tbuckley/cabot-search huggingface dataset:
FRI0039 Measuring health realted quality of life (EQ-5D) in patients with rheumatoid arthritis after one year treatment with csdmards and biologic dmards
Authors: V.V. Boyadzhieva, N. Stoilov, G. Petrova, R. Stoilov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Health-related quality of life (HRQoL) is a multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning. It goes beyond direct measures of patients' health, and focuses on the impact health status has on quality of life. <h3>Objectives</h3> To measure the QoL (EuroQol – 5D) of patients with RA and analyse their change after one year treatment with csDMARDs and biologic DMARDs (bDMARDs). <h3>Methods</h3> For the purpose of the study were selected 220 patients: 29 males (13%) and 86 women (87%) meet the classification criteria for RA by ACR 1987 Patient's age is between 18–85 years (mean age for DMARDs – 54.8, biologic DMARDs – 55.3 years). The duration of the disease is between 0.5–44 years. In our study 96 patients are treated with DMARDs and 124 with bDMARDs. Patients with significant comorbidity, infectious diseases, congestive heart failure (NYHA class III or IV), malignant hypertension, psychiatric illness, a history of lymphoproliferative disease or neoplasia were excluded from the study. All of the patients completed the questionnaire EuroQol-5D on baseline, 6th and 12th month of treatment. The results were calculated via licensed calculator <h3>Results</h3> On Baseline, first part of EQ-5D mean values in patients with biologic therapy were significantly lower than those in the csDMARDs group (p=0.001). During the follow-up period patients on biologic DMARDs experienced significant improvement in this indicator in both time intervals (6th month – 63.24±16.52 SD, 12th month – 76.38±14.85). After 6 months of treatment the group on bDMARDS have higher mean values for EQ-5D than the patients on csDMARDs (57.64±20.2 SD), which shows significantly higher Quality of life (p=0.0025). During the following period from 6th to 12th month the patients on csDMARDs didn't have significant improvement in QoL (58.65±22.41 SD) (p=0.214). On the 12th month of the treatment the patients on bDMARDs have significantly higher QoL than the group on csDMARDs (p=0.000). Analysing the data from the second part of the questionnaire, we found similar results with the data obtained from the first. Patients on biological therapy experienced a significant improvement in quality of life during the entire follow-up period. In contrast, patients on csDMARDS had significant improvement in the mean values of the EQ-5D – 0.51±0.2 3SD to 6th month, after which there was a non-significant reduction of EQ-5D=0.49±0.23 SD to 12th month (p=0.266). <h3>Conclusions</h3> The patients on biologic DMARDs have significantly higher QoL than the patients on csDMARDs on the 6th and 12th month of treatment period. <h3>Disclosure of Interest</h3> None declared
Abstract 13225: Which Oral Anti-Coagulant Do Patients Prefer for Stroke Prevention in Non-Valvular Atrial Fibrillation?
Authors: Gregory Y Lip, Paolo Verdecchia, Tommi Tervonen, Anastasia Ustyugova, Jutta Heinrich-Nols, Savion Gropper, Ryan Kwan, Sumitra Sri Bhashyam, Kevin Marsh
Journal: Circulation (2016)

Introduction: There are various oral anticoagulants available for stroke prevention in patients suffering from non-valvular atrial fibrillation (NVAF) with some drug-related variations in clinical profile and non-clinical attributes. Patient preferences should be taken into account in anticoagulant prescription decisions. Hypothesis: Patient valuation of different anticoagulant characteristics in stroke prevention allows for meaningful comparison of the non-VKA oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and Vitamin K Antagonist (VKA, ie. warfarin). Methods: Multi-criteria decision analysis was developed with 5 clinical and 3 non-clinical criteria. Criteria weights were defined using results from two discrete choice experiments (DCEs). The evaluation model contained more fine-grained events than the DCEs, and therefore preference weights from DCEs needed to be distributed to the evaluation criteria. The weights were distributed according to event fatality rates, which were obtained from the RE-LY trial that compared dabigatran to warfarin. An additive model was used to combine treatment performance with the weights to estimate the overall value of each oral anticoagulant. Probabilistic and structural sensitivity analyses were performed. Results: Dabigatran obtained the highest overall value (see Figure: weighted contribution of different evaluation criteria to the overall value of five oral anticoagulants) and the highest first rank probability (88%) in the probabilistic sensitivity analysis. Rivaroxaban performed worse than the other NOACs, but better than VKA (both with 0% first rank probability). The results were insensitive to removing availability of reversal agent from the model. Conclusions: Patient preferences on treatment characteristics allows to discriminate oral anticoagulants for stroke prevention in NVAF, with dabigatran ranking highest and warfarin lowest.
Regulation of Endothelial Nitric Oxide Synthase Expression by Albumin-Derived Advanced Glycosylation End Products
Authors: ArmandoRojas, SheylaRomay, DeyarinaGonzález, BeatrizHerrera, ReneDelgado, KarelOtero
Journal: Circulation Research (2000)

Abstract—We examined whether albumin-derived advanced glycosylation end products (AGEs) downregulate the expression of endothelial nitric oxide synthase (NOS). Significant reductions in NOS activity and cGMP levels in bovine aortic endothelial cells were observed when exposed to different concentrations of albumin-derived AGEs. Western and Northern blot analyses showed significant decreases at the protein and transcript levels. Both reductions became evident after 24 hours of exposure. Nuclear run-on assays showed that AGE-BSA did not modify the transcription rate of the NOS III gene; however, AGE-BSA treatment markedly reduced the half-life of NOS III mRNA. In addition, AGE-treated endothelial cells displayed significant reduction on their antiplatelet properties. These results indicate that NOS expression is reduced by AGEs by increasing the rate of mRNA degradation and may be relevant to the impairment of some endothelial functions observed in diabetes and aging. The full text of this article is availa...
Abstract P198: Association Between Parity and Inflammation Varies by Acculturation Level Among Mexican American Women of Childbearing Age
Authors: Natalya Rosenberg, Martha L Daviglus, Kamal Eldeirawi
Journal: Circulation (2016)

Introduction: Parity is an independent risk factor for cardiovascular health. Its association with cardiovascular disease risk among Mexican American women is less established, even though this population currently has the highest fertility rate in the U.S. We examined the association of parity with a cardiovascular risk biomarker, C-reactive protein (CRP), among Mexican American women of childbearing age. Methods: Participants (N=1,346) were currently non-pregnant women of Mexican background, aged 16-49 years, in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. The association between parity status [classified as live birth ≤ one year ago, live birth &gt; one year ago, or nulliparous (reference group)] and elevated CRP (&gt;3.0 mg/L) was examined using binary logistic regression. Since greater acculturation is associated with greater cardiovascular health risk among Mexican American women, an interaction between parity and acculturation was considered. Acculturation (scores 0 to 5) was defined based on nativity status, duration of residence in the U.S. (0-Mexico-born, U.S. resident &lt; 10 years, 1-Mexico-born, U.S. resident 10-19 years, 2-Mexico-born, U.S. resident ≥20 years, 3- U.S. born), and language use at home (0-Spanish, 1-bilingual, 2-English). Scores 0-1, 2-3, 4-5 represented low, moderate, and high acculturation level, respectively. Results: The association of parity status with elevated CRP varied by acculturation level ( P for interaction = 0.01). In stratified analyses, live birth ≤ one year ago and live birth &gt; one year ago, compared to nulliparity, was associated with higher odds of elevated CRP among women with low acculturation but not among women with moderate or high acculturation level. Additional adjustment for access to health care and lifestyle factors did not change results. Conclusions: In this cross-sectional study, parity is associated with a higher likelihood of elevated CRP in women with low acculturation.
Abstract 816: Antibody-drug conjugate targeting glypican-1 shows potent antitumor effect in pancreatic cancer
Authors: Satoshi Serada, Takahiko Nishigaki, Takahito Sugase, Yurina Saito, Tsuyoshi Takahashi, Kosuke Hiramatsu, Minoru Fujimoto, Masaki Mori, Yuichiro Doki, Tetsuji Naka
Journal: Cancer Research (2018)

Abstract Pancreatic cancer is the most lethal malignancy; thus developing new treatment options is urgently required. We confirmed that enhanced expression of glypican-1 (GPC1) was observed in pancreatic cancer. In this study, we aimed to develop novel antibody-drug conjugate (ADC) targeting GPC1 as a new therapy for pancreatic cancer. By the immunohistochemical analysis, enhanced expression of GPC1 was observed in pancreatic cancer. Among pancreatic cancer cell lines, BxPC3 and T3M4 cells expressed high expression of GPC1 compared to SUIT2 cells. We developed new anti-GPC1 monoclonal antibody (mAb) and selected a clone having highly internalizing activity. The anti-GPC1 mAb was conjugated with cytotoxic agent monomethyl auristatin F (MMAF). Compared with the control ADC, this GPC1-ADC showed potent antitumor effect toward BxPC3 and T3M4, while little activity in SUIT2 cells. In BxPC3 xenograft model, GPC1-ADC had significant and potent tumor growth inhibition in a dose dependent manner. In addition, using patient derived tumor xenograft (PDX) model with GPC1-positive pancreatic cancer, GPC1-ADC also showed significant tumor growth inhibition. In the tumor tissue, GPC1-ADC-mediated G2/M phase cell cycle arrest was detected in GPC1-ADC treated mice compared to control-ADC treated mice. In summary, our newly developed GPC1-ADC showed significant tumor growth inhibition against not only GPC1-positive pancreatic cell line but also patient derived GPC1-positive pancreatic cancer. Our preclinical data demonstrated that targeting GPC1 by ADC is a promising therapy for patients with GPC1-positive pancreatic cancer. Citation Format: Satoshi Serada, Takahiko Nishigaki, Takahito Sugase, Yurina Saito, Tsuyoshi Takahashi, Kosuke Hiramatsu, Minoru Fujimoto, Masaki Mori, Yuichiro Doki, Tetsuji Naka. Antibody-drug conjugate targeting glypican-1 shows potent antitumor effect in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 816.
Effect of Resynchronization Therapy Stimulation Site on the Systolic Function of Heart Failure Patients
Authors: ChristianButter, AngeloAuricchio, ChristophStellbrink, EckartFleck, JiangDing, YinghongYu, EtienneHuvelle, JulioSpinelli
Journal: Circulation (2001)

Background— Cardiac resynchronization therapy (CRT) improves systolic function in heart failure patients with ventricular conduction delay by stimulating the left ventricle (LV) or both ventricles (biventricular, BV). Optimal LV site selection is of major clinical interest for CRT device implantation; however, the dependence of hemodynamics on LV stimulation site has not been established. Thus, the objective of this study was to compare the hemodynamic response to CRT for 2 LV coronary vein sites: the free wall and anterior wall. Methods and Results— A total of 30 patients (mean NYHA class, 2.7; mean QRS interval, 152 ms; mean PR interval, 194 ms) enrolled in the PATH-CHF-II trial were studied. CRT was administered with LV and BV stimulation in VDD mode at 4 AV delays. LV stimulation was at the lateral free wall or anterior wall, whereas right ventricular stimulation was fixed near the apex. LV+dP/dtmax and aortic pulse pressure changes from baseline during CRT were compared for LV sites. Free wall sites ...
Abstract 16815: Long Term Follow up of the Two Incision Technique for Implantation of the Subcutaneous Implantable Cardioverter Defibrillator
Authors: Reinoud Knops, Tom Brouwer
Journal: Circulation (2015)

Introduction: The fully Subcutaneous Implantable Cardioverter Defibrillator (SICD) has been introduced as a less invasive option for the prevention of Sudden Cardiac Death (SCD). According to the labeling, the implantation of the device requires three incisions: one pocket incision for the pulse generator and two parasternal incisions to tunnel the lead. These parasternal incisions are a potential source of discomfort and infection. Also the superior parasternal incision leaves a cosmetically notable scar on the upper chest. A less invasive, two incision, implantation technique has recently been introduced that omits the superior parasternal incision. Short term follow-up in a small patient cohort has shown that it is a safe and efficacious alternative for S-ICD implantation and may help to reduce complications. No long term follow up data is available on this technique. Hypothesis: Long term follow up in a large patient cohort continues to show the safety and effectiveness of the two incision technique for S-ICD implantation. Methods: The two incision technique has been described previously. It makes use of a peelable sheeth to avoid the superior parasternal incision. We performed a retrospective analysis of all the patients in our center that have been implanted with this technique. Results: A total of 107 S-ICD patients were implanted with the two incision technique (56% male, mean age 40±16, BMI 25 (16.6-37.3). During a total follow up of 180 years patient years (mean 12 months, range 1-48) no dislocations were observed. One S-ICD system was repositioned due to DFT failure. First shock efficacy during DFT was 96% and 75% (6/8) for spontaneous episodes (100% efficacy with multiple shocks). The 1 year inappropriate shock rate was 7.4%. Device function was normal in all patients, and no inappropriate sensing occurred related to the implantation technique. Four infections occurred of which one originated from the parasternal incision. Conclusions: Long term follow up in a large patient cohort continues to show the safety and effectiveness of the two incision technique for S-ICD implantation. This technique offers physicians a less invasive and simplified implantation procedure for the S-ICD.
Loss of Baroreflex Bradycardia in Renal Hypertensive Rabbits
Authors: Nataliealexander, Marjoriedecuir
Journal: Circulation Research (1966)

The degree of reflex bradycardia elicited by a sudden, brief rise in arterial pressure was used as an index of sino-aortic reflex activity in conscious rabbits with early renal hypertension. Change in heart rate was measured every 6 seconds after injected angiotensin which caused a rise in blood pressure of 15 to 60 mm Hg. Ninety-one tests for reflex bradycardia were made in 30 normal rabbits; 14 of them were tested intermittently during the 1 to 40 day period following unilateral nephrectomy and latex encapsulation of the opposite kidney. A total of 62 tests were made after arterial pressure had risen 10 to 80 mm Hg, average 35, above control values. Average decrease in heart rate was significantly less and frequency of negligible reflex bradycardia was much higher in hypertensives than controls. Individual rabbits showed no tendency for reflex bradycardia to return toward normal magnitude. However, the vasomotor component of the sino-aortic reflex mechanism in renal hypertensive rabbits buffered the pre...
Spontaneous Seroclearance of Hepatitis B Surface Antigen and Risk of Hepatocellular Carcinoma
Authors: Ci Song, Jian Zhu, Zijun Ge, Chengxiao Yu, Ting Tian, Hui Wang, Jing Han, Hongbing Shen, Juncheng Dai, Jianquan Lu, Zhibin Hu
Journal: Clinical Gastroenterology and Hepatology (2018)
Abstract 17990: Common PCSK9 Gain-of-function E32K Variant Carriers Reveal Milder LDL-C but Higher TG Elevation Compared With LDLR Mutations
Authors: Atsushi Nohara, Masa-aki Kawashiri, Hayato Tada, Mie Yoshida, Mika Mori, Chiaki Nakanishi, Kunimasa Yagi, Akihiro Inazu, Takeshi Kobayashi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2015)

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) gene is the third causal gene of familial hypercholesterolemia (FH), and is now an emerging therapeutic target. We have found Gain-of-function mutation E32K in PCSK9 gene is common in Japanese FH. We investigated clinical characteristics of gain-of-function PCSK9 variant carriers. Methods: A total of 940 Clinically diagnosed FH heterozygotes were investigated for LDLR, PCSK9, and APOB gene. High-resolution melting (HRM) method followed by Sanger sequence were used for point mutation, and multiplex ligation-dependent probe amplification methods were applied for large rearrangements in LDLR. Fasting lipid levels without lipid-lowering drugs were analyzed. Results: LDLR mutations were identified in 732 patients (78%) and 10% of them were large rearrangements. PCSK9 E32K mutation was identified in 56 patients (6%). No APOB mutations causing FH were identified, and 143 patients showed no known FH-gene mutations. LDLR mutation carriers showed significantly higher LDL-C (LDLR 268±73, PCSK9 198±82, No mutation 198±65 mg/dL, p &lt;0.001) and higher apoB (183±51, 130±49, 148±42 mg/dL, p &lt;0.001) compared with other two groups. On the other hand, PCSK9 and No mutation group had higher TG compared with LDLR mutations (126±94, 150±84, 145±74 mg/dL, p &lt;0.05 in log-transformed TG). Hypertriglyceridemia was common in PCSK9 mutation (25%, 41%, 36%, p &lt;0.01). HDL-C was higher in No mutation group (47±15, 51±51, 55±27 mg/dL, p &lt;0.01). Achilles tendon xanthoma was more frequent in LDLR mutations. Lp(a) levels did not significantly different with PCSK9 mutation. Results: PCSK9 gain-of-function mutation E32K showed mild LDL-C elevation, but with frequent hypertriglyceridemia. This result will support basic reports that PCSK9 regulates not only LDL-R degradation but also VLDL metabolism.
Effects of Alcohol on the Electrocardiogram
Authors: Georgesereny
Journal: Circulation (1971)

The electrocardiograms of 1,000 chronic alcoholic patients were examined and analyzed. Evidence is presented that excessive consumption of alcohol, in the absence of organic heart disease, may produce changes in the electrocardiogram. The predominant abnormalities were sinus tachycardia and nonspecific T-wave changes. These abnormalities were present in the majority of the patients, provided that electrocardiograms were taken while the patients were still intoxicated. It is suggested that the changes are caused by two known effects of alcohol: stimulation of catecholamine secretion from the adrenal medulla and alteration of cell membrane permeability.
Celecoxib, a Cyclooxygenase-2 Inhibitor, Reduces Neointimal Hyperplasia Through Inhibition of Akt Signaling
Authors: Han-MoYang, Hyo-SooKim, Kyung-WooPark, Hyun-JeongYou, Soo-InJeon, Seock-WonYoun, Sung-HwanKim, Byung-HeeOh, Myoung-MookLee, Young-BaePark, KennethWalsh
Journal: Circulation (2004)

Background— Celecoxib has been shown to have antitumor effects that may be mediated through the cyclooxygenase-independent inhibition of Akt signaling. Here, we examined the effects of celecoxib on neointimal formation after balloon injury and its mechanism of action. Methods and Results— In vitro experiments were performed to evaluate the effects of celecoxib on the Akt/GSK signaling axis and the viability of rat vascular smooth muscle cells (VSMCs). In vivo experiments examined the effects of celecoxib, aspirin, and vehicle on neointimal growth after denudation injury to rat carotid arteries. In vitro, celecoxib suppressed the phosphorylation of Akt and GSK in cultured VSMCs, leading to a reduction in viable cell number, which was reversed by transduction of constitutively active Akt. Such a reduction in cell number was mediated by inhibition of proliferation and induction of apoptosis. In vivo, celecoxib reduced injury-induced phosphorylation of Akt and GSK, reduced VSMC proliferation, and increased ca...
Dilated Cardiomyopathy Associated With Hepatitis C Virus Infection
Authors: AkiraMatsumori, YoshikiMatoba, ShigetakeSasayama
Journal: Circulation (1995)

Background Myocarditis is thought to be commonly caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. In many cases, however, the evidence is only circumstantial, and direct conclusive proof is not available. Polymerase chain reaction (PCR) has been used to detect enterovirus RNA in myocardial tissue, but the wide discrepancy in results emphasizes the need for further study. Methods and Results We investigated hepatitis C virus infection in patients with dilated cardiomyopathy. The presence, type, and quantity of hepatitis C virus RNA were evaluated in the sera, and the presence of positive and negative strands of hepatitis C virus RNA in the heart was investigated with the PCR technique. Anti–hepatitis C virus antibody was present in the sera of 6 of 36 patients (16.7%) with dilated cardiomyopathy and in 1 of 40 patients (2.5%) with ischemic heart disease, showing a statistically significant (P<.05) difference. At an earlier...
Abstract 5724: Homologous recombination repair gene mutations for DNA repair and immune oncology drug combinations
Authors: Jonathan R. Dry, Zhongwu Lai, Brian Dougherty, Carl Barrett, Steven Criscione
Journal: Cancer Research (2018)

Abstract Exciting clinical benefit has been seen from both immune checkpoint inhibitors and PARP inhibitors in several cancer types. Initial reports have suggested the tumor mutational burden (TMB) may be a tumor agnostic marker for predicting immunotherapy (IO) response. Deficiencies in DNA damage repair (DDR) resulting from BRCA1 and BRCA2 mutations can lead to an accumulation of tumor mutations, and sensitivity to PARP inhibitors. We hypothesized that patients with germline or somatic mutations in BRCA1/2 or other homologous recombination repair (HRR) genes, termed “HRRm”, will have higher TMB, higher immune infiltration and activity, and greater benefit from the combination of DDR and IO therapies. We investigated the relationship between DDR deficiencies, TMB, PDL1, transcriptomic immunoscores and drug response across The Cancer Genome Atlas (TCGA) disease cohorts, data from AstraZeneca's clinical studies and a linked NSCLC genomic and EHR dataset from Foundation Medicine and FlatIron Health. HRRm cancer samples show higher TMB in several cancer types. This does trend with higher PDL1 but does not associate with transcriptomic immunoscores. HRRm could be a practical clinical biomarker to select patients with DDR defects likely to benefit from combination of DDR and IO therapies. Citation Format: Jonathan R. Dry, Zhongwu Lai, Brian Dougherty, Carl Barrett, Steven Criscione. Homologous recombination repair gene mutations for DNA repair and immune oncology drug combinations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5724.