tbuckley/cabot-search huggingface dataset:
THE DISEASE ECOLOGY OF STROKE IN SOUTHERN WEST VIRGINIA USING AN EMERGING HOT SPOT ANALYSIS FROM 2000 - 2018
Authors: Frank Annie, Mark C. Bates, Aravinda Nanjundappa, Muhammad Khan, Josh Wyner, Elise Anderson, Ali Farooq, Megan Wood, Abhiram Challa
Journal: Journal of the American College of Cardiology (2020)
Abstract 15884: Stress Hormone Inhibition of Estrogen Transcriptional Regulation of the Serotonin Receptor 2b in the Heart Exacerbates Cardiomyocyte Apoptosis in Ischemia Reperfusion Injury
Authors: Natalie Carroll, Shripa Amatya, Lilly Kamberov, Wayne Anthony Orr, John A Cidlowski, Diana Cruz-Topete
Journal: Circulation (2019)

Introduction: When compared to men of the same age, incidences of myocardial infarction (MI) in pre-menopausal women have become more frequent. This increase in MI can be associated with exposure t...
Insulin-like growth factor 1 (IGF-1R) protein expression (PE) and gene copy number (GCN) for discrimination of response and outcome to figitumumab in NSCLC.
Authors: Murry W. Wynes, Simon Ekman, Bernadette Reyna Asuncion, Rafal Dziadziuszko, Bonnie S. Glisson, Ignacio I. Wistuba, Fred R. Hirsch
Journal: Journal of Clinical Oncology (2012)

7597 Background: Early clinical data suggested figitumumab (F), an anti-IGF-1R antibody, had clinical activity in several tumor types. However, two phase III studies, A4021016 carboplatin/paclitaxel (CP) +/- F in 1st line treatment or A4021018 erlotinib (E) +/- F in 2nd line therapy for patients with advanced NSCLC, were closed prematurely due to futility. Neither study used biomarker driven selection criteria. The aim of this study was to retrospectively examine the phase III specimens in order to determine if IGF-1R PE or GCN could discriminate response and/or outcome to F. Methods: IGF-1R PE was determined by immunohistochemistry (IHC) and the tumor specimens were scored using the H-score method (0-300) with separate enumeration of membranous and cytoplasmic components and then combination of these scores. GCN was evaluated by bright field silver in situ hybridization (SISH) with recording the average copy number for 50 tumor cells. Results: IHC was evaluable in 25 CP+F, 20 CP, 27 E+F and 26 E specimens whereas SISH was evaluable in 24, 17, 21 and 22 specimens, respectively. Median PE for membrane, cytoplasm and both in A4021016 were 130, 110 and 120 and in A4021018 they were 135, 140 and 140. Median GCN was 1.88 and 1.98 for A4021016 and A4021018, respectively. There were no significant differences in PE or GCN between treatment arms within each study. Neither PE nor GCN were able to discriminate between response/non-response or disease control/progression in either study. Likewise, neither study showed a significant difference in OS or PFS when using the median cut-points for either PE or GCN. Conclusions: Neither IGF1R PE or GCN were able to discriminate response or outcome in the limited quantity of specimens available from two studies that examined the IGF-1R targeted therapy figitumumab.
The financial impact of trastuzumab in metastatic breast cancer: The experience of the Institut Curie
Authors: M. A. Doz, C. D. Le Tourneau, M. S. Guilhaume, V. Dieras, A. Vincent-Salomon, M. Courbard, B. Le Vu, C. C. Buron, A. Livartowski
Journal: Journal of Clinical Oncology (2006)

663 Purpose: To estimate, in term of public health on the scale of a region, the cost of trastuzumab and to point out the financial impact of this new targeted therapy in the adjuvant setting. Methods: To understand the consequences of the spending on of trastuzumab at a macroeconomic level in the French hospital financing system, we decided to focus on an establishment in particular, and to analyze the increasing spending of trastuzumab at a micro-economic level, to provide a cost analysis of patients treated with trastuzumab for HER2-overexpressing metastatic breast cancer. We retrospectively reviewed 137 medical reports of patients who received trastuzumab either in combination with chemotherapy or as a single agent and in maintenance therapy. Median age of the patients was 52 years (range 32- to 79+). Eighty five percent had 3+ HER2 overexpression and fifteen percent had 2+ HER2 (FISH amplified). Results: Median survival from first treatment with trastuzumab was 38.5 months (range 0,04–53,06+). The cost of the first year treatment is in average €43,435.58 per patient, for the second year €36,419.01 and for the third year €37,198.94. Drugs cost represents 78% of the hospital stays cost for a patient and 2.9% of the budget of Institut Curie. Conclusions: This retrospective analysis showed the very high level of expenses of trastuzumab to treat metastatic breast cancers. With the adjuvant use of trastuzumab, it is expected that these expenses are going to increase exponentially. No significant financial relationships to disclose.
A Cancer Research UK two-stage multicenter phase II study of imatinib in the treatment of patients with c-kit positive metastatic uveal melanoma (ITEM).
Authors: Paul D. Nathan, Ernest Marshall, Catrin Tudur Smith, Matthew Bickerstaff, Carles Escriu, Maria Marples, Bertil Damato, Helen Kalirai, Sarah Coupland
Journal: Journal of Clinical Oncology (2012)

8523 Background: The median overall survival (OS) for metastatic uveal melanoma is less than 6 months with a median progression free survival(PFS) of 3 months. No systemic or regional therapy has shown a survival advantage over best supportive care. Despite pre-clinical evidence suggesting anti-tumour activity for the KIT tyrosine kinase inhibitor imatinib, there are several negative phase II trials in unselected patients. Our primary aim was to test the efficacy of imatinib in patients with prospectively-tested c-kit immunopositive metastatic uveal melanoma. Secondary aims included assessment of toxicity and patient recruitment. Methods: A phase II UK multicentre single-arm, two-stage Gehan design recruited 25 evaluable patients receiving imatinib 400mg OD until progression/unacceptable toxicity. Primary efficacy outcome was PFS at 3 months. Secondary outcomes were OS, overall PFS, disease response (RECIST) and toxicity. Prospective sample collection for putative biomarkers was included. Results: After 16.6 months 37 patients were screened, with 25 were registered and included in final efficacy analyses. The sample included PS 0-1 patients with a median age of 63 yrs and a median 9.3 months from diagnosis of metastatic disease. 82% had high LDH levels (&gt;460IU/L), 65% had no previous treatment for metastatic disease and 8% did not have liver involvement by metastasis. Preliminary final results indicate the estimated proportion of patients progression free at 3 months is 0.24 (95% CI, 0.09 to 0.45). Median PFS and OS were 12.0 weeks (95% CI,11.6 to 14.3) and 29.6 weeks (95% CI, 19.3 to 61.0) respectively. Two patients had confirmed PR with response duration of 93 and 112 weeks, respectively, despite the absence of mutations in exons 11, 13, and 17 of the c-KIT gene. Conclusions: The trial successfully recruited to target in this rare disease area failing to convincingly show improved PFS in a selected cohort of c-kit immunopositive patients. Both patients with PR experienced long periods of disease control. Response was not dependent upon the presence of activating mutations in KIT. Further translational studies are ongoing to determine putative biomarkers of response.
Biomarkers of vincristine neuropathy in Kenyan children.
Authors: Jodi L Skiles, ChienWei Chiang, Claire Li, Lang Li, Gilbert Olbara, Celestine Tallam, Festus Njuguna, Jamie L. Renbarger
Journal: Journal of Clinical Oncology (2012)

2601 Background: In a U.S. population, cytochrome P450 (CYP) 3A5 high-expressers metabolize vincristine (VCR) more efficiently than low-expressers and vincristine-induced peripheral neuropathy (VIPN) is less common in African-Americans than Caucasians. We test the hypothesis that more children in Kenya are CYP3A5 high-expressers compared to U.S. children and as such experience less VIPN. Methods: This study was conducted in Kenyan children with cancer (n=78) being treated with VCR at Moi University AMPATH Oncology Institute in partnership with Indiana University. Saliva Oragene kits for DNA extraction and genotyping were obtained. Whole blood was collected via finger stick on Whatman protein saver dried blood spot cards for analysis of VCR concentrations. VIPN was assessed prospectively using two neuropathy assessment tools (Modified Total Neuropathy Score (TNS) and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0). Results: Compared to 14% in the U.S. sample, 94% of Kenyan subjects are CYP3A5 high-expressers (p&lt;2.2x10 -16 ). Kenyan children have significantly lower VCR plasma concentrations (11.15ng/ml/mg ± 1.051) compared to US (primarily Caucasian) children (13.26ng/ml/mg ± 2.897) one hour following the administration of VCR (p=0.011). By TNS VIPN assessment, 71% of Kenyan children developed VIPN compared to 100% of U.S. children (p=8.8x10 -7 ). CYP3A5 high-expresser genotype is associated with lower TNS VIPN severity scores than low-expresser genotypes (p=0.006). TNS VIPN assessments show that height is positively correlated with severity of VIPN (p=0.025). CTCAE VIPN assessments also showed a positive correlation with height (p=0.036), but did not show any association with CYP3A5 genotype. Conclusions: Kenyan children are more likely to be CYP3A5 high-expressers than U.S. children and as such may metabolize VCR more efficiently. Supporting these data is that Kenyan children experience significantly less VIPN than U.S. children. CYP3A5 genotype and height are independent predictors of VIPN in Kenyan children with cancer. The CTCAE may lack sufficient sensitivity to detect VIPN for use in future studies aimed at optimizing VCR dosing strategies.
PROTEOMIC CHARACTERIZATION OF STAGE C AND D HEART FAILURE: IDENTIFICATION OF A CORE PROTEIN SIGNATURE AND EFFECT OF TREATMENT
Authors: Sam Michelhaugh, Alexander Camacho, Nasrien E. Ibrahim, Hanna Gaggin, David A. D'Alessandro, Erin E. Coglianese, Gregory D. Lewis, James Januzzi
Journal: Journal of the American College of Cardiology (2020)
ANTIPLATELET DURATION STRATEGIES AFTER PERCUTANEOUS CORONARY INTERVENTION WITH STENTING: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS
Authors: Leonardo Mees Knijnik, Marcelo Fernandes, Manuel Rivera Maza, Vanessa Blumer, Rhanderson Cardoso, Abhinav Goyal, Michael C. McDaniel, Henry Liberman, Laurence S. Sperling, Mauricio G. Cohen
Journal: Journal of the American College of Cardiology (2020)
Representing utility and deploying the body
Authors: David Spurrett
Journal: Behavioral and Brain Sciences (2020)

Abstract Comprehensive accounts of resource-rational attempts to maximise utility shouldn't ignore the demands of constructing utility representations. This can be onerous when, as in humans, there are many rewarding modalities. Another thing best not ignored is the processing demands of making functional activity out of the many degrees of freedom of a body. The target article is almost silent on both.
Combinatorial treatment with CTO and temozolomide in sc-implanted human LOX 1MVI melanoma.
Authors: Rashida A. Karmali, Yulia Maxuitenko, Greg Gorman
Journal: Journal of Clinical Oncology (2012)

e19006 Background: Carboxyamidotriazole orotate (CTO) is the orotic acid salt of 5-amino-1.(4-(4-chlorobenzoyl)-3,5-dichlorobenzyl)-1, 2, 3-triazole-4-carboxamide. CTO possesses increased solubility. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor –opertated calcium channel- mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, inhibition of FGF-2-induced tyrosine kinase, VEGF-mediated activation of phospholipase Cγ, generation of IP3 and nitric oxide synthase activation, and induction of apoptosis in imatinib mesylate resistant CML cells by downregulating bcr-abl. Methods: Different combinations of CTO and temozolomide (TEM) were first tested in female athymic NCr-nu/nu mice to evaluate tolerance of the combination. The tolerated combinations were then tested to evaluate the antitumor activity against subcutaneously –implanted human LOX 1MVI melanoma xenografts. Results: Oral CTO at doses of 513 or 342 mg/kg/dose Q1Dx14 resulted in inhibition of tumor growth (p&lt;0.001 and p=0.004). Oral TEM at doses of 90 and 60mg/kg/dose Q4Dx3 resulted in dose-dependent inhibition of tumor growth (p&lt;0.001 and p&lt;0.001). Oral CTO at 513 or 342 mg/kg/dose in combination with TEM 90mg/kg/dose resulted in comparable tumor inhibition to TEM alone. However, oral CTO at 513mg/kg/dose in combination with TEM 60mg/kg/dose resulted in additive antitumor activity compared to each drug alone. Also, CTO at 342mg/kg/dose in combination with TEM 60mg/kg/dose had more than additive antitumor activity and was statistically different from the group treated with TEM 60mg/kg/dose alone (p=0.001). Conclusions: These results suggest that CTO enhances the sensitivity of TEM and may permit use of lower doses of TEM to obtain an optimum antitumor effect in combination therapy thus reducing toxicity of high TEM doses in this melanoma model.
HIS BUNDLE PACING COMBINED WITH ATRIOVENTRICULAR NODAL ABLATION: A NOVEL STRATEGY FOR REFRACTORY HEART FAILURE LED BY ATRIAL FIBRILLATION COMPLICATED WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Songyun Chu, Han Jin, Erdong Chen, Qinhui Sheng, Ying Yang, Jianxing Qiu, Jing Zhou, Jie Jiang, Yansheng Ding
Journal: Journal of the American College of Cardiology (2020)
Letter to the Editor: Emergence of Zoonotic Rat Hepatitis E Virus Infection
Authors: Cornelia Adlhoch, Sally A. Baylis
Journal: Hepatology (2020)

To the Editor: We noted the identification of further rat hepatitis E virus (HEV) cases in humans in Hong Kong.(1) This emergence, infection of a Canadian United Nations worker in Africa,(2) and serological evidence of exposure in German foresters(3) and hospitalized Vietnamese patients(4) raises the question of how widespread rat HEV infection is globally. Rat HEV (Orthohepevirus C or HEV-C) is distinct from epidemic HEV strains circulating in Africa, Asia, and to zoonotic pig strains responsible for disease burden in industrialized countries (Orthohepevirus A or HEV-A). In Europe, hepatitis E is not notifiable, and, until recently, lack of awareness by physicians and poorly standardized diagnostics led to underreporting. In 2019, the European Centre for Disease Prevention and Control developed guidance on HEV surveillance (data collection/reporting, case definitions, and testing)(5); this and other guidelines do not currently consider HEV-C. Despite similar clinical presentation of HEV-C and HEV-A (acute and chronic), molecular assays used clinically and for blood donor screening do not detect HEV-C. A commonly used anti-immunoglobulin M (IgM) assay can detect anti-HEV-C antibodies; however, HEV-A/HEV-C-discriminatory assays are unavailable. Of the 169 anti-IgM-positive patients, Sridhar et al. identified 5 HEV-C1 and 82 HEV-A RNA-positive patients.(1) Is more data on the remaining 82 HEV-IgM-positive/RNA-negative patients available? Could variability of HEV-C strains contribute to missed cases? There is a need to develop specific molecular and serological assays and associated control materials for HEV-C, to assess case frequency in previously healthy immunocompetent as well as immunosuppressed individuals and understand the risk to humans. Zoonotic HEV-A is transmitted primarily through consumption of contaminated meat. While Sridhar et al. mentioned the proximity of the HEV-C-infected patients to rat infestations and droppings, there was no discussion about possible transmission of HEV-C by consumption of rat meat or contaminated meat products. More detailed epidemiological investigations (environmental risk factors, consumption habits, and water contamination) are needed to identify infection sources and transmission patterns.
LONG TERM OUTCOMES IN MIXED AORTIC VALVE DISEASE
Authors: Nicolas Isaza, Milind Y. Desai, Samir R. Kapadia, Amar Krishnaswamy, L. Leonardo Rodriguez, Richard A. Grimm, Julijana Conic, Eric Roselli, A. Marc Gillinov, Douglas Johnston, Lars G. Svensson, Brian P. Griffin, Zoran Popovic
Journal: Journal of the American College of Cardiology (2020)
LIPID TESTING, LIPID MODIFYING THERAPY AND PCSK9 INHIBITOR ELIGIBILITY IN 22,603 PATIENTS WITH INCIDENT ACUTE CORONARY SYNDROME
Authors: Bradley Sarak, Anamaria Savu, Padma Kaul, Finlay McAlister, Robert Welsh, Andrew Yan, Shaun Goodman
Journal: Journal of the American College of Cardiology (2020)
Sixty seconds on . . . AA
Authors: Gareth Iacobucci
Journal: BMJ (2020)

No, wrong one, this provides a very different type of assistance. AA is of course Alcoholics Anonymous, the long running support programme run by and for people with alcohol use disorder. Originating in the US 85 years ago, it’s based around attending group meetings with peers and following a 12 step programme to recovery.

This has been notoriously difficult to get to the bottom of. A 2006 Cochrane Collaboration review1 of eight studies concluded that there wasn’t …
18F-FLUORIDE PET/MR IN CARDIAC AMYLOID: A COMPARISON STUDY WITH AORTIC STENOSIS, MYOCARDIAL INFARCTION AND HEALTHY VOLUNTEERS
Authors: Jack Andrews, Maria Giovanna Trivieri, Russell Everett, Nicholas Spath, Gillian MacNaught, Alastair Moss, Mhairi Doris, Tania Pawade, Edwin Van Beek, Christophe Lucatelli, David E. Newby, Zahi A. Fayad, Philip Robson, Marc Dweck
Journal: Journal of the American College of Cardiology (2020)
Definition of Naturally Processed Peptides Reveals Convergent Presentation of Autoantigenic Topoisomerase I Epitopes in Scleroderma
Authors: Eleni Tiniakou, Andrea Fava, Zsuzsanna H. McMahan, Tara Guhr, Robert N. O'Meally, Ami A. Shah, Fredrick M. Wigley, Robert N. Cole, Francesco Boin, Erika Darrah
Journal: Arthritis & Rheumatology (2020)

Objective Autoimmune responses to DNA topoisomerase I (topo I) are found in a subset of scleroderma patients who are at high risk for interstitial lung disease ( ILD ) and mortality. Anti–topo I antibodies ( ATA s) are associated with specific HLA – DRB 1 alleles, and the frequency of HLA – DR –restricted topo I–specific CD 4+ T cells is associated with the presence, severity, and progression of ILD . Although this strongly implicates the presentation of topo I peptides by HLA – DR in scleroderma pathogenesis, the processing and presentation of topo I has not been studied. Methods We developed a natural antigen processing assay ( NAPA ) to identify putative CD 4+ T cell epitopes of topo I presented by monocyte‐derived dendritic cells (mo‐DCs) from 6 ATA ‐positive patients with scleroderma. Mo‐DCs were pulsed with topo I protein, HLA – DR –peptide complexes were isolated, and eluted peptides were analyzed by mass spectrometry. We then examined the ability of these naturally presented peptides to induce CD 4+ T cell activation in 11 ATA ‐positive and 11 ATA ‐negative scleroderma patients. Results We found that a common set of 10 topo I epitopes was presented by Mo‐DCs from scleroderma patients with diverse HLA – DR variants. Sequence analysis revealed shared peptide‐binding motifs within the HLA – DR β chains of ATA ‐positive patients and a subset of topo I epitopes with distinct sets of anchor residues capable of binding to multiple different HLA – DR variants. The NAPA ‐derived epitopes elicited robust CD 4+ T cell responses in 73% of ATA ‐positive patients (8 of 11), and the number of epitopes recognized correlated with ILD severity ( P = 0.025). Conclusion These findings mechanistically implicate the presentation of a convergent set of topo I epitopes in the development of scleroderma.
DENTAL AND PERIODONTAL HEALTH STATUS IN PATIENTS WITH LEFT-VENTRICULAR ASSIST DEVICE: A CROSS SECTIONAL STUDY
Authors: Jens Garbade, Gerhard Schmalz, Christian Binner, Sven Lehmann, Mirjam Eisner, Justus Wagner, Josephine Rast, Dirk Ziebolz, Michael A. Borger
Journal: Journal of the American College of Cardiology (2020)
VISUALIZATION OF PERIPROCEDUAL BLOOD FLOW DYNAMICS WITH FOUR-DIMENSIONAL FLOW MAGNETIC RESONANCE IMAGING IN PATIENTS WITH SEVERE AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Hirokazu Komoriyama, Kiwamu Kamiya, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Yuta Kobayashi, Yoshiya Kato, Kazunori Omote, Takao Konishi, Takuma Sato, Shingo Tsujinaga, Hiroyuki Iwano, Yasushige Shingu, Satoru Wakasa, Toshihisa Anzai
Journal: Journal of the American College of Cardiology (2020)
BALLOON AORTIC VALVULOPLASTY FOLLOWED BY IMPELLA®-ASSISTED LEFT MAIN CORONARY ARTERY STENT IN PATIENTS WITH SEVERE AORTIC STENOSIS AS A BRIDGE TO TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Luis Diaz Quintero, Eileen Gajo, Mayra Guerrero, Ted Feldman, Justin Levisay
Journal: Journal of the American College of Cardiology (2020)
Risk Factors for Small Adult Height in Childhood Cancer Survivors
Authors: Charlotte Demoor-Goldschmidt, Rodrigue S. Allodji, Neige Journy, Carole Rubino, Wael Salem Zrafi, Ghazi Debiche, Damien Llanas, Cristina Veres, Cécile Thomas-Teinturier, Hélène Pacquement, Giao Vu-Bezin, Brice Fresneau, Delphine Berchery, Stephanie Bolle, Ibrahima Diallo, Nadia Haddy, Florent de Vathaire
Journal: Journal of Clinical Oncology (2020)

Between 10% and 20% of childhood cancer survivors (CCS) experience impaired growth, leading to small adult height (SAH). Our study aimed to quantify risk factors for SAH or growth hormone deficiency among CCS.The French CCS Study holds data on 7,670 cancer survivors treated before 2001. We analyzed self-administered questionnaire data from 2,965 CCS with clinical, chemo/radiotherapy data from medical records. SAH was defined as an adult height ≤ 2 standard deviation scores of control values obtained from a French population health study.After exclusion of 189 CCS treated with growth hormone, 9.2% (254 of 2,776) had a SAH. Being young at the time of cancer treatment (relative risk [RR], 0.91 [95% CI, 0.88 to 0.95] by year of age), small height at diagnosis (≤ 2 standard deviation scores; RR, 6.74 [95% CI, 4.61 to 9.86]), pituitary irradiation (5-20 Gy: RR, 4.24 [95% CI, 1.98 to 9.06]; 20-40 Gy: RR, 10.16 [95% CI, 5.18 to 19.94]; and ≥ 40 Gy: RR, 19.48 [95% CI, 8.73 to 43.48]), having received busulfan (RR, 4.53 [95% CI, 2.10 to 9.77]), or > 300 mg/m2 of lomustine (300-600 mg/m2: RR, 4.21 [95% CI, 1.61 to 11.01] and ≥ 600 mg/m2: RR, 9.12 [95% CI, 2.75 to 30.24]) were all independent risk factors for SAH. Irradiation of ≥ 7 vertebrae (≥ 15 Gy on ≥ 90% of their volume) without pituitary irradiation increased the RR of SAH by 4.62 (95% CI, 2.77 to 7.72). If patients had also received pituitary irradiation, this increased the RR by an additional factor of 1.3 to 2.4.CCS are at a high risk of SAH. CCS treated with radiotherapy, busulfan, or lomustine should be closely monitored for growth, puberty onset, and potential pituitary deficiency.