tbuckley/cabot-search huggingface dataset:
OP0026 Sustained and cumulated response over time in ra patients treated with rituximab after initial failure of anti-TNF agents:
Authors: I. Ancuta, C. Codreanu, R. Ionescu, M. Parvu, M. Bojinca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although anti-TNF therapies moved forward the treatment of rheumatoid arthritis (RA), failure of the first anti-TNF medication is not uncommon. Many times modifying dosage/frequency of the initial drug or prescribing a different TNF inhibitor proves to be still inadequate. Using instead a biologic with a different mechanism of action, such as Rituximab (RTX), may be beneficial in terms of RA treatment to target. <h3>Objectives</h3> Based on EULAR-T2T and ACR criteria we analysed response following each RTX course (2 g at every 24 weeks). <h3>Methods</h3> Longitudinal (2002 to date), observational, population-based, cohort study. The analysis was performed based on data from the National Health Insurance House (NHIH) for 400 out of 1126 patients treated with RTX for RA in October 2011 in the NHIH database. The patients' selection is statistically representative and homogenous at national level. All patients had an anti-TNF medication as first treatment stage for 2.5 years (average). In the second stage, 208 patients were switched to RTX after the initial anti-TNF failure. The remaining 192 patients followed one or two more anti-TNF therapy and only then continued with RTX. A total of 5 RTX courses were administered to both groups. Before each RTX course patient were monitored for DAS28 and EULAR response. <h3>Results</h3> Average DAS28 before RTX was 6.7 (N=400), reaching 4.5 (before C2), then 3.41 (before C3). At the time of this analysis 335 patients followed C3 and 211 C4. Before RTX start, 93% of the total number of patients was in HDA and 8% in MDA. After 2 RTX courses 38.25% of the patients reached LDA or remission. After 18 months (before C4) 63.88% patients were in LDA or remission, while before C5 86.73% of the 211 patients having C4 were in LDA or remission (48.82% in remission). In terms of EULAR response after 4 RTX cycles 84.36% had a good response and 15.64% a moderate response, compared to previous treatment with anti-TNF in the same interval (2 years): 5.03% good response and 91.82% moderate response. <h3>Conclusions</h3> Each RTX course led to an increased and cumulative clinical DAS28 response compared to the previous one. With each following RTX course all patients registered consolidation of lower DAS28 response, and continuously growing LDA or remission percentage. Response was sustained and cumulated regardless their rheumatoid factor status. Introducing Rituximab to patients with no response or intolerance to anti-TNF agents proved to be an adequate choice, therefore we consider its prescription after the first anti-TNF failure as a preferred option in terms of clinical response. <h3>Disclosure of Interest</h3> None Declared
AB0275 14-3-3 eta is an independent marker of joint damage that complements CRP and anti-CCP:
Authors: D. van der Heijde, R. Landewé, C.F. Allaart, P.P. Tak, A. Marotta, W.P. Maksymowych
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a progressive multi-factorial disease that if left untreated can lead to severe disability in approximately 20 - 30% of patients. To improve outcomes, an early definitive diagnosis, estimating the relative risk of developing erosive irreversible disease together with proposing an optimal treatment strategy is essential. We have previously reported that serum 14-3-3η is a highly specific marker of RA, combines with RF and anti-CCP to improve diagnosis in both early and established disease, and behaves as an extracellular ligand activating factors involved in joint degradation (MMPs and RANKL). Levels of this marker in both synovial fluid and serum significantly correlate with levels of MMP-1 and MMP-3 further characterizing 14-3-3η's involvement in the joint damage process. <h3>Objectives</h3> To investigate the association between serum 14-3-3η expression and joint damage in RA. <h3>Methods</h3> To evaluate 14-3-3η's expression in RA patients with and without joint damage, the serum of 50 patients from the year-three time-point of the BeSt (Behandel-Strategieën) study were measured using an investigational-grade 14-3-3η ELISA. There were 35 patients with joint damage (SHS ≥0.5) and 15 age and DAS-matched patients with no joint damage (SHS &lt;0.5). Two-tailed t-tests were run to compare group differences. Pearson correlations were generated to determine relationships between 14-3-3η, RF, anti-CCP or CRP. Regression analyses were performed to identify which variables were independently associated with and which combined best to mark joint damage. <h3>Results</h3> Mean 14-3-3η serum concentrations were statistically significantly higher in patients with joint damage when compared to those without; 5.23 versus 1.31ng/ml, respectively (p=0.048). Across the entire cohort, 14-3-3η did not correlate with titres of either RF (r=0.18), anti-CCP (r=0.07) or CRP (r=-0.08) underscoring its independence of these serum markers. As shown in the table below, titres of CRP, anti-CCP, 14-3-3η were indicative of joint damage status. RF positivity too was indicative of joint damage although the model was not strengthened by combining it with any of the serological markers. Adding 14-3-3η to CRP and anti-CCP significantly improved the association of these markers with joint damage as shown below. CRP with anti-CCP delivered an ROC AUC of 0.80 (Chi-Sq =11.7) whereas when combined with 14-3-3η the ROC AUC increased to 0.85 (Chi-Sq =15.3). <h3>Conclusions</h3> Serum 14-3-3η expression is independent of other RA serological markers and when used in combination with CRP and anti-CCP serves as a disease-specific biomarker to independently inform the joint damage process. <h3>Disclosure of Interest</h3> D. van der Heijde: None Declared, R. Landewé: None Declared, C. Allaart: None Declared, P. Tak: None Declared, A. Marotta Shareholder of: Co-founder, W. Maksymowych: None Declared
PTH-086 Comparison Of Clinical Presentations And Outcome Of Hepatocellular Carcinoma Between Hepatitis C And Nonalcoholic Fatty Liver Cirrhosis: A Single Centre Experience
Authors: NN Than, N Tehami, J Hodson, S Shetty
Journal: Gut (2014)

<h3>Introduction</h3> Hepatocellular carcinoma (HCC) is the most common primary liver tumour, and represents the third leading cause of cancer death worldwide.<sup>1,2</sup> The most important risk factor is liver cirrhosis, mainly due to chronic infections such as hepatitis B or C<sup>.2</sup> Increasing HCC cases are seen in nonalcoholic fatty liver disease (NAFLD). <h3>Methods</h3> The aim of the study was to compare demographics, treatments and survival among hepatitis C virus (HCV/HCC) and NAFLD (NAFLD/HCC) cohort of patients. Data were collected from medical electronic case notes, imaging reports and HCC multidisciplinary meetings. <h3>Results</h3> Among 292 patients, 212 patients (73%) had underlying HCV/HCC and 80 patients (27%) had NAFLD/HCC. The median age at diagnosis was significantly higher in NAFLD/HCC (p &lt; 0.001). The majority (82%) were male. Body mass index (BMI) was significantly higher in NAFLD/HCC (p &lt; 0.001). The majority were Caucasian (96%) in NAFLD/HCC, whilst the HCV/HCC cohort was significantly more ethnically diverse (p &lt; 0.001). Diabetes mellitus was more common in NAFLD/HCC patients (p &lt; 0.001). The median alpha fetoprotein level in HCV/HCC patients were 32.0 compared to 12.0 in NAFLD/HCC (p = 0.085). Patients with HCV/HCC were significantly more likely to be transplanted during the study period than NAFLD/HCC (30% vs. 15%, p = 0.010). Both transarterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) were significantly more likely to be used as a single treatment in NAFLD patients, compared to HCV patients (p = 0.042, p = 0.021). Sorafenib was used as the only treatment in 6% of HCV/HCC and 3% of NAFLD/HCC cohorts (p = 0.364). Post transplant survival appeared to be worse in HCV-HCC patients compared to NAFLD/HCC, although it did not reach statistical significance (p = 0.081). Overall five year survival rates were similar between the two groups regardless of any treatment therapies (p = 0.424). <h3>Conclusion</h3> Despite the NAFLD/HCC being older and with higher metabolic risk factors, a significant proportion could undergo active therapy. Furthermore, patients with NAFLD/HCC selected for transplantation seemed to have better long term outcomes, possibly due to stricter selection for transplantation as well as variations in tumour biology between the two groups. <h3>References</h3> 1 Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. <i>J Clin Gastroenterol</i> 2013;47 Suppl:S2–6 2 Lu T , <i>et al</i>. <i>P</i>revention of hepatocellular carcinoma in chronic viral hepatitis B and C infection<i>.</i><i>World J Gastroenterol</i> 2013;19(47):8887–8894 <h3>Disclosure of Interest</h3> None Declared.
STAT1 and STAT3 synergistically suppress EGF-induced MMP-9 activity in SKBR3 human breast cancer cell line.
Authors: S Kim, J Choi, H Lim, S Lee, W Kim, J Yang, S Nam, J Lee
Journal: Cancer Research (2009)

Abstract Abstract #2064 Background: EGF is a cytokine associated with cell proliferation, migration, and tumor invasion through EGFR activation in various cancer cells. EGFR activates its downstream molecules such as protein kinase C-δ, ERK, PI3-kinase, STAT-3. It has been shown that EGFR induces matrix metalloproteinase-9 (MMP-9), leading to invasion and migration of cancer cells. However, it has not been fully elucidated the roles of STAT-1 and STAT-3 in breast cancer cells. We investigated the regulatory mechanism of STAT-1 and STAT-3 on EGF-induced MMP-9 activity in SKBR3 cells.&amp;#x2028; Material and Methods: EGF-induced MMP-9 activity regarding to ERK, JNK, PI-3 kinase and STAT-3 were evaluated by Western blot. Then, we transfected SKBR-3 cells with adenoviral vectors containing STAT-1 and STAT-3 to make SKBR-3 cells overexpressing each gene. We also treated SKBR-3 cells with STAT-3 siRNA. Overexpression and silencing of genes were identified with Western blot. With the treatment of EGF, MMP-9 activity was measured with gelatinase Zymography.&amp;#x2028; Results: We confirmed that EGF increases MMP-9 activity and induces the phosphorylation of ERK, JNK, PI-3 kinase and STAT-3 in dose-dependent manner. We found that EGF-induced MMP-9 activity was significantly decreased by MEK1/2 inhibitor, UO126, and PI3-kinase inhibitor, LY294002, respectively, but not by JNK inhibitor, SP600125. In contrast to previous study, EGF-induced MMP-9 activity was inhibited by STAT-3 overexpression. We also found that it was increased by STAT-3 siRNA transfection. Moreover, we found that STAT-1 and STAT-3 co-overexpression synergistically decreased EGF-induced MMP-9 activity in STAT-1 and STAT-3 co-overexpressing SKBR-3 cells.&amp;#x2028; Discussion: We demonstrated that EGF-induced STAT-3 activation suppresses tumor invasion through down-regulation of MMP-9 in SKBR-3 cells. Moreover, we found that there is a synergistic relationship between STAT-1 and STAT-3, inhibiting EGF-induced MMP-9 activity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2064.
Abstract 5379: Combination treatment with Bevacizumab, Lenalidomide, Docetaxel and Prednisone (ART-P) does not impact the immune response in patients with metastatic castration-resistant prostate cancer
Authors: Caroline Jochems, Jo A. Tucker, Diane J. Poole, Melony Beatson, Marcia Mulquin, Ravi A. Madan, William D. Figg, William L. Dahut, James L. Gulley, Jeffrey Schlom, Kwong-Yok Tsang
Journal: Cancer Research (2012)

Abstract Purpose: Investigation of the effect of combination therapy for 5 cycles with bevacizumab, lenalidomide, docetaxel and prednisone (ART-P) on the immune response in patients with metastatic castration-resistant prostate cancer (mCRPC). The aim was to ascertain if treatment containing prednisone and docetaxel would impact immune responses, which could compromise the efficacy of subsequent immunotherapy. Experimental Design: We report here a study of immune responses in 12 patients enrolled in a phase II trial of ART-P at the National Cancer Institute (NCI). We compared peripheral blood mononuclear cells (PBMC) and serum samples collected at baseline and post 5 3-week cycles of ART-P treatment. PBMCs were analyzed using flow cytometry to characterize phenotypes of T-cells, regulatory T-cells, myeloid derived suppressor cells (MDSC) and natural killer (NK) cells, and T-cell proliferation as well as NK-cell functional activity were evaluated. Serum samples were analyzed for levels of cytokines, chemokines and vascular endothelial growth factor (VEGF) with ELISA assays. Results: The baseline characteristics for the 12 patients were: median age 65.7 years, Gleason score 8, and PSA 74 ng/ml. Greater than 50% decreases in PSA were seen in 9/12 patients, with a median decrease of 74%. Of the 12 patients 7 had a partial response, and 5 had stable disease by RECIST criteria. After 5 cycles of ART-P treatment we found no significant differences from baseline in T-cell proliferation and NK-cell function, or the frequencies of T-cells, regulatory T-cells, MDSC and NK-cells. There was also no change in the serum levels of cytokines and chemokines except for IL-6, which decreased. As expected, the serum levels of VEGF substantially decreased with therapy. Conclusions: Treatment of mCRPC patients with ART-P for 5 cycles did not alter the immune response in a way that would decrease the likelihood of successful immunotherapy, pre or post treatment with ART-P. 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 5379. doi:1538-7445.AM2012-5379
ASSESSMENT OF VENTRICULO-VASCULAR PROPERTIES IN REPAIRED COARCTATION USING CARDIAC MRI DERIVED AORTIC, LEFT ATRIAL AND LEFT VENTRICULAR STRAIN
Authors: Quanliang Shang, Shivani Patel, Phalla Ou, David Danford, Andreas Schuster, Phillip Beerbaum, Samir Sarikouch, Shelby Kutty
Journal: Journal of the American College of Cardiology (2015)
Abstract 4155: Personalized chemosensitivity profiling of cancers isolated from genetically-engineered mice.
Authors: Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Jun O. Liu, Anirban Maitra, James R. Eshleman
Journal: Cancer Research (2013)

Abstract BACKGROUNDHigh-throughput functional chemosensitivity testing is a potentially effective way to customize personalized chemotherapy treatment. This testing requires low-passage patient-specific cancer cell lines, however, generating such cell lines from patients’ tumors is difficult, due in large part, to contaminating fibroblasts that often overgrow the malignant cells. METHODSWe constructed a series of hypoxanthine phosphoribosyl transferase (hprt) null immunodeficient mice. These include nude hprt-null, SCID hprt-null and NOD-SCID hprt-null mice. During growth of xenografted human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Tumors from patients were implanted and expanded in these mice. Explanted tumors were then grown in tissue culture flasks with selection media (hypoxanthine, aminopterin, thymidine; HAT media) to eliminate the mouse biochemically-defective fibroblasts and produce pure human cancer cell lines. We screened one cell line against the Johns Hopkins Drug Library containing ∼3,100 drugs. Selected potent drugs were used for in vivo xenograft tumor inhibition studies. RESULTSWe successfully established several pancreatic cancer cell lines from patients using the hprt null immunodeficient mice. We performed chemosensitivity profiling on one of the pancreatic cancer cell lines using 3,100 drugs. From the profiling, we selected potent drugs, which are FDA-approved but are not currently used for pancreatic cancer. We chose two drugs that demonstrated greater in vitro chemosensitivity compared to control cell lines. The two drugs were tested against mouse xenografts where both drugs demonstrated superior in vivo efficacy to the sensitive cell line tumors compared to control tumors. CONCLUSIONSChemotherapy for cancer may be personalized using low passage cell lines derived from patients through biochemically selectable mice. Further tests are needed to determine whether in vitro chemosensitivity testing of low-passage patient-specific cancer cell lines can predict clinical patient response. Citation Format: Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Jun O. Liu, Anirban Maitra, James R. Eshleman. Personalized chemosensitivity profiling of cancers isolated from genetically-engineered mice. [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 4155. doi:10.1158/1538-7445.AM2013-4155
THE IMPACT OF LIPID-CONTAINING PLAQUE COMPOSITION MEASURED BY NEAR-INFRARED SPECTROSCOPY ON CORONARY ARTERIAL REMODELING
Authors: Hideaki Ota, Marco Magalhaes Pereira, Smita Negi, Thibault Lhermusier, Ricardo Escarcega Alarcon, Nevin Baker, Sarkis Kiramijyan, Edward Koifman, Rebecca Torguson, Itsik Ben-Dor, Lowell Satler, William Suddath, Augusto Pichard, Ron Waksman
Journal: Journal of the American College of Cardiology (2015)
Pancreatic sphincterotomy for pancreatitis associated with main duct intraductal papillary mucinous neoplasm
Authors: Y. Oh, K. Dua
Journal: Endoscopy (2011)

Recurrent acute or chronic pancreatitis can be presenting symptoms of main duct intraductal papillary mucinous neoplasm (main duct IPMN). Given the risk of malignancy with main duct IPMN, surgery is generally recommended [1]. In patients who are not candidates for surgery, pancreatic sphincterotomy can be considered as a possible way to alleviate pancreatitis due to main duct IPMN by facilitating drainage of mucus.
Hypovitaminosis D in Medical Inpatients
Authors: Melissa K. Thomas, Donald M. Lloyd-Jones, Ravi I. Thadhani, Albert C. Shaw, Donald J. Deraska, Barrett T. Kitch, Eleftherios C. Vamvakas, Ian M. Dick, Richard L. Prince, Joel S. Finkelstein
Journal: New England Journal of Medicine (1998)

Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown.
P650 HIGH IP10 LEVELS AND LOW HBsAg/HBVDNA RATIO DURING PREGNANCY PREDICT HEPATIC FLARE POST-DELIVERY
Authors: M. Horner, M. Bruce, M.-A. Badot, T. Bowyer, K. Oakes, K. Stone, I. Fletcher, D. Shang, T. Al-Chalabi, P.M. Harrison, K. Agarwal, I. Carey
Journal: Journal of Hepatology (2014)
Thyroid Hormone and the Cardiovascular System
Authors: I Klein, K Ojamaa
Journal: New England Journal of Medicine (2001)

Thyroid hormone has many effects on the heart and vascular system.1 Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormone to alter cardiovascular hemodynamics.2 The hemodynamic effects of hypothyroidism are opposite to those of hyperthyroidism, although the clinical manifestations are less obvious. This review will integrate what is known about the mechanisms of thyroid hormone action on the heart25 with recent observations from both experimental and clinical studies of hyperthyroidism and hypothyroidism. We will also address the potential role of thyroid hormone treatment in patients with acute or chronic cardiac disease.Effects of . . .
Minimum safe staffing levels may be set for emergency departments and elderly care wards
Authors: I. Torjesen
Journal: BMJ (2012)

The public inquiry into the high number of deaths at Mid Staffordshire NHS Foundation Trust is expected to recommend that minimum staffing ratios be set for total numbers and the skills mix of doctors and nurses in accident and emergency and elderly care wards in England to ensure the safety of care.

In a written statement submitted to the inquiry’s chairman before Christmas, the counsel to the inquiry, Tom Kark QC, said “that consideration should be given to the production of model staffing guidelines for certain types of wards and departments against which the Care Quality Commission should assess the acceptability of staffing.”

Mr Kark pointed out that the real danger in accident and emergency services at Mid Staffordshire was understaffing, inadequate training, and poor governance. And he questioned why external scrutiny of …
HEAD-TO-HEAD COMPARISON OF A CAMERA-BASED SMARTPHONE APPLICATION CARDIIO RHYTHMTM WITH ALIVECOR ® HEART MONITOR FOR ATRIAL FIBRILLATION SCREENING IN PRIMARY HEALTHCARE SETTING
Authors: David Siu, Chun Ka Wong, Pak Hei Chan, Yuk Kee Poh, Ming-Zher Poh
Journal: Journal of the American College of Cardiology (2016)
P5-19-06: Highly Effective of Gemcitabine and Cisplatin (GP) as First-Line Combination Therapy in Patients with Triple-Negative Metastatic Breast Cancer: Final Report of a Phase II Trial.
Authors: Z Wang, X Hu, B Wang, L Wang, J Zhang, H Wang, G Liu, Z Hu, J Wu, Z Shao
Journal: Cancer Research (2011)

Abstract Background Triple-negative breast cancer (TNBC) contributes to poor prognosis and there is no established standard chemotherapy this subtype of patients. It has been postulated that related cancers would confer sensitivity to certain cytotoxic agents like cisplatin. Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer and preclinical data support synergy of the combination. The objective of this study was to evaluate doublet with gemcitabine/Cisplatin (GP) as first-line therapy in patients with metastatic TNBC. Material and Methods: This is a prospective single-institutional, open-label, phase II trial. The primary endpoint was progression free survival (PFS). Eligible subjects were aging from 18 to 75 years old, with no prior chemotherpay for MBC, with tumors negative for ER, PR or HER2, with at least one measurable disease according to the RECIST criteria, with ECOG PS of 0–1, and with adequate organ function. All patients received 21-day cycles of gemcitabine 1,000mg/m2 on days 1 and 8 and cisplatin 25 mg/m2 on days 1 through 3. Treatment was continued until disease progression or unacceptable toxicity or up to 8 cycles. (ClinicalTrials.gov number, NCT00601159) Results: A median age was 49 years (range: 29–74 years). 58 patients had received neo/adjuvant chemotherapy (53 patients with anthracycline and/or taxane). The median number of treatment cycles was six (range: 2–8 cycles). In 64 assessable patients, we observed 10 complete response (CR; 15.6%), 30 partial responses (PR; 46.9%), 17 patients (26.6%) with stable disease (SD), and 7 patients (10.9%) with progressive disease, for an overall response rate of 62.5% (95% CI, 50.3% to 74.7%)..*** The median PFS was 7.7 months (95% CI, 6.0 to 9.4). With a median follow-up time of 28 months, the median overall survival was 19.1 months (95% CI, 12.5 to 25.7). Grade 3 or 4 toxicities were neutropenia 42.2%, thrombocytopenia 29.7%, anemia 18.8%, nausea/vomiting 15.6%, fatigue 14.1%, constipation 3%, sensory neuropathy 1.6%, 2 patients developed febrile neutropenia. The chemotherapy doses were reduced in 13.3% (6 pts) because of toxicity. There were no treatment-related deaths. Conclusion: Significant activity and favorable toxicity profile of GP regimen as first-line chemotherapy in patients with metastatic TNBC. It provided a basis for considering GP for further evaluation in phase III trials for women with metastatic TNBC in China. (ClinicalTrials. gov number, NCT01287624) Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-06.