tbuckley/cabot-search huggingface dataset:
Abstract 9151: Presentation, Management, and Outcomes of 25,748 Acute Coronary Syndrome Admissions in Kerala, India: Results from the Kerala ACS Registry
Authors: P.P. Mohanan, Rony Mathew, S. Harikrishnan, M.N. Krishan, Geevar Zachriah, Jhony Joseph, Mark D Huffman, Koshy Eapen, Mathew Abraham, Jaideep Menon, P. Manoj, Sonny Jacob, Dorairaj Prabhakaran
Journal: Circulation (2011)

Introduction: There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. The Cardiological Society of India - Kerala Chapter developed a prospective ACS registry to address this gap. Hypothesis: We hypothesized that patients presenting with STEMI would be younger, have lower education levels, be more likely to undergo PCI, and be more likely to die during index hospitalization and 30-day follow-up than patients with non-STEMI and unstable angina. Methods: We prospectively collected data on 25,748 consecutive ACS admissions from 2007-2009 in 125 hospitals in Kerala, India. Results: The Table describes the differences among STEMI (37%), non-STEMI (31%), and unstable angina (32%) patient presentation, management, and outcomes. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types, but unstable angina admissions were more likely to be men and have a prior history of diabetes and MI than other ACS types. In-hospital aspirin and clopidogrel rates were high (&gt;90%) and similar across ACS types, whereas in-hospital heparin and beta-blocker rates were lower overall (&lt;75%) and more commonly used in non-STEMI and unstable angina admissions compared with STEMI admissions. Angiography rates were similar across the 3 groups, and PCI rates were slightly higher in STEMI (13%) compared with non-STEMI (12%) and unstable angina (11%). Discharge medication rates were variable and generally suboptimal (&lt;80%). In-hospital and 30-day death rates were highest for STEMI admissions (8.2% and 14.6%, respectively). Presentation, management, and outcomes differ from data from a US-based cohort such as the NCDR ACTION Registry-Get-With-The-Guidelines. Conclusions: In conclusion, these data represent the largest ACS registry in India to date and will serve as the baseline for future ACS quality improvement efforts in Kerala.
A phase II trial of second-line axitinib following prior antiangiogenic therapy in advanced hepatocellular carcinoma (HCC).
Authors: Mairead Geraldine McNamara, Anne M Horgan, Alex Aspinall, Eric Xueyu Chen, Kelly Burak, Neesha C. Dhani, Jennifer Petronis, Mehrdad Sinaei, Tae Kyoung Kim, Patrik Rogalla, Oliver F. Bathe, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2013)

314 Background: Second-line options in treatment of HCC are limited. Axitinib is a multi-targeted tyrosine kinase inhibitor (TKI) of VEGFRs 1, 2, and 3, PDGFR and c-KIT that warrants exploration in HCC. Methods: This is an open-label, single-arm, two-stage phase II trial of axitinib in advanced HCC. Eligible patients (pts) are Child-Pugh A/B7, with measurable progressive disease after TKIs/antiangiogenic drugs. Axitinib starts at 5 mg bid orally, titrated to 10 mg bid as tolerated. Treatment continues to progression (PD) or intolerable toxicity. Primary endpoint is response defined by reduction in size by RECIST 1.1 on CT scan at 16 wks, secondary endpoints to compare response by RECIST 1.1 to Choi criteria and modified RECIST, explore dynamic imaging models, feasibility, safety, PFS and overall survival. Results: We present results of 15 (of 29) pts enrolled from 01/11 - 09/12. Median age; 62y (range 18-78) with ECOG PS 0 (5 pts), 1 (10 pts) with prior therapy of Temsirolimus/Bevacizumab (2 pts), sorafenib (13 pts). A planned safety/futility interim analysis was passed. Most common axitinib-related AEs were hypertension (HTN) (60%), hand-foot skin reaction (HFSR) (60%), diarrhea (60%), fatigue (50%). Most common axitinib-related grade 3 (G3) AEs were HTN (20%) and diarrhea (20%). There were no G3 HFSR. There was 1 G4 hyperbilirubinaemia. 60% of pts had dose interruptions due to AEs; most common reasons included fatigue (20%), HTN (10%), and HFSR (10%). 20% required dose reductions, 14% of pts tolerated dose escalation above 5 mg bid. As of 09/12, 8 pts remain on study, 7 pts discontinued (4pts: PD, 3pts: AEs). Med duration of treatment; 4.0 mo (range 6 d - 15.5 mo). Out of 9 evaluable for response, there was 1 confirmed PR per RECIST 1.1; 3 other pts had tumor reduction; 10%, 22%, 23%, 2 PR by Choi criteria and none by modified RECIST. Early on-treatment perfusion changes were noted on functional imaging. Of the 9 pts with evaluable AFP response, 3 (33%) had &gt;50% decrease from baseline. 11 pts are still alive, 4 pts are deceased secondary to PD. Conclusions: Axitinib is tolerated and has shown preliminary efficacy in this VEGF pretreated HCC pt population.This is early analysis and updated data will be presented. Clinical trial information: NCT01334112.
Community-level evidence for SARS-CoV-2 vaccine protection of unvaccinated individuals
Authors: Oren Milman, Idan Yelin, Noga Aharony, Rachel Katz, Esma Herzel, Amir Ben-Tov, Jacob Kuint, Sivan Gazit, Gabriel Chodick, Tal Patalon, Roy Kishony
Journal: Nature Medicine (2021)

Mass vaccination has the potential to curb the current COVID-19 pandemic by protecting individuals who have been vaccinated against the disease and possibly lowering the likelihood of transmission to individuals who have not been vaccinated. The high effectiveness of the widely administered BNT162b vaccine from Pfizer-BioNTech in preventing not only the disease but also infection with SARS-CoV-2 suggests a potential for a population-level effect, which is critical for disease eradication. However, this putative effect is difficult to observe, especially in light of highly fluctuating spatiotemporal epidemic dynamics. Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are associated with a substantial later decline in infections among a cohort of individuals aged under 16 years, who are unvaccinated. On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold. These results provide observational evidence that vaccination not only protects individuals who have been vaccinated but also provides cross-protection to unvaccinated individuals in the community.
Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial
Authors: Axel Bauer, Michael Schreinlechner, Nikolay Sappler, Theresa Dolejsi, Herbert Tilg, Benedikt A Aulinger, Günter Weiss, Rosa Bellmann-Weiler, Christian Adolf, Dominik Wolf, Markus Pirklbauer, Ivo Graziadei, Hannes Gänzer, Christian von Bary, Andreas E May, Ewald Wöll, Wolfgang von Scheidt, Tienush Rassaf, Daniel Duerschmied, Christoph Brenner, Stefan Kääb, Bernhard Metzler, Michael Joannidis, Hans-Ulrich Kain, Norbert Kaiser, Robert Schwinger, Bernhard Witzenbichler, Hannes Alber, Florian Straube, Niels Hartmann, Stephan Achenbach, Michael von Bergwelt-Baildon, Lukas von Stülpnagel, Sebastian Schoenherr, Lukas Forer, Sabine Embacher-Aichhorn, Ulrich Mansmann, Konstantinos D Rizas, Steffen Massberg, Marcin Bantkowiak, Gabriele Baur, Monika Baylacher, Marcel Beaucamp, Manuel Berger, Lisa Besch, Stefan Brunner, Stephan Budweiser, Heiko Bugger, Raffaele Coletti, Uwe Dorwarth, Jozsef Egresits, Elodie Eiffener, Christian Faul, Armin Finkenstedt, Konstantinos Gatos, Nadine Gauchel, Frank Gindele, Wilhelm Grander, Markus Gunschl, Frank Hartig, Moritz Hecht, Tobias Heer, Lukas Heger, Marcus Hentrich, Lena Horvath, Dritan Keta, Stefan Kiechl, Rudolf Kirchmaier, Andreas Klein, Mathias Klemm, Ewald Kolesnik, Andreas König, Hans Christian Kossmann, Jana Kropacek, Lukas Lanser, Achim Lother, Anja Löw, Amir-Abbas Mahabadi, Stefan Malleier, Gert Mayer, Christoph Müller, Dirk Müller-Wieland, Bernhard Nagel, Hannes Neuwirt, Christoph Olivier, Thomas Raunegger, Martin Reindl, Sebastian Reinstadler, Lisa Riesinger, Michael Schäffner, Johannes Schier, Julia Schock, Peter Schönherr, Martina Schulz, Thomas Schütz, Johannes Schwarz, Johannes Siebermair, Marcus Siry, Anna Spaur, Wolfgang Sturm, Kristin Tessadri, Fabian Theurl, Markus Theurl, Liz Thommes, Christina Tiller, Michael Toifl, Matthias Totzeck, Hedda von zur Mühlen, Nadine Vonderlin, Reza Wakili, Clemens Wendtner, Felix Wenner, Daniela Wimmert-Roidl, August Zabernigg
Journal: The Lancet Respiratory Medicine (2021)
Comparative effectiveness of combination first-line therapies for metastatic renal cell carcinoma (mRCC).
Authors: Rebecca C. Shay, Andrew Nicklawsky, Elaine Tat Lam
Journal: Journal of Clinical Oncology (2021)

e16549 Background: Numerous immunotherapy (IO) and vascular endothelial growth factor receptor inhibitors (VEGFI) options are approved for first-line (1L) treatment of mRCC. We performed a systematic review and meta-analysis to compare the oncologic outcomes and adverse events of these therapies. Methods: We searched databases for randomized controlled trials (RCT) evaluating agents that are currently FDA-approved or on the NCCN compendium for 1L mRCC, with sunitinib (S) as a comparator. Primary outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 and 4 (G3/G4) adverse events (AEs). We attempted network meta-analysis (NMA) to estimate relative effects of the comparative treatments. Survival outcomes were summarized using hazard ratios (HR). In the case that the HR was not reported but a Kaplan-Meier curve was available, the curve was digitized using Engauge Digitizer software. A frequentist fixed-effects NMA model was applied to each outcome. Results: 798 articles were identified, of which 47 were eligible for full text screening, and 8 were included for evidence synthesis. Eight RCTs recruiting a total of 5,565 pts with advanced or metastatic treatment-naïve RCC were included. The summary of all included studies is reported in Table 1. Ordered from the most to least effective, treatments with greatest mOS benefit include Nivolumab plus Cabozantinib (NC), Pembrolizumab plus Axitinib (PA), and Nivolumab plus Ipilimumab (NI); treatments with greatest mPFS benefit include Cabozantinib (C), NC, and Avelumab plus Axitinib (AA); treatments with the highest ORR include C, NC, and AA. Ordered from least to most toxic, treatments with G3/G4 AEs less frequent than sunitinib include Pazopanib (P), NI, and AA. Conclusions: OS generally favored IO-IO or IO-VEGFI combinations, while PFS and ORR favored single agent C or IO-VEGFI. The lowest risks of G3/G4 AE were seen with P or IO-IO. IO-VEGFI combinations had similar risks for G3/G4 AE. Longer real-world follow-up is needed. We recognize the limitations of cross-trial comparisons, but sought a summative view of the current data.[Table: see text]
Correction: Long-Term Exposure to Ambient PM2.5 and Increased Risk of Chronic Kidney Disease Prevalence in China
Journal: Journal of the American Society of Nephrology (2021)

Guoxing Li, Jing Huang, Jinwei Wang, Minghui Zhao, Yang Liu, Xinbiao Guo, Shaowei Wu, Luxia Zhang: Long-Term Exposure to Ambient PM2.5 and Increased Risk of Chronic Kidney Disease Prevalence in China. J Am Soc Nephrol 32: 448-458, 2021; doi: <https://doi.org/10.1681/ASN.2020040517>. In Table 2, the
Abstract 13443: Influence of Depression on Self-Care Behaviors in Older Adults With Multiple Chronic Conditions: A Multivariate Analysis
Authors: Paolo Lovino, Ercole Vellone, Maddalena De Maria, Silvia Lorini, Davide Ausili, Maria Matarese, Barbara J Riegel
Journal: Circulation (2019)

Introduction: Multiple chronic conditions (MCC) are highly prevalent in cardiac patients. People with MCC experience depressive symptoms more frequently than the general population. Self-care has b...
EMBR-24. YB1 IS CRITICAL FOR MEDULLOBLASTOMA TUMOR MAINTENANCE AND DNA REPAIR FOLLOWING THERAPEUTIC INTERVENTION
Authors: Leon McSwain, Anna Kenney, Victor Chen, Tiffany Huang
Journal: Neuro-Oncology (2021)

Abstract Medulloblastoma (MB) is the most common pediatric central nervous system malignancy. Although the current standard of care leads to ~70% patient survival, the therapies are highly toxic, leading to life-long side effects, and recurrence due to therapeutic resistance is fatal. We sought to investigate mediators of radiation response in mouse models for the Sonic hedgehog (SHH) subgroup MB as well as human cell lines. We previously identified Y-box binding protein 1 (YB1) as a downstream effector of YAP-mediated MB radiation resistance. YB1 is a crucial, yet understudied, protein highly expressed across all 4 subgroups of MB. Through its DNA- and RNA-binding cold shock domain, YB1 mediates both transcriptional and translational changes important for tumor maintenance and therapeutic response. We show that following ionizing radiation, YB1 mediates DNA repair through PARP and that PARP inhibition abrogates YB1-mediated DNA repair in cells overexpressing YB1. Additionally, through its inhibitory effects on p53, YB1 is capable of mediating anti-apoptotic effects in response to genotoxic insult. By targeting YB1 with short hairpin RNA, we show that cells are more amenable to ionizing radiation induced double strand breaks. Additionally, we utilize RNA binding protein immunoprecipitation sequencing to investigate post transcriptional regulation of RNAs bound by YB1. We show that YB1 binds numerous transcripts critical for the identity of early cerebellar progenitor cells, the putative cell of origin for SHH subgroup tumors, in addition to transcripts important for cell cycling and migration.
Abstract 14867: Pulmonary Venous and Arterial Remodeling in Experimental Group 2 Pulmonary Hypertension
Authors: Michael S Sabbah, Ahmed U Fayyaz, Leigh G Griffiths, William D Edwards, Surendra Dasari, Barry A Borlaug, Margaret M Redfield
Journal: Circulation (2019)

Introduction: Left heart disease (LHD) leads to pulmonary venous hypertension (PVH) and isolated post-capillary (IpcPH) or combined post-capillary and pre-capillary (CpcPH) pulmonary hypertension (...
Predictors of lymph node metastasis in T1 colorectal cancer in young patients: Results from a national cancer registry.
Authors: Jameel Kenneth Singh, Daryl Ramai, Peter Bhandari, Tarik Kani, Mohamed Barakat MD, Waqqas Tai, Saurabh Chandan, Antonio Facciorusso
Journal: Journal of Clinical Oncology (2021)

e15590 Background: The incidence of colorectal cancer in young adults ( &lt; 44 years) is on the rise. Identifying young patients at risk of regional lymph node metastasis (LNM) is crucial for long-term survival. Prior studies have examined rates of LMN in average risk patients. The objective of this study is to fill the knowledge gap by examining predictors of LMN in young patients using a national cancer registry. Methods: Patients diagnosed with T1 colorectal cancer were identified in the Surveillance, Epidemiology, and End Results register 2000-2017. Potential predictors of LNM and its impact on cancer-specific survival were assessed in logistic and Cox regression with and without multivariable adjustment. Results: In total, 692 patients with T1 colorectal cancer were identified. Most tumors occurred in White race (77.7%), between 40-44 years of age (49.4%), grade III tumor differentiation (59.8%), 1 to 1.9 cm in size (32.2%), and were left sided tumors (61.1%). The overall LNM rate was 22.5 % (n = 149). Using multivariate analysis, LMN was associated with tumor grade IV (undifferentiated) (odds ratio (OR) 2.94, CL: 1.06-8.12; p = 0.038), and increasing tumor size (1 cm – 1.9 cm: OR 2.92, CL: 1.71-4.97, p &lt; 0.001; 2.0 cm – 2.9 cm: OR 2.00, CI: 1.05-3.77, p = 0.034; and ≥ 3.0 cm: OR 2.68, CI: 1.43-5.01, p = 0.002). Five-year cancer-specific survival for patients with LNM was 91% and for patients without LNM 98%. Adjusted cox proportion models showed that LMN was associated with four times higher rate of mortality (hazard ratio (HR) 4.43, CI: 1.27-15.52, p = 0.020). Conclusions: In conclusion, the overall LNM rate is approximately 22% for T1 CRC in young patients (less than 45 years). Tumor size and tumor grade are significant predictors for LNM in patients with T1 CRC cancer. Moreover, positive lymph node involvement is a significant prognostic factor for cancer specific survival. Thus, careful preoperative assessment of lymph node status is essential in clinical decision making, to achieve better long-term outcomes
Neurotrophins in the brain of C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice with B16/F10 melanoma growing with comorbid pathology.
Authors: Elena M. Frantsiyants, Irina V. Kaplieva, Valeria A. Bandovkina, Ekaterina I. Surikova, Irina V. Neskubina, Lidia K. Trepitaki, Natalia D. Cheryarina, Ludmila A. Nemashkalova, Natalia S. Lesovaya, Yuriy V. Przhedetskiy, Viktoria Yu. Przhedetskaya, Viktoria V. Pozdnyakova, Natalia A. Zakharova, Olga Khokhlova, Oleg I. Kit, Alla I. Shikhlyarova, Galina V. Zhukova
Journal: Journal of Clinical Oncology (2021)

e21557 Background: 10% of cancer patients have comorbidities accompanied by chronic pain. Neurotrophins and fibrinolytic system are involved in carcinogenesis and pain pathogenesis. The purpose of the study was to measure levels of neurotrophins in white matter of the brain of urokinase-deficient (uPA–) mice with B16/F10 melanoma growing in presence of chronic neuropathic pain (CNP). Methods: The study included female mice С57ВL/6 (normal genome uPA+, n = 40) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu (urokinase gene-knockout uPA–, n = 28) with B16/F10 melanoma (M) implanted subcutaneously 2 weeks after bilateral sciatic nerve ligation (CNP model). Intact mice (I) were controls. Levels of brain-derived neurotrophic factor BDNF, nerve growth factor NGF-β and neurotrophins 3 and 4 (NT3, NT4) were measured by ELISA in white matter of the brain after 3 weeks of tumor growth in presence of CNP. Results: Tumor volume in (uPA–) females by week 3 of carcinogenesis was 0.04 cm 3 , which was 70 times smaller than in (uPA+) females. Tumor volume in (uPA–) females with CNP was 5.76 cm 3 , which was 144 times larger than in (uPA–) females without CNP, and in (uPA+) females – 2.5 cm 3 . The brain of I (uPA–) showed higher levels of NT3 (by 1.3 times, p &lt; 0.05), NT4 (by 2.6 times) and NGF-β (by 1.9 times, p &lt; 0.05) and lower BDNF (by 1.7 times, p &lt; 0.05), compared to I (uPA+). Both strains of mice with M or CNP demonstrated decreased levels of NGF-β, more pronounced in animals with a combination of these factors. (uPA–) females with CNP+M showed a decrease of NT3 and BDNF by 2 times, with NGF-β 2.2 times higher than in (uPA+) mice. Conclusions: The study revealed underlying differences in levels of neurotrophins in the brain of (uPA–) females which could contribute to the creation of conditions for the inhibition of tumor growth. Changes in the levels of NGF-β in mice with melanoma or CNP were nonspecific. Changes in the BDNF, NT3 and NGF-β balance in the brain of (uPA–) mice may be part of the mechanism of greater stimulation of melanoma growth under the influence of CNP.
Analysis of correlations between driver mutations and biomarkers with response to immunotherapy in patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Jiang Yio, Brian Wolf, Amber Yang, Ashrei Y. Bayewitz, Yiqing Xu
Journal: Journal of Clinical Oncology (2021)

e21022 Background: Next-generation sequencing (NGS) performs genomic profiling on tumor tissue and provides information on mutations on 300+ selected genes. While driver mutations have targeted therapy options, apt therapies for passenger mutations are not clearly defined. The level of PD-L1 expression and the total mutation burden (TMB) score for NSCLC have independent predictive values in response to check-point inhibition immunotherapy. Using NGS data, we aimed to evaluate the correlations of driver mutations and other biomarkers with immunotherapy response. Methods: We performed a retrospective analysis on the NGS results for NSCLC patients treated between November 2011 and February 2018. Patients were identified from the Foundation Medicine Company database and were linked to records at our cancer center. Patients’ demographics and treatment data were assessed. Results: 99 NSCLC patients (44 males and 55 females) were included with a median age of 65 (range 32-89). Races included Asian (n=42), Caucasian (n= 40), African American (n=8), and Hispanic (n=7). 49 patients possessed driver mutations, which were EGFR (n=22), ALK (n=5), RET (n=5), ROS (n=2), BRAF (n=5), MET amplification (n=5), BRCA 1 or 2 (n=4), and NTRK (n=2); 3 patients had both a driver and a non-driver mutation. In the entire cohort, 40 patients (58 total, 69%) had PD-L1 tumor proportion score (TPS) &gt; 0% and 31 (53%) had TPS ≥10%. 30 patients (48 total, 63%) had TMB &lt;10 and 18 (37%) had TMB ≥10. Patients with driver mutations had a lower probability of high TMB (p=0.007), but no difference in PD-L1 expression (p=0.61). PD-L1 TPS score had no correlation with TMB high or low scores (Table). In patients with driver mutations, other mutations were detected by NGS. In EGFR+ patients, the most common additional mutations were TP53 and CDKN2A/B. 23 patients received immunotherapy; the response rate in non-mutation carriers was 45.4% (5/11). Among the 7 patients with an EGFR mutation, 4 had PD-L1 TPS ≥30% and none had TMB ≥10; based on RECIST 1.1, stable disease (SD) was the best response in 2 patients. One patient with a BRAF mutation and another patient with an ALK mutation had partial responses (PR); both had TMB ≥ 10. Conclusions: NGS provides additional information in NSCLC patients with driver mutations. In patients with driver mutations, while PD-L1 expression may not be associated with response to immunotherapy, a high TMB level may be a predictive biomarker, which warrants further study.[Table: see text]