. Multivariate logistic regression analysis was performed to identify factors associated with vertebral fractures. <h3>Results</h3> Of 255 axSpA patients, 28 (11%) had 31 vertebral fractures. The mean TBS was 1.39±0.11 and 1.30±0.13 in patients without and with vertebral fractures, respectively (&lt;0.001). BMD in the femoral neck was lower in patients with vertebral fractures (p=0.027), but BMDs in the lumbar spine and total hip were not. In the multivariate analyses, low TBS and the presence of syndesmophytes were significantly associated with vertebral fractures, independently of BMD (OR [95% CI]=3.6 [1.2–11.1] and 3.3 [1.0–10.7], respectively). For the total hip, TBS has a better discriminatory value than BMD for prediction of vertebral fractures in axSpA patients (p=0.034). <h3>Conclusions</h3> TBS values are lower in axSpA patients with vertebral fractures. Low TBS and syndesmophytes were independently associated with prevalent vertebral fractures. TBS has better predictive value to BMD for the discrimination of vertebral fractures and could help to detect axSpA patients with vertebral fractures. <h3>Disclosure of Interest</h3> None declared
A phase I trial of veliparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and topotecan (TPT) in patients with solid tumors.
Authors: Andrea Elisabeth Wahner Hendrickson, Michael E. Menefee, Lynn C. Hartmann, Harry J. Long, Donald W. Northfelt, Joel M. Reid, Fleix Boakye-Agyeman, Karen S Flatten, Guy G Poirier, Janet Lensing, Charles Erlichman, Scott H. Kaufmann, Paul Haluska
Journal: Journal of Clinical Oncology (2015)

TPS2618 Background: PARPs are a highly conserved family of enzymes whose predominant function is to preserve genomic integrity following DNA damage. Preclinical studies demonstrated that PARP inhibitors enhance the cytotoxicity of DNA damaging agents. Specifically, PARP inhibition sensitizes tumor cells to topotecan in vitro and in vivo by trapping PARP1 on damaged DNA and preventing repair of topo I-induced DNA damage (Patel et al., J. Biol. Chem. 287:4198, 2012). Veliparib has been combined with daily topotecan but found to be quite myelosuppressive, requiring reduction in doses of both agents (Kummar et al., Cancer Res. 71:5626, 2011). Based on these data, we sought to determine the maximum tolerated dose (MTD) of veliparib in combination with the less myelosuppressive weekly administration of topotecan in patients with solid tumors. Correlative studies were included to assess the impact of topotecan and veliparib on poly(ADP-ribose) levels in peripheral blood mononuclear cells as well as the pharmacokinetics of both agents. Methods: Eligible patients include any histologically confirmed solid tumor malignancy that is metastatic or unresectable with measurable disease (longest diameter > 2 cm with conventional CT) in patients 18 or older who have received < 2 chemotherapy regimens, ECOG PS < 2 and adequate bone marrow, renal and hepatic function. Using a standard 3+3 design, patients have been treated with veliparib PO twice daily on days 1-3, 8-10 and 15-17 and topotecan IV on days 2, 9 and 16 every 28 days. The trial is currently enrolling at veliparib 300 mg PO twice daily and topotecan 3 mg/m2/dose. Once MTD is established, a phase II clinical trial in platinum resistant ovarian, peritoneal and fallopian tube malignancies is planned. Supported in part by UM1 CA186686 and P50 CA136393. Clinical trial information: NCT01012817 Clinical trial information: NCT01012817.
Boron delivery agents for neutron capture therapy of cancer
Authors: Rolf F. Barth, Peng Mi, Weilian Yang
Journal: Cancer Communications (2018)

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic modality based on the nuclear capture and fission reactions that occur when the stable isotope, boron-10, is irradiated with neutrons to produce high energy alpha particles. This review will focus on tumor-targeting boron delivery agents that are an essential component of this binary system. Two low molecular weight boron-containing drugs currently are being used clinically, boronophenylalanine (BPA) and sodium borocaptate (BSH). Although they are far from being ideal, their therapeutic efficacy has been demonstrated in patients with high grade gliomas, recurrent tumors of the head and neck region, and a much smaller number with cutaneous and extra-cutaneous melanomas. Because of their limitations, great effort has been expended over the past 40 years to develop new boron delivery agents that have more favorable biodistribution and uptake for clinical use. These include boron-containing porphyrins, amino acids, polyamines, nucleosides, peptides, monoclonal antibodies, liposomes, nanoparticles of various types, boron cluster compounds and co-polymers. Currently, however, none of these have reached the stage where there is enough convincing data to warrant clinical biodistribution studies. Therefore, at present the best way to further improve the clinical efficacy of BNCT would be to optimize the dosing paradigms and delivery of BPA and BSH, either alone or in combination, with the hope that future research will identify new and better boron delivery agents for clinical use.
Integrated Histogenetic Analysis Reveals <i>BAP1</i> -Mutated Epithelioid Mesothelioma in a Patient With Cancer of Unknown Primary
Authors: Tilmann Bochtler, Volker Endris, Anna Reiling, Jonas Leichsenring, Michal R. Schweiger, Sebastian Klein, Fabian Stögbauer, Benjamin Goeppert, Peter Schirmacher, Alwin Krämer, Albrecht Stenzinger
Journal: Journal of the National Comprehensive Cancer Network (2018)

This case report presents a male patient with epithelioid mesothelioma that was initially misdiagnosed as cancer of unknown primary (CUP) and correctly identified using molecular panel sequencing. The patient had a prior history of colon and breast cancer. To assess the enlarged mediastinal lymph nodes, retrosternal lymphadenectomy was performed in 2016. The lymph nodes were histologically deemed unrelated to the known breast cancer by the reference pathologist, thus leading to the diagnosis of a CUP syndrome. When the patient presented to our center, targeted deep sequencing of both breast cancer and presumed CUP was performed to address the clonal relationship between both malignancies. A missense mutation in BAP1 was revealed in both samples, with coverage data indicating a germline event. The patient was subsequently counseled by a human geneticist and underwent genetic testing, which confirmed the germline nature of this mutation. Collectively, these data led to the diagnosis of BAP1 (BRCA1-associated protein-1) tumor predisposition syndrome (TPDS). With the knowledge of an underlying BAP1 mutation and its known frequent association with epithelioid mesothelioma, the histology was reassessed and the diagnosis was revised to epithelioid mesothelioma. At this point, peritoneal involvement of mesothelioma could be diagnosed and histologically confirmed. This case illustrates the potential of integrated histopathologic and molecular diagnostics in helping to decipher CUP syndromes and establish the correct diagnosis. Additionally, this case highlights typical features of BAP1 TPDS with its general susceptibility to cancers, with pleural and peritoneal mesotheliomas as most prevalent clinical entities and the typically more benign course of these epithelioid mesotheliomas compared with BAP1-unrelated cases of mesotheliomas.