tbuckley/cabot-search huggingface dataset:
A1.85 Can rituximab treatment in rheumatoid arthritis patients decrease cardiovascular risk?
Authors: Tania Gudu, Diana Mazilu, Alexandra Peltea, Daniela Opris, Ruxandra Ionescu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Rheumatoid arthritis (RA) is not only a chronic inflammatory joint disease, but also a condition associated with a high risk for cardiovascular diseases, mostly due to the inflammatory burden. Therefore, EULAR recommends using a modified assessment of cardiovascular risk, mSCORE which is obtained by multiplying SCORE by 1.5. The objective of this study is to evaluate the impact of rituximab on cardiovascular risk. <h3>Materials and Methods</h3> 42 RA patients initiating rituximab in 2010 were included and were prospectively followed for 18 months. They all had active disease and were non-responders to DMARD therapy (synthetic and/or biologic). The cardiovascular risk was evaluated by mSCORE (at baseline and at 18 months). Response to rituximab therapy was assessed using EULAR response at 6 months (ER6) and at 18 months (ER18). The study is still ongoing, in order to assess long-term impact of rituximab on cardiovascular risk in RA patients. <h3>Results</h3> ER at 6 months was negatively correlated to mSCORE at 18 months (r = -0.353, p = 0.032). Disease duration seems to have a high impact on cardiovascular risk (correlation with mSCORE at baseline: r = 0.993, p &lt; 0.001, with mSCORE at 18 months: r = 0.668, p &lt; 0.001). Drugs such as statins and methotrexate which are known to be protective for cardiovascular diseases do not influence mSCORE at 18 months (r = 0.191, p = 0.239, respectively r = -0,156, p = 0.337). Cardiovascular risk in patients initiating rituximab is still high after a year and a half of treatment, regardless of using cardiovascular protective drugs. The negative correlation between ER6 and mSCORE at 18 months suggests that anti CD20 therapy might be useful for decreasing cardiovascular burden in RA patients. Though, in patients with a longer duration of disease, mSCORE remains high after 18 months of treatment. <h3>Conclusions</h3> Although an early good clinical and biological response at 6 months to rituximab therapy seems to decrease the cardiovascular risk after 18 months of treatment, the cardiovascular burden is still high (even with protective drugs), probably due to previous inflammatory status.
Abstract 21: Survival prognostic significance of TNFRII, TGFa, TIMP1 &amp; CRP in high-risk melanoma patients.
Authors: Ahmad A. Tarhini, Yan Lin, William A. LaFramboise, Sandra Lee, John Kirkwood
Journal: Cancer Research (2013)

Abstract Background: The E1694 trial tested the GM2-KLH-QS21 (GMK) vaccine versus high dose interferon-alpha2b as adjuvant therapy for patients with operable high-risk stage IIB/III melanoma in relation to relapse-free survival (RFS) and overall survival (OS). Multiplex analysis of candidate serum analytes utilizing banked specimens from patients participating in this trial was evaluated to develop biomarkers of prognostic or therapeutic predictive value. Methods: The Aushon Multiplex Platform was used to simultaneously quantitate the serum levels of 115 candidate analytes selected based on previous data. Univariate proportional hazard (PH) model was used to assess the association between each marker and OS or RFS. The Benjamini and Hochberg's method was used to adjust for multiple testing. Baseline serum samples from 40 patients treated with the GMK vaccine were analyzed. The least absolute shrinkage and selection operator proportional hazard regression (LASSOPH) was used to select markers that are most informative for RFS and OS. We then fit the regular PH models using the markers selected by the LASSOPH. The survival ROC analysis was used to evaluate the ability of the models to predict 1 year RFS and 5 year OS. Leave-one-out cross validations (LOOCVs) were used to avoid over fitting. Results: A panel of four markers, Tumor Necrosis Factor alpha Receptor II (TNFRII), Transforming Growth Factor alpha (TGFa), Tissue Inhibitor of Metalloproteinases 1 (TIMP1), and C-reactive protein (CRP), at baseline was found to be most informative to OS after GMK vaccine treatment (high serum levels correlate with worse prognosis). The dichotomized risk score based on the four markers can separate the OS curves well (log rank test p-value=0.0005). When using the 4 marker PH model to predict the 5 year OS, we achieved an AUC of 89% (cross validated AUC=72%). High baseline TNFRII was also identified as the most informative marker of worse RFS after GMK vaccine. The RFS of patients with high (above median) baseline TNFRII was significantly lower than that of patients with low (below median) baseline TNFRII (log rank test p-value=0.01). Conclusions: Our modeling analysis yielded a panel of four serum biomarkers that is significantly prognostic of survival in patients with high-risk melanoma and warrants further investigation. Citation Format: Ahmad A. Tarhini, Yan Lin, William A. LaFramboise, Sandra Lee, John Kirkwood. Survival prognostic significance of TNFRII, TGFa, TIMP1 &amp; CRP in high-risk melanoma patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 21. doi:10.1158/1538-7445.AM2013-21
Management of the Unruptured Intracranial Aneurysm
Authors: Robert G. Ojemann
Journal: New England Journal of Medicine (1981)

Controversy continues in the neurosurgical literature concerning the treatment of patients with intracranial aneurysms. To some extent this is due to the paucity of data on the natural history of these lesions. Most patients who are found to have an intracranial aneurysm first present with symptoms and signs of subarachnoid hemorrhage. Complications of recurrent hemorrhage, ischemia due to vasospasm, and treatment of the ruptured aneurysm have been the subjects of a previous article and an editorial in the Journal. 1 , 2 In the past few years, Jane, Winn, and Richardson have gathered evidence on the long-term prognosis of patients who have . . .
Abstract 5732: Human papillomavirus infection in Southern Chinese women - a population-based study
Authors: Stephanie S. Liu, Kelvin KY Chan, Rebecca CY Leung, May HM Luk, Sue ST Lo, Daniel YT Fong, Annie NY Cheung, Zhong Qiu Lin, Hextan YS Ngan
Journal: Cancer Research (2010)

Abstract Cervical cancer is a leading cause of death in women worldwide. Persistent infection of high-risk (HR) type human papillomavirus (HPV) is recognized as a necessary cause of cervical cancer. Additionally, the presence of certain predisposing factors in combination of HPV infection will significantly increase the risk of developing cervical cancer. Previous epidemiological studies showed different HPV genotype prevalence between different geographic regions. The objectives of the present study were to study and compare the prevalence and the spectrum of HPV infection in healthy women living in Hong Kong (HK) and Guangdong (GD) regions of China and the association between the potential risk factors and HPV infection. This was a cross-sectional study, and 1526 and 1300 healthy women were recruited from HK and GD, respectively. The overall and type-specific HPV prevalence were studied and compared between the two regions. The results showed that healthy women in GD with normal or abnormal cytology had significantly higher HPV prevalence (10% or 54.5%) than those in HK (6.2% or 33%, p≤0.001). The patterns of age-specific HPV prevalence were also different between the two regions. In HK, the highest HPV prevalence was in the youngest (20-30 years) and the eldest (60 and above) age groups, whereas the highest HPV prevalence in GD was observed in the youngest age group (20-30) and declined as the age increased. HPV16 and HPV52 were the most common high-risk type found in HK and GD, respectively. In HK, younger women had significantly higher risk of HPV infection, whereas lifetime number of sexual partner was strongly associated with the risk of HPV infection in GD. Lack of previous cervical screening, current smoker and having previous sexual transmitted diseases had increased risk of HPV infection for women in both regions. In summary, the overall and type-specific HPV prevalence were found different in healthy women between HK and GD. Together with the understanding of the association between the potential risk factors and HPV infection will be essential for the implementation of effective public health program for prevention of cervical cancer in Southern Chinese women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5732.
Abstract 5070: Cell-free endo180 reveals additional level of endocytic receptor functioning in meningioma.
Authors: Venkateswara Rao Gogineni, Arun Kumar Nalla, Kiran Kumar Velpula, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Endo180, also known as uPAR associated protein (uPARAP), is a member of the tri-molecular complex formed by uPA along with uPAR in the endocytic processing of collagen degradation. In the present study, we found that this membrane-bound protein was released into culture supernates of meningioma and other cancer cell types. In addition, we report a tremendous increase of Endo180 transcript and protein levels in irradiated meningioma cells and their culture filtrates. While non-denaturing immunoprecipitation studies suggested that Endo180 interacts with uPA in cell-free conditions, uPA binding was significantly quenched by deglycosylation of solubilized Endo180. Myc-tagged cDNA expression suggested shedding of Endo180 against secretion from meningioma cells. Function blocking and knockdown of Endo180 adversely affected the proliferation of meningioma cells with concomitant decrease in uPA activity and uPAR expression. We also observed a significant rise of Endo180 expression in meningioma clinical samples and tumors in animal models. A further increase of expression was observed among the brain sections of mice infused with irradiated meningioma cells. Taken together, our results demonstrate that solubilization of Endo180 characterizes a different hierarchy of endocytic receptor functioning in meningioma. Citation Format: Venkateswara Rao Gogineni, Arun Kumar Nalla, Kiran Kumar Velpula, Jasti S. Rao. Cell-free endo180 reveals additional level of endocytic receptor functioning in meningioma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5070. doi:10.1158/1538-7445.AM2013-5070
Lassa Fever in the United States
Authors: Gary P. Holmes, Joseph B. McCormick, Susan C. Trock, Robert A. Chase, Steven M. Lewis, Carol A. Mason, Patricia A. Hall, Lynnette S. Brammer, Gilda I. Perez-Oronoz, Mary Kay McDonnell, James P. Paulissen, Lawrence B. Schonberger, Susan P. Fisher-Hoch
Journal: New England Journal of Medicine (1990)

LASSA fever, first identified in northeastern Nigeria in 1969,1 is endemic in much of western Africa. Mastomys natalensis, a rat that is common around human habitations in the region, is the host of enzootic Lassa fever virus.2 The virus is spread to humans primarily through the urine of infected rats and is also transmissible from person to person. Its incubation period ranges from 7 to 18 days.3 Lassa fever virus may cause as many as 300,000 human infections and 5000 deaths per year in areas where the disease is endemic.4 Lassa fever is infrequently encountered in areas where the disease . . .
Comparing Regulation of the connexin43 Gene by Estrogen in Uterine Leiomyoma and Pregnancy Myometrium
Authors: J Andersen
Journal: Environmental Health Perspectives (2000)

Classical estrogen receptor (ER)-alpha is expressed in human myometrial and leiomyoma tissues from nonpregnant women. A comparison of these tissues shows that leiomyomas overexpress ER-alpha compared to normal myometrium. It was hypothesized that overexpression of ER-alpha in leiomyomas may account for observed overexpression of pregnancy-associated genes that are regulated by estrogen. For this reason, regulation of the labor-associated gene connexin43 cx43 was compared in primary cultures of myometrial and leiomyoma cells. It was shown that a DNA element called activating protein (AP)-1 in the cx43 promoter is necessary for induction of cx43 gene transcription in primary uterine smooth muscle cells after activation of cellular protein kinases. However, estrogen did not induce myometrial cx43 gene transcription in vitro; instead, it inhibited AP-1 induction of cx43 expression. This is likely because the myometrial and leiomyoma cells begin to express the novel ER-beta upon culturing, and agonist-bound ER-beta is known to inhibit AP-1 activity. Interestingly, ER-beta is the predominant ER in myometrial tissue from pregnant women at term. Results from an examination of pregnancy myometrial tissue support the concept that AP-1 activity is involved in the induction of myometrial cx43 expression at term and that suppression of ER-beta expression is needed for this induction. As pregnancy myometrium expresses primarily ER-ss, and nonpregnancy leiomyomas express primarily ER-Alpha, AP-1 activity is predicted to be suppressed in pregnancy myometrium and elevated in leiomyomas under the influence of estrogen. This may be important in understanding tumor pathology, as AP-1 activity is associated with cell growth.
A new animal model for studying EUS changes of chronic pancreatitis
Authors: MS Bhutani, GS Raju, SY Xiao, I Ahmed, D Brining, PJ Pasricha
Journal: Endoscopy (2006)

Background: Due to difficulty in obtaining pancreatic histology in humans we here report an animal model for studying serial changes of chronic pancreatitis by EUS and correlating it with histology.
AB0559 Hospitalization of individuals with spondyloarthritis and biologic treatment: an analysis of 139 patients
Authors: S. A. Rodriguez Montero, M. León García, A. Muñoz Jimenez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We performed a retrospective study of our patients with spondyloarthritis (SpA) in biologic therapy admitted to hospital over the past 14 years. <h3>Methods</h3> Patients with SpA attending clinics at the Department of Rheumatology were analyzed to determine how many of them required hospitalization from January 1999 until December 2012. We recorded: age, sex, duration of disease, type of SpA, number and reasons for admission, and its outcome. <h3>Results</h3> A total of 139 patients were identified from an electronic database, 61 were admitted to hospital at least once, mean age at admission 45.9 years, 44 male. We obtained 74 hospitalizations over 14 years. Mortality rate: 3,2%. Readmission rate: 18%. Type of SpA: 37.7% axial spondyloarthritis, 39,3% peripheral spondyloarthritis, 23% mixed type of disease. Anti-TNF: Etanercept 28 patients, infliximab 16 patients, adalimumab 10 patients. Reasons for admission in order of frequency: Orthopedic surgery (17 cases). General surgery (15). Cardiac diseases (7). Infection (6) Obstetric Pathology (5) Respiratory disease (4) Among the most serious diseases we found an acute liver failure which needed liver transplantation, a miliary tuberculosis, and a severe interstitial lung disease that caused the patient's death three months after diagnosis. <h3>Conclusions</h3> In our cohort, 43.8 % of patients required hospitalization, the reasons for admission were basically orthopedic surgery followed by general surgery. Despite immunosuppressive state caused by TNF blockers, there were only a few cases of infection, although two of these cases were life-threatening. The spondyloarthritis are still among diseases with serious medical, social and economic involvements. <h3>Disclosure of Interest</h3> None Declared
SAT0562 Directly Reprogrammed Osteoblasts Genetically Engineered to Produce Interleukin-10 Significantly Suppress Osteoclastgenesis
Authors: K. Fujioka, T. Kishida, Y. Kukida, H. Nagahara, W. Fujii, K. Murakami, T. Seno, A. Yamamoto, M. Kohno, O. Mazda, Y. Kawahito
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recent reports demonstrated that somatic cells such as fibroblasts can be directly reprogrammed into other cell types including neurons and cardiomyocytes by introducing critical transcription factors involved in the differentiation of the corresponding cell lineages<sup>1,2</sup>. Such procedures in combination with co-transduction of a particular gene may allow creation of the cells with desired functions. If patient specific osteoblasts can be induced and engineered to produce IL-10, autologous transplantation of such cells may suppress inflammation and bone destruction in rheumatoid arthritis by modulating immune responses and osteoclast development. <h3>Objectives</h3> To generate IL-10-producing mouse osteoblast-like cells from fibroblasts, and estimate potential effect of the cell supernatants on osteoclast differentiation. <h3>Methods</h3> Various combinations of transcription factors were transduced into mouse embryonic fibroblasts (MEFs) with retroviral vectors and the efficiency of conversion into osteoblast-like cells were estimated by alizarine red S staining. IL-10 gene was also transduced to the cells that received the most effective combination of the transcription factors, and resultant cells were characterized by qRT-PCR, alkaline phosphatase staining, and alizarine red S staining. IL-10 production was measured by qRT-PCR and ELISA. The supernatant was added to a mouse macrophage cell line Raw264.7 cells that were induced to differentiate into osteoclasts by an addition of RANKL. <h3>Results</h3> MEFs were successfully induced to massively produce bone matrix that were mineralized by calcium phosphate. Co-transduction of the IL-10 gene by means of a retrovirus vector resulted in establishment of osteoblasts that produced IL-10 at a significant level. The culture supernatant of the cells significantly suppressed osteoclast differentiation from Raw264.7 cells. <h3>Conclusions</h3> IL-10-secreting osteoblasts were successfully generated from fibroblasts by direct reprogramming procedures. The cells may be useful in novel cell-based therapy against RA in the future. <h3>References</h3> Ieda, M. et al.: Cell, 142: 375-386, 2010. Vierbuchen T.: Nature, 463: 1035-1041, 2010. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2247
Eventration of the Diaphragm on Radionuclide Ventriculography
Authors: WILLIAM H. MARTIN
Journal: Clinical Nuclear Medicine (1998)

A 67-year-old man was referred for a radionuclide ventriculogram because of progressive dyspnea. Although the radionuclide ventriculogram demonstrated normal systolic left ventricular function, a large focus of extracardiac activity lateral and posterior to the heart was unexpected. A chest radiograph and subsequent CT scan revealed eventration of the left hemidiaphragm with clear lung fields and no evidence of a pulmonary arteriovenous malformation. The scintigraphic abnormality was caused by physiologic blood pool activity within the spleen, which was displaced upward due to the congenitally hypoplastic diaphragm.
VALUE OF CORONARY ARTERY CALCIUM SCORE AS A TRIAGING TOOL IN ACUTE CHEST PAIN PATIENTS WITHOUT KNOWN CORONARY ARTERY DISEASE IN EMERGENCY DEPARTMENT: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Kongkiat Chaikriangkrai, Patompong Ungprasert, Hye Yeon Jhun, Faisal Nabi, John Mahmarian, Su Min Chang
Journal: Journal of the American College of Cardiology (2016)
Abstract 297: Effect of hypoxia on the expression of the T cell co-inhibitory ligands B7-H3 and B7-H1 in cancer
Authors: Chelsea A. Smallwood, Ivraym B. Barsoum, Charles H. Graham
Journal: Cancer Research (2012)

Abstract Escape from adaptive immunity is important for malignant progression. B7-H3 and B7-H1 ligands provide co-inhibitory signals to T cells resulting in T cell anergy or apoptosis. Their expression has been shown to increase in cancer cells and to correlate with disease progression. Tumour hypoxia is a major contributor to the spread of cancer and resistance to radiation and chemotherapy. We proposed that hypoxia results in the up-regulation of the B7 molecules B7-H3 and B7-H1, thus contributing to immune escape. Using breast and prostate cancer cell lines, we investigated whether hypoxia increases the expression of these ligands and, if so, whether the transcription factor hypoxia-inducible factor-1 (HIF-1) is required for this hypoxic effect. We incubated MDA-MB-231 breast cancer cells and DU145 prostate cancer cells in standard culture conditions (20% O2, 37°C, 5% CO2), hypoxic conditions (0.5% O2, 37°C, 5% CO2), or with 100μM CoCl2 (known to stabilize HIF-1α) for 24 hours. Our findings revealed that B7-H3 expression is not increased in hypoxia. However, hypoxia and exposure to CoCl2 increased B7-H1 expression, which correlated with the levels of HIF-1α accumulation. Furthermore, HIF-1α knockdown attenuated B7-H1 mRNA levels. These results indicate a role for hypoxia in the up-regulation of B7-H1 on cancer cells, thus potentially contributing to immune escape of cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 297. doi:1538-7445.AM2012-297
Giant Lambl's Excrescences
Authors: Atul Aggarwal, Bruce J Leavitt
Journal: New England Journal of Medicine (2003)

University of Vermont College of Medicine Burlington, VT 05401 66-year-old, previously healthy woman presented with an acute onset of weakness on the left side of the body. A computed tomographic scan of the head revealed a small infarction involving the right parietal subcortical region. The results of carotid ultrasonography, magnetic resonance imaging, and tests for a hypercoagulable state failed to reveal a cause for the stroke. A transesophageal echocardiogram (Panel A) showed long, hypermobile, filiform echodensities on the left coronary cusp of the aortic valve — a finding consistent with the presence of giant Lambl’s excrescences of the aortic valve (arrow); they were presumed to be the cause of the stroke. The patient had complete neurologic recovery but had another stroke three weeks later, despite adequate anticoagulant therapy. At the time of aortotomy, slender, filamentous masses with two major trunks measuring 2.5 cm in length (Panel B) were excised from the aortic leaflet, and the native valve was left intact. Histologic examination of sections of the specimens showed a densely hyalinized central core lined by bland-looking, endocardial-type spindle cells — findings again consistent with the diagnosis of giant Lambl’s excrescences. Lambl’s excrescences appear to be wear-and-tear lesions that originate in the endothelium of the contact margins of a valve, commonly the aortic valve. Excision may be necessary in cases of cryptogenic stroke.
EFFICACY AND SAFETY OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 INHIBITORS TREATMENT ON CHOLESTEROL LEVELS: A COMPREHENSIVE META-ANALYSIS OF ALL RANDOMIZED CLINICAL TRIALS
Authors: Armaghan Y. Soomro, Mark Ediger, Bhavi Pandya, Muhammad Rehan Raza, Zaka Khan, Mustafain Meghani, Sarah Tareen, Thomas Vazzana, James Lafferty
Journal: Journal of the American College of Cardiology (2016)