tbuckley/cabot-search huggingface dataset:
Meta-analysis of OS for pancreatic cancer patients receiving 5FU and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy.
Authors: Zev A. Wainberg, Kynan Feeney, Myung Ah Lee, Andres J. Muñoz Martín, Antonio Cubillo Gracián, Sara Lonardi, Baek-Yeol Ryoo, Annie Hung, Yong Lin, Johanna C. Bendell, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2019)

202 Background: Pancreatic cancer is the 3 rd most common cause of cancer-related death in US. After progression on first-line gemcitabine-based therapy, guidelines suggest that 5FU with nanoliposomal irinotecan/irinotecan is the preferred regimen. Oxaliplatin (OXA) is not endorsed as prominently, as conflicting results have emerged on the efficacy of 5FU/OXA. This large variability in efficacy outcomes may be due to the heterogeneity of patient performance status (PS) or other confounding factors. We performed a meta analysis in an attempt to estimate the median (m) OS of patients receiving 5FU/OXA-containing regiments after failing first-line treatment with gemcitabine-containing therapy. Methods: A systematic review of literature and existing meta analyses for second-line treatment of pancreatic cancer was performed. Selection inclusion criteria included: prior gemcitabine treatment, second-line treatment of locally advanced or metastatic pancreatic cancer, 5FU and OXA; exclusion criteria included: oral 5FU (S1), irinotecan, capecitabine/cisplatin, no ECOG disclosure. A Bayesian fixed effect meta analysis was performed for the mOS with PS as predictor. A non-informative prior was used to establish the relationship between mOS and PS. The posterior median of OS and 95% predictive interval (PI) were summarized. Results: Eleven studies (454 patients) met the selection criteria for analysis. Median OS for patients receiving second-line 5FU and OXA-based therapy with ECOG PS 0-1 was 6.2 months (95% PI 5.4, 7.1). Restricting to FOLFOX (6 studies, 258 patients), mOS was 6.3 months (95% PI, 5.4, 7.4). Median OS were comparable to those observed with nanoliposomal irinotecan (NAPOLI-1) where 90% patients had ECOG 0-1. Some of the most frequent ( &gt; 10%) grade 3-4 AEs for 5FU and OXA included neutropenia, thrombocytopenia, anemia, and fatigue, comparable to that reported with irinotecan-based therapy. Conclusions: This meta analysis suggests that after progression on a first-line gemcitabine containing regimen, 5FU and OXA-based therapy (eg. FOLFOX) may be a viable and acceptable treatment for patients with pancreatic cancer with good PS.
Abstract P025: Trimethylamine N-oxide Not Associated with Coronary Artery Calcium in Healthy, Young Adults with Normal Kidney Function: Coronary Artery Risk Development in Young Adults Study, 2000-2011
Authors: Katie A Meyer, Thomas Z Benton, Brian Bennett, David R Jacobs, Donald M Lloyd-Jones, Myron D Gross, Penny Gordon-Larsen, Steven H Zeisel
Journal: Circulation (2016)

Objective: Trimethylamine N-oxide (TMAO), a gut microbiota-dependent nutrient metabolite, has been implicated in the development of cardiovascular disease (CVD). TMAO is excreted in the urine and high levels may reflect poor kidney function, an independent risk factor for CVD. We tested the association between TMAO and coronary artery calcium (CAC) in a young, healthy sample of US adults with normal kidney function. Methods: Study participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter cohort of black and white Americans established in 1985/86 (baseline n=5,115; ages 18-30). CAC was measured at follow-up years 15, 20, and 25 with computed tomography (CT). Among a subsample of participants with no detectable CAC at year 15 who had complete CAC data (years 15, 20, 25) and covariate data (year 15) (n=746), we measured TMAO (uM) in year 15 stored plasma (-70 C) and defined incident CAC as having total Agatston units ≥ 0 across all arteries at year 20 or 25. TMAO was measured by using liquid chromatography mass spectrometry. Multivariable-adjusted logistic regression was used to estimate the 10-year incidence of CAC (% who developed any CAC) across quartiles of year 15 TMAO. Results: Among 746 participants without CAC at year 15, 184 developed CAC over the 10-year study period. TMAO was not associated with incident CAC in multivariable-adjusted logistic regression models, controlling for demographic, behavioral, and biologic covariates (see Table). Comparing quintiles 1 and 5 of TMAO, the multivariable-adjusted risk (%) of the cohort who developed CAC over the 10-year period was 26% (95% CI: 18%-36%) and 22% (16%-31%), respectively. Conclusion: In this population-based cohort of healthy middle-aged US adults with normal kidney function (99% eGFR≥60 ml/min/1.73 m2), TMAO was not associated with incident CAC over 10 years of follow-up. These findings do not support a role for TMAO in the progression of atherosclerosis among young (33-45 y) healthy individuals with normal kidney function.
Abstract MP028: Bi-directional Relationship Between Sleep and Sedentary Behavior in Adults Who Are Overweight and Obese
Authors: Christopher C Imes, Christopher E Kline, Bonny Rockette-Wagner, Lynn M Baniak, Dara D Mendez, Eileen R Chasens, Susan M Sereika, Lora E Burke
Journal: Circulation (2017)

Introduction: It is assumed that inadequate sleep is associated with sedentary behavior and that being active during the day improves sleep. Given the emergence of sedentary behavior as an independent risk factor for cardiovascular disease (CVD), a better understanding of this bi-directional relationship in adults who are obese is needed for developing CVD-risk reducing interventions. Hypotheses: Total sleep time (TST) is negatively associated with next day sedentary time (SED) and SED is negatively associated with that night’s TST in adults who are obese. Methods: We used objective baseline data from the EMPOWER Study, a 12-mo study of lapses during weight loss. We instructed subjects to wear accelerometers on the waist (ActiGraph GT3X) for 7 days and wrist (Actiwatch 2) for 14 days to assess daily activity and sleep, respectively. Subjects with ≥2 weekdays and 2 weekend days of overlapping data were included. SED was defined as &lt;150 counts/min. Linear mixed modeling was used to examine the associations between TST and SED; each directional relationship was examined separately. Covariates included sex, race, body mass index (BMI), age, and day of the week. Results: The majority of subjects (N=109) were white (82.6%), employed (92.6%), and female (89.0%) with mean (±SD) age of 50.6±10.6 years and BMI of 33.8±4.6 kg/m 2 . Mean daily TST and SED were 409.5±83.0 min and 638.8±132.2 min, respectively. Previous night’s TST independently predicted the next day’s SED (p&lt;.001) with each 3 min increase in TST being associated with a 1 min decrease in SED. SED did not predict that night’s TST. Weekends were associated with less SED (p&lt;.001) and greater TST (p&lt;.001; see Table). Conclusions: Sedentary behavior and decreased TST were prevalent in this sample of mostly middle-aged working women. Less TST was associated with greater SED and weekdays were associated with greater SED and less TST, highlighting how weekdays influences these behaviors. These findings point to a need for interventions to increase TST in an effort to reduce SED and CVD risk.
Global, regional, and national burden of multiple sclerosis 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Authors: Mitchell T Wallin, William J Culpepper, Emma Nichols, Zulfiqar A Bhutta, Tsegaye Tewelde Gebrehiwot, Simon I Hay, Ibrahim A Khalil, Kristopher J Krohn, Xiaofeng Liang, Mohsen Naghavi, Ali H Mokdad, Molly R Nixon, Robert C Reiner, Benn Sartorius, Mari Smith, Roman Topor-Madry, Andrea Werdecker, Theo Vos, Valery L. Feigin, Christopher J L Murray
Journal: The Lancet Neurology (2019)

Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level.
ALKBH5 Functions As an Oncogene in Acute Myeloid Leukemia
Authors: Chao Shen, Yue Sheng, Rui Su, Xiaolan Deng, Sean Robinson, Zhe Yin, Lei Dong, Huilin Huang, Hengyou Weng, Chenying Li, Zhijian Qian, Xi Jiang, Jianjun Chen
Journal: Blood (2018)
Omadacycline for Community-Acquired Bacterial Pneumonia
Authors: Roman Stets, Monica Popescu, Joven R. Gonong, Ismail Mitha, William Nseir, Andrzej Madej, Courtney Kirsch, Anita F. Das, Lynne Garrity-Ryan, Judith N. Steenbergen, Amy Manley, Paul B. Eckburg, Evan Tzanis, Paul C. McGovern, Evan Loh
Journal: New England Journal of Medicine (2019)

Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia.In a double-blind trial, we randomly assigned (in a 1:1 ratio) adults with community-acquired bacterial pneumonia (Pneumonia Severity Index risk class II, III, or IV) to receive omadacycline (100 mg intravenously every 12 hours for two doses, then 100 mg intravenously every 24 hours), or moxifloxacin (400 mg intravenously every 24 hours). A transition to oral omadacycline (300 mg every 24 hours) or moxifloxacin (400 mg every 24 hours), respectively, was allowed after 3 days; the total treatment duration was 7 to 14 days. The primary end point was early clinical response, defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours, without receipt of rescue antibacterial therapy. A secondary end point was investigator-assessed clinical response at a post-treatment evaluation 5 to 10 days after the last dose, with clinical response defined as resolution or improvement in signs or symptoms to the extent that further antibacterial therapy was unnecessary. A noninferiority margin of 10 percentage points was used.The intention-to-treat population included 386 patients in the omadacycline group and 388 patients in the moxifloxacin group. Omadacycline was noninferior to moxifloxacin for early clinical response (81.1% and 82.7%, respectively; difference, -1.6 percentage points; 95% confidence interval [CI], -7.1 to 3.8), and the rates of investigator-assessed clinical response at the post-treatment evaluation were 87.6% and 85.1%, respectively (difference, 2.5 percentage points; 95% CI, -2.4 to 7.4). Adverse events that emerged after treatment initiation were reported in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group; the most frequent events were gastrointestinal (10.2% and 18.0%, respectively), and the largest difference was for diarrhea (1.0% and 8.0%). Twelve deaths (8 in the omadacycline group and 4 in the moxifloxacin group) occurred during the trial.Omadacycline was noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia in adults. (Funded by Paratek Pharmaceuticals; OPTIC ClinicalTrials.gov number, NCT02531438 .).
Time to Progression Post-Induction Predicts Outcomes of Ixazomib Based Therapy for Relapsed/Refractory Myeloma: Real World Data from a Multi-Site Israeli Registry Study
Authors: Yael C Cohen, Hila Magen, Noa Lavi, Moshe E. Gatt, Evgeni Chubar, Natalia Kreiniz, Tamar Tadmor, Svetlana Trestman, Roy Vitkon, Ory Rouvio, Olga Shvetz, Adir Shaulov, Irit Avivi
Journal: Blood (2018)
Abstract 16285: The Benefits of a 6 Minute Walk Test on Exercise Confidence Are Not Sustained Long-Term in Chronic Heart Failure Patients
Authors: Francis Ha, Samia R Toukhsati, Abigail Sheed, Penelope Cropper, Louise Moncur, Isabella Freijah, David L Hare
Journal: Circulation (2017)

Introduction: Exercise confidence is a predictor of adherence to exercise. Completion of a single trial 6 minute walk test improves exercise confidence in chronic heart failure (CHF) patients, howe...
Prothrombin Complex Concentrate Is Safe and Effective for Achieving Hemostasis in the Setting of Urgent Surgery for Patients Treated with Direct Xa Inhibitors
Authors: Merav Barzilai, Ilya Kirgner, Arza Steimatzky, Dalit Salzer Gotler, Yulia Belnick, Irit Avivi, David Varon, Adi Shacham, Vered Yahalom, Sigal Nakav, Ethan Yussim, Gil Bahar, Uri Rozovski, Galia Spectre
Journal: Blood (2018)
Global Longitudinal Strain as a Predictor of First and Subsequent Arrhythmic Events in Remotely Monitored ICD Patients With Structural Heart Disease
Authors: Federico Guerra, Alessandro Malagoli, Daniele Contadini, Erika Baiocco, Alessio Menditto, Paolo Bonelli, Luca Rossi, Concetta Sticozzi, Alessia Zanni, Jianwen Cai, Poulami Maitra, Giovanni Q Villani, Alessandro Capucci
Journal: JACC. Cardiovascular imaging (2019)
Clinicopathological features and outcomes of fibrolamellar hepatocellular carcinoma.
Authors: Sakti Chakrabarti, Anuhya Kommalapati, Sri Harsha Tella, Brandon M. Huffman, Siddhartha Yadav, Irbaz Bin Riaz, Gaurav Goyal, Mitesh J. Borad, Amit Mahipal
Journal: Journal of Clinical Oncology (2019)

393 Background: Clinicopathological features and the outcomes of patients with fibrolamellar hepatocellular carcinoma (FLHCC) are not clearly defined. Methods: Data were collected by retrospective chart review on 42 patients with FLHCC treated between 1990 and 2017 at the Mayo Clinic. Clinicopathological characteristics, response to treatment, recurrence pattern and survival were analyzed. Results: Of 42 patients (17 males and 25 females; median age at diagnosis 22 years, range 15 to 39), 10 patients (23%) had stage I disease and 32 patients (77%) had stage II to IVB disease. All 10 patients with stage I disease and 21 of 32 patients with stage II-IVB disease underwent resection at presentation. In stage I patient group, 6 patients experienced recurrence with a median time to recurrence of 30.5 months, resulting in a 5 year overall survival (OS) of 86%. Patients with stage II to IVB disease who underwent resection (n=21) at presentation had a median OS of 32.5 months and 5 year OS of 44%. In the upfront surgery group, 71% of the patients experienced recurrent disease. The median OS of patients with unresectable disease (n=11) was 10 months. Systemic therapy was given to 17 patients which included sorafenib, FOLFOX (5-fluorouracil/leucovorin and oxaliplatin), gemcitabine plus oxaliplatin, single agent adriamycin or gemcitabine, capecitabine plus interferon alfa, gemcitabine plus cisplatin, cisplatin plus adriamycin and nivolumab . Sorafenib was given to 9 patients and 4 patients achieved stable disease (SD) with duration ranging from 5 months to 5 years. One programmed cell death receptor positive-1 patient had a durable complete response after 2 months of therapy with nivolumab. Conclusions: In FLHCC, surgical resection was associated with prolonged OS. However, recurrences were common after the surgery. Limited benefit was derived from the systemic treatment. In rare cases, therapy with a checkpoint inhibitor may provide a viable treatment option.
Abstract 13801: Tachycardia is Associated With Lower and Not Higher Left Atrial and Ventricular Filling Pressures
Authors: Mehdi Rambod, Robert Lobel, Daniel Lustgarten, Markus Meyer
Journal: Circulation (2017)

Background: It is a common concern that higher heart rates (HR) reduce coronary flow due to a shortened diastolic interval and increase left atrial and ventricular filling pressures. Translational ...
Abstract 16867: Decreased Contractile Response of Peripheral Arterioles to Serotonin After CPB in Diabetic Patients
Authors: Sharif Sabe, Jun Feng, Yuhong Liu, Laura Schrimgeour, Afshin Ehsan, Frank Sellke
Journal: Circulation (2017)

Introduction and Hypothesis: Regulation of coronary vasomotor tone by serotonin is significantly changed after cardioplegic arrest and reperfusion. The current study investigated whether cardiopulmonary bypass (CPB) may also affect peripheral arteriolar response to serotonin in patients with or without diabetes. Methods and Results: Human peripheral microvessels (90-180 μm in diameter) were dissected from harvested skeletal muscle tissues from diabetic (DM) and non-diabetic (ND) patients before and after CPB and cardiac surgery (n = 6/group). In vitro contractile response to serotonin was assessed by videomicroscopy in the presence or absence of serotonin alone (10-9-10-5M) or combined with the selective serotonin 1B receptor (5-HT1B) antagonist, SB224289 (10-6M). 5-HT1A/1B protein expression of the skeletal muscle was measured by Western-blot and immunohistochemistry. There were no significant differences in the contractile response of peripheral arterioles to serotonin (10-5M) pre-CPB between DM and ND ...
Abstract 15539: A Novel Compound Tanshinol Prolongs Cardiac Allograft Survival Induced by Rapamycin
Authors: Zhen H Dai, Anyu Zhou
Journal: Circulation (2015)

Introduction: Cardiac transplantation provides a cure for end-stage heart diseases. Achieving long-term cardiac allograft survival without continuously global immunosuppression is a highly desirable goal because long-term immunosuppression causes serious side effects. This study is to induce long-term cardiac allograft survival without long-term conventional immunosuppression via treatments with Tanshinol, a major compound derived from traditional Chinese medicine, Danshen, which has been shown to improve tissue microcirculation and reduce inflammation. Hypothesis: Tanshinol alone, or in combination with mTOR inhibitor rapamycin, prolongs cardiac allograft survival. Methods: In this study, C57BL/6 mice were transplanted with a Balb/C heart and treated with Tanshinol (5mg/kg/day i.p. on days 0, 2, 4, 6, 8, 10 and 14) and/or rapamycin (1 mg/kg/day for 3 weeks). In vivo CD4+FoxP3+ Treg numbers from draining LNs and graft-infiltrating cells were quantified by FACS 3 weeks after transplantation. Results: We found that Tanshinol alone did not extend cardiac allograft survival compared to control group (MST = 8 vs. 7 days, n=7-8) while rapamycin delayed the rejection significantly (MST = 28 vs. 7 days, n=6-7, P&lt;0.05). Interestingly, treatments with both Tanshinol and rapamycin further prolonged allograft survival (MST = 63 versus 28 days, n=7-8, P&lt;0.05). Moreover, Tanshinol did not increase CD4+FoxP3+ Treg numbers in draining LN (DLN) (2.5±0.4 vs 2.2±0.3, x10000, P&gt;0.05) while rapamycin did so (3.9±0.5 vs 2.2±0.3, P&lt;0.05). In contrast, Tanshinol increased Treg number in grafts (13.5±0.9 vs 7.4±0.6, P&lt;0.05) while rapamycin did not (8.1±0.7 vs 7.4±0.6, P&gt;0.05). Tanshinol plus rapamycin augmented Treg numbers in both DLNs and grafts compared to untreated group. Thus, our studies reveal that Tanshinol and rapamycin synergistically prolong cardiac allograft survival without long-term immunosuppression by promoting Treg generation and migration to LNs and allografts. Conclusion: Our data, for the first time, demonstrate that Tanshinol synergizes with rapamycin to prolong cardiac allograft survival via enhancing both generation and migration of Tregs.
Alternative dosing of omalizumab as an adjunct therapy during multiallergen oral immunotherapy in food allergic patients
Authors: Sayantani B. Sindher, Andrew J. Long, Natasha Purington, Divya Kumar, Alexandra Scheiber, Katherine O'Laughlin, Margaret Woch, Tiffany Tan, R. Sharon Chinthrajah, Stacey Skura Zedeck, Maria I. Garcia Lloret, Kari C. Nadeau
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 20859: A Novel Method of Rapidly Engineering Multi-Level Cell Sheet Derived Human Vessels Results in Functional and Patent Bypass Conduits
Authors: Daniel von Bornstädt, Michael J Paulsen, Andrew B Goldstone, Anahita Eskandari, Masashi Kawamura, Vi Nha Truong, Kevin J Jaatinen, Amanda N Steele, Akshara Thakore, Justin Farry, Ioannis Karakikes, Y Joseph Woo
Journal: Circulation (2017)

Objective: Cell-sheet derived vessels have been successfully tested as bypass grafts with proven patency and vasoreactivity in both animal models and patients. However, their construction is time c...
Abstract 13735: External Defibrillation During MRI: Feasibility and Safety
Authors: Vladimir Shusterman, Denice Hodgson-Zingman, Daniel Thedens, Xiaodong Zhu, Stacy Hoffman, Jessica Sieren, Gina M Morgan, Anthony Faranesh, Rajiv Ramasawmy, Adrienne Campbell-Washburn, Barry London
Journal: Circulation (2017)

Introduction: Establishing the safety of external defibrillation inside the MRI magnet is crucial for the emerging field of MRI-guided EP procedures. Objective: To examine the feasibility and safet...
Prospective clinical study using expressed sequencing variants on stool-derived eukaryotic RNA transcripts (seRNA) for colorectal cancer screening.
Authors: Erica Kay Barnell, Yiming Kang, Katie Marie Campbell, Andrew Ross Barnell, Kimberly Ray Kruse, Elizabeth Marie Wurtzler
Journal: Journal of Clinical Oncology (2019)

516 Background: Colorectal cancer (CRC) is the second leading cause of cancer related deaths in the United States. The high mortality rate is largely attributable to the high frequency of late-stage diagnoses, caused by low patient compliance with screening guidelines. A reliable and noninvasive screening alternative is needed for the 40 million noncompliant patients. The development of a novel nucleic acid extraction method to isolate stool-derived eukaryotic RNA (seRNA) permits reliable and noninvasive evaluation of biomarkers derived from the gastrointestinal (GI) epithelium. This method enables sequencing-based tools for the detection of patients with CRC and adenomas. Methods: Stool samples were obtained from 96 individuals prior to undergoing a screening colonoscopy. Fecal immunochemical tests (FITs) were obtained for each sample. RNA isolates underwent custom library preparation, next-generation sequencing, and somatic variant identification. An seRNA assay assessed the probability of CRC risk using results from the FIT, mutational burden of transcripts implicated in precancerous change (APC), and mutational burden of transcripts associated with malignant transformation (KRAS / TP53). Results: When compared to results from a colonoscopy and subsequent biopsy, the seRNA risk assessment attained a 100% sensitivity for CRC, a 71.4% sensitivity for advanced adenomas, and an 88.5% specificity for no neoplastic findings. Conclusions: A single-center, IRB-approved, prospective and blinded clinical study is being conducted in 450 patients to further develop this seRNA assay. Supplemental data will include expression from 408 seRNA transcripts. Preliminary analysis described herein indicates this assay could be the most sensitive noninvasive screening test for the detection of CRC and adenomas. [Table: see text]