tbuckley/cabot-search huggingface dataset:
Results of the first interim assessment of rEECur, an international randomized controlled trial of chemotherapy for the treatment of recurrent and primary refractory Ewing sarcoma.
Authors: Martin G. McCabe, Veronica Moroz, Maria Khan, Uta Dirksen, Abigail Evans, Nicola Fenwick, Nathalie Gaspar, Jukka Kanerva, Thomas Kühne, Alessandra Longhi, Roberto Luksch, Cristina Mata, Marianne Phillips, Kirsten Sundby Hall, Claudia Maria Valverde Morales, Andrew J. Westwood, Mark Winstanley, Jeremy Whelan, Keith Wheatley
Journal: Journal of Clinical Oncology (2019)

11007 Background: 5-year survival of RR-ES is about 15%. Several chemotherapy regimens are used, but without robust evidence. rEECur, the first randomised controlled trial in this setting, is defining a standard of care, balancing efficacy and toxicity. Methods: Patients aged 4 to 50 with RR-ES and fit to receive chemotherapy were randomised 2, 3 or 4 ways between topotecan &amp; cyclophosphamide (TC), irinotecan &amp; temolozomide (IT), gemcitabine &amp; docetaxel (GD) or high-dose ifosfamide (IFOS). Primary outcome measure was objective response (OR) after 4 cycles by RECIST 1.1. Secondary outcomes included PFS, OS and toxicity. A probability-based Bayesian approach was used. The first interim assessment to determine which arm should be closed occurred when 50 evaluable patients had been recruited to 3 arms and evaluated for the primary outcome measure. Results: 242 patients (89% RECIST-evaluable) recruited between 18/12/14 and 21/06/18 were randomised to TC (n=75), IT (71), GD (66) and IFOS (30). Median age was 21 years (range 4 to 49). Patients had: refractory ES (20%), 1st recurrence (63%), &gt;1st recurrence (17%); initial primary disease arose in bone in 60%; disease progression sites were primary site (17%), pleuropulmonary (29%) or other metastatic (54%). Median follow up was 11.3 months. Outcomes in the GD arm were: response rate 11.5% (95% CI: 4.4 to 23%), median PFS 3.0 months (95% CI: 1.6 to 8.0), median OS 13.7 months (95% CI: 10.1 to 23.9). The table shows, for each pairwise comparison of GD with the other arms (randomly labelled A, B, C to maintain blinding of open arms), the probabilities given the observed data that OR, PFS and OS were better for GD than for each other arm (RR: relative risk, HR: hazard ratio). For OR and PFS, all comparisons favoured the other arms. There were fewer grade 3/4 adverse events with GD than with the other arms pooled (58% v. 74%). Conclusions: rEECur has shown that GD is a less effective treatment than TC, IT or IFOS in reducing tumour burden or prolonging PFS in RR-ES. Recruitment continues to the remaining arms. Clinical trial information: ISRCTN36453794. [Table: see text]
Identifying psychosocial distress in cancer patients in a community center.
Authors: Deepali Pandey, Masood Pasha Syed, Shekhar Patil, Mohamed Hassan, Matthew Frederick, Donna LaCerte-Blais, Gary P. Blanchard, David Scott Shepro, Ahmad Daniyal Siddiqui
Journal: Journal of Clinical Oncology (2019)

e23193 Background: Psychosocial distress is common in cancer patients. It can cause decreased treatment adherence, lesser treatment satisfaction, low quality of life, and lower survival rate. Distress management is critical to improving cancer survivorship. National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) is widely used to assess psychosocial problems in cancer patients in five categories - practical, family, emotional, spiritual and physical problems. The aim of our study is to identify the distress pattern in cancer patients undergoing chemotherapy in our center using DT adapted from the NCCN. Methods: This is a retrospective study. Total 192 cancer patients undergoing chemotherapy were included, who were screened with DT at initial visit. Patients were asked to rate their level of distress from 0-10 on DT and select categories. We collected data on distress score, selected categories, age, gender, and primary cancer site. Distress score &lt; 4 were defined as low and = &gt; 4 as high. Our objective was to evaluate distress categories and if distress level (high vs low) is dependent on age ( &lt; 65 vs = &gt; 65), gender, and primary cancer site (top 7 cancer types in our clinic by volume). Statistical test used - Chi-square. Results: Median age - 66.5 years (range: 29-96); Gender: Male/Female - 44.3%/55.7%. Median distress score - 3. Low distress was reported by 55.2% and high distress by 44.8%. Cancer types: Breast (29.7%); Lung (17.7%); Prostate (10.9%); Hematological malignancies (7.3%); Lymphoma (6.7%); Urothelial (6.7%); Head and Neck (6.2%); Others (13.4%). Overall, physical problems were the most common (63.5%) followed by emotional (56.3%), practical and family (32.3%), and spiritual (2.1%). Among patients with high distress, 84.9% reported emotional problems, while 83.7% reported physical problems. Distress level was not dependent on age, gender and primary cancer site. Conclusions: Emotional and physical problems are the most common problems among our study population with high distress level which requires further interventions/referrals. Identifying psychosocial needs of cancer patients with DT can help optimize their care.
Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas
Authors: Fumiharu Ohka, Keiko Shinjo, Shoichi Deguchi, Yusuke Matsui, Yusuke Okuno, Keisuke Katsushima, Miho Suzuki, Akira Kato, Noboru Ogiso, Akane Yamamichi, Kosuke Aoki, Hiromichi Suzuki, Shinya Sato, Nirmala Arul Rayan, Shyam Prabhakar, Jonathan Göke, Teppei Shimamura, Reo Maruyama, Satoru Takahashi, Akio Suzumura, Hiroshi Kimura, Toshihiko Wakabayashi, Hui Zong, Atsushi Natsume, Yutaka Kondo
Journal: Cancer Research (2019)

Abstract Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase (IDH) status. Although IDH-wild-type diffuse astrocytic glioma (DAG) shows a more aggressive phenotype than IDH-mutant type, lack of knowledge regarding relevant molecular drivers for this type of tumor has hindered the development of therapeutic agents. Here, we examined human IDH-wild-type DAGs and a glioma mouse model with a mosaic analysis with double markers (MADM) system, which concurrently lacks p53 and NF1 and spontaneously develops tumors highly comparable with human IDH-wild-type DAG without characteristic molecular features of glioblastoma (DAG-nonMF). During tumor formation, enhancer of zeste homolog (EZH2) and the other polycomb repressive complex 2 (PRC2) components were upregulated even at an early stage of tumorigenesis, together with an increased number of genes with H3K27me3 or H3K27me3 and H3K4me3 bivalent modifications. Among the epigenetically dysregulated genes, frizzled-8 (Fzd8), which is known to be a cancer- and stem cell reprogramming–related gene, was gradually silenced during tumorigenesis. Genetic and pharmacologic inhibition of EZH2 in MADM mice showed reactivation of aberrant H3K27me3 target genes, including Fzd8, together with significant reduction of tumor size. Our study clarifies a pathogenic molecular pathway of IDH-wild-type DAG-nonMF that depends on EZH2 activity and provides a strong rationale for targeting EZH2 as a promising therapeutic approach for this type of glioma. Significance: EZH2 is involved in the generation of IDH-wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma.
Age disparities among cancer clinical trial participants: The role of industry sponsorship.
Authors: Ethan B. Ludmir, Walker Mainwaring, Austin B. Miller, Timothy Lin, Amit Jethanandani, Andres F. Espinoza, Clifton David Fuller
Journal: Journal of Clinical Oncology (2019)

11527 Background: Randomized controlled trials (RCTs) in oncology, which often establish the standard of care for cancer patients, do not necessarily enroll trial participants representative of the broader patient population. We sought to characterize age disparities for cancer patients enrolled on RCTs, and asked whether certain trial-related factors (such as industry sponsorship) predispose trials to larger age disparities between trial enrollees and the general population. Methods: All phase 3 RCTs in clinical oncology with results available were identified through ClinicalTrials.gov. Only randomized multi-arm trials assessing a therapeutic intervention for cancer patients were included. The scope of trials was limited to breast, colorectal, lung, and prostate disease sites. Trial participant median ages were compared to national SEER data for population median ages by disease site. Results: Three-hundred and two trials met inclusion criteria. For all trials, the trial median age was an average 6.23 years younger than the population median age (95% CI: -5.55 to -6.91 years, p &lt; 0.001). Trials with industry sponsorship had significantly younger trial patient populations compared with non-industry-sponsored trials (mean difference from population -6.57 vs -4.48 years, p = 0.02). Younger patients were enrolled on trials evaluating targeted agents (p = 0.04), superiority-design trials (p = 0.02), and trials utilizing a surrogate primary endpoint (p = 0.03). By disease site, lung cancer trials enrolled the youngest patients relative to the population median (-8.98 years), followed by breast (-7.76 years), colorectal (-6.96 years), and prostate (+2.66 years, p &lt; 0.001). Conclusions: Industry-funded clinical trials are associated with larger age disparities among trial participants; we believe this represents a novel finding both in clinical oncology and academic medicine more broadly. Underrepresentation of older patients on RCTs has major ramifications for the generalizability of results as well as equity of access to care; future efforts to address trial participant age disparities may focus on those trials at greatest risk for disparities based on the identified risk factors, including industry sponsorship.
US Preventive Services Task Force Breast Cancer Recommendation Statement on Risk Assessment, Genetic Counseling, and Genetic Testing for <i>BRCA</i>-Related Cancer
Authors: Lisa Newman
Journal: JAMA Surgery (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Synthesis of a long acting nanoformulated emtricitabine ProTide
Authors: Dhruvkumar Soni, Aditya N. Bade, Nagsen Gautam, Jonathan Herskovitz, Ibrahim M. Ibrahim, Nathan Smith, Melinda S. Wojtkiewicz, Bhagya Laxmi Dyavar Shetty, Yazen Alnouti, JoEllyn McMillan, Howard E. Gendelman, Benson J. Edagwa
Journal: Biomaterials (2019)
SAT0030 Relationship between disease severity and hla-b27 at time of diagnosis in ankylosing spondylitis
Authors: K Sivrioglu, M Aydogan, S Bayram, J Irdesel, S Kucukoglu, O Ozcan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> This retrospective study was designed in order to evaluate the relationship between disease severity and HLA-B27 at time of diagnosis in ankylosing spondylitis (AS). <h3>Methods</h3> Medical records of patients admitted to the outpatient clinic of Uludag University Medical Faculty, Department of Physical Medicine and Rehabilitation since 1988, who were diagnosed to have AS according to the 1966 New York Criteria were retrospectively reviewed. Forty-four patients were first diagnosed and had HLA-B27 evaluation. Further analysis was performed for this group which constituted the study population including sex, age at onset, disease duration until admission, HLA-B27 status, family history of AS, rheumatic symptoms, morning stiffness duration, presence of arthritis, sacroiliac tests, ESR (mm/hr), CRP (mg/dl), radiographic grade of sacroiliitis, and lumbar flexibility (assessed by Schober?s test), lumbar lateral flexion limitation, finger-to-floor distance, occiput-wall distance, chin-to-manibrium distance, chest expansion. <h3>Results</h3> Out of the study population (11 female, 33 male; n = 44) with a mean age of 34.5 ± 10.2 years, 35 patients (79.5%) were HLA-B27 (+). Mean age of disease onset was 30.0 ± 9.9 years, and mean time of disease duration until diagnosis was 55.6 ± 47.5 months. Eight patients (13.8%) had a positive family history, 9 (20.5%) had heelpain, 5 (11.4%) had chestpain, 42 (95.5%) had backpain, and 3 (6.8%) had systemic involvement at admission. Radiographic sacroiliitis was found as Grade:2 in 15 patients, Grade:3 in 16 patients, and Grade 4 in 13 patients. Disease duration until admission was significantly less in HLA-B27 (+) patients compared to B27(-) ones (p = 0.027). Duration of morning stiffness was significantly higher (p = 0.050), and significantly more B27(+) patients had positive sacroiliac tests (p = 0.048). However, physical parameters such as lumbar lateral flexion and chest expansion was significantly better (p = 0.003 and 0.018, respectively) in B27 (+) patients. No significant difference was observed in other clinical and physical parameters. <h3>Conclusion</h3> Our results suggest that B-27(+) AS patients tend to admit earlier with more severe clinical symptoms and signs before the development of physical limitations.
Forced oscillation technique as method to document and monitor the efficacy of mepolizumab in treating severe eosinophilic asthma
Authors: Leonardo Antonicelli, Chiara Tontini, Aureliano Marchionni, Beatrice Lucchetti, Maria Stella Garritani, Maria Beatrice Bilò
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Post-Thaw Recovery of Cryopreserved Chimeric Antigen Receptor (CAR) T-Cells during Manufacture Is Better Than That of Cryopreserved Peripheral Blood CD3+ Cells
Authors: Nasha Elavia, Andrew McManus, Steven L Highfill, Jiaqiang Ren, Nirali N Shah, Terry J. Fry, Jennifer Brudno, James N. Kochenderfer, David Stroncek, Sandhya R. Panch
Journal: Blood (2017)
Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats
Authors: Ruoshi Xu, Daimo Guo, Xuedong Zhou, Jianxun Sun, Yachuan Zhou, Yi Fan, Xin Zhou, Mian Wan, Wei Du, Liwei Zheng
Journal: International Journal of Oral Science (2019)

Bone remodelling keeps going through the lifespan of human by bone formation and bone resorption. In the craniofacial region, mandibles act as the main force for biting and chewing, and also become susceptible to a common bone-loss disease, namely, apical periodontitis, once infected dental pulp is not treated timely, during which bone resorption occurs from the apical foramen to the apical bone area. Although conventional root canal treatment (RCT) can remove the most of the infection, chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging, and this process has scarcely been specifically studied as a bone remodelling issue in rat models. Therefore, to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo, we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva, which simulates gradually progressive apical periodontitis, as observed in the clinical treatment of chronical and refractory apical periodontitis. We show that bone-loss is inevitable and progressive in this case of apical periodontitis, which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone formation. Interestingly, bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards, as shown by the time course study of the modified model. Suggesting that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed manner. Hopefully, our findings can provide insights for future bone regenerative treatment for apical periodontitis-associated bone loss.
Immune-phenotype assessment of ovarian cancer stem cells.
Authors: Maria Jose Martinez, Miguel Caballero, Sergio Martinez-Serrano, Laura Vidal, Aranzazu Fernandez, Marta del Pino, Ramon Vilella
Journal: Journal of Clinical Oncology (2013)

e22200 Background: Current evidence suggests the presence of cancer stem cells (CSC) in epithelial ovarian cancer (EOC) and their role in chemoresistance and relapse. CD44+/CD24-, CD117+ and CD133+ expression have been reported as potential markers for CSC. Methods: Tumor cells from 5 patients with chemo-naive EOC and cells of ovarian and tubal epithelium from 5 healthy menopausal women undergoing surgery for benign pathology were cultured in standard medium (mediumA) and medium for embrionic cells (mediumB).Cells forming non-adherent spheres where considered CSC-like, and adherent cells as non-CSC-like. The percentages of CD24+, CD44+, CD117+, CD133+ and VEGF-R+ cells were determined by flow-cytometry. Results: After 1-7 week sphere formation was observed in all EOC-cells cultured in mediumB but in none of the healthy controls. Mean percentages of markers expression are shown below. Conclusions: Contrary to published data, expression of CD44+/CD24- was lower in CSClike; in Non-CSClike CD133+ was higher in EOC-cells compared to controls. Inmunophenotype of CSClike is still lacking and further investigation is warranted. [Table: see text] [Table: see text]
Science Should Drive Vaccine Policy
Authors: Tara C. Smith, Maimuna S. Majumder
Journal: JAMA Network Open (2019)

David R. Sinclair, PhD; John J. Grefenstette, PhD; Mary G. Krauland, PhD; David D. Galloway, MS; Robert J. Frankeny, MSIS; Clayton Travis, MSSW; Donald S. Burke, MD; Mark S. Roberts, MD, MPP
eHealth tools for the self-testing of visual acuity: a scoping review
Authors: Wai Kent Yeung, Piers Dawes, Annie Pye, Anna-Pavlina Charalambous, Malcolm Neil, Tariq Aslam, Christine Dickinson, Iracema Leroi
Journal: npj Digital Medicine (2019)

Uncorrected refractive error is a major cause of vision impairment, and is indexed by visual acuity. Availability of vision assessment is limited in low/middle-income countries and in minority groups in high income countries. eHealth tools offer a solution; two-thirds of the globe own mobile devices. This is a scoping review of the number and quality of tools for self-testing visual acuity. Software applications intended for professional clinical use were excluded. Keyword searches were conducted on Google online, Google Play and iOS store. The first 100 hits in each search were screened against inclusion criteria. After screening, 42 tools were reviewed. Tools assessed near and distance vision. About half (n = 20) used bespoke optotypes. The majority (n = 25) presented optotypes one by one. Four included a calibration procedure. Only one tool was validated against gold standard measures. Many self-test tools have been published, but lack validation. There is a need for regulation of tools for the self-testing of visual acuity to reduce potential risk or confusion to users.
Response to Placebo, Measured by Endoscopic Evaluation of Crohn’s Disease Activity, in a Pooled Analysis of Data From 5 Randomized Controlled Induction Trials
Authors: Marjolijn Duijvestein, Jenny Jeyarajah, Leonardo Guizzetti, Guangyong Zou, Claire E. Parker, Tanja van Viegen, Niels VandeCasteele, Reena Khanna, Annegret Van Der Aa, William J. Sandborn, Brian G. Feagan, Geert R. D’Haens, Vipul Jairath
Journal: Clinical Gastroenterology and Hepatology (2019)
BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors
Authors: Omar Hasan Ali, David Bomze, Sandra S. Ring, Fiamma Berner, Mirjam Fässler, Stefan Diem, Marie-Therese Abdou, Christoph Hammers, Shirin Emtenani, Anne Braun, Antonio Cozzio, Bernhard Mani, Wolfram Jochum, Enno Schmidt, Detlef Zillikens, Christian D. Sadik, Lukas Flatz
Journal: Journal of the American Academy of Dermatology (2019)

Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.We measured skin-specific IgG via enzyme-linked immunosorbent assay in patients with non-small cell lung cancer (NSCLC) who received anti-PD1/PD-L1 treatment between July 2015 and September 2017 at the Kantonsspital St. Gallen. Sera were sampled at baseline and during therapy after 8 weeks.Analysis of publicly available tumor expression data revealed that NSCLC and skin coexpress BP180, BP230, and type VII collagen. A skin irAE developed in 16 of 40 recruited patients (40%). Only elevated anti-BP180 IgG at baseline significantly correlated with the development of skin irAEs (P = .04), therapy response (P = .01), and overall survival (P = .04).The patients were recruited in a single tertiary care center.Our data suggest that the level of anti-BP180 IgG of NSCLC patients at baseline is associated with better therapy response and overall survival and with a higher probability to develop skin irAEs during anti-PD1/PD-L1 treatment.
Edzard Ernst blames rise in measles on increased popularity of complementary and alternative therapies
Authors: Pat Lok, Stijntje Dijk
Journal: BMJ (2019)

The rising popularity of complementary and alternative medicine (CAM) is an undeniable contributing factor in the UK’s loss of its measles-free status,1 says Edzard Ernst, professor and researcher of complementary medicine.

He spoke about CAM’s rising popularity at the launch of his new book on a critical assessment of 150 CAM modalities, held in London on 20 August.

“The real danger of CAM is not direct harm, but rather the indirect harm it causes,” said Ernst, emeritus professor of complementary medicine at the University of Exeter.

He referred to a study in JAMA Oncology , which showed …
Corrigendum to “Identification of a sodium pump Na+/K+ ATPase α1-targeted peptide for PET imaging of breast cancer” [Journal of Controlled Release 281C (2018) 178–188]
Authors: Qian Wang, Shi-Bing Li, Yi-Ying Zhao, Da-Nian Dai, Hui Du, Yan-Zhu Lin, Jia-Cong Ye, Jing Zhao, Wei Xiao, Yan Mei, Yi-Tai Xiao, Shi-Chu Liu, Yan Li, Yun-Fei Xia, Er-Wei Song, Gang-Hua Tang, Wei-Guang Zhang, Zhi-Jian Li, Xiao-Bin Zheng, De-Hai Cao, Man-Zhi Li, Qian Zhong, Zhong-Ping Chen, Chao-Nan Qian, Wei Fan, Guo-Kai Feng, Mu-Sheng Zeng
Journal: Journal of Controlled Release (2019)