tbuckley/cabot-search huggingface dataset:
The aggressive variant prostate carcinoma (AVPC) molecular signature (-MS) and platinum-sensitivity in castration resistant prostate cancer (CRPC).
Authors: Ana Aparicio, Lianchun Xiao, Elsa Li Ning Tapia, Anh Hoang, Naveen Ramesh, Wenhui Wu, Haidee Chancoco, Elisabeth I. Heath, Eleni Efstathiou, Timothy C. Thompson, Patricia Troncoso, Bradley McIntosh Broom, Amado J. Zurita, Nicholas Navin, Christopher Logothetis, Paul Gettys Corn
Journal: Journal of Clinical Oncology (2017)

5013 Background: The AVPC are a subset of prostate cancers that share the clinical, therapy response and molecular profiles of the small cell prostate carcinomas, a histological variant of the disease that responds poorly to androgen receptor directed therapies. The AVPC are characterized by a molecular signature of combined tumor suppressor defects (≥ 2 alterations in Tp53, RB1 and/or PTEN by immunohistochemistry or genomic analyses). We conducted a randomized phase II study of cabazitaxel (CAB) plus or minus carboplatin (CARB) in men with CRPC and asked whether the AVPC-MS predicted for platinum benefit. Methods: 160 men with metastatic CRPC were randomized 1:1 to receive IV CAB (25 mg/m2) or CAB/CARB (25 mg/m2; AUC4) Q21 days with growth factor support until disease progression, unacceptable toxicity or for up to 10 cycles. Imaging occurred every 2 cycles. The primary endpoint was progression free survival (PFS). 73 tumor samples obtained within 1 year of registration from 65 of the 160 patients (pts) were stained for Tp53, RB1, PTEN, AR-N terminus, AR-C terminus and Ki67. DNA of sufficient quantity for sequencing was extracted from 27 tumors and 70 plasma samples. Results: At a median follow up of 21.6 months (mo), median PFS (mPFS) in the overall population (n = 160) is 4.6 mo (95%CI 3.5, 5.8) with CAB vs 7.4 mo (95% CI 5.6, 8.3) with CAB/CARB (p = 0.004). Men with AVPC-MS-positive tumors had a mPFS of 4.5 mo (95%CI 1.5, NA) with CAB [n = 9] vs 8.0mo (95%CI 6.11-9.7) with CAB/CARB [n = 23] (p = 0.0036) whereas men with AVPC-MS-negative tumors had a mPFS of 6.8mo (95%CI 5.2, NA) with CAB [n = 12] vs 5.4mo (95%CI 3.72, NA) with CAB/CARB [n = 12] (p = 0.1445). Analysis of plasma DNA samples is ongoing and will be presented at the meeting. Conclusions: The AVPC-MS identifies a subset of men platinum-sensitive CRPC tumors. These findings should serve as the foundation for a therapeutically relevant classification of prostate cancer. Clinical trial information: NCT01505868.
SP0089 How to prevent and treat cardiovascular comorbidity with exercise?
Authors: H Dagfinrud
Journal: Annals of the Rheumatic Diseases (2017)

Low cardiorespiratory fitness is a strong predictor of cardiovascular disease and all-cause mortality in healthy people as well as in patient groups. Unfit individuals have twice the risk of death from all causes, and tailored exercise is important to improve fitness. It is well established that patients with inflammatory rheumatic diseases have increased risk for cardiovascular disease compared with healthy population, and it is therefore particularly important that these patients benefit from the risk-reducing effect of exercise. Exercise has traditionally been recommended as part of the treatment for patients with rheumatic diseases, but exercise programs has mainly focused on improving mobility and reducing pain. Further, patients with active disease has been recommended to exercise with low intensity. To increase cardiorespiratory fitness, however, high intensity exercise is needed. It is therefore encouraging that recent studies show that patients with active rheumatic disease tolerate intensive cardiorespiratory- and strength exercises and can benefit from such health-enhancing training. Recent research in this field will be presented and discussed. <h3>Disclosure of Interest</h3> None declared
FRI0343 Cognitive disorders in behÇet's disease: some clinical and pathogenesis relations
Authors: P Ovcharov, T Lisitsyna, D Veltishchev, D Burenchev, D Ishchenko, O Seravina, O Kovalevskaya, Z Alekberova, E Nasonov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> the cognitive disorders (CD) is a special psychopathological problem for Behçet9s Disease (BD) patients. The causes of CD aren9t enough investigated. Anxiety/depressive disorders and primary neural parenchymal lesions due to BD usually related to CD in these patients. <h3>Objectives</h3> to determine the prevalence of CD in BD patients and its associations with some clinical and magnetic resonance imaging (MRI) scan features. <h3>Methods</h3> the investigation has been realized in accordance with the interdisciplinary program "Stress factors and mental disorders in immune-mediated inflammatory rheumatic diseases". 106 BD patients were enrolled in the study. The majority of patients were men (72,6%), natives of the North Caucasus (51,9%), with mean age (M±m) 33,3±0,98 years. All the patients met the criteria of the International Study Group for BD (1990) classification. The disease activity was assessed by scoring system BDCAF. CD were diagnosed with psychology and neuropsychology methods. Mental disorders (MD) were diagnosed by psychiatrist in accordance with the ICD-10 in semi-structured interview. The severity of depression and anxiety was evaluated by Montgomery–Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). Brain MRI including T1- weighted images, T2- weighted images and fluid-attenuated inversion-recovery images (FLAIR) was done in 44 (41,5%) BD patients. <h3>Results</h3> CD of mild to moderate severity were diagnosed in 82 (77,4%) of BD patients. The mechanical memory (50%) and attention deficit (80,5%) were the most frequent manifestations of CD, impairment of associative memory (31,7%) and logical thinking (36,6%) were less frequent. The presence of CD didn9t depend on BD activity, severity and duration, as on patient9s ethnicity, use of prednisone and immunosupressive agents. The frequency of neurological manifestations (headache, seizures, myelopathy, ataxia) did not differ significantly in patients with and without CD (28% vs 32%, p=0,44). The patients with CD were older (34,3±1,07 vs 29,0±2,14, p=0,006), more often had chronic/recurrent depressive disorders (84,1% vs 50,0%, p=0,001) of moderate severity (MADRS 16,1±0,74 vs 12,2±1,06, p=0,005), chronic stressful life events (91,5% vs 62,5%, p=0,001) and multifocal subcortical parenchymal MRI changes (57,6% vs 9%, p=0,005). <h3>Conclusions</h3> the results have shown high rates of different CD in BD patients. CD were not associated with BD activity and presence of neurological symptoms. CD were related to the diagnoses of stress-related mild to moderate chronic depressive disorders and minor brain multifocal subcortical parenchymal MRI lesions. <h3>Disclosure of Interest</h3> None declared
AB0354 Prevalence of signs of connective tissue dysplasia in patients with rheumatoid arthritis and characteristics of the course of combined pathology
Authors: R Demidov, S Lapshina, L Myasoutova
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Connective tissue dysplasia (CTD) has a common pathogenesis with rheumatoid arthritis (RA). Question of peculiarities in such combination remains little known. <h3>Objectives</h3> To analyze the peculiarities of RA in patients with signs of CTD. <h3>Methods</h3> Among the 107 patients with RA, seen in the rheumatology departments in Kazan city, 18 (16.8%) patients (15 women and 3 men, mean age 47,9±12,89 years) with reliable signs of CTD were selected, identified clinically and the analysis of their documentation was performed. By DAS28 low RA activity was detected in 1 (5.6%) patients, average - 13 (72.2%), high - 4 (22.2%). The clinical-laboratory and instrumental methods of diagnosis, standardized and independently developed questionnaire for the presence of CTD in selected group of patientswere used <h3>Results</h3> The most frequently following signs of CTD syndrome - vegetative-vascular dystonia - 14 (77.7%), myopia - in 9 (50%), mitral valve prolapse- in 6 (33.3%), small heart abnormalities - in 8 (44.4%), flat feet - 6 (33.3%), scoliosis - in 5 (27.7%), hyperkyphosis - in 2 (11.1%), hypermobility of joints - in 2 (11 1%), anomaly of kidney structure- in 2 (11.1%), rhythm and conduction disturbances- in 7 (38.8%). Osteoporosis was observed in 11 (61.1%) patients. We select two group of patients: the first (n=9) from 1 to 5 CTD signes and the second (n=9) – from 6 to 9 dysplasia symptoms. In the second group RA activity by DAS28 was significantly (p≤0.05) higher (4.52±1,20) than in the first (DAS28 =3.95±0.81). Obtained differences in RA activity, depending on the availability of myopia (DAS28 =4,68±0,87) or its absence (DAS28 =3,78±1,06); flatfoot (DAS28 =4,53±1,05) or its absence (DAS28 =4,04±1,02) were evaluated. A significant (p≤0.05) difference was found in patients with osteoporosis, the availability for activity (DAS28 =4.68±0.97), pain intensity VAS (1,44sm ± 6.90), compared with normal bone density tissue (DAS28 =3,36±0,36, pain VAS =5,83±2,22 cm). <h3>Conclusions</h3> Among patients with RA CTD signes occur more frequently than in the population (16.8% versus 10%). The most frequently detected are myopia, vegetative-vascular dystonia, cardiac diseases, osteoporosis. Patients with signs of dysplasia had a trend towards a higher activity of RA. <h3>Disclosure of Interest</h3> None declared
FRI0291 CD4 and CD8 count in patients with systemic lupus erythematosus – associations with infection and disease activity
Authors: H Baharuddin, N Zainudin, A Ahmad, A Rosman, M Mohd Zain
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease driven by the activation of autoreactive T and B cells. Decreased levels of CD4 counts were found in these patients, although there are conflicting data on whether CD4 is associated with SLE disease activity.<sup>1,2,3</sup> <h3>Objectives</h3> To investigate the associations between CD4 and CD8 counts with (1) active SLE and (2) infection in patients with SLE. <h3>Methods</h3> This was a cross-sectional study conducted in a rheumatology referral centre in Malaysia. Inclusion criteria included patients who fulfilled SLICC SLE classification and was admitted to rheumatology ward for active SLE or infection. We excluded patients who had overlap syndrome, retroviral disease or underlying malignancy. SLE Disease Activity Index (SLEDAI) score was assessed by the same rheumatologist. Statistical analysis was performed using SPSS 20 and a p-value of &lt;0.05 was considered significant. Pearson correlation was used to analyse associations between 2 continuous variables, while comparison between 2 continuous data was performed using student9s t test. <h3>Results</h3> Forty-two patients participated in this study. Majority (90.5%) were females with a mean age of 33.05 (±11.42) years and SLE duration of 8.69 (±5.26) years. There were 40 (95.2%) ANA positive, 23 (54.8%) anti-dsDNA positive, 13 (31.0%) anti-smith positive, 24 (57.1%) low C3 and 16 (38.1%) low C4 in this cohort. There were significant correlations between SLEDAI score and CD4 (r=-0.59, p&lt;0.01) and CD8 counts (r=-0.57, p&lt;0.01). CD4 and CD8 counts were significantly lower in patients with clinically active SLE vs non-active, however, there were no significant differences in CD4 and CD8 counts in patients with infection vs no infection. We also found significantly high anti-dsDNA level and low complement 3, but not complement 4, in active SLE. White cell count was significantly higher in patients with infection. The details are tabulated in Table 1. <h3>Conclusions</h3> There were significant negative correlations between SLEDAI score and CD4 and CD8 counts, with low CD4 and CD8 counts found in patients with active SLE. There were no significant differences in CD4 and CD8 counts during infection. <h3>References</h3> Ferreira S, Vasconcelos J, Marinho A et al. CD4 lymphocytopenia in systemic lupus erythematosus. Acta Rheumatol Port 2009; 34: 200–206. Bonelli M, Savitskaya A, von Dalwigk K et al. Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE). Int Immunol 2008; 20: 861–868. Liu MF, Wang CR, Wu CR. Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus. Scand J Immunol 2004; 59: 198–202. <h3>Disclosure of Interest</h3> None declared
Perioperative and Oncologic Outcomes of Nephrectomy and Caval Thrombectomy Using Extracorporeal Circulation and Deep Hypothermic Circulatory Arrest for Renal Cell Carcinoma Invading the Supradiaphragmatic Inferior Vena Cava and/or Right Atrium
Authors: Alessandro Nini, Umberto Capitanio, Alessandro Larcher, Paolo Dell’Oglio, Federico Dehò, Nazareno Suardi, Fabio Muttin, Cristina Carenzi, Massimo Freschi, Roberta Lucianò, Giovanni La Croce, Alberto Briganti, Renzo Colombo, Andrea Salonia, Alessandro Castiglioni, Patrizio Rigatti, Francesco Montorsi, Roberto Bertini
Journal: European Urology (2017)
Childhood onset inflammatory bowel disease and risk of cancer: a Swedish nationwide cohort study 1964-2014
Authors: O Olén, J Askling, MC Sachs, P Frumento, M Neovius, KE Smedby, A Ekbom, P Malmborg, JF Ludvigsson
Journal: BMJ (2017)

Objective To assess risk of cancer in patients with childhood onset inflammatory bowel disease in childhood and adulthood.Design Cohort study with matched general population reference individuals using multivariable Cox regression to estimate hazard ratios.Setting Swedish national patient register (both inpatient and non-primary outpatient care) 1964-2014.Participants Incident cases of childhood onset (<18 years) inflammatory bowel disease (n=9405: ulcerative colitis, n=4648; Crohn's disease, n=3768; unclassified, n=989) compared with 92 870 comparators from the general population matched for sex, age, birth year, and county.Main outcome measures Any cancer and cancer types according to the Swedish Cancer Register.Results During follow-up through adulthood (median age at end of follow-up 27 years), 497 (3.3 per 1000 person years) people with childhood onset inflammatory bowel disease had first cancers, compared with 2256 (1.5 per 1000 person years) in the general population comparators (hazard ratio 2.2, 95% confidence interval 2.0 to 2.5). Hazard ratios for any cancer were 2.6 in ulcerative colitis (2.3 to 3.0) and 1.7 in Crohn's disease (1.5 to 2.1). Patients also had an increased risk of cancer before their 18th birthday (2.7, 1.6 to 4.4; 20 cancers in 9405 patients, 0.6 per1000 person years). Gastrointestinal cancers had the highest relative risks, with a hazard ratio of 18.0 (14.4 to 22.7) corresponding to 202 cancers in patients with inflammatory bowel disease. The increased risk of cancer (before 25th birthday) was similar over time (1964-1989: 1.6, 1.0 to 2.4; 1990-2001: 2.3, 1.5 to 3.3); 2002-06: 2.9, 1.9 to 4.2; 2007-14: 2.2, 1.1 to 4.2).Conclusion Childhood onset inflammatory bowel disease is associated with an increased risk of any cancer, especially gastrointestinal cancers, both in childhood and later in life. The higher risk of cancer has not fallen over time.
OP0244 Family matters: value of family history of spondyloarthritis in the diagnostic work-up of patients with chronic back pain: results from the space and desir cohorts
Authors: Z Ez-Zaitouni, A Hilkens, L Gossec, IJ Berg, R Landewé, R Ramonda, M Dougados, D van der Heijde, F van Gaalen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A positive family history (PFH) of spondyloarthritis (SpA) is considered a risk indicator for the presence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP). In the ASAS classification criteria, a PFH of SpA is defined as the presence of any of the following diseases in first- or second-degree relatives: ankylosing spondylitis (AS), acute anterior uveitis (AAU), reactive arthritis (ReA), inflammatory bowel disease (IBD), and psoriasis. It is however not known if a PFH for each of these diseases contributes equally well to making a diagnosis of axSpA in patients presenting with CBP. <h3>Objectives</h3> To assess which SpA diseases in family members are associated with HLA-B27 and axSpA in patients with CBP. <h3>Methods</h3> The SPACE cohort includes patients with CBP (≥3 months, ≤2 years, onset &lt;45 years) from various European rheumatology centers. DESIR is a French prospective multicenter cohort of patients with inflammatory back pain (IBP; ≥3 months, &lt;3 years, onset &lt;50 years), suggestive of axSpA. Patients underwent a full diagnostic work-up at baseline including MRI and radiographs of sacroiliac joints (local reading), laboratory assessments (e.g. HLA-B27), and assessment of all other SpA features. Patients were asked about the presence of SpA diseases in first- or second-degree relatives (AS, AAU, ReA, IBD, and psoriasis). The associations between a PFH and HLA-B27, sacroiliitis, axSpA diagnosis by the rheumatologist, and fulfilment of the ASAS classification criteria in CBP patients were assessed. <h3>Results</h3> In 438 patients from the SPACE cohort and 647 patients from the DESIR cohort, a PFH of AS (odds ratio (OR) 5.9 (3.5–9.9) and OR 3.3 (2.1–5.2), respectively for SPACE and DESIR) and a PFH of AAU (OR 9.8 (3.3–28.9) and OR 21.6 (2.9–160.1)) were significantly associated with presence of HLA-B27 (Table 1).Furthermore, in both cohorts a PFH of AS and a PFH of AAU were positively associated with fulfilment of the ASAS-criteria, but not with sacroiliitis on imaging (data not shown). In SPACE, but not in DESIR, a PFH of AS or AAU was associated with axSpA diagnosis (data not shown). In both cohorts, a PFH of ReA, IBD, or psoriasis was not positively associated with HLA-B27 positivity, sacroiliitis on imaging, axSpA diagnosis or meeting the ASAS criteria for axSpA. <h3>Conclusions</h3> In two recent CBP cohorts, a PFH of ReA, IBD, or psoriasis did not contribute to identifying axSpA in CBP patients indicating these family elements may not be very useful for diagnosis. A PFH of AS or AAU however may be useful in finding cases in low prevalence settings as these were correlated with HLA-B27 carriership. <h3>Disclosure of Interest</h3> None declared
Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation
Authors: Thomas Riffelmacher, Alexander Clarke, Felix C. Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W. Jacobsen, Anna Katharina Simon
Journal: Immunity (2017)

Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive. Here, we have shown that metabolism and autophagy are developmentally programmed and essential for neutrophil differentiation in vivo. Atg7-deficient neutrophil precursors had increased glycolytic activity but impaired mitochondrial respiration, decreased ATP production, and accumulated lipid droplets. Inhibiting autophagy-mediated lipid degradation or fatty acid oxidation alone was sufficient to cause defective differentiation, while administration of fatty acids or pyruvate for mitochondrial respiration rescued differentiation in autophagy-deficient neutrophil precursors. Together, we show that autophagy-mediated lipolysis provides free fatty acids to support a mitochondrial respiration pathway essential to neutrophil differentiation.
Type of Atrial Fibrillation and Outcomes in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Ulrik M. Mogensen, Pardeep S. Jhund, William T. Abraham, Akshay S. Desai, Kenneth Dickstein, Milton Packer, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Lars Køber, John J.V. McMurray
Journal: Journal of the American College of Cardiology (2017)

Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658)