tbuckley/cabot-search huggingface dataset:
Genome Instability Profiles Predict Disease Outcome in a Cohort of 4,003 Patients with Breast Cancer
Authors: Annette Lischka, Natalie Doberstein, Sandra Freitag-Wolf, Ayla Koçak, Timo Gemoll, Kerstin Heselmeyer-Haddad, Thomas Ried, Gert Auer, Jens K. Habermann
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The choice of therapy for patients with breast cancer is often based on clinicopathologic parameters, hormone receptor status, and HER2 amplification. To improve individual prognostication and tailored treatment decisions, we combined clinicopathologic prognostic data with genome instabilty profiles established by quantitative measurements of the DNA content. Experimental Design: We retrospectively assessed clinical data of 4,003 patients with breast cancer with a minimum postoperative follow-up period of 10 years. For the entire cohort, we established genome instability profiles. We applied statistical methods, including correlation matrices, Kaplan–Meier curves, and multivariable Cox proportional hazard models, to ascertain the potential of standard clinicopathologic data and genome instability profiles as independent predictors of disease-specific survival in distinct subgroups, defined clinically or with respect to treatment. Results: In Cox regression analyses, two parameters of the genome instability profiles, the S-phase fraction and the stemline scatter index, emerged as independent predictors in premenopausal women, outperforming all clinicopathologic parameters. In postmenopausal women, age and hormone receptor status were the predominant prognostic factors. However, by including S-phase fraction and 2.5c exceeding rate, we could improve disease outcome prediction in pT1 tumors irrespective of the lymph node status. In pT3-pT4 tumors, a higher S-phase fraction led to poorer prognosis. In patients who received adjuvant endocrine therapy, chemotherapy or radiotherapy, or a combination, the ploidy profiles improved prognostication. Conclusions: Genome instability profiles predict disease outcome in patients with breast cancer independent of clinicopathologic parameters. This applies especially to premenopausal patients. In patients receiving adjuvant therapy, the profiles improve identification of high-risk patients.
Abstract 14925: Percutaneous or Surgical Revascularization Are Associated With Survival Benefit in Stable Coronary Artery Disease
Authors: Robert J Miller, Robert O Bonow, Heidi Gransar, Rebekah Park, Cecilia Hurtado, John Friedman, Sean Hayes, Louise E Thomson, Balaji Tamarappoo, Alan Rozanski, Torsten Doenst, Daniel Berman
Journal: Circulation (2019)

Introduction: Myocardial ischemia is a significant predictor of cardiovascular events, and the presence of more than 10% ischemia of the left ventricular myocardium may identify patients who benefi...
Abstract A16: Patient-derived organoid-based models for endometrial cancer
Authors: Hege F. Berg, Tina Fonnes, Elin Strand, Heidi Espedal, Ingunn M. Stefansson, Emmet McCormack, Line Bjørge, Jone Trovik, Ingfrid S. Haldorsen, Erling A. Hoyvik, Camilla Krakstad
Journal: Cancer Research (2020)

Abstract Introduction: Comprehensive profiling of tumors using omics technologies has improved our understanding of the molecular landscape of endometrial cancer (EC), building the foundation for precision medicine. However, targeted therapies that show promise in preclinical research are failing clinical trials, which is partly explained by the lack of models that mimic the physiopathology of patients. We aimed at establishing organoids and organoid-based patient-derived xenograft (O-PDX) models as part of a new preclinical platform for endometrial cancer. Methods: Aggregates of tumor cells were isolated from fresh tumor samples, followed by long-term culturing as organoids in a chemically defined medium. Established organoids were implanted into the left uterine horn of NSG mice, and tumor growth was monitored using near-infrared fluorescence imaging (NIRF). Patient tissue, organoids, and corresponding O-PDXs were characterized by histology and whole-exome sequencing and by immunohistochemical staining of important endometrial cancer biomarkers. For proof of concept, selected models were treated with conventional therapeutic agents, including in vivo treatment with carboplatin. Results: Organoids and orthotopic O-PDXs representing different subtypes of endometrial cancer were successfully established. Histologic and molecular profiles of organoids are similar to patient tissue, also after long-term culturing, and characteristics of O-PDXs were sustained after rederivation in vivo. Proof-of-concept drug testing shows heterogenous sensitivity to clinically administered chemotherapeutics. Conclusion: We have extended the collection of EC organoids and established O-PDX models for in vivo studies. This state-of-the-art preclinical platform enables more clinically relevant drug testing that will facilitate translation into relevant clinical trials. Citation Format: Hege F. Berg, Tina Fonnes, Elin Strand, Heidi Espedal, Ingunn M. Stefansson, Emmet McCormack, Line Bjørge, Jone Trovik, Ingfrid S. Haldorsen, Erling A. Hoyvik, Camilla Krakstad. Patient-derived organoid-based models for endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A16.
Endoscopic full-thickness resection (eFTR) of colorectal lesions: results from the Dutch colorectal eFTR registry
Authors: Liselotte W. Zwager, Barbara A. J. Bastiaansen, Maxime E. S. Bronzwaer, Bas W. van der Spek, G. Dimitri N. Heine, Krijn J. C. Haasnoot, Hedwig van der Sluis, Lars E. Perk, Jurjen J. Boonstra, Svend T. Rietdijk, Hugo J. Wolters, Bas L. A. M. Weusten, Lennard P. L. Gilissen, W. Rogier ten Hove, Wouter B. Nagengast, Frank C. Bekkering, M. P. Schwartz, Jochim S. Terhaar sive Droste, Marije S. Vlug, Martin H. M. G. Houben, Francisco J. Rando Munoz, Tom C. J. Seerden, Hanneke Beaumont, Rogier de Ridder, Evelien Dekker, Paul Fockens
Journal: Endoscopy (2020)

Abstract Background Endoscopic full-thickness resection (eFTR) is a minimally invasive resection technique that allows definite diagnosis and treatment for complex colorectal lesions ≤ 30 mm unsuitable for conventional endoscopic resection. This study reports clinical outcomes from the Dutch colorectal eFTR registry. Methods Consecutive patients undergoing eFTR in 20 hospitals were prospectively included. The primary outcome was technical success, defined as macroscopic complete en bloc resection. Secondary outcomes were: clinical success, defined as tumor-free resection margins (R0 resection); full-thickness resection rate; and adverse events. Results Between July 2015 and October 2018, 367 procedures were included. Indications were difficult polyps (non-lifting sign and/or difficult location; n = 133), primary resection of suspected T1 colorectal cancer (CRC; n = 71), re-resection after incomplete resection of T1 CRC (n = 150), and subepithelial tumors (n = 13). Technical success was achieved in 308 procedures (83.9 %). In 21 procedures (5.7 %), eFTR was not performed because the lesion could not be reached or retracted into the cap. In the remaining 346 procedures, R0 resection was achieved in 285 (82.4 %) and full-thickness resection in 288 (83.2 %). The median diameter of resected specimens was 23 mm. Overall adverse event rate was 9.3 % (n = 34/367): 10 patients (2.7 %) required emergency surgery for five delayed and two immediate perforations and three cases of appendicitis. Conclusion eFTR is an effective and relatively safe en bloc resection technique for complex colorectal lesions with the potential to avoid surgery. Further studies assessing the role of eFTR in early CRC treatment with long-term outcomes are needed.
Consensus report from the Food Allergy Research &amp; Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit
Authors: Amber N. Pepper, Amal Assa’ad, Michael Blaiss, Emily Brown, Sharon Chinthrajah, Christina Ciaccio, Mary Beth Fasano, Ruchi Gupta, Nurry Hong, David Lang, Todd Mahr, Erin Malawer, Anita Roach, Wayne Shreffler, Scott Sicherer, Kathleen Vickers, Brian P. Vickery, Richard Wasserman, Kimberley Yates, Thomas B. Casale
Journal: Journal of Allergy and Clinical Immunology (2020)
Diagnostic performance of direct immunofluorescence microscopy studies by biopsy sites in autoimmune subepidermal blistering dermatoses: a prospective study
Authors: S. Haefliger, S. Sitaru, S. Cazzaniga, A. Rammlmair, L. Feldmeyer, M.P. Horn, L. Borradori
Journal: British Journal of Dermatology (2020)
评估接受 Dupilumab 治疗的中度至重度特应性皮炎患者进行常规安全性检测的必要性
Authors: A. Wollenberg, L.A. Beck, A. Blauvelt, E.L. Simpson, Z. Chen, Q. Chen, B. Shumel, F.A. Khokhar, T. Hultsch, E. Rizova, A.B. Rossi, N.M.H. Graham, G. Pirozzi, Y. Lu, M. Ardeleanu
Journal: British Journal of Dermatology (2020)

特应性皮炎(又称 AD 或湿疹)是一种常见的皮肤病,可引起强烈和持续的瘙痒和皮疹。对于一些中度至重度 AD 患者来说,护肤霜或软膏不合适或不起效。这些患者可能需要口服或注射药物。 其中一些口服或注射治疗可能具有毒性,常常会产生不想要的副作用,特别是在使用时间较长的情况下,因此必须定期对患者进行检测,查看这些治疗是否在损害他们的血液或器官。 Dupilumab 是一种治疗中度至重度 AD 的较新的注射药物。Dupilumab 专门作用于体内导致 AD 的关键分子。在安慰剂对照临床试验中已经在 2000 多名患者身上对 Dupilumab 进行了长达一年的测试。在这些试验中,患者在接受 Dupilumab 或安慰剂(模拟药物)治疗时提供血液和尿液样本进行实验室检测。 本文中,来自德国和美国的作者分析了血细胞、血生化和尿生化在治疗过程中的变化,以检查是否可以在不需要进行定期实验室检测的情况下安全地使用 Dupilumab。 在对患者的血液和尿液进行了许多常规实验室检测后,他们发现,检测结果中没有可能与 Dupilumab 有关的临床重要变化。因此得出结论,使用 Dupilumab 治疗的中度到重度 AD 患者不需要进行定期实验室检测。 本摘要涉及研究: Dupilumab 治疗中重度特应性皮炎的实验室安全性: 三项 III 期试验 (LIBERTY AD SOLO 1、LIBERTY AD SOLO 2 LIBERTY AD CHRONOS)的结果
Patient Satisfaction and Quality of Life Before and After Treatment of Pancreatic and Periampullary Cancer: A Prospective Multicenter Study
Authors: Tara M. Mackay, Lennart B. van Rijssen, Jurr O. Andriessen, Mustafa Suker, Geert-Jan Creemers, Ferry A. Eskens, Ignace H. de Hingh, Lonneke V. van de Poll-Franse, Mirjam A.G. Sprangers, Olivier R. Busch, Johanna W. Wilmink, Casper H. van Eijck, Marc G. Besselink, Hanneke W. van Laarhoven, _ _
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: This study sought to assess patient satisfaction and quality of life (QoL) before and after treatment of pancreatic and periampullary cancer. Methods: We conducted a prospective multicenter study of patients treated for pancreatic and periampullary cancer. General patient satisfaction was measured using the EORTC satisfaction with care questionnaire (IN-PATSAT32) at baseline and 3 months after treatment initiation, with a 10-point change on the Likert scale considered clinically meaningful. QoL was measured using the EORTC Core Quality of Life Questionnaire (QLQ-C30). The influence of treatment (curative and palliative) on patient satisfaction and QoL was determined. Results: Of 100 patients, 71 completed follow-up questionnaires. General satisfaction with care decreased from 74.3 before treatment to 61.9 after treatment ( P &lt;.001), whereas global QoL increased from 68.4 to 71.4 ( P =.39). Clinically meaningful reductions were also observed for the reported interpersonal skills of doctors (from 73.4 to 63.3) and exchange of information within the care team (from 63.5 to 52.5). Satisfaction scores were lower for patients treated with curative intent than for those treated with palliative intent regarding interpersonal skills of doctors ( P =.01), information provision by doctors ( P =.004), information provision by nurses ( P =.02), availability of nurses ( P =.004), exchange of information within the care team ( P =.01), and hospital access ( P =.02). In multivariable analysis, clinicopathologic or QoL factors were not independently associated with general patient satisfaction. Conclusions: Satisfaction with care, but not QoL, decreased after pancreatic cancer treatment. Improvements in communication and interpersonal skills are needed to maintain patient satisfaction after treatment.
FRI0551 PERFORMANCE OF THE 2019 AMERICAN COLLEGE OF RHEUMATOLOGY/EUROPEAN LEAGUE AGAINST RHEUMATISM SYSTEMIC LUPUS ERYTHEMATOSUS CLASSIFICATION CRITERIA
Authors: C. Vrancianu, I. Conea, A. Boca, M. Bolboceanu, C. Draganesscu, M. Sasu, C. Ciofu, L. Macovei, M. Milicescu, M. Bojinca, I. Ancuta, C. Mihai, V. Stoica, A. M. Gheorghiu
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease, with increased morbidity and mortality, often diagnosed in advanced stages. The recently published 2019 American College Of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for SLE are weighted, hierarchically clustered criteria developed to increase reliability and the identification of early SLE. Objectives: To compare the sensitivity and specificity of the 2019 ACR/EULAR criteria with the 2012 SLICC criteria in a large single-centre cohort of patients with SLE, diagnosed according to expert oppinion. Methods: Data of SLE patients evaluated in our centre between 1996-2019 have been retrospectively analyzed. The control cohort included patients with positive antinuclear antibodies of other ethiology than SLE, evaluated between 2001-2019. The sensitivity and specificity of the 2019 ACR/EULAR and 2012 SLICC criteria were tested using the McNemar test for correlated proportions. Results: Four hundred and forty-six patients with SLE (413 women, mean±SD age 40.5±12.7 years, disease duration 10.1±9.2 years) and 67 controls (63 women, mean±SD age 50.4±12.6 years, disease duration 7.6±6.9 years; 29 systemic sclerosis (SSc), 18 mixed connective tissue dissease (MCTD), 15 undifferentiated CTD, 2 rheumatoid arthritis (RA), 2 SSc – RA overlaps and 1 dermatomyositis) were included. The sensitivity of the 2019 ACR/EULAR and 2012 SLICC criteria were similar 85.4% and 83.6 %, respectively (p=0.3). The specificity of the 2019 ACR/EULAR and 2012 SLICC criteria were 70.2 % and 86.6%, respectively (p=0.007). In the SLE group, patients missclassified according to the new 2019 ACR/EULAR criteria were 65, whereas according to the 2012 SLICC criteria were 73; of them, 44 patients did not fulfill any criteria. In the control group, patients misclassified had mainly MCTD (13/20 patients according to the new 2019 ACR/EULAR, and 8/9 according to the 2012 SLICC criteria). Conclusion: In this real-life cohort, the 2019 ACR/EULAR criteria have a similar sensitivity and lower specificity than the 2012 SLICC criteria, misclassifying especially MCTD patients. These results might be due to the long disease duration in our cohort. References: [1] Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019;71(9):1400–1412. doi:10.1002/art.40930 Disclosure of Interests: None declared
生物药物 ixekizumab 和 guselkumab 治疗中度至重度斑块型银屑病的比较研究
Authors: A. Blauvelt, K. Papp, A. Gottlieb, A. Jarell, K. Reich, C. Maari, K.B. Gordon, L.K. Ferris, R.G. Langley, Y. Tada, R.G. Lima, H. Elmaraghy, G. Gallo, L. Renda, S.Y. Park, R. Burge, J. Bagel
Journal: British Journal of Dermatology (2020)
GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts
Authors: Bjørn O. Eriksen, Runolfur Palsson, Natalie Ebert, Toralf Melsom, Markus van der Giet, Vilmundur Gudnason, Olafur S. Indridason, Lesley A. Inker, Trond G. Jenssen, Andrew S. Levey, Marit D. Solbu, Hocine Tighiouart, Elke Schaeffner
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement In populations, mean GFR is lower in older age, but whether healthy aging is associated with preserved rather than lower GFR in some individuals is unknown. In a meta-analysis of three large European-based cohorts, the authors investigated the cross-sectional association of being healthy (defined as having no major chronic disease or risk factors for CKD), age, and iohexol clearance measurements. The mean and the 97.5th percentile of the GFR distribution were higher in older persons who were healthy than in those who were unhealthy, but lower than in middle-aged people who were healthy. The GFR-age association was more negative in women than in men. These results suggest that, although being healthy is associated with higher GFR in old age, healthy aging is probably not associated with preserved GFR in old age. Background Population mean GFR is lower in older age, but it is unknown whether healthy aging is associated with preserved rather than lower GFR in some individuals. Methods We investigated the cross-sectional association between measured GFR, age, and health in persons aged 50–97 years in the general population through a meta-analysis of iohexol clearance measurements in three large European population-based cohorts. We defined a healthy person as having no major chronic disease or risk factors for CKD and all others as unhealthy. We used a generalized additive model to study GFR distribution by age according to health status. Results There were 935 (22%) GFR measurements in persons who were healthy and 3274 (78%) in persons who were unhealthy. The mean GFR was lower in older age by −0.72 ml/min per 1.73 m 2 per year (95% confidence interval [95% CI], −0.96 to −0.48) for men who were healthy versus −1.03 ml/min per 1.73 m 2 per year (95% CI, −1.25 to −0.80) for men who were unhealthy, and by −0.92 ml/min per 1.73 m 2 per year (95% CI, −1.14 to −0.70) for women who were healthy versus −1.22 ml/min per 1.73 m 2 per year (95% CI, −1.43 to −1.02) for women who were unhealthy. For healthy and unhealthy people of both sexes, both the 97.5th and 2.5th GFR percentiles exhibited a negative linear association with age. Conclusions Healthy aging is associated with a higher mean GFR compared with unhealthy aging. However, both the mean and 97.5 percentiles of the GFR distribution are lower in older persons who are healthy than in middle-aged persons who are healthy. This suggests that healthy aging is not associated with preserved GFR in old age.
Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women
Authors: Tobias Kurth, Pamela M. Rist, Paul M Ridker, Gregory Kotler, Vadim Bubes, Julie E. Buring
Journal: JAMA (2020)

Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear.To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors.Female health professionals in the US (the Women's Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018.Self-reported migraine with aura compared with migraine without aura or no migraine at baseline.The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort.The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes.In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.
Pseudoprogression on 68Ga–Prostate-Specific Membrane Antigen-11 PET/CT in a Treated Glioblastoma
Authors: Manoj Gupta, Partha Sarathi Choudhury, Munish Gairola, Ishwar Chandra Premsagar, Sriram Avinash Rao
Journal: Clinical Nuclear Medicine (2020)

After standard treatment of glioblastoma, pseudoprogression versus true progression is a clinical challenge. Indeed, to differentiate these 2 on contrast MRI (cMRI) is problematic. In recent time, Ga-prostate-specific membrane antigen-11 (Ga-PSMA) PET/CT has been suggested to have high accuracy in glioblastoma recurrence. We present a case of a 40-year-old man with right frontotemporal glioblastoma underwent surgery and radiotherapy. One month posttreatment cMRI showed a new enhancing lesion in the right hippocampal region, which was also positive on Ga-PSMA-11 PET/CT. On follow-up with conservative management, both cMRI and Ga-PSMA-11 PET/CT showed regression in new lesion, hence suggest pseudoprogression.
Mandatory Bicycle Helmet Use—Victoria, Australia
Journal: JAMA (1993)

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