tbuckley/cabot-search huggingface dataset:
AB0980 Long term tolerability and effectiveness of a single injection of 6ml hylan G-F 20 in 451 patients with knee osteoarthritis pain
Authors: J.-P. Wagner, G. Bonacker, H. Wolf, M. Frömel, K. Leonhardt, A. Schulz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To determine the tolerability and effectiveness of a single injection of 6 ml hylan G-F 20 treatment in patients with symptomatic Osteoarthritis (OA) in standard clinical practice over a period of 1 year. <h3>Methods</h3> 91 orthopaedic and trauma surgeons in Germany recorded tolerability and short term effectiveness in knee OA patients receiving a single intra-articular injection of 6 ml hylan G-F 20 one week after treatment. Then, patients were followed up by standardized telephone interview through an independent observer. Tolerability, knee OA pain (reported on a 5-Point Likert-Scale), patients’ global assessment and quality of life (SF12) were obtained after 3, 6, 9 and 12 months. <h3>Results</h3> 451 patients [Age: 61,98 years (mean); BMI: 27,82 (mean); Female: 50,4%; Knee OA Grade III: 51,9%; Grade II: 38,8%; Grade I: 9,3%] met the inclusion/exclusion criteria out of 571 patients which have been enrolled. Tolerability was assessed on all 571 patients and treatment-related adverse events (AEs) were observed in 1,93% of patients. None of these AEs was serious. Telephone follow-up was possible in 243, 237, 199 and 148 patients after 3, 6, 9 and 12 months. Knee OA pain significantly decreased already one week after the injection and showed a significant improvement over 12 months (p≤0,001 at each timepoint). Also patients’ global assessment at all timepoints and assessment of physical composites score of the SF 12 at 3, 6, 9 and 12 months showed significant improvement (p≤0,001). Mental composite score of the SF 12 showed significant improvement after 9 and 12 month (p≤0,05). Physicians assessed the results of a single injection of 6 ml hylan G-F 20 as “very well” and “well“ in 79,1% of the treated patients. High baseline pain value was identified as a potential predictor of hylan G-F 20 effectiveness by logistic regression. Only 20 patients (8.5%) were re-treated with hylan G-F 20 at month 9 or 12. <h3>Conclusions</h3> A single injection of 6 ml hylan G-F 20 is a well-tolerated treatment option in patients with symptomatic knee osteoarthritis with a low incidence of local, treatment-related AEs. A significant reduction of knee OA pain was observed as early as one week after the injection and was durable for the whole follow up period of 12 months. The single injection of 6 ml hylan G-F 20 allows a reduced risk of injection-associated joint infections, and its fast onset of lasting pain relief provides an important therapeutical benefit in daily practice. <h3>Disclosure of Interest</h3> J.-P. Wagner Grant/Research support from: Genzyme, G. Bonacker Grant/Research support from: Genzyme, H. Wolf Grant/Research support from: Genzyme, M. Frömel Grant/Research support from: Genzyme, K. Leonhardt Grant/Research support from: Genzyme, A. Schulz Employee of: Genzyme
Abstract 937: Nicotinic acetylcholine receptor polymorphisms, secondhand smoke and lung cancer risk
Authors: Kofi Asomaning, Rihong Zhai, Chau-Chyun Sheu, Rebecca Heist, Feng Chen, Geoffrey Liu, Li Su, Xihong Lin, David Christiani
Journal: Cancer Research (2010)

Abstract Introduction: Passive or secondhand smoke (SHS) exposure is an independent risk factor for adult non-small cell lung cancer (NSCLC). In 2008, three genome wide association studies (GWAS) identified a locus on chromosome region 15q24-25.1 that was strongly associated with lung cancer. In this study, we assessed the interaction of the two most significant single nucleotide polymorphisms (SNPs) reported (rs8034191, rs1051730) with SHS on lung cancer risk. We hypothesize that after adjusting for active cigarette smoking, individuals with the risk alleles and the highest cumulative exposure to SHS are at the greatest risk of lung cancer. Methods: This study population is derived from a large ongoing case control study evaluating the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital. The polymorphisms were genotyped by the 5V nuclease assay (Taqman) using the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA). Interviewer-administered questionnaires collected information on demographics, and detailed smoking histories from each subject. Second hand smoke exposure duration and frequency was self-reported for three different activities (leisure, work and at home). The cumulative SHS exposure was the sum of all durations multiplied by their frequency weight. We used the co-dominant genetic model for individual SNPs, controlling for age, gender, pack years, years since smoking cessation and smoking status. We tested for interaction using the Likelihood Ratio Test by incorporating cross product interaction terms of indicator variables for each SNP and quartiles of cumulative exposure. Results: A total of 2071 cases and 1506 controls were analyzed. Among cases, exposure to SHS at home 1924(93%), work 1727 (83%), leisure 1791 (86%); among controls 1328 (88%), 1044 (69%) and 1233 (82%) respectively. In stratified analysis, for study participants in the highest quartile of cumulative SHS exposure and comparing the homozygous variant to the wildtype, the adjusted odds ratio (AOR) for lung cancer was 1.55 (0.99-2.44) (rs8034191) and 1.66 (1.05-2.62) (rs1051730). In the lowest quartile of SHS exposure the corresponding results were 0.94 (0.47-1.89) (rs8034191) and 0.91(0.45-1.84) (rs1051730). There was no evidence for gene-SHS interaction. Conclusion: Our results indicate that secondhand smoke does not modify the association of rs1051730 and rs8034191 with non-small cell lung cancer. 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 937.
Abstract 708: Integrated analysis of drug resistance networks in breast cancer
Authors: Kakajan Komurov, Jen-Te Tseng, Melissa Muller, Prahlad T. Ram
Journal: Cancer Research (2011)

Abstract Targeted inhibition of HER2 tyrosine kinase receptor presents a promising strategy in the treatment of HER2-positive breast cancer patients. However, despite favorable response during the acute phase, majority of patients develop resistance to anti-HER2 drugs during the chronic phase of treatment. Here, we developed a cell culture model of chronic lapatinib (a dual inhibitor of EGFR and ERBB2 receptor tyrosine kinases) treatment by continuous passaging of HER2-overexpressing SKBR3 cells in increasing doses of lapatinib over a year. The resultant cell line, SKBR3-R, is almost 100-fold more resistant to lapatinib-induced growth inhibition when compared to the parental line. We have verified that this difference in lapatinib sensitivity is not due to altered expression or signaling at the level of HER2 or HER3 receptors in SKBR3-R cells. By integrating genome-wide gene expression profiling with our novel network-based genomic data analysis approach, we show that 1) cell toxicity mediated by acute lapatinib treatment in HER2-positive cells is associated with nutrient starvation and energy stress, and 2) chronic lapatinib treatment leads to the activation of compensatory cellular networks involved in the response to nutrient starvation, which confers resistance to lapatinib-induced cell death. Accordingly, while imposing a glucose starvation response phenotype on SKBR3 cells protects from lapatinib-mediated cell death, pharmacological inhibition of the nutrient starvation response in SKBR3-R cells reverses lapatinib resistance. In order to see if these networks play a role in breast cancer pathogenicity within clinical settings, we carried out a detailed network-based correlations of tumor gene expression profiles of breast cancer patients with their clinical data. Importantly, we found that the metabolic networks associated with lapatinib resistance are also associated with poor outcome within clinical settings. This study implicates nutrient deprivation response as a major factor in the acquired resistance of breast cancer cells to lapatinib, and suggests novel targets for combinatorial therapy of HER2-positive breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 708. doi:10.1158/1538-7445.AM2011-708
DIAGNOSIS OF NECROTIC INTRAPLAQUE CORES BY DUAL ENERGY CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY IN VICTIMS OF SUDDEN CORONARY DEATH: VALIDATION TO A PATHOLOGIC GOLD STANDARD
Authors: Kimberly Elmore, Iksung Cho, Briain O Hartaigh, Joshua Schulman-Marcus, Jackie Szymonifka, James Earls, Kazuyuki Yahagi, Guanglei Xiong, Anna Starikov, Michael Joner, Renu Virmani, James Min
Journal: Journal of the American College of Cardiology (2015)
ST-SEGMENT DEPRESSION IN LEAD AVR PREDICTS 30-DAY ADVERSE OUTCOMES IN PATIENTS WITH INFERIOR ACUTE MYOCARDIAL INFARCTION
Authors: Masami Kosuge, Toshiaki Ebina, Kiyoshi Hibi, Kengo Tsukahara, Noriaki Iwahashi, Nobuhiko Maejima, Eiichi Akiyama, Satoshi Umemura, Kazuo Kimura
Journal: Journal of the American College of Cardiology (2016)
Abstract 1273: Identification of differentially expressed proteins in human papillary thyroid carcinoma using proteomic analysis
Authors: Chizuru Sugimoto, Dai Susuki, Yuichi Kimura, Norihiko Narita, Shigeharu Fujieda
Journal: Cancer Research (2012)

Abstract Papillary thyroid carcinoma (PTC) is one of the most common malignant tumors of the thyroid glands. It tends to grow slowly but is associated with a poor prognosis when metastasis happens. To better understand basic mechanisms of tumor development and identify potential new biomarkers of PTC, we examined protein expression profiling in clinical PTC tissue and matched normal thyroid tissue using fluorescence two-dimensional difference gel electrophoresis (2D-DIGE). To identify the proteins, peptide mass fingerprinting via MALDI-TOF mass spectrometry was carried out. Using these strategies, 85 up-regulated or down-regulated proteins were found in PTC. Imaging software determined 26 proteins to be differentially expressed at the two-fold (or greater) level. Among them, Cathepsin B and Lamin A/C were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in clinical PTC tissue compared to normal thyroid tissue. We are presently investigating those roles in PTC. Proteomic analysis of PTC using 2D-DIGE and mass spectrometry could provide novel potential biomarkers and insights into global pathophysiologic changes in PTC. 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 1273. doi:1538-7445.AM2012-1273
FRI0571-HPR Physitherpy Treatment of Knee OA in Norway and Its Concordance with Eular Recommendations
Authors: G. Grønhaug, K.M.L. Grønhaug, A.K. Stensdotter
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Evidence-based recommendations have the potential to improve the quality of health care by promoting interventions of proven benefit and discouraging unnecessary, ineffective, or harmful interventions. Osteoarthritis (OA) treatment recommendations are generally addressing strength training and training to increase aerobic capacity together with referral to, or treatment by, physiotherapists. Previous research has revealed that treatment of patients with OA by medical doctors show low adherence with recommendations (1). Little is not known about the treatment provided by physiotherapists in Norway and whether the treatment provided is in concordance with general recommendations for OA treatment. <h3>Objectives</h3> To investigate knee OA treatment performed by physiotherapists in Norway and its concordance with EULAR recommendations for non-pharmacological treatment modalities. <h3>Methods</h3> Patient records in the hospital region of middle Norway were searched to identify patients with knee OA. A letter was sent to the identified patients (N=87) asking for information about which physiotherapist they had seen for treatment. A letter was sent to the physiotherapists asking for the discharge summary, in which they are obliged to send to the referring doctor. A survey of the discharge summaries was conducted independently by 3 health professionals (two physiotherapists, one physician) to categorise and group the treatment given. <h3>Results</h3> Response rate from patients was 93% (N=81). Of the 81, 13 (15%) had not been referred to physiotherapy treatment. Response rate from physiotherapists (N=68) was 38 (56%). Of the treatment described in the discharge summaries 7 (10%) was partly in line with EULAR recommendations; of these, all 7 used strengthening exercises and 0 used improvement of aerobic capacity as their choice of therapeutic modality. <h3>Conclusions</h3> According to our findings it may seem that physiotherapy treatments are not always in line with recommendations for knee OA treatment. The incidence of total knee replacement is increasing, raising costs personal and societal. Physiotherapy treatment in line with recommendations may help prevent OA from progression and prevent prosthesis operations to further increase. There seems to be a need for further work to make physiotherapists implement the EULAR guidelines in their day to day work with knee OA patients. <h3>References</h3> Østerås N, Garratt A, Grotle M, Natvig B, Kjeken I, Kvien TK, Hagen KB. Patient-reported quality of care for osteoarthritis: development and testing of the osteoarthritis quality indicator questionnaire. Arthritis Care Res (Hoboken). 2013 Jul;65(7):1043-51. <h3>Acknowledgements</h3> This study was given economic support from the central norway regional heath authority. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5148
Abstract 599: Development of poly(Asp-DET) cationic polymers for nonviral gene delivery
Authors: Janni Mirosevich, Gregoire Cardoen, Kevin Sill, Brian Burke
Journal: Cancer Research (2010)

Abstract Cationic polymers have received much attention as promising non-viral vectors for gene transfer. However, identification of polymers able to systemically deliver nucleic acids continues to be a significant hurdle to the success of this methodology. The purpose of this study was to develop a new biocompatible and biodegradable cationic polymer system as a non-viral gene delivery agent for plasmid DNA. Poly-aspartate-diethylene triamine (“P(Asp-DET)”) polymers were synthesized and utilized to complex plasmid DNA. The resulting polymer/DNA complexes, also known as “polyplexes,” were further modified by covalent coupling with polyethylene glycol (PEG), known as “PEGylation,” and characterized. Polyplexes were evaluated for efficiency of encapsulation, particle size, zeta potential and morphology by TEM. Stability of the complexed plasmid DNA was assessed by challenging polyplexes with nucleases. Efficacy of DNA delivery and gene expression was examined by performing transfection experiments using HCT-116 cells. In vivo DNA delivery was also investigated using tumor-bearing nude mice. Asp-DET polymers were found to bind to plasmid DNA with polymer to DNA (+/-) charge ratios of above 1.5. In addition, these polymers formed polyplex particles of approximately 50-150 nm with zeta potentials between neutral and +40 mV. TEM showed that the polyplexes were uniform and spherical in shape. It was also demonstrated that the polyplexes maintained the structural integrity of DNA following incubation in nucleases. The polyplexes were also capable of transfecting HCT-116 culture cells, with non-PEG complexes having significantly higher GFP and luciferase expression. Tail vein injections of post-PEGylated polyplexes into tumor bearing nude mice did not reveal any observable toxicities. Notably, nucleic acid accumulation was found in tumors with expression detected in lymph nodes. P(Asp-DET) cationic polymers show enormous potential as non-viral drug delivery agents. Further, the surface modification of described polyplexes with PEG allowed for systemic delivery of nucleic acids to tumors. The characterization of post-PEGylated Asp-DET/DNA polyplexes provides insights that can be used to design vectors for targeted nucleic acid delivery. 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 599.
SAT0392 Clinical Features of Fibromyalgia and Chronic Widespread Pain Syndrome in Patients with Mild Psoriasis. Application and Comparison of the 1990 and 2010 ACR Classification Criteria
Authors: G. D. Marco, A. Cattaneo, C. G. Carrera, N. Battafarano, P. Gibertini, A. Marchesoni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Fibromyalgia (FM) is a frequent cause of chronic widespread pain (CWP). Although its occurrence in psoriatic subjects represents a clinical challenge in terms of diagnosis and management, such issue is still poorly investigated. <h3>Objectives</h3> Our aim was to describe the features of CWP syndromes in a series of patients wild mild psoriatic subjects and to compare the existing classification criteria for FM. <h3>Methods</h3> In a cohort of psoriatic patients followed in a dermatological clinic dedicated to psoriasis care, 307 were consecutively enrolled for an epidemiological study. Patient on biological treatment and those unable to give informed consent were not eligible. All candidates underwent a thorough rheumatological evaluation. Details about history of pain and somatoform symptoms (SS) were collected as well. Imaging and laboratory investigations were performed as needed. Diagnosis was established through expert opinion. <h3>Results</h3> The 307 studied patients had mean age of 53.8 years (SD 16.4); 188 (61.2%) were males. Median psoriasis duration was 11 years (IQR 4.5-20), median PASI score was 3.1 (IQR 1.6-6.5). Systemic therapies were prescribed to 91 (29.6%) subjects. Chronic pain history was reported by 151 patients (49.2%), in 34 (11.1%) cases it was widespread. Median number of SS was 2 (IQR 1-3), median SS scale score was 2.5 (IQR 1-4). Pain on examination was observed in 105 patients (34.2%) and it was widespread in 13 (4.2%) cases. Two hundreds-forty-eight subjects (80.8%) had no tender point. In this series, 21 patients (6.8%) were diagnosed as CWP syndromes, only 3 satisfied the 1990 ACR criteria for FM (sensitivity 14.3%), 9 satisfied the 2010 criteria (sensitivity 42.9%), none satisfied both, 8 cases were close to satisfy at least one set of criteria. CWP syndromes were more frequent in females (P&lt;0.001), but there was no difference in terms of age, psoriasis duration or PASI score from the rest of studied patients. Scores of SS scale, WPI, tender points, reported or objective widespread pain were significantly more frequent (all P&lt;0.001) in CWP syndrome patients. After logistic regression analysis only the number of SS (OR 54.7, 95% CI 1.4-2076.8; P=0.03) and reported widespread pain (OR 178.8, 95% CI 1.7-18533; P=0.02) remained significant. ROC curve analysis of SS yielded AUC=0.95 with a cut off of 4 (sensitivity 80.4%, specificity 93%). <h3>Conclusions</h3> In this study, CWP was not common in psoriatic patients. The more recent classification criteria for FM proved to be were more sensitive than the older criteria, but problems of classification with borderline cases remained. The number of SS correlates well with CWP syndromes, representing a potential help in the diagnostic work up. <h3>Disclosure of Interest</h3> None Declared
EUS-guided gallbladder drainage therapy for obstructive jaundice
Authors: Imai Hajime
Journal: Endoscopy (2011)

Background: Endoscopic biliary drainage (EBD) is the most effective method for obstructive jaundice or acute cholecystitis. However we often experience difficult because of duodenal deformity or stenosis caused by tumor invasion or surgical restruction. Percutaneous transhepatic drainage, which involves an external drainage tube, decreases the ability of patient to carry out their normal daily activities. Recently, EUS-guided biliary drainage has been reported to be useful for obstructive jaundice with unsuccessful EBD. EUS-guided drainage is also applied to decompression of gallbladder with acute cholecystitis. We employed the new technique, EUS-guided gallbladder drainage (EUS-GBD), for treatment of obstructive jaundice, and evaluated its feasibility. Patients and methods: A total of 4 patients (2 men, 2 women, median age 69 years, 3 pancreatic cancer, 1 bile duct cancer) underwent EUS-GBD for treatment of obstructive jaundice. In all cases, EBD was unsuccessful. An echoendoscope (GF-UCT240-AL5, OLYMPUS) was introduced into the stomach. Following visualization of a swollen gallbladder adjacent to antrum or the duodenal bulb, the echoendoscope was manipulated in order to identify an appropriate puncture route that has no intervening vessels. The gallbladder was punctured with 19G needle under echoendoscope guidance. After the gallbladder was irrigated by saline to avoid the peritonitis by leakage of bile, a 0.035-inch guide wire was introduced into the gallbladder. In case that dilation of the puncture hole by biliary dilation catheters (6.7and 9Fr) through the guide wire was successful, a double-pigtail stent was deployed between the gallbladder and stomach. Technical success rate, complication rate and stent patency were assessed. Technical success was defined as the passage of the stent across the stomach or duodenum. Function success was defined as a decrease in bilirubin to <80% of pretreatment value within two weeks. Result: The gallbladder was successfully punctured by the needle and irrigated in all patients.