tbuckley/cabot-search huggingface dataset:
A phase III, multicenter, randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine (G) as first-line therapy for metastatic adenocarcinoma of the pancreas: The GAMMA trial.
Authors: Charles S. Fuchs, Sergio Jobim Azevedo, Alfredo Carrato, Vincent Haddad, Lara Rachel Lipton, Jesse S. McGreivy, Malcolm J. Moore, Takuji Okusaka, Hanno Riess, Cezary Szczylik, Jean-Luc Van Laethem
Journal: Journal of Clinical Oncology (2012)

TPS4135 Background: Ganitumab (AMG 479) is an investigational, fully human, monoclonal antibody inhibitor of the IGF1R. In a randomized phase II study in patients with metastatic pancreatic cancer, addition of ganitumab 12 mg/kg every 2 weeks (Q2W) to G prolonged progression-free survival (PFS) and overall survival (OS) (Kindler. Ann Onc. 2010;21:741P). Exposure-efficacy analysis showed that patients with higher ganitumab exposure levels (AUC ss at or above median) had longer PFS and OS (Lu. JCO. 2011;29:4049). Methods: In this phase III study, patients are randomized 2:2:1 to placebo + G, ganitumab 12 mg/kg + G, or ganitumab 20 mg/kg + G. Patients receive ganitumab or placebo IV days (D) 1 and 15 and G 1000 mg/m 2 IV D 1, 8, and 15 every 28 D. Patients receiving 20 mg/kg ganitumab are expected to achieve ganitumab levels above the median in phase 2. Key eligibility criteria: untreated metastatic adenocarcinoma of the pancreas; ECOG score 0 or 1; ≥ 18 years old; adequate organ function; and fasting (or non-fasting) glucose ≤ 160 mg/dL. The primary endpoint is OS. A log-rank test stratified by ECOG, presence of liver metastases, and geographic region will compare OS independently for each ganitumab arm at an overall one-sided 2.5% significance level for declaring superiority of ganitumab + G vs placebo + G. Key secondary endpoints include PFS, objective response, safety, and patient-reported outcomes. An additional objective is to define a subpopulation with improved OS based upon baseline levels of circulating biomarkers. Enrollment began in April 2011. As of January 23, 2012, 463 of 825 patients have been enrolled. The study is overseen by an independent data monitoring committee. Status: open. Supported by Amgen Inc. in collaboration with Takeda Global Research &amp; Development Center, Inc.; ClinicalTrials.gov: NCT01231347.
Abstract 18561: Complementary Value of Heart Failure Risk Scores on Long-term Mortality in Patients Hospitalized With Acute Heart Failure Preserved Ejection Fraction
Authors: Kalyani A Boralkar, Yukari Kobayashi, Vedant S Pargaonkar, Kegan J Moneghetti, Mirela Tuzovic, Gomathi Krishnan, Sara Bouajila, Matthew Wheeler, Dipanjan Banerjee, Benjamin D Horne, Kirk U Knowlton, Paul A Heidenreich, Francois Haddad
Journal: Circulation (2017)

Introduction: Heart Failure preserved Ejection Fraction (HFpEF) is a major burden on the healthcare system and better understanding risk prediction in this population may help guide management. Our...
Abstract 18722: New Therapeutic Approach in Cardiomyopathy Induced by the Mutant Mfn2 Q400
Authors: Antonietta Franco, Agostinho G. Rocha, Ray Hershberger, Ali J. Marian, Gerald W Dorn
Journal: Circulation (2017)

Hearts require mitochondrial fusion mediated by outer mitochondrial membrane mitofusins (Mfn) 1 and 2 and inner mitochondrial membrane optic atrophy 1 (Opa1). Cardiomyocyte-targeted genetic ablatio...
Author Correction: Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity
Authors: Robert C. Kaplan, Zheng Wang, Mykhaylo Usyk, Daniela Sotres-Alvarez, Martha L. Daviglus, Neil Schneiderman, Gregory A. Talavera, Marc D. Gellman, Bharat Thyagarajan, Jee-Young Moon, Yoshiki Vázquez-Baeza, Daniel McDonald, Jessica S. Williams-Nguyen, Michael C. Wu, Kari E. North, Justin Shaffer, Christopher C. Sollecito, Qibin Qi, Carmen R. Isasi, Tao Wang, Rob Knight, Robert D. Burk
Journal: Genome biology (2020)

Following publication of the original paper [1], an error was reported in the third paragraph in the section "Analysis of GMB composition and its correlates" (page 3 of the PDF). The first sentence of the text should refer to Table 2, but mistakenly refers to Table 1.
Analysis of neuroendocrine, signal transduction and adhesion proteins in SCLC tissue to predict the tumor response and the rogression free survival (PFS) in limited stage SCLC (SCLC-LS) patients subjected to chemo-radiation therapy
Authors: G. Benedetti, S. Damiani, A. Cancellieri, E. Magrini, M. Fedele, S. Tamberi, G. Frezza, L. Crino
Journal: Journal of Clinical Oncology (2006)

17075 Background: Most of SCLC-LS patients (pts) relapse within 12 months because of chemo and radio resistance. This phenomenon seems related to the induction of morphologically variant cells, which lack the neuroendocrine expression proteins and seem to trigger Akt-dependent inhibition of apoptosis. We analyzed neuroendocrine, signal transduction and adhesion molecules on tumor tissue from pts treated with chemoradiation therapy for SCLC-LS. Methods: We treated twenty-two pts with cisplatin/etoposide and concurrent thoracic irradiation. Paraffin blocks of the tumor obtained from each pt were used in the immunohistochemical analysis (IHA). Sections were stained with antibodies against phospho-Akt (p-Akt), phospho-MAP Kinase (p-MAPK), by a routine IHA method. Sections were stained in parallel with an automated immunostainer with antibodies against chromogranin A (ChrA), Neuron Specific Enolase (NSE), E-cadherin (Cad). Results: A preliminary IHA analysis obtained in ten out of twenty-two pts demonstrated that 9 out of 10 (9/10) tumor were NSE-positive; 6/10 ChrA-positive; 8/10 Cad-positive; 3/10 p-MAPK-positive; 5/10 p-Akt-positive. The correlation with tumor response and progression free survival (PFS) showed that the five patients with prolonged (10–60 months) complete remission (CR) had a p-Akt-positive, on the opposite the pts with short CR (6–18 months ) or partial remission (PR) had a p-Akt-negative staining. The two patient with prolonged and mantained CR (30+ and 60+ months) had a p-Akt-positive and Cad-negative profile. Conclusions: The expression of p-Akt and the absence of E-cadherin seems predict a prolonged CR after chemo-radiation therapy in SCLC-LS pts. Conclusive analysis will be presented at the meeting. No significant financial relationships to disclose.
Mistletoe as complementary treatment in patients with advanced non-small cell lung cancer treated with carboplatin-based combinations: A randomized phase II study.
Authors: Gil Bar-Sela, Mira Wollner, Liat Hammer, Abed Agbarya, Elizabeth Dudnik, Nissim Haim
Journal: Journal of Clinical Oncology (2012)

9052 Background: The mistletoe preparation, iscador, is commonly used in complementary medicine for improving the quality of life (QoL) of cancer patients, but its efficacy needs to be further proved. This randomized phase II study was aimed at assessing the value of iscador as a modifier of chemotherapy-induced toxicity in chemotherapy-naïve non-small-cell lung cancer (NSCLC) patients treated with carboplatin containing regimens. Methods: Patients with stage IIIA or IIIB/IV NSCLC, ECOG performance status 0-2, and no history of brain metastasis were randomized to receive either chemotherapy alone (arm-1) or chemotherapy plus iscador Q 10mg SC injections 3 times weekly until tumor progression (arm-2). Chemotherapy consisted of 21-day cycles of IV carboplatin area under curve 5.0, day 1, combined with IV gemcitabine 1000mg/m 2 , days 1, 8, or with IV pemetrexed 500mg/m 2 , day 1. Results: Seventy-two patients were enrolled, 39 to arm-1 and 33 to arm-2. The arms were well balanced except that more patients with PS-0 were in arm-1 (p=0.041). Most patients (65%) were in stage IV and 62% had squamous histology. Median overall survival was 11 months in both arms. Median TTP was 4.8 months (arm-1) and 6 months (arm-2) (p=0.07). Carboplatin dose reductions and delays in gemcitabine on day 8 were more frequent in arm-1 (44% vs. 13% in arm-2, p&lt;0.005; 31% vs. 13% in arm-2, p&lt; 0.013). The difference in grade 3-4 hematological toxicity was not significant. More non-hematological toxicity was observed in arm-1 (41% compared to 16% in arm-2, p=0.043). The number of hospitalizations was higher in arm-1, 54%, compared to 24% in arm-2 (p=0.016). No significant difference was seen in QoL using the EORTC QLQ-C30 questionnaire; However, significant improvement in arm-2 was seen in coughing (p=0.013) and peripheral neuropathy (p=0.019). Conclusions: Chemotherapy dose reductions, severe non-hematological side effects, and hospitalizations were less frequent in patients treated with iscador. Further investigation of iscador as a modifier of chemotherapy-related toxicity is warranted.
USE OF ARTIFICIAL INTELLIGENCE BY MEDICAL STUDENTS TO ENABLE ACCURATE POINT-OF-CARE ECHOCARDIOGRAPHIC ASSESSMENT OF EJECTION FRACTION
Authors: Ziv Dadon, David Rosenmann, Adi Butnaru, Michael Glikson, Liat Alper-Suissa, Evan Avraham Alpert
Journal: Journal of the American College of Cardiology (2020)
Helen Salisbury: What might we learn from the covid-19 pandemic?
Authors: Helen Salisbury
Journal: BMJ (2020)

Events are moving so quickly that whatever I write today (15 March) is likely to be out of date by the time it’s printed. Last week most GPs realised that waiting for instructions was inappropriate, so we’ve radically rearranged and reprioritised our work. Perhaps the first lesson I’ve learnt is that it’s OK to be brave about making disruptive decisions. Although I may get it wrong, doing nothing is likely to be riskier.

Looking ahead, old fashioned GPs like me may undergo a rapid conversion to remote consulting. Maybe we’ll discover that more is possible than we imagined. We’ll inevitably have to make important clinical decisions with less …
Association of pain and quality of life (QOL) response with PSA response and survival of patients (pts) with metastatic hormone refractory prostate cancer (mHRPC) treated with docetaxel or mitoxantrone in the TAX-327 study
Authors: D. R. Berthold, G. Pond, R. De Wit, M. A. Eisenberger, I. F. Tannock
Journal: Journal of Clinical Oncology (2006)

4516 Background: The TAX-327 study compared 3 weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 pts with mHRPC. Survival and symptom control were superior following D3+P as compared to M+P (Tannock et al, NEJM 2004;351;1502–12). Here we investigate associations between pain and QOL response with PSA response and survival. Methods: Pts were evaluated for pain, PSA and QOL at baseline and 3 weekly during treatment. Pain response (pts with initial pain) was defined by ≥ 2-point reduction in Present Pain Intensity (PPI) with no increase in analgesic score (AS) or ≥ 50% in AS with no increase in PPI. PSA response required ≥ 50% reduction in PSA from baseline. QOL response required ≥ 16-point reduction in FACT-P score (range: 0–156). Responses were confirmed ≥ 3 weeks later. Results: There were414 pts assessable for both pain and PSA response: PSA response was seen in 52.4% of 124 pts with pain response and 28.3% of 290 pts without pain response (p &lt; 0.001). There were 704 pts evaluable for both QOL and PSA response: PSA response occurred in 56.5% of 147 pts with QOL response and 37.5% of 557 pts without QOL response (p &lt; 0.001). The table shows associations of pain or QOL response and survival. Landmark analysis will be presented at the meeting. After adjustment for PSA and QOL response, pain response was an independent predictor of survival (HR = 0.47, p = 0.003). Conclusions: Pain and QOL response were associated with PSA response and pain response was an independent predictor of survival. [Table: see text] [Table: see text]
A first-in-human phase I study of the CDK4/6 inhibitor, LY2835219, for patients with advanced cancer.
Authors: Geoffrey Shapiro, Lee S. Rosen, Anthony W. Tolcher, Jonathan Wade Goldman, Leena Gandhi, Kyriakos P. Papadopoulos, Sara M. Tolaney, Muralidhar Beeram, Drew Warren Rasco, Palaniappan Kulanthaivel, Qian Li, Tianle Hu, Damien Cronier, Edward M Chan, Keith Flaherty, Patrick Y. Wen, Amita Patnaik
Journal: Journal of Clinical Oncology (2013)

2500 Background: Cyclin dependent kinases 4 and 6 (CDK4/6) act with D-type cyclins to inactivate the retinoblastoma (Rb) tumor suppressor protein and enable cell cycle progression from G1 to S phase. LY2835219 is a selective inhibitor of CDK4/6 that shows antitumor activity in preclinical models of human cancer and also distributes efficiently to the brain. We performed a phase 1 study to evaluate safety, pharmacokinetics, pharmacodynamics, and antitumor activity of LY2835219. Methods: 3+3 dose escalation was followed by expansions in 5 tumor types (brain metastases permitted): non-small cell lung cancer (NSCLC), glioblastoma, breast cancer, melanoma, and colorectal cancer. LY2835219 was taken orally every 12 or 24 hours (in escalation) and every 12 hours (in expansions) on days 1-28 of a 28-day cycle. Results: 55 patients (pts) received LY2835219. In escalation, 33 pts received LY2835219 on 1 of 2 schedules: 50, 100, 150, 225 mg every 24 hours (Q24H) or 75, 100, 150, 200, 275 mg every 12 hours (Q12H). On the Q24H schedule, the maximum tolerated dose (MTD) was not identified. On the Q12H schedule, the MTD was 200mg Q12H with dose limiting toxicity of G3 fatigue at 200 mg (1/6 evaluable pts) and 275 mg (2/3 evaluable pts). At 200mg Q12H, the mean C max and AUC 0-24hr at steady state were 285 ng/mL and 5502 ng-hr/ml, respectively. In skin, LY2835219 induced pharmacodynamic inhibition of both Rb phosphorylation and topoisomerase IIα expression. In the ongoing expansions, 22 pts have received LY2835219. Across the study, the most common related adverse events were diarrhea (52%, including 5% G3), nausea (30%, 4% G3), fatigue (21%, 7% G3), vomiting (18%, 2% G3), and neutropenia (16%, 7% G3). 15 pts have reached ≥4 cycles for stable disease or better with 3 pts achieving 8, 16, and 26 cycles. One pt with ovarian cancer had a durable CA-125 response with &gt;50% decrease for 16 cycles. One pt with KRAS mutant NSCLC had a 27% decrease by RECIST. One pt with CDKN2A -/- NRAS mutant melanoma had a confirmed partial response. Early clinical activity has been observed in ovarian cancer, NSCLC, breast cancer, and melanoma. Conclusions: LY2835219 shows acceptable safety and early clinical activity as a single agent for patients with advanced cancer. Clinical trial information: NCT01394016.
Vysis ALK non-small cell lung cancer assay performance on archival tissue and cytology specimens.
Authors: Gu Li, Kristine B Jacobson, Paul E Matushek, Thomas B Perez, Christine Herman, Karen L Sachs, Ekaterina Pestova
Journal: Journal of Clinical Oncology (2012)

e21060 Background: Rearrangements of ALK gene on chromosome 2p23 create a constitutively activated tyrosine kinase implicated in the development of NSCLC and targeted by novel therapeutic agents. The Vysis ALK Break Apart (BAP) FISH Probe assay was developed to detect chromosome 2p23 rearrangements in NSCLC FFPE tissue by fluorescence in situ hybridization. Performance of the ALK assay was assessed on FFPE tissue specimens and FFPE cell lines. The ALK probe was also tested on lung cytology cell suspensions. Methods: The ALK FISH assay success rate on primary NSCLC was tested with 30 FFPE tumor resection specimens, four 5-μm section slides each, judged by qualitative rating of fluorescent signal specificity, intensity, and background. Assay performance was further assessed on 15 FFPE biopsy specimens of 4 metastatic sites including mediastinal and axillary lymp nodes, pleural cavity, brain, and adrenal gland. Each specimen was tested in duplicate and evaluated by 2 reviewers. Assay reproducibility on FFPE cell pellets was tested with 3 lots of ALK Negative and ALK Positive Control Slides (cell lines) on 5 non-consecutive days. Slides were enumerated by 3 reviewers to determine % ALK positive cells, to a total of 45 results per control slide type. Additionally, the ALK BAP probe was tested with a modified assay protocol on ThinPrep lung cytology samples from 8 specimens. Results: The assay success rate on FFPE resection specimens was 99.2 % (90% CI 96.1% - 100%). The core biopsy specimens yielded 95% overall success rate. All Control Slides (FFPE cell lines) tested in the reproducibility study were enumerable within assay ranges, and were correctly classified per specifications of 0-8% and ≥20% ALK positive cells in ALK Negative and ALK Positive Control Slides, respectively. All of the lung cytology specimens prepared by ThinPrep hybridized successfully, however 2 specimens had low cellularity for ALK enumeration. Conclusions: The Vysis ALK BAP FISH assay demonstrated reproducible performance on FFPE cell lines and was shown to yield interpretable results on FFPE lung tissue specimens retrieved by resection or biopsy, from primary tumor or metastatic sites. Feasibility using lung cytology cell suspensions was demonstrated.
PROVIDING OPTIMAL REGIONAL CARE FOR TIME SENSITIVE CARDIAC EMERGENCIES BY USING SMART PHONES - A STUDY UTILIZING WHATSAPP AS A TOOL TO INTEGRATE LOCAL HEALTH NETWORK IN REMOTE AREAS OF NORTH INDIA: SAVE HEART KASHMIR
Authors: Imran Hafeez, Nasir Shamas, Muzaffar Zargar, Irfan Ahmad Bhat, Syed Afaq Jallali, Masood Rashid, Rehana Qaunsar
Journal: Journal of the American College of Cardiology (2020)
Persistent Stridor in a 10-Year-Old Patient with Cystic Fibrosis
Authors: Benno Kohlmaier, Volker Strenger, Markus Egger, Manfred Modl, Andreas Pfleger, Markus Gugatschka, Luka Brcic, Gregor Gorkiewicz, Ernst Eber
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
INACTIVATION OF MANGANESE SUPEROXIDE DISMUTASE BY IRREVERSIBLE COVALENT OXIDATIVE MODIFICATION IN CARDIOVASCULAR DISEASE
Authors: Daniel R. Anderson, Michael Duryee, Jake Walker, Johnathan H. Hall, Geoffrey M. Thiele, Lynell Klassen, Matt Zimmerman, Rebekah L. Gundry, Dahn L. Clemens
Journal: Journal of the American College of Cardiology (2020)
Integrated genomic analysis of EGFR-mutant non-small cell lung cancer immediately following erlotinib initiation in patients.
Authors: Trever Grant Bivona, Petros Giannikopoulos, Carlota Costa, Niki Karachaliou, Santiago Viteri, M. Rosario Garcia-Campelo, John St. John, Andrew V. Uzilov, Anne S. Wellde, William Reilly Polkinghorn, Margarita Majem, Enriqueta Felip, Enric Carcereny, Cordula Nicole Heidecke, Bartomeu Massuti, George W. Wellde, Jonathan S. Weissman, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

11067 Background: Major obstacles limiting the clinical success of EGFR TKI therapy in non-small cell lung cancer (NSCLC) patients are heterogeneity and variability in the initial anti-tumor response to treatment. The underlying molecular basis for this heterogeneity has not been explored in patients immediately after initiation of therapy. Methods: We conducted CT-guided core needle biopsies immediately prior to erlotinib treatment initiation and at 6 days post erlotinib initiation in a patient with histologically confirmed NSCLC harboring an established activating mutation in EGFR. DNA from the paired frozen biopsies and matched normal tissue was analyzed by whole exome sequencing and RNA from the biopsies was analyzed by whole transcriptome sequencing. High-resolution CT images were obtained at the time of each biopsy to compare the degree of molecular and radiographic response observed. Results: Two established activating somatic mutations were identified in EGFR (p.G719A and p. R776H). Selective depletion of each EGFR mutant allele, but not the EGFR wild type allele, was observed upon erlotinib treatment. Gene expression analysis of the paired transcriptomes revealed that erlotinib treatment resulted in significant upregulation of proapoptotic genes including BAD, BAX, BID, CASP3 and growth inhibitory genes including CDKN1A, GADD45B, GADD45G and downregulation of growth-promoting genes including CCNB1 and CCND3. Several unexpected and novel molecular biomarkers were identified by transcriptome analysis and the complete dataset will be presented. High-resolution CT scans revealed no interval radiographic changes in the target lesion and no clinical complications were encountered. Conclusions: This study is the first reported integrated genomic analysis of EGFR-mutant NSCLC immediately following EGFR TKI initiation. We documented the feasibility, safety and utility of this strategy to establish initial drug efficacy at the molecular level prior to any radiographic evidence of response. Additional, serial integrated genomic analysis is ongoing in the index patient and others on therapy to enhance the management of NSCLC patients on targeted therapy.
IMPACT OF PATIENT PROSTHESIS MISMATCH ON CLINICAL OUTCOMES OF PATIENTS UNDERGOING EDWARDS SAPIEN 3 TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR)
Authors: Srilakshmi Vallabhaneni, Marsel Matka, Purujit Thacker, Matthew Carey, Christopher Sarnoski, Raymond Durkin, Jill Stoltzfus, Jamshid Shirani
Journal: Journal of the American College of Cardiology (2020)
CHANGE IN TRANSMITRAL GRADIENT IN PATIENTS WITH CONCOMITANT MITRAL STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Priya Bansal, Hamza Lodhi, Ramez Morcos, Sanjay Chandrasekhar, Andrew Fahmy, Divyesh Doddapaneni, Haider Al Taii, Adithya Mathews, Houman Khalili, Brijeshwar Maini
Journal: Journal of the American College of Cardiology (2020)
MORBIDITY AND MORTALITY IN ADULT FONTAN PATIENTS REFERRED FOR TRANSPLANT: A REPORT FROM THE FOSTER STUDY
Authors: Matthew J. Lewis, Christiane Haeffele, Sharon Chen, Leigh Reardon, Jamil A. Aboulhosn, Natalia Nugaeva, Heather Joan Ross, Yuli Kim, Richard A. Krasuski, Anne Marie Valente, Matthew Carazo, Eric Krieger, Jilian Angiulo, Wendy Book, Fred Rodriguez, Alexander Egbe, Roni Jacobson, Michael Earing, Jonathan W. Cramer, Ari M. Cedars, Jong Ko, Chris Broda, Peter Ermis, Marlon Rosenbaum
Journal: Journal of the American College of Cardiology (2020)
USE AND ADHERENCE WITH STATINS AND ASPIRIN THERAPY AMONG PATIENTS WITH PREMATURE ATHEROSCLEROTIC CARDIOVASCULAR DISEASE: AN ANALYSIS FROM THE VITAL (VETERANS WITH PREMATURE ATHEROSCLEROSIS) REGISTRY
Authors: Dhruv Mahtta, David Ramsey, Mahmoud Al Rifai, Khurram Nasir, Zainab Samad, Hani Jneid, Christie M. Ballantyne, Laura Petersen, Salim Virani
Journal: Journal of the American College of Cardiology (2020)
OVERLAPPING PHENOTYPES: A CASE REPORT OF LEFT VENTRICULAR NONCOMPACTION CONCEALED IN HYPERTROPHIC CARDIOMYOPATHY WITH PROGRESSING HEART FAILURE
Authors: Yulong Xia, Min Li, Kang Li, Qinhui Sheng, Haoyu Weng, Wenhui Ding, Jing Zhou, Kai Zhao
Journal: Journal of the American College of Cardiology (2020)