tbuckley/cabot-search huggingface dataset:
Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site
Authors: Hidetoshi Hayashi, Takayasu Kurata, Yuichi Takiguchi, Makoto Arai, Koji Takeda, Kohei Akiyoshi, Koji Matsumoto, Takuma Onoe, Hirofumi Mukai, Nobuaki Matsubara, Hironobu Minami, Masanori Toyoda, Yusuke Onozawa, Akira Ono, Yoshihiko Fujita, Kazuko Sakai, Yasuhiro Koh, Ayano Takeuchi, Yasuo Ohashi, Kazuto Nishio, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2019)

Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP.Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate.One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types.Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.
Feasibility of myomatous tissue extraction in laparoscopic surgery by contained in – bag morcellation: A retrospective single arm study
Authors: Rajesh Devassy, Cristina Cezar, Harald Krentel, Hugo Christian Verhoeven, Rohan Devassy, Maya Sophie de Wilde, Luz Angela Torres-de la Roche, Rudy Leon de Wilde
Journal: International Journal of Surgery (2019)
AB0384 Rheumatic arthritis patients with very high cardiovascular risk: poor results in changes in lifestyle during follow-up
Authors: N. Vegas-Revenga, V. Portilla, L.C. Domínguez-Casas, J.L. Martín-Varillas, B. Atienza-Mateo, M. Agudo, J. Rueda-Gotor, J.L. Hernández, R. Blanco, M.A. González-Gay, A. Corrales
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis, which results in high cardiovascular morbidity and mortality. The European Atherosclerosis Society recommends a strict control of cardiovascular (CV) risk factors, focusing in a healthy lifestyle, for the prevention of future CV events. <h3>Objectives</h3> Our aim was to assess the characteristics of healthy lifestyle in patients with RA and very high risk of CV events. <h3>Methods</h3> Prospective study that included a group of 113 patients, of whom 65 presented carotid plaques on carotid ultrasound study and, due to this, were categorised as having very CV high risk at the baseline visit. At this time, patients were informed about the risks associated to their disease and the high risk of having CV events. They were even warned of the need of healthy lifestyle habits. Data on lifestyle, smoking, obesity and diabetes mellitus were collected at baseline and last visit (with an interval of more than 5 years) <h3>Results</h3> The results of the 65 patients at the last visit are shown in table<b> 1</b>. The average age was of 67 years, with a disease duration of 17 years and high prevalence of dyslipidemia (72%), HTA (62%) and obesity (40%). Data obtained at the basal and last visit (with an average difference of 5.5 years) were compared in table<b> 2.</b> At last follow-up none of the smokers at baseline had discontinued smoking. There were no significant differences in the body mass index (BMI) average. Nevertheless, there was increase in the number of patients with a BMI &lt;30 (36% vs 31%). Only a few patients claimed to go on any type of diet (20%), although the majority (88%) had classic CV risk factors (DM, HTA, obesity or dyslipidemia) at baseline that required adequate diet regime. Yet, more than half of the patients (62%) made regular exercise (&gt;3 times/week) and did not have a sedentary lifestyle (50%), despite having a mean age of 67 years and long disease duration at baseline. Poor control of diabetes mellitus (DM), was found in more than half of the patients. <h3>Conclusions</h3> Despite having been informed on the high risk of CV events, patients with RA included in the category of very high CV risk performed poor long-term control of factors that include a healthy lifestyle. <h3>Disclosure of Interest</h3> None declared
Abstract 17280: Metformin Inhibits Transforming Growth Factor-β1 And Cardiac Fibrosis by Targeting Hepatocyte Nuclear Factor 4α
Authors: Han Xiao, Ruifei Chen, Yenan Feng, Jimin Wu, Yao Song, Youyi Zhang
Journal: Circulation (2016)

Introduction: Metformin, a widely used antihyperglycaemic agent, is well-known as an adenosine monophosphate-activated protein kinase (AMPK) activator. Our previous study found that metformin inhib...
Real-World Outcomes of Adjuvant Chemotherapy for Node-Negative and Node-Positive HER2-Positive Breast Cancer
Authors: Zachary Veitch, Omar F. Khan, Derek Tilley, Domek Ribnikar, Xanthoula Kostaras, Karen King, Patricia Tang, Sasha Lupichuk
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Comparative real-world outcomes for patients with HER2-positive (HER2+) breast cancer receiving adjuvant trastuzumab outside of clinical trials are lacking. This study sought to retrospectively characterize outcomes for patients with node-negative and node-positive breast cancer receiving adjuvant trastuzumab in combination with docetaxel/cyclophosphamide (DCH), docetaxel/carboplatin/trastuzumab (TCH), or fluorouracil/epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (FEC-DH) chemotherapy in Alberta, Canada, from 2007 through 2014. Methods: Disease-free survival and overall survival (OS) analyses for node-negative cohorts receiving DCH (n=111) or TCH (n=371) and node-positive cohorts receiving FEC-DH (n=146) or TCH (n=315) were compared using chi-square, Kaplan-Meier, or Cox multivariable analysis where appropriate. Results: Median follow-up was similar in node-negative (63.9 months) and node-positive (69.0 months) cohorts. The 5-year OS rates in patients with node-negative disease receiving DCH or TCH were similar (95.2% vs 96.9%; P=.268), whereas 5-year OS rates were higher but nonsignificant for patients with node-positive disease treated with FEC-DH compared with TCH (95.2% vs 91.4%; P=.160). Subgroup analysis of node-positive cohorts showed significantly improved OS with FEC-DH versus TCH in patients with estrogen receptor (ER)/progesterone receptor (PR)–positive breast cancer (98.3% vs 91.6%, respectively; P=.014). Conversely, patients with ER/PR-negative disease showed a nonsignificant trend toward higher OS rates with TCH versus FEC-DH (91.6% vs 83.3%, respectively; P=.298). Given the retrospective design, we were unable to capture all potential covariates that may have impacted treatment assignment and/or outcomes. Furthermore, cardiac toxicity data were unavailable. Conclusions: Survival rates of patients with HER2+ breast cancer in our study are comparable to those seen in clinical trials. Our findings support chemotherapy de-escalation in patients with node-negative disease and validate the efficacy of FEC-DH in those with node-positive disease.
FRI0504 Diffuse alveolar haemorrhagein anca-associated vasculitis: can we predict outcome? an italian multicentre retrospective long-term study of 102 patients
Authors: L. Quartuccio, M. Bond, S. Monti, M. Felicetti, F. Furini, S. Murgia, A. Berti, G. Emmi, G. Pazzola, E. Bozzolo, P. Leccese, B. Raffeiner, I. Leccese, F. Cianci, S. Bettio, P. Sainaghi, A. Ianniello, V. Ravagnani, S. Bellando Randone, P. Faggioli, C. Lomater, P. Stobbione, S. Barsotti, M. Colaci, G. Alfieri, F. Carubbi, G. Erre, A. Giollo, N. Franzolini, S. Balduzzi, R. Padoan, R. Bortolotti, A. Bortoluzzi, A. Cariddi, A. Padula, E. Silvestri, G. Di Scala, E. Gremese, F. Conti, S. D’Angelo, M. Isola, L. Dagna, G. Paolazzi, C. Salvarani, D. Roccatello, F. Schiavon, M. Govoni, R. Caporali, S. De Vita
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Diffuse alveolar haemorrhage (DAH) is a rare and severe manifestation of ANCA-associated vasculitides (AAV). <h3>Objectives</h3> To identify predictors of survival in patients with AAV-DAH. <h3>Methods</h3> A retrospective study of 102 consecutive patients (50% females; mean age 59±17 years) from 27 Italian Centres diagnosed with AAV-DAH was planned. Cox regression unadjusted analyses were performed. <h3>Results</h3> Among AAV patients, 47% had Granulomatosis with Polyangiitis (GPA), 47% Microscopic Polyangiitis (MPA) and 6% Eosinophilic Granulomatosis with Polyangiitis (EGPA). At DAH onset, mean BVAS was 20±8 and most patients had renal involvement (RI). Admission to Intensive Care Unit was needed in 27% of patients, while ventilatory support (VS) was required in 46%. At least one cardiovascular risk factor (CVRF) was recorded in 48%. Over a median follow-up of 39 months (25%–75% IQR 66 months), 19/102 patients (18.6%) died (figure 1). All patients received high-dose glucocorticoids in association with Cyclophosphamide (CYC 78%, mean cumulative dose 8±7 g) or Rituximab (37%). Plasma exchange was performed in 46%. Infections occurred in 38%. Age&gt;65 years (HR 3.05 [95% CI 1.18–7.9], p=0.04), CVRF ≥2 (HR 8.85 [95% CI [AG7] 2.34–33.50], p=0.01), BVAS (v.3) (HR 1.07 [95% CI 1.01–1.13], p=0.01) were associated with mortality, whereas FFS was not. The need for VS (HR 4.54 [95% CI 1.48–13.85], p=0.008) and infections (HR 3.98 [95% CI 1.48–10.69] were also associated with mortality. <h3>Conclusions</h3> Older age, VS, CVRF and infections affect the survival in AAV. There is a need for specific outcome measeures. <h3>Disclosure of Interest</h3> None declared
Neutrophil-derived microRNAs put the (DNA) breaks on intestinal mucosal healing
Authors: Eóin N. McNamee
Journal: Journal of Clinical Investigation (2019)

A predominant feature of intestinal inflammation is the accumulation of neutrophils, which dictates a fine balance between epithelial repair or progression to chronic inflammation. While the processes of mucosal healing are well studied, how neutrophils advance an inflammatory insult towards epithelial neoplasia is less understood. In this issue of the JCI, Butin-Israeli et al. outline a mechanism whereby neutrophils control epithelial fitness and genomic instability via delivery of miR-23a–and miR-155–containing microparticles. Localized delivery of antisense oligonucleotides targeting miR-23a and miR-155 reversed this genomic instability and accelerated mucosal healing. This mechanism of neutrophil-derived microRNA shuttling opens up new therapeutic potential to enhance epithelial healing and limit mucosal injury.
AB0680 Non ophtalmological neurologic ischaemic manifestations of giant cell arteritis
Authors: L. Coronel Tarancón, I. Monjo, E. Fernández, A. Balsa, E. De Miguel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Giant cell arteritis (GCA) is a very infrequent cause of stroke. It is diagnosed in 0.15% of brain infarctions. On the other hand, in scientifical literature there are very little patients with ischaemic brain infarctions that describes stroke as the clinical presentation of GCA. It might suggest that it is a underdiagnosed condition. <h3>Objectives</h3> To check the frequency of stroke as presentation symptom of GCA and other findings related with it. <h3>Methods</h3> Retrospective observational study of 123 consecutive patients diagnosed of GCA in our hospital. We reviewed the past medical history to obtain sings, symptoms and ultrasound parameters of the first medical evaluation. We searched for: age, sex, hypertension, diabetes, dyslipidemia, anterior ischaemic optic neuropathy (AION), headache, visual disturbances, Polymyalgia Rheumatica (PMR), jaw claudication, general symptoms, non oftalmological brain ischaemic symptoms, disease outbreak and laboratory test: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), Haemoglobin (Hb). For the analysis we divided the sample into two groups: a). Neurological symptomps b). Other presentations. For statistical comparisons, we used SPSS version 17.0. Descriptive analysis and comparison was performed of the two groups. X<sup>2</sup> was used for qualitative values and means comparisons for quantitative. <h3>Results</h3> Of our 123 patient's cohort: 37 patients (30.08%) suffered from ischaemic events of the internal carotid artery, 25 patients (20.32%) of AION and 12 patients (9.8%) presented with neurological symptoms different from AION. Out of the 12 patients with non ocular ischaemic symtomps of the central nervous system: 5 (44.66%) were diagnosed of transitory ischaemic accident (TIA), 4 (33.33%) of stroke, 2 (16.66%) of VI cranial nerve paresis, one the patients that presented with III and VI par paresis suffered also from TIA, at last, one patient presented ischaemic phenomena related with small-vessels vasculitis and one patient with dizziness due to cerebellum affectation. Clinical and analytical data are presented in the table: No patient was presented with PMR or jaw claudication. 3 (25%) patients died during the follow up in the neurologic symptoms group in comparison with 11 (9.90%) of the non neurological (p 0.11). <h3>Conclusions</h3> Stroke is not a rare form of presentation of GCA and should be suspected in all ischaemic brain events that are associated with high acute phase reactants in elderly patients. It is important to identify these patients due to the severity of the disease and the possibility of specific treatment that may avoid new events. <h3>References</h3> [1] Roaa S. Alsolaimani, et al. Severe intracraneal involvement in Giant Cell Arteritis: 5 Cases and literature Review. J Rheumatol2016; <i>4</i>3:3. <h3>Disclosure of Interest</h3> None declared
AB0401 Echo-cardiographic abnormalities in rheumatoid arthritispatients compared to age and sex-matched controls
Authors: S. Hannawi, K. Naeem
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of the joints with several extra-articular features. Cardiovascular disease (CVD) mortality accounts for 40%–50% of all deaths in RA. Apart from atherosclerotic heart disease other cardiac abnormalities had been found to be prevalent in RA; including, pericarditis, heart failure, coronary vasculitis and valve disease. <h3>Objectives</h3> Due to scarcity of data regarding cardiac disease in the Middle East population, we studied echocardiographic features in RA patients compared to their age, sex, and traditional CVD risk factors matched controls. <h3>Methods</h3> In a cross-sectional study, we recruited 39 RA patients meeting the 1987 revised criteria of RA and 37 age, sex and traditional CVD risk factors matched controls. Standard trans-thoracic echocardiography examination was carried out by a specialties cardio-sonographer who was blinded to the status of the participants. Left ventricular dimensions, wall geometry, ejection fraction, diastolic parameters, right ventricular size and function, valve structure and function, pericardium, pulmonary pressures and aortic root dimensions were assessed by echocardiography. t-test and chi-2 test were used to compare the echocardiographic findings between the two groups. P value of&lt;0.05 was considered significant. <h3>Results</h3> Thirty-nine RA patients (34 F, 4 M) and 37 controls (32 F, 5 M) were studied. Among RA, 27 (69%) were RF positive. The two groups were similar in terms of age (p=0.86), gender (p=0.71), and traditional cardiovascular risk factors. No significant difference was found between RA and the controls in term of left ventricular ejection fraction, wall geometry, diastolic parameters, right ventricular size and function, valve disease, pulmonary pressures, pericardium and aortic root dimensions. However, left ventricular end-diastolic diameter (43.11±1.14 vs. 39.35±0.84 mm respectively, p=0.01), end-systolic diameter (24.39±0.70 mm vs. 26.96±0.96, respectively, p=0.03) and Left ventricular mass index (79.83±5.11 vs. 63.64±3.15, respectively, p=0.01) were significantly higher in RA patients than in the controls. <h3>Conclusions</h3> Patients with rheumatoid arthritis have higher left ventricular end-diastolic and end-systolic dimensions, and greater left ventricular mass index compared to their age, sex and traditional CVD risk factors-matched controls. As the increase in the left ventricular mass index is a predictor of cardiac sudden death, echocardiography might be a simple non-invasive tool for cardiac risk screening in RA. <h3>Disclosure of Interest</h3> None declared
MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma <i>In Situ</i>
Authors: Qianyu Guo, Vivian Z. Li, Jessica N. Nichol, Fan Huang, William Yang, Samuel E.J. Preston, Zahra Talat, Hanne Lefrère, Henry Yu, Guihua Zhang, Mark Basik, Christophe Gonçalves, Yao Zhan, Dany Plourde, Jie Su, Jose Torres, Maud Marques, Sara Al Habyan, Krikor Bijian, Frédéric Amant, Michael Witcher, Fariba Behbod, Luke McCaffrey, Moulay Alaoui-Jamali, Nadia V. Giannakopoulos, Muriel Brackstone, Lynne-Marie Postovit, Sonia V. del Rincón, Wilson H. Miller
Journal: Cancer Research (2019)

Abstract The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A–derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. Significance: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.
Patients with negative patch tests: Retrospective analysis of North American Contact Dermatitis Group (NACDG) data 2001-2016
Authors: Erin M. Warshaw, Amy J. Zhang, Donald V. Belsito, Joseph F. Fowler, James S. Taylor, Howard I. Maibach, Toby Mathias, Denis Sasseville, James G. Marks, Vincent A. DeLeo, Anthony F. Fransway, Kathryn A. Zug, Melanie D. Pratt, Matthew J. Zirwas, Joel G. DeKoven
Journal: Journal of the American Academy of Dermatology (2019)
SAT0596 Thoracic involvement at diagnosis drives a differentiated clinical presentation of sarcoidosis: analysis of 1245 patients (SARCOGEAS-SEMI)
Authors: S. Retamozo, P. Brito-Zerón, R. Pérez-Alvarez, B. Kostov, C. Feijoo Masso, G. Fraile, R. Gómez-de-la-Torre, B. De-Escalante, M. López-Dupla, A. Alguacil, J. Chara-Cervantes, M. Pérez-Conesa, J. Rascón, J.S. Garcia-Morillo, P. Perez-Guerrero, E. Fonseca, M. Akasbi, M. Bonet, J.L. Callejas, G. De-la-Red, E. Calvo, C. Soler, E. Peral-Gutiérrez, J.F. Gómez-Cerezo, G. Cruz-Caparrós, S. Rodríguez-Fernández, B. Pinilla, A. Gato, A. Rolo, C. Morcillo, A. Robles, I. Ojeda, M.J. Vives, B. de-Miguel, M. Penadés, M. De-Vicente, X. Bosch, M. Pérez-de-Lis, A. González-García, C. Yllera, B. Gracia-Tello, A. Perez-Gonzalez, M. Pedrosa, C. Tolosa, L. Pallarés, M. Ramos-Casals
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To analyse whether thoracic involvement at diagnosis is associated with a specific clinical presentation of sarcoidosis. <h3>Methods</h3> The SARCOGEAS-SEMI is a nationwide registry of patients with sarcoidosis. Radiographic stages at diagnosis were classified as stage 0 (normal), stage I (only bilateral hilar lymphadenopathy -BHL-), stage II (BHL +pulmonary infiltrates), stage III (only infiltrates) and stage IV (fibrosis). <h3>Results</h3> The cohort consisted of 1245 patients (722 women, 523 men, mean age at diagnosis 47 years). Pulmonary imaging data at diagnosis was available in 1230 patients including 395 (32%) with stage I, 500 (40%) with stage II, 195 (16%) with stage III and 42 (3%) with stage IV. Patients with no thoracic involvement (stage 0) were more frequently women (73% vs 56%, p=0.002), older (52.1 vs 46.8 years, p=0.001) and had a higher frequency of skin (54% vs 34%, p&lt;0.001) and neurological (14% vs 6%, p=0.004) involvements in comparison with those with stages I-IV. Patients without ILD (stage I) were more frequently women (61% vs 54%, p=0.031), had a higher frequency of fever (27% vs 19%, p=0.002), skin (43% vs 29%, p&lt;0.001) and salivary gland involvement (8% vs 3%, p=0.001), and a lower frequency of respiratory symptoms (37% vs 54%, p&lt;0.001) and liver involvement (9% vs 16%, p=0.001) with respect to those with ILD (stages II-IV). <h3>Conclusions</h3> A specific clinical and epidemiological pattern of disease presentation was found in patients with no thoracic involvement and in those presenting with interstitial lung disease at diagnosis. <h3>Disclosure of Interest</h3> None declared