tbuckley/cabot-search huggingface dataset:
Adjuvant treatment of early-stage HER2+ elderly breast cancer patients: A retrospective, multicenter French study.
Authors: Philippe Barthelemy, Karine Bassot, Florence Joly, Isabelle Ray Coquard, Gilles Freyer, Patrick Regis Dufour, France Campos, Jean Emmanuel Kurtz
Journal: Journal of Clinical Oncology (2012)

636 Background: Trastuzumab (T) is the standard of care for the adjuvant treatment of early stage, HER2+ breast cancer (BC). However, few data are available for elderly HER2+ breast cancer patients in this setting. In this current study, the patterns of care for elderly HER2+ early stage BC in 7 French cancer centres was evaluated. Methods: Medical records of all consecutive early stage HER2+ BC patients over 70 years old treated between 2006 and 2011 among participating centres were retrospectively reviewed. Specific factors such as age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics, follow-up and cardiotoxicity data were analysed. Results: One hundred and two patients were identified, median age 75.4 (range 70-95). Elderly patients presented mostly (57%) large tumors (pT ≥2), and positive lymph node involvement (n=61). Trastuzumab-based adjuvant treatment was administered in 62% of patients (n=63). 54% of patients (n=55) received adjuvant chemotherapy whereas five patients received neoadjuvant chemotherapy. Chemotherapy without T was administered in 2 additional patients. Anthracyclines (A)-Taxanes (Ta) combination-based chemotherapy was given in 27% of patients (n=16), whereas 38% received a Ta-based chemotherapy (n=23), 35% (n=19) an A-based chemotherapy. Five patients received single-agent T. Treatment delays for T were required in 37% of patients (n=23) among whom 15 and 8 permanently or temporarily stopped T, respectively. The most frequent reason for interrupting or delaying therapy was cardiotoxicity (n=12) as well as patients refusal (n=7). A ≥ 10% decrease in LVEF was observed in 18/63 (29%) of patients, among whom T was stopped in 12. After a median 33 months follow-up, the median progression-free survival was not reached in patients receiving T-based therapy. The 2 and 3-year PFS rate were 94 and 89.5%, respectively. Conclusions: In routine practice only 62% of elderly early stage HER2+ BC patients are treated with a neoadjuvant or adjuvant T-based regimen. However, less than 50% of all patients completed their therapy. A-based chemotherapy was administered in around 60% of treated patients, and could explain cardiotoxicity in this setting.
Routine detection of EGFR gene mutations in lung carcinomas: A 2-year single-center experience.
Authors: Audrey Vallee, Christine Sagan, Anne-Gaelle Le Loupp, Sandrine Theoleyre, Thomas Dejoie, Sandrine Hiret, Marc G. Denis
Journal: Journal of Clinical Oncology (2012)

e21117 Background: Activating mutations in the tyrosine kinase domain of the EGFR gene in lung carcinoma has been associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice to predict patient response. We have analyzed the results of the tests we performed during years 2010 and 2011. Methods: DNA was extracted from formalin-fixed paraffin-embedded tissues, following macrodisection, using an iPrep robot (Invitrogen). The p.L858R and p.L861Q substitutions (exon 21) were assessed by allele-specific PCR and exon 19 deletions by PCR amplification followed by DNA fragment analysis (polyacrylamide gel electrophoresis). These techniques allowed us to detect these mutations when present in at least 2% of the cells. Results: During these 2 years, we analyzed samples from 1,041 patients (including 907 adenocarcinomas, 71 large cell carcinomas and 28 squamous cell carcinomas). The EGFR mutational status could not be determined in 51 cases : DNA could not be amplified in 23 cases (2.2%), and 28 samples (2.7%) contained a limited percentage (&lt;10%) of cancer cells. The EGFR status could thus be successfully determined in 990 (95.1%) samples. EGFR mutations were detected in 142 (14.3%) patients : 74 exon 19 deletions, and 68 p.L858R mutation. The mutation rate was, as expected, higher in women (24.0%) than in men (7.2%), and mutated patients were significantly older than non mutated patients (median age : 71 y vs 63 y). Furthermore, the mutation rate was much higher in tumors expressing the TTF-1 antigen (117/638; 18.3%) than in TTF-1 negative tumors (5/228; 2.2%). Similar mutation rates were obtained with primary tumors (89/661; 13.5%) and metastases (40/274; 14.6%), and with surgical specimen (43/325; 13.2%), fiberoptic bronchial biopsies (36/250; 14.4%), CT-guided needle biopsies (25/181; 13.8%) and transbronchial needle aspirates (5/38; 13.2%). Conclusions: The results obtained through routine analysis of more than 1000 samples indicated that our procedure is very efficient. All types of samples can be analyzed without any significant bias. TTF-1 immunostaining might be used to predict for negative EGFR mutation status.
Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication
Authors: E J Topol, J J Ferguson, H F Weisman, J E Tcheng, S G Ellis, N S Kleiman, R J Ivanhoe, A L Wang, D P Miller, K M Anderson, R M Califf
Journal: JAMA (1997)

Abciximab, a monoclonal antibody fragment against the platelet receptor alphaIIb beta3 integrin, prevents platelet aggregation. A randomized, placebo-controlled study showed that abciximab improves outcomes for patients undergoing percutaneous coronary angioplasty at 30 days and at 6 months.To determine whether abciximab improves outcomes 3 years after coronary angioplasty.Double-blind, placebo-controlled, randomized trial.A total of 56 academic and community hospitals in the United States.A total of 2099 high-risk patients undergoing coronary angioplasty were randomized. Sufficient time elapsed for 2.5 years of follow-up among 2001 patients and for 3 years of follow-up among 1599 patients.Abciximab bolus of 0.25 mg/kg followed by infusion at 10 microg/min for 12 hours; abciximab bolus of 0.25 mg/kg followed by placebo infusion; or placebo bolus followed by placebo infusion.The primary outcome was the composite of death, myocardial infarction, or coronary revascularization. Secondary outcomes were death, myocardial infarction, or coronary revascularization individually. Subgroups having refractory unstable angina or evolving myocardial infarction and having different elevations of creatine kinase during initial angioplasty were analyzed.At 3 years, composite end points occurred in 41.1% of those receiving abciximab bolus plus infusion; 47.4% of those receiving abciximab bolus only; and 47.2% of those receiving placebo only (for abciximab bolus plus infusion vs placebo, P=.009). Death occurred in 6.8%, 8.0%, and 8.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.20); myocardial infarction in 10.7%, 12.2%, and 13.6%, respectively (for abciximab bolus plus infusion vs placebo, P=.08); and revascularization in 34.8%, 38.6%, and 40.1%, respectively (for abciximab bolus plus infusion vs placebo, P=.02). Among those with refractory unstable angina or evolving myocardial infarction, death occurred in 5.1%, 9.2%, and 12.7%, respectively (for abciximab bolus plus infusion vs placebo, P=.01). Death rates increased as periprocedural creatine kinase levels increased.Abciximab bolus with infusion given at the time of coronary angioplasty improves outcomes as long as 3 years after the procedure.
Vasculogenic mimicry in carcinogenesis and clinical applications
Authors: Qingxi Luo, Jun Wang, Wenyuan Zhao, Zhenzi Peng, Xianyu Liu, Bin Li, Heng Zhang, Bin Shan, Chunfang Zhang, Chaojun Duan
Journal: Journal of Hematology & Oncology (2020)

Abstract Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.
Abstract 16269: Decreased Skeletal Muscle, but Not Increased Fat is Independently Associated With Coronary Microvascular Dysfunction and Adverse Cardiovascular Outcomes
Authors: Ana Carolina d Souza, Michael Rosenthal, Sanjay Divakaran, Michael T Osborne, Navkaranbir S Bajaj, Courtney F Bibbo, Jon Hainer, Ron Blankstein, Sharmila Dorbala, Marcelo F Di Carli, Viviany R Taqueti
Journal: Circulation (2019)

Introduction: BMI is an imperfect marker of cardiovascular prognosis. Coronary microvascular dysfunction (CMD) is prevalent in obese patients and a better discriminator of risk than BMI, but the as...
Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation
Authors: Shan H. Siddiqi, Stephan F. Taylor, Danielle Cooke, Alvaro Pascual-Leone, Mark S. George, Michael D. Fox
Journal: American Journal of Psychiatry (2020)

Treatment of different depression symptoms may require different brain stimulation targets with different underlying brain circuits. The authors sought to identify such targets, which could improve the efficacy of therapeutic brain stimulation and facilitate personalized therapy.The authors retrospectively analyzed two independent cohorts of patients who received left prefrontal transcranial magnetic stimulation (TMS) for treatment of depression (discovery sample, N=30; active replication sample, N=81; sham replication sample, N=87). Each patient's TMS site was mapped to underlying brain circuits using functional connectivity MRI from a large connectome database (N=1,000). Circuits associated with improvement in each depression symptom were identified and then clustered based on similarity. The authors tested for reproducibility across data sets and whether symptom-specific targets derived from one data set could predict symptom improvement in the other independent cohort.The authors identified two distinct circuit targets effective for two discrete clusters of depressive symptoms. Dysphoric symptoms, such as sadness and anhedonia, responded best to stimulation of one circuit, while anxiety and somatic symptoms responded best to stimulation of a different circuit. These circuit maps were reproducible, predicted symptom improvement in independent patient cohorts, and were specific to active compared with sham stimulation. The maps predicted symptom improvement in an exploratory analysis of stimulation sites from 14 clinical TMS trials.Distinct clusters of depressive symptoms responded better to different TMS targets across independent retrospective data sets. These symptom-specific targets can be prospectively tested in a randomized clinical trial. This data-driven approach for identifying symptom-specific targets may prove useful for other disorders and facilitate personalized neuromodulation therapy.
Association Between Lottery Prize Size and Self-reported Health Habits in Swedish Lottery Players
Authors: Robert Östling, David Cesarini, Erik Lindqvist
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Poor health and unhealthy lifestyles are substantially more prevalent among individuals with low income than among individuals with high income, but the underlying mechanisms are not well understood. <h3>Objective</h3> To evaluate whether changes to unearned wealth from lotteries are associated with long-term health behaviors and overall health. <h3>Design, Setting, and Participants</h3> In this quasi-experimental cohort study, 4820 participants (aged 18-70 years at the time of winning) in 3 Swedish lotteries were surveyed from September 1, 2016, to November 11, 2016, between 5 and 22 years after a lottery event. Outcomes of participants in the same lottery who were randomly assigned prizes of different magnitudes by the lotteries but were ex ante identical in terms of their probability of winning different prizes were compared. Data were analyzed from December 22, 2016, to November 21, 2019. <h3>Exposures</h3> Lottery prizes ranged from $0 for nonwinning players to $1.6 million. <h3>Main Outcomes and Measures</h3> Four lifestyle factors (smoking, alcohol consumption, physical activity, and a healthy diet index) and 2 measures of overall health (subjective health and an index of total health derived from responses to questions about 35 health conditions). <h3>Results</h3> The survey was returned by 3344 of 4820 individuals (69%; 1722 [51.5%] male), which corresponded to 3362 observations. The mean (SD) age was 48 (11.8) years in the year of the lottery win and 60 (11.0) years at the time of the survey. There were no statistically significant associations between prize amount won and any of the 6 long-term health outcomes. Estimated associations expressed in SD units per $100 000 won were as follows: smoking (−0.006, 95% CI, −0.038 to 0.026); alcohol consumption (0.003, 95% CI, −0.027 to 0.033); physical activity (0.001, 95% CI, −0.029 to 0.032); dietary quality (−0.007, 95% CI, −0.040 to 0.026); subjective health (0.013, 95% CI, −0.017 to 0.043); and index of total health (−0.003, 95% CI, −0.033 to 0.027). <h3>Conclusions and Relevance</h3> In this study of Swedish lottery players, unearned wealth from random lottery prize winnings was not associated with subsequent healthy lifestyle factors or overall health. The findings suggest that large, random transfers of unearned wealth are unlikely to be associated with large, long-term changes in health habits or overall health.
Comparison of survival for non-small cell lung cancer (NSCLC) between premenopausal and postmenopausal women: An analysis of the National Surveillance, Epidemiology and End Results (SEER) Database
Authors: A. B. Oton, C. Belani, C. Cai, T. Owonikoko, W. Gooding, J. Siegfried, S. Ramalingam
Journal: Journal of Clinical Oncology (2006)

7038 Background: Estrogen signaling has been implicated in lung cancer formation and progression by pre-clinical studies. Estrogen receptor (ER) Beta is overexpressed in NSCLC. To understand the clinical impact of the estrogen pathway, we analyzed the national SEER database to compare the outcomes for NSCLC in premenopausal vs. postmenopausal women. Methods: Data from the national SEER registry between the years of 1988–2002 was analyzed. Women between the ages 40–44 were chosen as representative of the pre-menopausal group and 55–59 year-old women represented the post-menopausal group. To control the effect of age alone as a determinant of outcome, we compared the survival between 1,534 men with ages of 40–44 and 8,807 men with ages of 55–59. Survival rates were analyzed by Kaplan-Meier method and compared by Z-test through SEER*Stat software version 6.1.4. Results: A total of 7,150 women, premenopausal (1,171) and postmenopausal (5,979) were included. Adenocarcinoma (ADC) was more commonly seen in premenopausal than in postmenopausal women (58% vs 47%). Distribution by stage at diagnosis was similar between the two groups. Premenopausal women with squamous cell carcinoma (SCC) or bronchioalveolar carcinomas (BAC) had inferior overall survival than postmenopausal women. Differences in outcome between men in the two age groups were not significant. Conclusions: Premenopausal women with SCC or BAC, but not ADC have inferior survival compared to postmenopausal women. Smaller and non-significant differences were observed between males of the same aged-groups. The results suggest varying estrogen effects between the histological sub-types of NSCLC and support clinical strategies to block the ER pathway for the treatment of NSCLC. [Table: see text] No significant financial relationships to disclose.
The Matrix Revolution: Matricellular Proteins and Restructuring of the Cancer Microenvironment
Authors: Casimiro Gerarduzzi, Ursula Hartmann, Andrew Leask, Elliot Drobetsky
Journal: Cancer Research (2020)

The extracellular matrix (ECM) surrounding cells is indispensable for regulating their behavior. The dynamics of ECM signaling are tightly controlled throughout growth and development. During tissue remodeling, matricellular proteins (MCP) are secreted into the ECM. These factors do not serve classical structural roles, but rather regulate matrix proteins and cell-matrix interactions to influence normal cellular functions. In the tumor microenvironment, it is becoming increasingly clear that aberrantly expressed MCPs can support multiple hallmarks of carcinogenesis by interacting with various cellular components that are coupled to an array of downstream signals. Moreover, MCPs also reorganize the biomechanical properties of the ECM to accommodate metastasis and tumor colonization. This realization is stimulating new research on MCPs as reliable and accessible biomarkers in cancer, as well as effective and selective therapeutic targets.
PREVALENCE, PATTERNS AND PREDICTORS OF OBSTRUCTIVE CORONARY ARTERY DISEASE AMONG PATIENTS UNDERGOING CORONARY ANGIOGRAPHY IN A TERTIARY HOSPITAL IN TANZANIA
Authors: Khuzeima S. Khanbhai, Pedro Pallangyo, Smita Bhalia, Regan Valerian, Mazen Albaghdadi, Peter Kisenge, Tulizo Shemu, Tatizo Waane, George Longopa, Yona Gandye, Nino Mihatov, Maarten Hoek, Peter O'Brien, Mohamed Janabi
Journal: Journal of the American College of Cardiology (2020)
Coronavirus Disease 2019 (COVID-19) in Italy
Authors: Edward Livingston, Karen Bucher
Journal: JAMA (2020)

Giacomo Grasselli, MD; Alberto Zangrillo, MD; Alberto Zanella, MD; Massimo Antonelli, MD; Luca Cabrini, MD; Antonio Castelli, MD; Danilo Cereda, MD; Antonio Coluccello, MD; Giuseppe Foti, MD; Roberto Fumagalli, MD; Giorgio Iotti, MD; Nicola Latronico, MD; Luca Lorini, MD; Stefano Merler, MS; Giuseppe Natalini, MD; Alessandra Piatti, MD; Marco Vito Ranieri, MD; Anna Mara Scandroglio, MD; Enrico Storti, MD; Maurizio Cecconi, MD; Antonio Pesenti, MD; COVID-19 Lombardy ICU Network; Emiliano Agosteo; Valentina Alaimo; Giovanni Albano; Andrea Albertin; Armando Alborghetti; Giorgio Aldegheri; Benvenuto Antonini; Enrico Barbara; Nicolangela Belgiorno; Mirko Belliato; Annalisa Benini; Enrico Beretta; Leonardo Bianciardi; Stefano Bonazzi; Massimo Borelli; Enrico Boselli; Nicola Bronzini; Carlo Capra; Livio Carnevale; Giampaolo Casella; Gianpaolo Castelli; Emanuele Catena; Sergio Cattaneo; Davide Chiumello; Silvia Cirri; Giuseppe Citerio; Sergio Colombo; Davide Coppini; Alberto Corona; Paolo Cortellazzi; Elena Costantini; Remo Daniel Covello; Gianluca De Filippi; Marco Dei Poli; Federica Della Mura; Giulia Evasi; Raquel Fernandez-Olmos; Andrea Forastieri Molinari; Marco Galletti; Giorgio Gallioli; Marco Gemma; Paolo Gnesin; Lorenzo Grazioli; Stefano Greco; Paolo Gritti; Paolo Grosso; Luca Guatteri; Davide Guzzon; Fabiola Harizay; Roberto Keim; Giovanni Landoni; Thomas Langer; Andrea Lombardo; Annalisa Malara; Elena Malpetti; Francesco Marino; Giovanni Marino; Maurizio Giovanni Mazzoni; Guido Merli; Antonio Micucci; Francesco Mojoli; Stefano Muttini; Adriana Nailescu; Mauro Panigada; Paolo Perazzo; Giovanni Battista Perego; Nicola Petrucci; Angelo Pezzi; Alessandro Protti; Danilo Radrizzani; Maurizio Raimondi; Marco Ranucci; Frank Rasulo; Mario Riccio; Roberto Rona; Claudio Roscitano; Patrizia Ruggeri; Antonello Sala; Giuseppe Sala; Luca Salvi; Pietro Sebastiano; Paolo Severgnini; Ilaria Sforzini; Francesco Donato Sigurtà; Matteo Subert; Paola Tagliabue; Carmine Troiano; Roberto Valsecchi; Uberto Viola; Giovanni Vitale; Massimo Zambon; Elena Zoia
EARLY FEASIBILITY STUDY OF CARDIOBAND TRICUSPID SYSTEM FOR FUNCTIONAL TRICUSPID REGURGITATION: 30 DAY OUTCOMES
Authors: Charles Davidson, Scott Lim, Robert Smith, Susheel Kodali, Robert Kipperman, Mackram Eleid, Mark Reisman, Jyothy Puthumana, Dale Fowler, Paul Grayburn, Rebecca Hahn, Konstantinos P. Koulogiannis, Sandra Abramson, Sorin Pislaru, Todd Zwink, Abdellaziz Dahou, William A. Gray
Journal: Journal of the American College of Cardiology (2020)
US Zika-Related Birth Defects in High-Transmission Areas
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

In US regions with widespread Zika virus transmission, birth defects that possibly were virus-related increased about 4-fold, from 1.3 per 1000 live births between January and March 2016 to 5.6 per 1000 live births in January to March 2017, according to a CDC report.
THE ASSOCIATION OF GROWTH DIFFERENTIATION FACTOR-15 AND RISK OF SHORT-TERM INCIDENT ATHEROSCLEROTIC CARDIOVASCULAR DISEASE, HEART FAILURE HOSPITALIZATION, AND ALL-CAUSE MORTALITY IN OLDER ADULTS: THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY
Authors: Mahmoud Al Rifai, Olive Tang, Wensheng Sun, Elizabeth Selvin, Kunihiro Matsushita, Josef Coresh, Aaron Folsom, Eric Boerwinkle, Vijay Nambi, Yu Bing, Salim Virani, Ron Hoogeveen, Christie M. Ballantyne
Journal: Journal of the American College of Cardiology (2020)
Simplification of bevacizumab (bev) administration: Do we need 90, 60, or even 30 minute infusion times?
Authors: L. B. Saltz, K. Y. Chung, J. Timoney, V. Park, E. Hollywood
Journal: Journal of Clinical Oncology (2006)

3542 Background: Bev is a humanized monoclonal antibody that targets VEGF. Due to concerns of infusion related hypersensitivity reactions, phase I trials of bev used an initial 90 minute infusion of bev, a 60 minutes for on the next dose, and 30 minutes for all doses thereafter. This has remained the administration schedule throughout development and registration. No significant infusion-related toxicities were reported in the pivotal phase III registration trial. We postulated therefore that bev could be safely given without initially prolonged infusion times. Methods: We obtained an IRB waiver of authorization to review the records of patients at Memorial Sloan Kettering Cancer Center (MSKCC) who were treated with bev in the first 3 months of commercial availability (cut-off date 5/15/05). Our institutional adverse drug reaction reporting program was utilized to identify any infusion reactions related to bev. Additionally, patient medical records were reviewed for further confirmation. Results: Following initial commercial availability of bev in February 2004, 202 consecutive colorectal cancer (CRC) patients were treated with bev (5 mg/kg) at MSKCC starting as a 90 minute, then 60 minute, then 30 minute infusion. No hypersensitivity reactions were seen. A decision was then made to establish an institutional practice of using 30 minute infusion times for all doses, including initial doses, of bev. Subsequently, 212 consecutive CRC patients were treated with bev 5 mg/kg, initially as a 30 minute infusion. No infusion reactions were observed. Conclusions: Administration of the initial dose of bev over 30 minutes appears to be safe and well-tolerated. This has been the standard initial infusion time at MSKCC for 5 mg/kg, 10 mg/kg and 15 mg/kg doses of bev. Based on our favorable experience with 30 minute infusions of 15 mg/kg (0.5 mg/kg/minute), as of Nov ’05 we have changed our institutional guidelines such that all non-protocol patients receiving bev are initiated at the infusion rate of 0.5 mg/kg/minute. Thus, our standard 5 mg/kg doses of bev are given over 10 minutes, 10 mg/kg doses are given over 20 minutes, and 15 mg/kg doses are given over 30 minutes. Active quality assurance and safety monitoring are maintained throughout. Data will be updated for the meeting. [Table: see text]