tbuckley/cabot-search huggingface dataset:
SAT0561 Usefulness of polymerase chain reaction for diagnosing whipple's disease in rheumatology
Authors: M Herbette, JB Cren, L Joffres, C Lucas, E Ricard, C Salliot, J Guinard, A Perdriger, E Solau-Gervais, B Bouvard, A Saraux
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> No consensus exists about the combination of clinical, laboratory, and radiological findings that warrant tests for Whipple9s disease. <h3>Objectives</h3> The primary aim of this multicentre retrospective study was to determine when patients evaluated for rheumatological symptoms should undergo <i>T. whipplei</i> PCR testing. Secondary aims were to describe the clinical patterns and treatments used, to determine the diagnostic yield of PCR testing, and to assess whether centres with higher numbers of tests also had a larger number of Whipple9s disease diagnoses. <h3>Methods</h3> In a retrospective observational study done in five hospitals, we assessed the clinical and radiological signs that prompted <i>T. whipplei</i> PCR testing between 2010 and 2014, the proportion of patients diagnosed with Whipple9s disease, the number of tests performed and the number of diagnoses according to the number of tests, the patterns of Whipple9s disease, and the treatments used. <h3>Results</h3> At least one PCR test was performed in each of 267 patients. Rheumatic signs were peripheral arthralgia (n=239, 89%), peripheral arthritis (n=173, 65%), and inflammatory back pain (n=85, 32%). The main extra-articular signs were constitutional symptoms (n=111, 41.8%), diarrhoea (n=70, 26.5%), fever (n=53, 20%), lymphadenopathy (n=14, 5.3%), and neurological signs (n=11, 4.2%). Whipple9s disease was diagnosed in 13 patients (4.9%). The main samples tested and the more frequently positive tests in the centres with diagnoses of Whipple9s disease were saliva and stool. In the centres with no diagnoses of Whipple9s disease, arthritis was less common, whereas constitutional symptoms, fever, and lymphadenopathy were more common. 11 patients with Whipple9s disease had CRP elevation. The annual incidence ranged across centres from 0 to 3.6/100000 inhabitants. The patients group with Whipple9s disease had a higher proportion of males, older age, and greater frequency of arthritis. <h3>Conclusions</h3> Males aged 40–75 years with unexplained intermittent seronegative peripheral polyarthritis, including those without constitutional symptoms, should have <i>T. whipplei</i> PCR tests on saliva, stool and, if possible, joint fluid. <h3>Disclosure of Interest</h3> None declared
Chronic Cigarette Smoke-Induced Epigenomic Changes Precede Sensitization of Bronchial Epithelial Cells to Single-Step Transformation by KRAS Mutations
Authors: Michelle Vaz, Stephen Y. Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M. O'Hagan, Lauren Murphy, Cynthia A. Zahnow, Edward Gabrielson, Victor E. Velculescu, Hariharan P. Easwaran, Stephen B. Baylin
Journal: Cancer Cell (2017)
Mesenchymal stem cells alleviate oxidative stress–induced mitochondrial dysfunction in the airways
Authors: Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H. Wiegman, Ian M. Adcock, Qizhou Lian, Judith C.W. Mak, Pankaj K. Bhavsar, Kian Fan Chung
Journal: Journal of Allergy and Clinical Immunology (2017)
AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC) in HIV-infected individuals and degree of immunosuppression.
Authors: Sandra Michelle Goldlust, David H. Henry
Journal: Journal of Clinical Oncology (2014)

e22096 Background: While AIDS-defining cancers (ADC) have been associated with greater immunosuppression in HIV-infected individuals, the relationship between non-AIDS-defining cancers (NADC) and immunosuppression is less well understood. Viral coinfection with low levels of immunosuppression may be associated with NADC. The purpose of this retrospective study was to investigate the relationships among immunosuppression, hepatitis coinfection, and NADC. Methods: We reviewed electronic charts of 124 HIV-infected patients obtained from the medical record database of the Cancer Center at Pennsylvania Hospital and collected data on CD4 counts, presence and type of cancer, and hepatitis coinfection. Results: Of 124 HIV-infected patients (110 male), ADC was confirmed in 36 patients (29%) and NADC was confirmed in 23 patients (22%). The two most common types of NADC were anal cancer and Hodgkin’s lymphoma. Of 104 patients (median age 50 years; range 29-73) with available data (ADC=31, NADC=16), no significant difference in immunosuppression was found between patients with NADC (mean CD4 count = 509 cells/μL) and the mean CD4 count of all HIV-infected patients included in the study (474 cells/ μL). However, using a Mann-Whitney Test, we found that patients with ADC tended to have a lower mean CD4 count of 304 cells/ μL as compared to patients with NADC (p-value = 0.0229). The prevalence of hepatitis coinfection (B and C combined) was 19% in patients with ADC and 18% in patients without cancer diagnosis. In patients with NADC, the prevalence of hepatitis coinfection was 31%. Conclusions: ADC in HIV-infected individuals appears to be associated with greater immunosuppression than does NADC, which does not appear to be associated with decreased CD4 counts. Additionally, hepatitis coinfection appears to have a higher prevalence in HIV-infected patients with NADC than it does in both patients with ADC and patients without cancer.
血管内皮成長因子と組み合わせたマイクロレンズトポグラフィーは血管性前駆細胞へのヒト間葉系幹細胞の内皮分化を誘導する【Powered by NICT】
Authors: Kukumberg Marek, Yao Jia Yi, J H Neo Dawn, K F Yim Evelyn
Journal: Biomaterials (2017)
P028 Treatment of BAFF transgenic mice with ANTI-TNF: monoclonal ANTI-TNF are associated with a higher risk of lymphoma than etanercept
Authors: G Nocturne, B Ly, S Boudaoud, S Bitoun, A Paoletti, R Seror, C Nicco, F Mackay, F Vincent, S Ferlicot, L Stimmer, S Roulland, R krzysiek, S Hacein Bey, F Batteux, X Mariette
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Risk of lymhoma in patients with rheumatoid arthritis (RA) and disease activity is the main risk factor. The impact of treatment, notably of anti-TNF, is unclear: decreasing the risk of lymphoma by controlling activity or alterring anti-tumour immunosurveillance. Anti-TNF are not associated with an increased risk of lymphoma in large epidemiologic studies. However, the risk might vary according to the type or to the dose of anti-TNF. <h3>Objectives</h3> To assess if the risk of lymphoma might differ according to the type of anti-TNF, comparing monoclonal anti-TNF to the soluble receptor. For that, we used BAFF transgenic (Tg) mice as a model of autoimmunity-associated lymphomas. They develop lupus and Sjögren and 3% of them spontaneously developed lymphoma at 12–18 months. <h3>Methods</h3> Six months aged BAFF-Tg mice were treated with anti-TNF for 12 months: etanercept (ETA) (n=15, 8 mg/kgx3/week), monoclonal anti-mouse TNF: TN3 19.12 (n=15, 20 mg/kg/week), adalimumab (ADA) (n=12, 20 mg/kg/week) or controls (n=22). Sera were assessed monthly. Crude mortality was compared among the different groups. Histological examination of the spleen was performed. The Fisher's exact test was used to compare the incidence of lymphoma among the groups. <h3>Results</h3> Adjunction of low dose of methotrexate during the 3 first days of treatment prevented immunisation in the 3 groups for life. Using L929 cells, a cell line sensitive to TNF induced death, we confirmed that ADA was 8 to 12 times less efficient than ETA to inhibit soluble murine TNF. As expected, the mean level of ETA, TN3 and ADA were 7 µg/ml, 69 µg/ml and 105 µg/ml, respectively. The level of auto-antibodies and serum Ig did not significantly differ among the groups. However, crude mortality was significantly higher in mice treated with monoclonal anti-TNF compared to controls (p=0.0001 for ADA and p=0.0003 for TN3) but not for mice treated with ETA. Incidence of lymphoma was higher in mice treated with monoclonal anti-TNF: <b>5/15</b><b> (33%)</b> with TN3 (p=0.03/ controls), <b>4/12</b><b> (33%)</b> with ADA (p=0.054/ controls), <b>0/15</b> with ETA and <b>1/22</b><b> (5%)</b> in controls. <h3>Conclusions</h3> Higher mortality and increased risk of lymphoma were observed in BAFF Tg mice treated with monoclonal anti-TNF compared to etanercept. This result may be linked either to the different mechanism of action between the soluble receptor and the monoclonals or to a difference of trough level observed in the different groups even if higher levels of ADA was mandatory given the difference of effect on mouse TNF. This study demonstrates the negative impact of a prolonged anti-TNF treatment on the risk of lymphoma in the context of BAFF increase. <h3>Disclosure of interest</h3> None declared
Effect of the Adition of Metformin on the expressión of Multidrug-Resistance Genes (ABCB1, ABCG2) in Acute Lymphoblastic Leukemia: In Vitro and In Vivo Study
Authors: Christian Omar Ramos Peñafiel, Irma Olarte Carrillo, Rafael Cerón Maldonado, Adrián Santoyo Sánchez, Humberto Baldemar Castellanos Sinco, Efreen Montaño Figueroa, Gloria Queipo García, Adolfo Martínez Tovar
Journal: Blood (2016)
AB1034 Scoring systems of muscle mri in idiopathic inflammatory myopathies
Authors: K Kubinova, H Mann, J Vencovsky
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> MRI is a widely used radiological method for assessing muscle involvement in idiopathic inflammatory myopathies (IIM). There is still no universally accepted and validated scoring protocol for the quantification of pathological changes in muscles. <h3>Objectives</h3> To identify MRI scoring systems used in previous studies. To summarize the most frequently evaluated MRI features and to suggest parameters for a unified scoring system, that has to be validated in the future. <h3>Methods</h3> A detailed literature search was conducted in the standard medical databases. Information regarding individual MRI scoring systems were obtained from the methodological explanations and their parameters were compared. <h3>Results</h3> We identified different scoring systems with a large variability of assessed localizations and parameters (Table 1). Muscle oedema as a sign of active muscle inflammation was evaluated in all studies. There were some studies using modified Mercuri score for evaluation of the fatty infiltration as a marker of chronic muscle damage or the Goutallier grading (1, 2), developed originally for the assessment of inherited neuromuscular disorders or structural changes in orthopedics. Perifascicular oedema or soft-tissue oedema were also assessed in some cases. There was no concordance between evaluated muscle groups. <h3>Conclusions</h3> MRI plays a significant role in the evaluation of pathological changes in IIM. This search demonstrated, that there is no widely used, standardized method for assessment of a MRI finding. According to our results, a future concept of MRI scoring system should include evaluation of muscle oedema, fatty infiltration and possibly also the presence of perifascicular (-fascial) and subcutaneous tissue inflammation. Muscle groups most convenient for evaluation have to be determined as well. <h3>References</h3> Goutallier D, et al. Influence of cuff muscle fatty degeneration on anatomic and functional outcomes after simple suture of full-thickness tears. J Shoulder Elbow Surg, 2003;12(6):550–4. Zheng Y, et al. Magnetic resonance imaging changes of thigh muscles in myopathy with antibodies to signal recognition particle. Rheumatology, 2015;54(6):1017–1024. <h3>Acknowledgements</h3> Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology). <h3>Disclosure of Interest</h3> None declared
LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression
Authors: Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T. Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B. Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R. Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C. Boutros, Cheryl H. Arrowsmith, Felix Y. Feng, Anthony M. Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H. He
Journal: Cancer Research (2017)

Androgen receptor (AR) signaling is a key driver of prostate cancer, and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant prostate cancer (CRPC). Here, we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell-cycle genes, including CENPE, a centromere binding protein and mitotic kinesin. CENPE was regulated by the co-binding of LSD1 and AR to its promoter, which was associated with loss of RB1 in CRPC. Notably, genetic deletion or pharmacological inhibition of CENPE significantly decreases tumor growth. Our findings show how LSD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its therapeutic targeting in this disease. Cancer Res; 77(20); 5479-90. ©2017 AACR.
SP0090 Comorbidity-adapted exercise for patients with knee osteoarthritis
Authors: M De Rooij
Journal: Annals of the Rheumatic Diseases (2017)

Exercise therapy is a key intervention in the management of patients with knee OA<sup>1</sup>. However, comorbidity is present in 68 to 85% of patients with OA (e.g. cardiac disease, diabetes type 2, obesity)<sup>2,3</sup>. Comorbidity interferes with exercise therapy. In clinical practice, comorbidity is a frequent reason to exclude patients from exercise therapy. If accepted into an exercise program, both therapists and patients tend to reduce exercise intensity to a level unlikely to be effective, because of fear of aggravating symptoms of the comorbid disease. Further, the effect of exercise therapy in patients with knee OA and severe comorbidity is not known. Patients with unstable medical conditions, precluding safe participation in an exercise program, are excluded from clinical trials. In view of the effectiveness of exercise therapy in knee OA and the high prevalence of comorbidity, there is a great need for comorbidity-related adaptations to exercise therapy. In this lecture a strategy (i3-S strategy) will be presented on how to develop comorbidity-related adaptations to exercise therapy in an index disease (e.g osteoarthritis)<sup>4</sup>. According this strategy we have developed a tailored exercise program for patients with knee OA and comorbidity. Subsequently, to evaluate the efficacy of the tailored exercise program for patients with knee OA and comorbidity (cardiac disease, diabetes type 2, COPD and obesity (body mass index ≥30kg/m<sup>2</sup>) a randomized controlled trial (n=126) was performed in a secondary care setting. The results showed that tailored exercise therapy greatly improved physical functioning, reduced pain and was also safe for patients with knee OA and (severe) comorbidity<sup>5</sup>. At present we are implementing and evaluating the protocol in primary care. <h3>References</h3> Fransen M, McConnell S, Harmer AR, Van der Esch M, Simic M, Bennell KL. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev 2015; 1:CD004376. Tuominen U, Blom M, Hirvonen J, Seitsalo S, Lehto M, Paavolainen P et al. The effect of co-morbidities on health-related quality of life in patients placed on the waiting list for total joint replacement. Health Qual Life Outcomes 2007; 5:16. van Dijk GM, Veenhof C, Schellevis F, Hulsmans H, Bakker JP, Arwert H et al. Comorbidity, limitations in activities and pain in patients with osteoarthritis of the hip or knee. BMC Musculoskelet Disord 2008; 9:95. Dekker J, de Rooij M, van der Leeden M. The i3-S strategy for developing comorbidity-related adaptations to exercise therapy. Disability and Rehabilitation 2016; 38:905–9. de Rooij M, van der Leeden M, van der Esch M, Cheung J, Häkkinen A, Haverkamp D, Roorda LD, Twisk J, Vollebregt J, Lems WF, Dekker J. Efficacy of tailored exercise therapy in patients with knee osteoarthritis and comorbidity: a randomized controlled trial. Accepted for publication in Arthritis Care &amp; Research (Hoboken), 2016. <h3>Disclosure of Interest</h3> None declared
AB0184 Chromosomal aberrations are associated with disease severity in a mouse model of bleomycin-induced scleroderma
Authors: R Luisetto, M Beggio, A Scanu, F Leite de Oliveira, E Pigatto, A Peruffo, E Zanatta, F Oliviero, P Sfriso, L Punzi, F Cozzi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Scleroderma (SSc) is a connective tissue disease characterized by immunomediated inflammation and fibrosis. The presence of autoantibodies against chromosome associate proteins,such as anti-centromere proteins and anti-topoisomerase I, was observed in SSc patients, however genotoxic events have never been evaluated (2). <h3>Objectives</h3> To assess the presence of aneuploidia, micronuclei (MN) and other chromosomal aberrations in peripheral lymphocytes in a bleomycin (BLM)-induced scleroderma mouse model. <h3>Methods</h3> BALB/c mice (n=20 per condition) were injected subcutaneously daily with BLM 2mg/kg or PBS (control) for 14 days. Urine was collected weekly and proteinuria was measured. At day 15 mice were sacrificed and organs harvested for histological analysis. The MN assay was performed on cultured peripheral lymphocytes isolated from mice spleens. Cells were treated with cytochalasin B (10 μg/ml) for 24 h and a minimum of 1000 binucleated cells/mouse were scored following the criteria of Fenech (1). The antikinetochore (CREST) staining was used to determine the origin of MN observed. <h3>Results</h3> In BLM treated mice was observed huge perivascular lung fibrosis and significant skin involvement. 17 out of 20 mice developed acute renal involvement with mean proteinuria levels of 730±48 mg/dl. In comparison with the control mice, a significant increase in MN number was observed in BLM treated mice (57,8±4,4 vs 6,3±0,6, p&lt;0.05). CREST staining was higher in MN derived from BLM treated mice (16,4±1,1 vs 3,7±0,7, p&lt;0,025), indicating that in this group lymphocyte MN arised mainly from lagging chromosomes. In addition, an increased frequency of ring chromosome was observed in mice with greater skin fibrosis and renal involvement.A correlation between the presence of CREST stained MN and disease severity parameters as renal failure, lung and skin fibrosis was observed (respectively R=0,4095; R=0,7507 and R=0,9471). <h3>Conclusions</h3> This study provides experimental evidence that significant chromosomal aberrations seem to be related to the severity of disease in a mouse model of SSc. Further investigations on lymphocytes obtained from SSc patients could be matched with results observed in mouse model to confirm the relationship between severity of the disease and chromosomal abnormalities. <h3>References</h3> Fenech M. Cytokinesis-block micronucleus cytome assay. Nature Protocols 2006, 2(5): 1084–1199. Korman BD and Criswell LA. Recent advances in the genetics of systemic sclerosis: toward biological and clinical significance. Curr Rheumatol Rep 2015, 17(3): 21–34. <h3>Disclosure of Interest</h3> None declared
Bone marrow xanthomas associated with hypertriglyceridemia
Authors: Nelson C. N. Chan, Chak‐Chung Chan, Natalie P. H. Chan
Journal: American Journal of Hematology (2017)

A 64-year-old man was referred for an incidental finding of isolated thrombocytopenia (73 × 109/L). He was emaciated and a splenomegaly was detected clinically. A computer tomography scan of the abdomen revealed a 13 cm splenomegaly with splenic varices and osteolytic and expansile lesions of the femurs and pelvis (Image 1A). A magnetic resonance imaging showed abnormal bone marrow signals of the axial and appendicular skeleton which were mildly hyper-intense in T1 (Image 1B) and hyper-intense in T2 (Image 1C). The findings were suspicious of infiltrative bone marrow disease and a bone marrow examination was performed. The trephine biopsy showed diffuse replacement of hematopoietic cells by foamy histiocytes (Image 1D, Hematoxylin and Eosin stain; ×100 magnification). The histiocytes were positive for CD68 and negative for CD1a and S100. The patient had a sky-high pre-treatment fasting triglyceride of 3787 mg/dL. He had hypertriglyceridemia and recurrent pancreatitis since young age but he defaulted medical follow-up. He had no neurological deficit and a BRAFV600E mutation was not detected. The overall findings were compatible with xanthomas of bone associated with familial hypertriglyceridemia and treatment with fibrate was initiated. A, Plain computer tomography scan of right hip. It showed ill-defined expansile osteolytic lesions associated with cortical thinning in right ilium and right proximal femur. B,C, Plain magnetic resonance imaging of pelvis. Multiple roundish lesions were observed in pelvic bones and bilateral proximal femurs. The lesions were heterogeneous in size and showed conglomeration. They were mildly hyper-intense with hypo-intense periphery in T1 and hyper-intense with hypo-intense rim in T2. D, Hematoxylin and Eosin staining of trephine biopsy at 100× magnification. Haematopoietic cells in bone marrow were replaced by foamy histiocytes [Color figure can be viewed at wileyonlinelibrary.com] Bone marrow xanthoma is a rare but well-recognized benign tumor that is mostly described in patients with hyperlipidemia.1, 2 Radiologically, it can closely mimic aggressive infiltrative bone lesions with differential diagnosis being plasmacytoma, metastatic carcinoma, Erdheim–Chester disease, and Rosai–Dorfman disease. Therefore, a correlation with clinical history and histology is essential to arriving at the correct diagnosis and ruling out more sinister pathologies.3 Nothing to report. Nelson C. N. Chan and Chak-chung Chan wrote the manuscript. Natalie P. H. Chan critically reviewed and approved the manuscript.