tbuckley/cabot-search huggingface dataset:
HOW APPROPRIATE ARE WE DOSING DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH LIVER DISEASE- A SINGLE CENTER EXPERIENCE
Authors: Azza M. Ahmed, Mustapha Amin, David Sanborn, Alan Sugrue, Medhat Farwati, Haarini Sridhar, Ramila Mehta, Malini Madhavan
Journal: Journal of the American College of Cardiology (2020)
BIODEGRADABLE POLYMER SIROLIMUS ELUTING STENT (ORSIRO) VERSUS SECOND GENERATION DURABLE POLYMER DRUG ELUTING STENTS: A META-ANALYSIS OF RANDOMISED TRIALS
Authors: Mohammad R. Monjur, Christian F. Said, Paul Bamford, Michael Parkinson, Richard Szirt, Thomas J. Ford
Journal: Journal of the American College of Cardiology (2020)
TRENDS, PREDICTORS AND OUTCOMES AFTER UTILIZATION OF TARGETED TEMPERATURE MANAGEMENT IN CARDIAC ARREST PATIENTS WITH ANOXIC BRAIN INJURY
Authors: Kinjan Patel, Bilal Munir, Muhammad U. Khan, Safi Khan, Mohammed Osman, Shahul Valavoor, Sudarshan Balla, Muhammad Zia Khan
Journal: Journal of the American College of Cardiology (2020)
COVID-19 and Cardiovascular Disease
Authors: Kevin J. Clerkin, Justin A. Fried, Jayant Raikhelkar, Gabriel Sayer, Jan M. Griffin, Amirali Masoumi, Sneha S. Jain, Daniel Burkhoff, Deepa Kumaraiah, LeRoy Rabbani, Allan Schwartz, Nir Uriel
Journal: Circulation (2020)

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.
COMPARISON OF PATIENTS’ PHENOTYPES, GUIDELINE-DIRECTED RECOMMENDATIONS COMPLIANCE AND RATES OF CARDIOTOXICITY BETWEEN CARIBBEAN AND UNITED STATES CARDIO-ONCOLOGY PROGRAMS
Authors: Pamela Piña Santana, Amparo Taveras, Amir Khan, Victor Bueno, Luis Cuello, Santiago Collado, Ann Mauer, Justin Coyle, Nishit Shah, Sorin Danciu, Cesar Herrera
Journal: Journal of the American College of Cardiology (2020)
Rape, asthma and dysfunctional breathing
Authors: Robert J. Hancox, Jane Morgan, Nigel Dickson, Jennie Connor, Joanne M. Baxter
Journal: European Respiratory Journal (2020)

Functional breathing disorders are common, but poorly understood, causes of respiratory symptoms, and often co-exist with asthma and other respiratory diseases [1–3]. Hyperventilation syndrome is the most recognised form of dysfunctional breathing. It has long been suspected that dysfunctional breathing may have emotional origins, but there is little empirical evidence to support this [4]. A history of rape is a risk factor for dysfunctional breathing in adults of both sexes and for late-onset asthma diagnosis in women <http://bit.ly/2TFhdAH> We thank the study members and their friends and families for their continued support. We also thank the interviewers and respiratory physiologists and who obtained the data, Richie Poulton, the study director, Phil A. Silva, the study founder, and Malcolm Sears, Terrie Moffitt and Avshalom Caspi for their support.
Synthetic lethality of EGFR blockade in the context of tumor hypoxia.
Authors: Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Debabrata Saha, Sandeep Burma, Chaitanya Nirodi
Journal: Journal of Clinical Oncology (2012)

10624 Background: Hypoxia induces a wide spectrum of biological responses in tumors that alter tumor radio-sensitivity. In several tumors, including non-small cell lung carcinoma (NSCLC), the epidermal growth factor receptor (EGFR) is frequently over-expressed and activated in response to hypoxia, although the precise role of EGFR in hypoxia-associated radioresitance is unclear. Activating mutations in EGFR have been clinically linked to dramatic responses to EGFR tyrosine kinase inhibitors. We previously demonstrated that NSCLCs harboring activating EGFR mutations are radiosensitive with severe deficits in the non homologous end-joining (NHEJ) repair of DNA damage. Methods: We investigated hypoxia associated radiation responses in a panel of NSCLC cell lines and immortalized human bronchial epithelial cells expressing wild type EGFR (WT) or expressed EGFR forms with somatic activating L858R or DE746-E750 mutations (MT). Results: (1) Relative to WT EGFR, MT EGFR expression is associated with significantly higher radiosensitivity under chronic hypoxia (2) Under hypoxic conditions, MT EGFR expression is associated with a unique spectrum of DNA damage responses (DDR) that significantly deviated from canonical response of WT EGFR expressing NSCLCs (3) Genome wide gene expression analysis identified a dramatic hypoxia-associated DDR shift to selective down-regulation of homologous recombination (HR). Moreover, MT EGFR deficits in NHEJ caused a synthetic lethality effect in the context of hypoxia through a simultaneous blockade of HR and NHEJ. (4) Blockade of WT EGFR by the anti-EGFR monoclonal antibody, cetuximab perfectly recapitulated the contextual synthetic lethality of MT EGFR expression. (5) Cetuximab had a dramatic synergistic effect on survival of rat lung orthotopic tumors where hypo-fractionated radiotherapy or cetuximab alone had marginally controlled tumors. Conclusions: The data support a critical role for EGFR-mediated DNA repair in hypoxia associated tumor radio-resistance. Furthermore, this role could be a target for refractory hypoxic EGFR-WT tumor especially in the context of hypo-fractionated radiotherapy which, in its current form, is potentially counter-productive for hypoxic tumors.
LONG-TERM OUTCOMES OF ACUTE MYOCARDIAL INFARCTION WITH CONCOMITANT CARDIAC ARREST AND/OR CARDIOGENIC SHOCK
Authors: Saraschandra Vallabhajosyula, LIndsey Sangaralingham, Jacob Colin Jentzer, Stephanie R. Payne, Kianoush B. Kashani, Nilay Shah, Abhiram Prasad, Shannon Dunlay
Journal: Journal of the American College of Cardiology (2020)
Integrated data review of the first-in-human dose (FHD) study evaluating safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral transforming growth factor-beta (TGF-ß) receptor I kinase inhibitor, LY2157299 monohydrate (LY).
Authors: Jordi Rodon, Michael Anthony Carducci, Juan Manuel Sepúlveda, Analia Azaro, Emiliano Calvo, Joan Seoane, Irene Brana, Elisabet Sicart, Ivelina Gueorguieva, Ann Cleverly, Sada Pillay, Durisala Desaiah, Michael M. F. Lahn, Luis Paz-Ares, Matthias Holdhoff, Jaishri O'Neill Blakeley, José Baselga
Journal: Journal of Clinical Oncology (2013)

2016 Background: Activated TGF-ß signaling has been associated with poor survival in several tumors, including glioma (GM). Hence, we investigated the safety, PK and antitumor responses of the novel TGF-ß inhibitor LY in cancer patients, mainly in GM. Methods: There were 3 study parts: Part A: dose escalation of LY monotherapy in patients with solid tumor (cohorts 1 and 2, continuous dosing) and with GM (cohorts 3 to 5, intermittent dosing 14 days on/14 days off); Part B: intermittent LY dosing in combination with lomustine; Part C: monotherapy of 300 mg/day in solid tumors after completing a relative bioavailability study. Safety, antitumor activity, PK and PD were assessed as previously described (Calvo-Aller, et al. JCO 2008;26:abstract #14554; Rodon, et al. JCO 2011;29:abstract #3011; Azaro, et al. JCO 2012;30:abstract #2042). Results: 79 patients participated in this study (Part A, n = 39, 7 solid tumor, 32 GM; Part B, n = 26, all GM; Part C, n = 14 solid tumor, 9 GM, 2 hepatic cell carcinoma [HCC], 2 gastrointestinal [GI] and 1 melanoma). The integrated safety and efficacy evaluation confirms that LY has a manageable toxicity profile with antitumor activity. For GM patients the median progression-free survival (PFS) in months (range) was: 2.5 (0.0 to 36.9) in Part A; 2.5 (0.0 to 20.5) in Part B; 1.9 (0.0 to 6.4) in Part C. PFS duration in months were (range): 2.1-3.8 for HCC; 1.2-3.9 for GI and 2.2 for melanoma patient. Responders were observed in primary GM (Part A: 3/16; Part B: 2/20) and secondary GM (Part A: 3/14; Part B: 4/6). As of January 2013, 3 GM patients are still on treatment for 54, 36, and 31 months. P450-inducing medications including proton pump inhibitors or enzyme-inducing anti-epileptic drugs did not influence the PK parameters. Approximately, 90 biomarkers have been assayed and the results will be presented during the meeting. Conclusions: Because of the manageable toxicity profile of LY, the 300 mg/day dose administered as an intermittent dosing has been advanced into phase II investigation, either as a monotherapy or in combination with approved chemotherapies. Clinical trial information: NCT01682187.
COMPARISON OF DIRECT ORAL ANTICOAGULANTS VERSUS VITAMIN K ANTAGONISTS IN PATIENTS WITH ATRIAL FIBRILLATION IN THE SETTING OF HYPERTROPHIC CARDIOMYOPATHY: A META-ANALYSIS
Authors: Matthew R. Lozier, Alexandra Sanchez, Esteban Escolar, John Lee, Vicente Font, Elie Donath, Felipe Albuquerque
Journal: Journal of the American College of Cardiology (2020)
CARDIOVASCULAR BIOMARKERS OF LIPIDS AND SUBCLINICAL MYOCARDIAL INJURY DIVERGE DURING RHEUMATOID ARTHRITIS FLARE
Authors: Brittany Weber, Nicole Yang, Zeling He, Marcelo Di Carli, Nancy Shadick, Michael Weinblatt, Nehal Mehta, Jonathan Coblyn, Jorge Plutzky, Katherine P. Liao
Journal: Journal of the American College of Cardiology (2020)
Treatment outcome in patients undergoing surgery for carcinoma larynx and hypopharynx: A follow-up study
Authors: B. T. Varghese, P. Sebastian
Journal: Journal of Clinical Oncology (2006)

15545 Background: In the Regional Cancer Centre (RCC) Trivandrum, India, carcinoma of the larynx account for approximately 5% of all new registries and carcinoma of the hypopharynx for another 3%. It is estimated that the division of surgical oncology RCC has performed about 200 laryngectomies since it’s beginning (1989). Currently i.e. after the year 2000,about 30–40 laryngectomies are estimated to be performed a year thus forming about 3–4% of overall major head and neck surgeries performed which is around 1000 cases per year. 80% of these surgeries are salvage procedures for failed radical radiation/chemoradiation. Aim: (1) To evaluate the role of surgery in disease free and overall survival. (2) To evaluate the prognostic significance of factors that generally affect the surgical outcome in laryngectomies. (3) To evaluate the morbidity associated with salvage surgeries and laryngectomies involving complex reconstructions. (4) To follow up all the patients and evaluate quality of life. (5) To evolve a protocol for selecting cases for primary and salvage laryngectomy. (6) To evolve a protocol for reconstructing the pharynx after laryngectomies. Methods: All patients who have undergone laryngectomy at the Division of Surgical Oncology RCC from June 1995 to Dec 2005 are included in the study which retrospectively records the age and sex distribution initial TNM staging and staging of recurrence/ residual disease at the time of surgical salvage, the indications and types of laryngectomy, and reconstructive options used and analyze the therapeutic outcome, disease free survival (DFS), overall survival (OS), voice preservation, post operative voice rehabilitation and quality of life. Major outcome measures Complications and factors contributing to it, DFS, OS, Voice Preservation, Postoperative rehabilitation and Quality of life. Results and Conclusions: An update of the results as on 31/12/05 the final conclusions and recommendations will be presented.( The study is currently on going with the Institutional Review Board (IRB) and the local Ethical committee (EC) clearance already obtained.and final document is expected to to be prepared by March 2006). No significant financial relationships to disclose.
Abstract 16782: Effects of Epinephrine in Association With Anesthesia in Dental Intervention in Patients With Heart Failure. Results of the Double-Blind Controlled Trial (Teeth-HF Study)
Authors: Sergio Quaresma, Ricardo Neves, Dante Giorgi, Maria Oliveira, Itamara Neves, César Grupi, Edimar A Bocchi
Journal: Circulation (2018)

Introduction: The use of a local anesthesia solution with vasoconstrictor for the dental intervention of patients with heart disease is controversial since it could generate adverse cardiovascular risk. Also, its safety has not been investigated in patients with heart failure (HF). Hypothesis: The objective of this study was to evaluate the cardiovascular risk and pain score after dental intervention under local anesthesia with and without epinephrine, specifically tooth extraction and restoration, in patients with HF. Methods: Prospective, parallel group, controlled, double-blind study. Patients with HF, ejection fraction &lt;45%, functional class II and III/IV and with optimized therapy were randomized to dental intervention using anesthesia solution lidocaine without epinephrine (LW) or anesthesia solution lidocaine with epinephrine (LE). Results: Seventy-two patients (50+/-10 years, 62% male, 27% ischemic) were randomized to LW (n=36) or LE (n=36). Systolic and diastolic blood pressure (BP) increased and maximum heart rate (HR) decreased significantly during intervention in relation to baseline phase in both groups (LW: BP, 120/79 to 125/82 mmHg and HR, 88 to 85 bpm, p&lt;0.05; LE: BP, 116/75 to 124/78 mmHg and HR, 91 to 83 bpm, p&lt;0.05). No differences were observed in BP, HR, arrhythmias and pain score before, during and after the dental intervention between the groups. However, it was observed a significant increase in the pain scale for the dental extraction in the LW group in comparison to the LE. Conclusions: Local anesthesia solution lidocaine with epinephrine seems to be safe and effective in patients with heart failure. This treatment did not cause adverse cardiovascular effects, and the pain score was lower in patients receiving LE in comparison with patients receiving LW. Patients with HF may benefit from the anesthesia solution with epinephrine for the dental intervention.
‘Theory on relativity’: why we need to be ‘absolute’ and regulate the reporting of injury risk outcome metrics in RCTs in sport and exercise medicine (Methods Matter series)
Authors: Mark Roe, Eamonn Delahunt, Fionn Büttner
Journal: British Journal of Sports Medicine (2020)

Can a healthcare intervention appear to have a substantial impact on an important outcome metric without really making a difference?

Understanding whether an intervention can really increase the likelihood of a positive outcome is essential when translating research findings into clinical practice. Selectively reporting outcome metrics in randomised controlled trials (RCTs) can mislead readers to believe that a healthcare intervention is more effective than it truly is. Interpreting whether healthcare interventions should be prescribed by clinicians requires not only critical appraisal by the reader, but also transparent reporting of outcome metrics by researchers.1 This seems like the proverbial ‘no brainer’, particularly as there are recommendations for reporting outcome measures.2

Best practice journal policy requires that RCTs must be registered and have their outcome domains (eg, injury), outcome measures (eg, injury risk) and associated outcome metrics (eg, relative risk) listed very specifically.2 Sadly, journal editors rarely police these reporting behaviours so investigators can, and do, choose to selectively present their most compelling results in the most impressive manner. Cherry-picking outcome metrics can mislead the reader (and/or policy maker) to think that an intervention ‘worked’ very effectively when it fact it only worked to some extent.

Consider the following worked example: Using an RCT design, investigators compared the risk of sustaining a …
Impact of treatment strategies on local control and survival in uterine carcinosarcomas.
Authors: Selim Yalcin, Omer Dizdar, Nadire Kucukoztas, Samed Rahatli, Ozlem Ozen, Polat Dursun, Nihan Haberal, Cagla Tarhan, Ferah Yildiz, Ozden Altundag, Ali Ayhan
Journal: Journal of Clinical Oncology (2013)

e16526 Background: Carcinosarcoma is a biphasic neoplasm composed of a mixture of malignant epithelial and mesenchymal components. Uterine carcinosarcomas comprise only 3% of all uterine malignancies, however they account for a disproportionally higher rate of mortality from uterine cancer because of their agressive nature. No standardized treatment has yet been established. The purpose of this study was to determine the clinical characteristics, patterns of recurrence and survival outcomes in patients with uterine carcinosarcoma treated in our institution. Methods: Records of the patients with uterine carcinosarcoma were retrospectively evaluated and 29 pts with carcinosarcoma diagnosed between 2007 and 2012 were identified. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy , bilateral pelvic and paraaortic lymph node dissection and omentectomy. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of relapse-free survival (RFS) and overall survival (OS) were analyzed. Results: Median age was 63 (range 43-78). 13 patients (45%) had stage I disease, 5 patients (17%) had stage III and 11 patients (38%) had stage IV disease at diagnosis. Median tumor size was 6 cm (range 1.7-20 cm) and lymphovascular invasion was present in 17 patients 59%). Twenty patients (69%) received chemotherapy (90% with paclitaxel and carboplatin) for 6 cycles. One patient received radiotherapy. Median follow up was 13 mos. Seventeen patients (59%) relapsed and 20 patients (69%) died on follow up. Two patients had vaginal cuff recurrence, 4 had pelvic, 4 had abdominal and 7 had distant recurrences. All recurrences were fatal. 3 year RFS was 31%. 3 year OS was 15%. Conclusions: Our data show that uterine carcinosarcomas tend to be more at more advanced stage at diagnosis and despite the use of chemotherapy and radiotherapy, overall prognosis is poor. Surgery remains the mainstay of treatment. More effective adjuvant strategies are needed to reduce relapse and death rates because recurrences are generally fatal.
Searching for predictors markers in renal cell carcinoma: A regression model.
Authors: Maria Quindós Varela, Vanessa Medina Villaamil, Isabel Santamarina Cainzos, Guadalupe Aparicio, Manuel Valladares Ayerbes, Luis M. Antón Aparicio
Journal: Journal of Clinical Oncology (2013)

e15542 Background: Renal cell carcinoma (RCC) is known to be resistant to chemotherapy. The need for the identification of biomarkers capable of determining RCC prognosis factors and metastatic potential that are obtainable from non-invasive or minimally invasive techniques are desirable. The purpose from this analysis was to derive predictive models which could predict more accurately than any one factor alone. Methods: By tissue micro-array (TMA) technology we assessed 29 markers involved in the cascade of events leading to the formation and progression of this disease. The ability of multivariate logistic regression to improve the diagnostic accuracy for RCC by combining determinations of proteins markers and pathological variables was evaluated. Univariate analysis was used to select factors (p&lt;0.05) for entry into a multivariate stepwise logistic regression model using the forward method. Odds ratios with 95% CI were calculated. A p-value of &lt; 0.05 was significant. Results: The regression equations obtained were the next: for lymphatic vessels invasion, Y(x)=6.815- 0.442 (EGFR value); for node status Y(x)=2.07+ 0.494(NOTCH1 value) - 0.269(GLUT5 value); for veins invasion Y(x)=57.61+ 6.01 (NOTCH2 value)- 9.3 (GLUT1 value)+ 1.73 (C-KIT value); for breaking capsule Y(x)=2.713- 0.261(EGFR value)+ 0.407 (NOTCH1 value)- 0.305(NOTCH2 value)+ 0.463 (GLUT1 value); for pelvis invasion Y(x)=8.624-0.198 (EGFR value)- 0.514 (DLL3 value). Receiver-operator characteristic (ROC) curve analyses were made to analyse the accuracy of the best candidate proteins. Should be noted from this analysis NOTCH1 and GLUT5 for node status prediction (AUC=0.833, 95% CI, 0.744-0.922; p&lt;0.001) and EGFR and DLL3 for pelvis invasion (AUC=0.777, 95% CI, 0.631-0.922; p=0.007). Conclusions: In the age of individual therapy, the approach to percutaneous image-guided RCC biopsy procedures plays an expanded role. Applying a 2 mm punch needle for constructing a TMA, thereby mimicking the percutaneous biopsy technique we could describe for the first time how are combined 29 protein markers in regression equations to predict in the most optimal way a number of pathological variables associated with RCC that may help in the diagnosis and prognosis of this disease.
Does RECIST-defined progression correlate with lack of further sunitinib (SU) benefit in advanced renal cell carcinoma (aRCC)?
Authors: MinYuen Teo, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2012)

e15093 Background: RECIST defined radiographic progression on SU may be confounded by the intermittent dosing schedule and scan timing. Response rates to second line agents are typically lower and of shorter duration We analysed the potential for continued clinical benefit from continuation on Sunitinib following RECIST-defined progression in selected pts . Methods: Our institutional database was reviewed to identify aRCC pts who: 1) received SU, 2) achieved response or stable disease, and 3) had continuation of SU after documentation of RECIST-defined progression. Treatment history was obtained from medical chart review. CT scans were retrospectively assessed by RECIST criteria, pattern of progression was documented. SU cessation reasons were identified. Progression-free survival (PFS), post-progression treatment duration (PPD) and overall survival (OS) estimated by Kaplan Meier method. Results: Of 39 patients (pts) treated with SU between 2006 and 2009, 13 met entry criteria. Median age was 62 years (range: 33 – 66) with 11(85%) males. Eleven (85%) had prior nephrectomy and 4 (31%) had prior immunotherapy. Number of pts with MSKCC good/intermediate/poor risk groups were 5/7/1. Best radiographic response achieved was complete response/partial response/stable disease in two, five and six pts. Median PFS was 16.4 mos (11.8 – 23.8). Seven (54%) had progression of existing lesions while the six developed new lesions. Pts continued on SU as progression was relatively minor and clinical status was maintained. Median PPD was 4.2 months (0.6 – 40.5). Most common reasons for SU cessation were on-going radiographic progression (71%) and toxicity (18%). Only 2 pts stopped SU secondary to clinical deterioration. 62% of pts received subsequent lines of treatment, with half receiving 3rd line therapy. Median OS for the cohort was 31.7 mos. Conclusions: Continuation of treatment with SU following RECIST progression appears feasible and safe with prolonged disease control in selected pts . This approach should be further validated prospectively in a larger patient cohort. In this group, current standards for disease response assessment may underestimate the duration of clinical benefit conferred.