tbuckley/cabot-search huggingface dataset:
PERSONALISED RATE-RESPONSE PROGRAMMING IMPROVES LONG-TERM EXERCISE TOLERANCE IN PEOPLE WITH PACEMAKER DEVICES AND HEART FAILURE
Authors: John Gierula, Judith Lowry, Maria F. Paton, Rowenna Byrom, Aaron Koshy, Cole Charlotte, Hemant Kumar Chumun, Lorraine Kearney, Straw Sam, T. Scott Bowen, Richard Cubbon, Anne-Maree Keenan, Deborah Stocken, Mark Kearney, Klaus Witte
Journal: Journal of the American College of Cardiology (2020)
Randomized trial of marker-directed versus standard schedule zoledronic acid for bone metastases from breast cancer.
Authors: Robert Edward Coleman, Jonathan Wright, Stephen Houston, Rajiv Agrawal, Om Pra-Kash Purohit, Larry Hayward, Peter Simmonds, Anna Waterhouse, Helen Marshall
Journal: Journal of Clinical Oncology (2012)

511 Background: Zoledronic acid (ZOL) reduces skeletal morbidity associated with metastatic bone disease by 30-50%. Current recommendations are for indefinite administration of intravenous 3-4 weekly (w) ZOL 4mg. Over recent years it has become clear that the risk of skeletal morbidity is related to the rate of bone resorption. We have compared a marker directed schedule of ZOL (M-ZOL), using measurements of urinary n-telopeptide of type I collagen (NTX), to a standard treatment schedule (S-ZOL) in patients with bone metastases from breast cancer. Methods: The primary endpoint was skeletal related events (SRE). A non-inferiority study was designed with 80% power and (one-sided) 5% alpha to demonstrate that M-ZOL retained 67% of the efficacy of S-ZOL. This required 1500 patients, assuming a SRE rate of 0.7/year. Following minimisation for known prognostic factors, patients were randomised to receive S-ZOL 3-4 w or M-ZOL (15-16w; 8-9 w or 3-4w if NTX levels were &lt;50, 50-100, &gt;100 nmol/mmol creatinine respectively), with the schedule adjusted according to NTX measured every 16 weeks. The study duration was 24 months. Results: Due to lower than expected recruitment, the study closed in 2009 following recruitment of 289 patients. 90% of patients had received &gt;4 cycles of ZOL or pamidronate prior to randomisation. The median number of ZOL infusions administered to S-ZOL patients was &gt;2x that received on M-ZOL. 46 (32%) S-ZOL and 55 (38%) M-ZOL patients experienced an SRE. The numbers of SRE were 94 and 138 in the S-ZOL and M-ZOL arms, with the excess in SRE being largely due to more patients on M-ZOL experiencing ≥2 SRE. Multivariate analysis adjusting for key minimisation factors and baseline NTX for all SRE showed a hazard ratio for M-ZOL vs. S-ZOL of 1.41 (90%CI 0.98-2.02, p=.12). NTX levels were significantly higher at all time points in the M-ZOL treated patients. Osteonecrosis of the jaw was uncommon with 3 cases with S-ZOL and 1 with M-ZOL. Conclusions: The study is underpowered to demonstrate non-inferiority in SRE outcome between the treatment strategies. However, the results suggest that the adjustment of ZOL schedule based on NTX values alone may represent sub-optimal management.
Efficacy and safety of rolapitant, a novel NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting in subjects receiving highly emetogenic chemotherapy.
Authors: Luis Enrique Fein, Allen Poma, Mary Lynne Hedley
Journal: Journal of Clinical Oncology (2012)

9077 Background: Management of chemotherapy-induced nausea and vomiting (CINV) improves quality of life and increases the likelihood that patients will continue to receive appropriate treatment. The objective of this dose finding study was to evaluate rolapitant for the prevention of CINV in subjects receiving highly emetogenic chemotherapy (HEC). Methods: A phase II, double blind study in which 454 subjects receiving HEC (≥70mg/m 2 cisplatin-based chemotherapy) were randomized in equal fashion prior to chemotherapy to receive ondansetron + dexamethasone + either placebo or 10, 25, 100 or 200mg of rolapitant. Subjects recorded episodes of emesis, severity of nausea, and use of rescue medication(s) daily within a subject diary from Days 1 through 6 of Cycle 1. Results: The rolapitant 200mg group had significantly greater complete response rates (no emesis and no use of rescue medication) in the overall (0 to 120 hours), acute (0 to ≤24 hours) and delayed (&gt;24 to 120 hours) phases compared to the placebo group (62.5% vs. 46.7%, p=0.032; 87.6% vs. 66.7%, p=0.001 and 63.6% vs. 48.9%, p=0.045, respectively). Moreover, the 200mg group had significantly greater rates of no emesis and no significant nausea in the overall, acute, and delayed phases and achieved statistically significant better QoL scores (FLIE questionnaire) compared to the placebo group. Rates for no emesis and no significant nausea for the 200mg dose group in Cycles 2 to 6 continued to demonstrate superior treatment effect vs. placebo. Treatment-related adverse events were mild and included constipation, headache, fatigue and dizziness. Overall, serious adverse events (SAEs) occurred with similar incidences across all treatment groups (9% - 14%). Most common SAEs were febrile neutropenia, neutropenia, vomiting, dehydration, nausea and pneumonia and were considered related to chemotherapy or underlying cancer and not to rolapitant. Conclusions: Administration of rolapitant 200mg with ondansetron and dexamethasone is safe and effective at preventing CINV in subjects receiving HEC.
Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes
Authors: Pier Alberto Testoni, Sabrina Testoni, Giorgia Mazzoleni, Giuseppe Pantaleo, Maria Bernadette Cilona, Giovanni Distefano, Lorella Fanti, Mario Antonelli, Sandro Passaretti
Journal: Endoscopy (2020)

Transoral incisionless fundoplication (TIF) with the Medigus ultrasonic surgical endostapler (MUSE) is a new intervention for the treatment of the gastroesophageal reflux disease (GERD). The aim of this study was to assess the 12-month clinical, functional, and endoscopic effects of TIF by MUSE.Patients undergoing MUSE completed the GERD-Health Related Quality of Life (GERD-HRQL) and Reflux Symptom Index (RSI) questionnaires, and underwent endoscopy, esophageal 24-hour pH-impedance recording, and high resolution manometry (HRM) before the TIF procedure and 12 months later, or after 6 months for HRM.Among the 37 patients treated, esophageal intubation was not possible in one and esophageal perforation occurred in another. Clinical and endoscopic follow-up at 12 months was completed in 20 patients, with significant improvements in GERD-HRQL, RSI, heartburn, regurgitation scores, and proton pump inhibitor (PPI) consumption observed. One patient required surgery for persisting symptoms. Functional follow-up was possible in 13 patients and showed no significant improvements in the analyzed parameters.TIF with MUSE significantly improved symptoms at 1-year follow-up, allowing the consumption of PPIs to be stopped or halved in 90 % of patients.
IMPACT OF WEIGHT ON THE ANTIPLATELET EFFECTS OF ASPIRIN-RESULTS OF A POOLED ANALYSIS OF TWO RANDOMIZED CROSSOVER STUDIES COMPARING A LIQUID ASPIRIN FORMULATION WITH ENTERIC COATED ASPIRIN
Authors: Deepak L. Bhatt, Dominick Angiolillo, Philippe Gabriel Steg, Weihong Fan, Carey Kimmelstiel, Roxana Mehran, George D. Dangas, Jayne Prats, Efthymios Deliargyris
Journal: Journal of the American College of Cardiology (2020)
Outcomes consequent to “early” COPD for interventional studies
Authors: Stephen I. Rennard
Journal: European Respiratory Journal (2020)

The recent paper by Çolak et al . [1] and colleagues adds to the growing body of information relating to early COPD. The study confirms the importance of symptoms among individuals prior to meeting the arbitrary threshold of forced expiratory volume in 1 s (FEV1) to forced vital capacity ratio <0.7, and that these individuals are at risk for serious morbidity and mortality. Importantly, this is demonstrated in a population-based sample. The authors clearly address the difficulty in distinguishing “early” from “mild” COPD, but have included younger individuals, which suggests that “early” disease is present in many. Data presented in the recent study by Çolak and co-workers permit estimates of trials to alter natural history of COPD using endpoints other than FEV1 <http://bit.ly/2sIxMSB>
Abstract P4-01-09: Phenotypic profiling of circulating tumor cells (CTCs) in patients with metastatic breast cancer reveals clinically-relevant heterogeneity in CTC morphology and marker expression
Authors: Tiziano Pramparo, Adam Jendrisak, Priscilla Ontiveros, Megan Kearney, Lincy Chu, Nadia Ebrahim, Joseph Schonhoft, Rick Wenstrup, Yipeng Wang
Journal: Cancer Research (2020)

Abstract Background: The choice between hormonal therapies and chemotherapy is a frequent decision in the standard of care of metastatic breast cancer (mBCa) patients. We previously developed quantitative measures of phenotypic CTC heterogeneity in metastatic prostate cancer and found that higher heterogeneity was associated with better survival on chemotherapy vs. targeted hormonal therapies in a risk adjusted analysis (Scher et al. 2017 Cancer Research). Here we sought to test the feasibility of measuring CTC heterogeneity in mBCa patients. Methods: 295 blood samples from 165 pts (84 HR+, 19 Her2+, 8 HR+/Her2+, 54 TNBC) from mBCa patients were processed for CTC analysis utilizing the Epic Sciences Functional Cell Profiling platform. Following enumeration, multi-dimensional phenotypic characterization analysis was performed utilizing protein expression and digital pathology features. Features from each CTC (3994 CTCs from 165 pts, were compared by unsupervised clustering to assess intra-patient CTC heterogeneity among mBCa CTC phenotypes. Results: CTCs were detected in 76.9% (227/295) of mBCa patients (med=2.4 CTC/mL, Range 0 - 747). Phenotypic profiling identified distinct CTC subtypes characterized by morphological and protein expression features that correlated with mBCa subtypes. Prevalent CTC features that associated with mBCa were either high cytokeratin (CK) expression or lower nuclear to cytoplasmic (N/C) ratio with lower CK expression. Analysis of mBCa subtypes showed that TNBC pts were characterized by CTCs with a large nuclear area and high CK expression. We observed marked differences in CTC heterogeneity across patients, with some patients having more uniform CTC profiles, and others having higher phenotypic diversity. mBCa subtypes had similar intra-patient heterogeneity level. Conclusions: Distinct CTC phenotypes can be visualized and quantified across patients and associated with specific mBCa subtypes. Our analysis revealed significant heterogeneity between individual CTCs both between and within patients. Identification of patients with high heterogeneity may help to identify patients unlikely to respond to targeted therapies. Studies to link heterogeneity to efficacy of specific therapies and patient outcome are ongoing. Citation Format: Tiziano Pramparo, Adam Jendrisak, Priscilla Ontiveros, Megan Kearney, Lincy Chu, Nadia Ebrahim, Joseph Schonhoft, Rick Wenstrup, Yipeng Wang. Phenotypic profiling of circulating tumor cells (CTCs) in patients with metastatic breast cancer reveals clinically-relevant heterogeneity in CTC morphology and marker expression [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-01-09.
LONG-TERM OUTCOMES AFTER REVASCULARIZATION FOR STABLE ISCHEMIC HEART DISEASE: AN INDIVIDUAL PATIENT-LEVEL POOLED ANALYSIS OF 19 RANDOMIZED CORONARY STENT TRIALS
Authors: Mahesh Madhavan, Bjorn Redfors, Ziad Ali, Megha Prasad, Bahira Shahim, Pieter Smits, Clemens von Birgelen, Zixuan Zhang, Roxana Mehran, Patrick Serruys, Akiko Maehara, Martin Leon, Ajay Kirtane, Gregg Stone
Journal: Journal of the American College of Cardiology (2020)
EARLY IMPACT OF TREATMENT WITH RIBAROXABAN ON THROMBOSIS REGRESSION ASSESSED BY QUANTITATIVE AND VOLUME MEASUREMENTS AMONG PATIENTS WITH ACUTE VENOUS THROMBUS: PROSPECTIVE MULTICENTER STUDY
Authors: Takayuki Kabuki, Shinji Hisatake, Shunsuke Kiuchi, Shintaro Dobashi, Takahiro Fujii, Takashi Oka, Takanori Ikeda
Journal: Journal of the American College of Cardiology (2020)
DIPEPTIDYL PEPTIDASE-4 INHIBITORS WERE ASSOCIATED WITH THE REDUCED LONG-TERM RISK OF ADVERSE CARDIOVASCULAR EVENTS IN JAPANESE DIABETIC PATIENTS FOLLOWING PERCUTANEOUS CORONARY INTERVENTION
Authors: Yuichi Chikata, Hiroshi Iwata, Takehiro Funamizu, Shinichiro Doi, Hirohisa Endo, Hideki Wada, Ryo Naito, Hirokazu Konishi, Manabu Ogita, Yoshiteru Kato, Iwao Okai, Tomotaka Dohi, Takatoshi Kasai, Kikuo Isoda, Shinya Okazaki, Kazunori Shimada, Katsumi Miyauchi
Journal: Journal of the American College of Cardiology (2020)
Comparison of Carboplatin Plus Pemetrexed Followed by Maintenance Pemetrexed With Docetaxel Monotherapy in Elderly Patients With Advanced Nonsquamous Non–Small Cell Lung Cancer
Authors: Isamu Okamoto, Hiroshi Nokihara, Shogo Nomura, Seiji Niho, Shunichi Sugawara, Hidehito Horinouchi, Koichi Azuma, Yasuto Yoneshima, Haruyasu Murakami, Yukio Hosomi, Shinji Atagi, Tomohiro Ozaki, Atsushi Horiike, Yuka Fujita, Hiroaki Okamoto, Masahiko Ando, Nobuyuki Yamamoto, Yuichiro Ohe, Kazuhiko Nakagawa
Journal: JAMA Oncology (2020)

Few clinical trials have been specifically designed for elderly patients with advanced non-small cell lung cancer (NSCLC), and the anticipated increase in the number of such patients has prompted a search for new treatment options that provide a greater palliative benefit.To determine whether treatment with carboplatin plus pemetrexed followed by pemetrexed maintenance is noninferior compared with docetaxel monotherapy with regard to overall survival (OS) for elderly patients with advanced nonsquamous NSCLC.This open-label, multicenter, noninferiority phase 3 randomized clinical trial was conducted at 79 institutions in Japan. Cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and age of 75 years or older were enrolled between August 2013 and February 2017. Data were analyzed from November 2018 to February 2019.Patients were randomized to receive either docetaxel monotherapy (60 mg/m2) every 3 weeks or 4 cycles of carboplatin (area under the curve of 5) plus pemetrexed (500 mg/m2) administered every 3 weeks followed by maintenance therapy with the same dose of pemetrexed for 3 weeks.The primary end point was OS analyzed on an intention-to-treat basis with a noninferiority margin of 1.154 for the upper limit of the 95% CI of the hazard ratio (HR) estimated with a stratified Cox regression model.Of the 433 enrolled patients, 250 (57.7%) were male, and the median (range) age was 78 (75-88) years. The median OS was 15.5 months (95% CI, 13.6-18.4) in the docetaxel group (n = 217) and 18.7 months (95% CI, 16.0-21.9) in the carboplatin-pemetrexed group (n = 216), with a stratified HR for OS of 0.850 (95% CI, 0.684-1.056; P for noninferiority = .003). Progression-free survival was also longer in the carboplatin-pemetrexed group (unstratified HR, 0.739; 95% CI, 0.609-0.896). Compared with those in the docetaxel group, those in the carboplatin-pemetrexed had lower rates of leukopenia (60 of 214 [28.0%] vs 147 of 214 [68.7%]) and neutropenia (99 of 214 [46.3%] vs 184 of 214 [86.0%]) of grade 3 or 4 and of febrile neutropenia (9 of 214 [4.2%] vs 38 of 214 [17.8%]) and higher rates of thrombocytopenia (55 of 214 [25.7%] vs 3 of 214 [1.4%]) and anemia (63 of 214 [29.4%] vs 4 of 214 [1.9%]) of grade 3 or 4. Dose reductions were less frequent with carboplatin-pemetrexed.Carboplatin-pemetrexed treatment followed by pemetrexed maintenance is a valid option for first-line treatment of elderly patients with advanced nonsquamous NSCLC.University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000011460.
OUTCOMES OF ECHOCARDIOGRAPHY-DETECTED RHEUMATIC HEART DISEASE: VALIDATING A SIMPLIFIED SCORE IN SCREENING COHORTS FROM DIFFERENT COUNTRIES
Authors: Bruno Ramos Nascimento, Maria Carmo Nunes, Amy E. Sanyahumbi, Nigel Wilson, Elizabeth Tilton, Marc G.W. Rémond, Graeme P. Maguire, Antonio L. Ribeiro, Peter N. Kazembe, Craig A. Sable, Andrea Z. Beaton
Journal: Journal of the American College of Cardiology (2020)
Outcomes in patients (pts) with colorectal cancer (CRC) treated with oxaliplatin-based chemotherapy (OC) following prior oxaliplatin exposure.
Authors: Nishin Anil Bhadkamkar, Ibrahim Halil Sahin, Yehua Shen, Hesham Mohamed Hassabo, Bryan K. Kee, Manal Hassan, Chris R. Garrett
Journal: Journal of Clinical Oncology (2013)

500 Background: Pts frequently treated with OC in the adjuvant, perioperative, or first-line setting for CRC may be retreated with oxaliplatin at the time of relapse or progression; the efficacy of retreatment is not known. Methods: Under an IRB-approved protocol, the pharmacy records identified 1,166 pts who received OC for CRC at our institution from 1/1/2004-12/30/2009. Pts were categorized as having previously received OC initially for the indication of adjuvant (group A, n=29), unresectable metastatic disease (group B, n=75), or perioperative therapy for metastasectomy (group C, n =22). Results: Four RECIST responses (14%) were seen in group A (2 of these pts received cetuximab in combination), four responses in group B (5%), and no responses in group C. Retreatment with OC following initial oxaliplatin exposure was associated with a low radiographic and biochemical response rate and a short time to progression or withdrawal of OC (Table). Retreatment duration was limited by cumulative neurotoxicity and allergic reactions (data not presented). Significant activity was observed more frequently when a novel biologic agent was added to the pt's treatment. Conclusions: Retreatment with OC demonstrated minimal clinical efficacy and is limited by cumulative neurotoxicity and hypersensitivity reactions. [Table: see text]
Detection of trastuzumab (T) level in human serum using quartz crystal microbalance (QCM) piezo-immunosensors by immobilization of a HER2 mimotope-derived synthetic peptide and its potential application in breast cancer.
Authors: Mohammad Muhsin Chisti, Yuqin Shang, Alaa Muslimani, Pankaj R Singh, Ray Mernaugh, Ishmael A. Jaiyesimi, Xiangqun Zeng
Journal: Journal of Clinical Oncology (2012)

628 Background: Varied clinico-pathological response to monoclonal antibodies like T has been reported either due to presence of antibodies, rapid clearance or low density of target receptor/antigens. This demands need for an assay to monitor serum T therapeutic levels to ensure appropriate dosage. Enzyme-linked immunosorbent assay (ELISA) is still the most widely used technique to detect T level in human serum which is expensive and time consuming. For the first time, we established a platform to detect T level by using a small (&lt;2.2 kDa), inexpensive, highly stable HER2 mimotope-derived synthetic peptide immobilized on the surface of a gold quartz electrode. Methods: HER2 mimotope was used as a substitute for the HER2 receptor protein in QCM assays to detect T level. The validation samples were prepared from the standard T solution in 10% human serum at three concentrations (10, 20 and 40 ug/ml). The changes in frequencies (ΔF) of sera from 3 female patients , 61, 32 and 44 years old , with ER/PR positive, HER2/neu positive metastatic breast cancer were obtained by calculating the differences between frequency shifts in pre and post T infusion.T level was calculated by equation, (ΔF +1.0022) ÷ 0.9997 μg / ml. Results: We showed that assay sensitivity was dependent upon the amino acids used to tether and link the peptide to the sensor surface and the buffers used. QCM assay was capable of detecting T serum level as low as 0.038 nM (linear operating range of 0.038–0.859 nM). T levels of 3 patients were 43.34, 121.96 and 193.18 μg /ml corresponding to pre and post infusion ΔF of 3.33, 11.19 and 18.31 respectively. The time frame of assay was 20-30 minutes. These results were in concordance with previously published results using ELISA. Conclusions: For the first time, we have established a low cost, highly sensitive, fast, synthetic peptide based QCM assay which could be used as a basis for developing a new generation of affinity-based Immunosensor assays to monitor serum levels of T and other monoclonal antibodies, helping physicians to determine the clinical efficacy of these drugs and ensuring appropriate dosages.
THE EFFECT OF RENAL FUNCTION ON INCIDENCE OF CONGESTIVE HEART FAILURE: THE ANTIHYPERTENSIVE AND LIPID-LOWERING TREATMENT TO PREVENT HEART ATTACK TRIAL (ALLHAT) STUDY
Authors: Maedeh Khayyat Kholghi, Suzanne Oparil, Barry Davis, Larisa G. Tereshchenko
Journal: Journal of the American College of Cardiology (2020)
Systemic AAV9.LAMP2B injection reverses metabolic and physiologic multiorgan dysfunction in a murine model of Danon disease
Authors: Ana Maria Manso, Sherin I. Hashem, Bradley C. Nelson, Emily Gault, Angel Soto-Hermida, Elizza Villarruel, Michela Brambatti, Julius Bogomolovas, Paul J. Bushway, Chao Chen, Pavan Battiprolu, Annahita Keravala, Jonathan D. Schwartz, Gaurav Shah, Yusu Gu, Nancy D. Dalton, Kirk Hammond, Kirk Peterson, Paul Saftig, Eric D. Adler
Journal: Science Translational Medicine (2020)

AAV9.LAMP2B corrects metabolic and physiologic manifestations of a murine model of Danon disease.
ELEVATED LEFT VENTRICULAR CIRCUMFERENTIAL STRAIN IN WOMEN WITH CORONARY MICROVASCULAR DYSFUNCTION: A REPORT FROM THE WOMEN’S ISCHEMIA SYNDROME EVALUATION - CORONARY VASCULAR DYSFUNCTION STUDY
Authors: T. Jake Samuel, Balaji Tamarappoo, Omeed Elboudwarej, Louise Thomson, Haider Aldiwani, Janet Wei, Puja K. Mehta, Susan Cheng, Behzad Sharif, Ahmed AlBadri, Eileen Handberg, John Petersen, Carl J. Pepine, Michael D. Nelson, C. Noel Bairey-Merz
Journal: Journal of the American College of Cardiology (2020)