tbuckley/cabot-search huggingface dataset:
Abstract 12417: Left Ventricular Assist Device Reimplantation for Recurrent Heart Failure After Myocardial Recovery and Weaning
Authors: TomohiroSaito, MichaelDandel, YuguoWeng, EvgenijPotapov, ThomasKrabatsch, RolandHetzer
Journal: Circulation (2014)

Object: In our experience, 5-10% of patients with dilative cardiomyopathy have presented myocardial recovery and could be weaned from long-term support with left ventricular assist device (LVAD). However, one third of them had a heart failure recurrence during follow-up. Subsequent treatment options are limited to heart transplantation or reimplantation of LVAD. We evaluated clinical outcome of the patients treated with LVAD reimplantation. Methods: Between 1995 and 2014, 64 patients implanted with LVAD for dilative cardiomyopathy (median age 43, range 16-71 years) were weaned from LVAD according to our institutional protocol. Among them, six patients required later reimplantation of LVAD due to recurrent heart failure. Hospital records were retrospectively reviewed. Results: LVAD reimplantation in the six patients was necessary at a median of 1638 (range, 393-5336) days after weaning from the first LVAD. Actual median duration of freedom from heart failure recurrence (from date of weaning from first LVAD...
Abstract 1366: <i>MBD4</i> guards against DNA damage from methylcytosine deamination
Authors: Edward Chew, Mathijs A. Sanders, Christoffer Flensburg, Annelieke Zeilemaker, Sarah E. Miller, Adil S. al Hinai, Ashish Bajel, Bram Luiken, Melissa Rijken, Tamara Mclennan, Remco M. Hoogenboezem, François G. Kavelaars, Marnie E. Blewitt, Eric M. Bindels, Warren S. Alexander, Bob Löwenberg, Andrew W. Roberts, Ian J. Majewski, Peter J. Valk
Journal: Cancer Research (2018)

Abstract Spontaneous methylcytosine (5mC) deamination is a common source of cytosine to thymine (C&amp;gt;T) mutations. These mutations accumulate over time, serving as a “molecular clock” that tracks cellular age. MBD4 is a thymine glycosylase that recognises sites of 5mC deamination and initiates base excision repair. Three patients (of whom 2 are siblings) with germline MBD4 loss of function (LOF) mutations developed acute myeloid leukemia (AML) at a young age (&amp;lt;35 years old). Whole exome (WES) and whole genome sequencing (WGS) showed an elevated C&amp;gt;T mutation rate ~33 times the average for AML. The mutations occurred nearly exclusively at CG dinucleotides. Reduced representation bisulfite sequencing showed the mutations occurred at previously methylated cytosines. The 3 AMLs had somatic C&amp;gt;T mutations in the same driver genes (DNMT3A and either IDH1 or IDH2), suggesting the methylation damage charts a recurrent path towards malignancy in the hematopoietic system. MBD4 is inactivated in other cancers, although this appears to be a rare event. Nine of 10,638 cancers in the TCGA database had MBD4 LOF mutations. In a uveal melanoma and a glioblastoma multiforme, there was also loss of heterozygosity of the wild-type MBD4. These 2 cancers with MBD4 deficiency exhibit the same mutational signature, with a high C&amp;gt;T mutation rate at CG dinucleotides. To verify the link between MBD4 and the 5mC damage signature, Mbd4-/- and Mbd4+/+ mouse bone marrow were cultured in semi-solid agar and WGS was performed on individual myeloid progenitor colonies. Mbd4-/- myeloid progenitor colonies displayed the same increase in C&amp;gt;T mutations at CG dinucleotides. This highlights the importance of MBD4 across species. Mbd4 deficient mice offer a model system to investigate mutation acquisition and cancer pathogenesis. Work on the interaction of MBD4 with other leukaemia initiating genes is underway. Citation Format: Edward Chew, Mathijs A. Sanders, Christoffer Flensburg, Annelieke Zeilemaker, Sarah E. Miller, Adil S. al Hinai, Ashish Bajel, Bram Luiken, Melissa Rijken, Tamara Mclennan, Remco M. Hoogenboezem, François G. Kavelaars, Marnie E. Blewitt, Eric M. Bindels, Warren S. Alexander, Bob Löwenberg, Andrew W. Roberts, Ian J. Majewski, Peter J. Valk. MBD4 guards against DNA damage from methylcytosine deamination [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 1366.
Cinaciguat (BAY 58–2667) Improves Cardiopulmonary Hemodynamics in Patients With Acute Decompensated Heart Failure
Authors: HaraldLapp, VeselinMitrovic, NorbertFranz, HubertusHeuer, MichaelBuerke, JudithWolfertz, WolfgangMueck, SigrunUnger, GeorgWensing, ReinerFrey
Journal: Circulation (2009)

Background— Cinaciguat (BAY 58–2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure ≥18 mm Hg). Methods and Results— After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 μg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by ≥4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 μg/h (n=2), 200 μg/h (n=12), and 400 μg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (−7.9 mm Hg), me...
Electrocardiographic Recognition of the Epicardial Origin of Ventricular Tachycardias
Authors: AntonioBerruezo, LluisMont, SantiagoNava, EnriqueChueca, EduardoBartholomay, JosepBrugada
Journal: Circulation (2004)

Background— Some ventricular tachycardias (VTs) originating from the epicardium are not suitable for endocardial radiofrequency ablation and require an epicardial approach. The aim of this study was to define the ECG characteristics that may identify an epicardial origin of VTs. Methods and Results— We analyzed the 12-lead ECG recordings during epicardial and endocardial left ventricular pacing in 9 patients to verify the hypothesis that the epicardial origin of the ventricular activation widens the initial part of the QRS complex. Then, we analyzed the ECG pattern in 14 VTs successfully ablated from the epicardium after a failed endocardial approach (group A), in 27 VTs successfully ablated from the endocardium (group B), and in 28 additional VTs that could not be ablated from the endocardium (group C). Four distinct intervals of ventricular activation were defined and measured: (1) the pseudodelta wave, (2) the intrinsicoid deflection time in V2, (3) the shortest RS complex, and (4) the QRS complex. VTs...
Proadrenomedullin N-Terminal 20 Peptide Hyperpolarizes the Membrane by Activating an Inwardly Rectifying K+ Current in Differentiated PC12 Cells
Authors: KojiTakano, ToshiroFujita
Journal: Circulation Research (1999)

Abstract—The mechanism of proadrenomedullin N-terminal 20 peptide (PAMP)–induced inhibition of catecholamine release from adrenergic nerve was investigated in nerve growth factor–treated PC12 cells that have differentiated characteristics somewhat similar to noradrenergic neurons. The effect of PAMP on the excitability of these cells was investigated with the use of perforated whole-cell clamp. PAMP hyperpolarized the membrane by increasing a K+ conductance in a dose-dependent manner. The current-voltage relationship (I-V) relationship of the PAMP-induced K+ conductance exhibited inward-going rectification. The activation was abolished by microinjecting GDPβS into the cells or pretreating the cells with pertussis toxin. These results indicate that a pertussis toxin–sensitive G protein is involved in the signal transduction. The PAMP-induced activation of the K+ conductance was attenuated by microinjecting antibody against the carboxyl terminus of Gαi3, but it was not influenced by microinjecting antibody ...
Abstract 2447: Loss of mitochondrial function and increases in levels of oxidative stress pinpointed in human lung cell cultures exposed to particulate matter from September 11, 2001
Authors: Ann Marie DiLorenzo, Lara Seder, Rebekah Madrid, Eric Tobias, Jonathan Ortiz, Vern Gatson
Journal: Cancer Research (2018)

Abstract Not only did more than 2,753 individuals pass away the morning of September 11,2001, but there have been individuals suffering from mental and physical illness ever since. Thousands of individuals suffered from breathing complications, asthma, and lung cancer. Clinical trials on cancer patients, including a patient who was exposed to the World Trade Center Dust (WTCD), have seen a decrease in the progression of tumor growth with use of oral nicotinamide adenine dinucleotide (NADH). NADH is naturally occurring within a cell's mitochondria and aids in the production of adenosine triphosphate (ATP), the energy of the cell. NADH is an anti-aging, energy enhancing, substance that also reduces fatigue and successfully treats degenerative medical conditions. NADH is becoming a possible treatment for tumor regression but it is still unknown, on a cellular level, why NADH reacts with these cells to prevent further tumor growth. In this study, the amount of NADH produced by normal MRC-5 lung fibroblast cells will be compared to lung cells exposed to World Trade Center Dust (WTCD), using a Promega NAD/NADH-Glo Assay. The same cells will be evaluated to note the decline in Glutathione to determine the amount Reactive Oxidative Species ( ROS) brought on to lung cells by WTCD. ROS can decrease GSH levels by causing oxidative stress that leads to apoptosis. It is important for the cells to maintain high levels of reduced GSH and low levels of oxidized GSH. PROMEGA GSH Glo Glutathione assay will be used to determine if the toxic, mutagenic and apoptotic effects of WTC dust can be shown as the result of oxidative stress. The cells will be exposed to various concentrations of WTCD, ranging from 25-250 ppm. It is hypothesized that the cells with the highest concentrations of this toxic particulate matter will experience the most accumulation of oxidative stress, resulting in less NAD+, being reduced to NADH, within the mitochondria and simultaneous decrease in protective antioxidants as shown in changes in levels of Glutatione. This should allow correlations to be made on a more precise cellular mechanism between exposure to this WTCD, oxidative stress, and loss of mitochondrial function seen in the diseases of the exposed first responder population. Citation Format: Ann Marie DiLorenzo, Lara Seder, Rebekah Madrid, Eric Tobias, Jonathan Ortiz, Vern Gatson. Loss of mitochondrial function and increases in levels of oxidative stress pinpointed in human lung cell cultures exposed to particulate matter from September 11, 2001 [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 2447.
Abstract 4067: Toll-like receptor 2 deficiency enhances KRAS-driven lung cancer
Authors: Chia-Hsin Liu
Journal: Cancer Research (2018)

Abstract Chronic infection and inflammation have been suggested to have a strong association with lung cancer in clinical and epidemiologic studies. Toll-like receptor 2 (TLR2) mediates inflammatory response and is essential in regulating innate and adaptive immunity. TLR2 has also been reported to play either pro-tumorigenesis or tumor-suppressive role depending on the oncogenic driver mutations and cell types. However, the role of TLR2 in lung cancer, especially in the lung adenocarcinoma harboring KRAS mutations, remains unknown. In an analysis using human lung adenocarcinoma cohort (TCGA RNAseq dataset), our results revealed that KRAS-mutant lung tumors showed lower TLR2 mRNA expression than the paired adjacent normal lung tissue. Furthermore, lung adenocarcinoma patients with lower TLR2 expression displayed worse survival outcome. To functionally test the role of TLR2 during KRAS-driven lung tumorigenesis, we generated a mouse model of lung adenocarcinoma mutated for K-ras, with and without TLR2 inactivation (K-rasG12D/+ TLR2-/- and K-rasG12D/+TLR2+/+, respectively). Interestingly, the tumor number and tumor area significantly increased in K-rasG12D/+ TLR2-/- mice compared to K-rasG12D/+TLR2+/+ mice. In addition, the inflammatory cells in bronchoalveolar lavage (BAL), especially the alveolar monocytes, significantly increased in K-rasG12D/+ TLR2-/- mice. Microdissected lung tumors from K-rasG12D/+ TLR2-/- mice showed significantly higher inflammatory chemokines and cytokines gene expression (Ccl1, Ccl2, Cxcl1, Cxcl2, Cxcl5, Csf1, IL-6, Tnf) than those from K-rasG12D/+TLR2+/+mice. Additionally, Cxcl1 was significantly higher in K-rasG12D/+ TLR2-/- when BAL fluid was analyzed for cytokines/chemokines by Luminex assays. Our results suggest that TLR2 deficiency may promote KRAS-mutation driven lung tumorigenesis through increased cancer-related inflammation. Furthermore, the expression may serve as a prognostic biomarker for which the lower TLR2 expression is associated with worse survival outcome in lung adenocarcinoma patients with KRAS mutation. Citation Format: Chia-Hsin Liu. Toll-like receptor 2 deficiency enhances KRAS-driven lung 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 4067.
Antihypertensive Medication Use Among US Adults With Hypertension
Authors: QiupingGu, RynePaulose-Ram, CharlesDillon, VickiBurt
Journal: Circulation (2006)

Background— High blood pressure can be controlled through existing antihypertensive drug therapy. This study examined trends in prescribed antihypertensive medication use among US adults with hypertension and compared drug utilization patterns with recommendations of the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Methods and Results— Persons aged ≥18 years from the National Health and Nutrition Examination Surveys were identified as hypertensive on the basis of either a blood pressure ≥140/90 mm Hg or self-reported current treatment for hypertension with a prescription medication. In 1999–2002, 62.9% of US hypertensive adults took a prescription antihypertensive medication compared with 57.3% during 1988–1994 (P<0.01). Men had the greatest increase in antihypertensive medication use (47.5%, 1988–1994 versus 57.9%, 1999–2002 [P<0.001]). In both surveys, antihypertensive medication use increased with age, was lower among men than among women, a...
Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata
Authors: Solam Lee, Beom Jun Kim, Young Bin Lee, Won-Soo Lee
Journal: JAMA Dermatology (2018)

Contact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies.To summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors.A database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric.Clinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded.The following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies.The main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate.Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment.Various factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.
Abstract 19598: Increased Risk of Repeat Coronary Revascularization is Reduced by Methotrexate or Tumor Necrosis Factor Inhibitor Treatments in Patients With Rheumatoid Arthritis
Authors: MarcSintek, ChristopherSparrow, EricNovak, JasvindarSingh
Journal: Circulation (2014)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of atherosclerosis and cardiovascular mortality. Long term data on outcomes after percutaneous coronary intervention (PCI) is lacking in this population, specifically with regards to repeat revascularization. We investigated target lesion(TLR) and target vessel revascularization(TVR) in this population. Methods: We performed a single center retrospective case control study of RA patients post PCI. Each treated RA lesion was matched to 3 control lesions based upon procedure date, drug eluting stent use, age, vein graft intervention and diabetes mellitus. Patients were censored following the last encounter in the medical record. Primary endpoints were time to TLR and TVR. Kaplan-Meier analyses and shared frailty Cox proportional hazards models were performed to compare event free survival. Results: A total of 228 lesions (142 patients) were identified in the RA cohort and matched to 677 control lesion...
Real-Time 3-Dimensional Transesophageal Echocardiography in the Evaluation of a Patient With Concomitant Double-Orifice Mitral Valve, Bicuspid Aortic Valve, and Coarctation of the Aorta
Authors: GunjanAggarwal, DominikSchlosshan, ConArronis, GitaMathur, GregCranney
Journal: Circulation (2009)
Abstract 3082: Epidermal-specific overexpression of T-cell protein tyrosine phosphatase in mouse attenuates chemically-induced skin carcinogenesis
Authors: Mihwa Kim, Liza D. Morales, Iksoon Jang, Andrew Tsin, Dae Joon Kim
Journal: Cancer Research (2018)

Abstract Tyrosine phosphorylation signaling, which is regulated by the counter-activities of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), is critical in maintaining cellular homeostasis. The aberrant increase of tyrosine phosphorylation by mutation and/or overexpression of PTKs can contribute to skin carcinogenesis. While PTKs have been extensively studied in skin carcinogenesis, PTPs have not been studied due to their inactivation by environmental toxicants. Our recent studies showed that T-cell protein tyrosine phosphatase (TC-PTP; encoded by Ptpn2) deficiency in mouse epidermis significantly increased skin tumor formation, demonstrating TC-PTP deficiency predisposes mice to skin carcinogenesis. To further examine the tumor suppressive role of TC-PTP in skin carcinogenesis, we generated epidermal-specific TCPTP-overexpressing (K5HA.Ptpn2) transgenic mice. TC-PTP overexpression led to sensitization to tumor initiator 7,12-dimethylbenz[a]anthracene (DMBA)-induced apoptosis both in vivo epidermis and in vitro keratinocytes. TC-PTP overexpression in epidermis significantly reduced epidermal thickness and hyperproliferation compared to wild-type control following treatment with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, TC-PTP overexpression significantly induced epidermal differentiation following TPA treatment as evidenced by the increased expression of epidermal differentiation markers loricrin, involucrin, keratin 10, and transglutaminase 5 in comparison to control. Two-stage skin carcinogenesis analysis using a DMBA/TPA regimen clearly revealed that K5HA.Ptpn2 mice exhibited delayed tumor development and significantly reduced tumor numbers compared to control mice. Taken together, our results suggest that TC-PTP is a potential therapeutic target for the prevention of skin cancer given its ability to promote epidermal apoptosis and differentiation and inhibit epidermal proliferation. Citation Format: Mihwa Kim, Liza D. Morales, Iksoon Jang, Andrew Tsin, Dae Joon Kim. Epidermal-specific overexpression of T-cell protein tyrosine phosphatase in mouse attenuates chemically-induced skin carcinogenesis [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 3082.
Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: Analysis of the National Cancer Database.
Authors: Jaymin Jhaveri, Lael Rayfield, Yuan Liu, Mudit Chowdhary, Richard John Cassidy, Nicholas Andrew Madden, Daniel G Tanenbaum, Mustafa Abugideiri, Theresa Wicklin Gillespie, Pretesh R Patel, Kirtesh Patel, Jerome Carl Landry
Journal: Journal of Clinical Oncology (2018)

735 Background: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation in the National Cancer Database (NCDB). Methods: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HR) and 95% confidence intervals (CI) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. Results: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n = 498, 46.8%) and HPV- (n = 565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR 0.60, CI 0.38-0.96; p = 0.034). However, for women, HPV infection did not significantly influence survival (HR 1.47, CI 0.96-2.25; p = 0.074). Conclusions: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.