tbuckley/cabot-search huggingface dataset:
First-line treatment selection and early monitoring patterns in chronic phase-chronic myeloid leukemia in routine clinical practice: SIMPLICITY
Authors: Stuart L. Goldberg, Jorge E. Cortes, Carlo Gambacorti‐Passerini, Rüdiger Hehlmann, H. Jean Khoury, Mauricette Michallet, Ron L. Paquette, Bengt Simonsson, Teresa Zyczynski, Aimee Foreman, Elisabetta Abruzzese, David Andorsky, Aart Beeker, Pascale Cony‐Makhoul, Richard Hansen, Elza Lomaia, Eduardo Olavarria, Michael J. Mauro
Journal: American Journal of Hematology (2017)

Achieving successful outcomes in chronic phase-chronic myeloid leukemia (CP-CML) requires careful monitoring of cytogenetic/molecular responses (CyR/MR). SIMPLICITY (NCT01244750) is an observational study exploring tyrosine kinase inhibitor use and management patterns in patients with CP-CML receiving first-line imatinib (n = 416), dasatinib (n = 418) or nilotinib (n = 408) in the US and 6 European countries in routine clinical practice. Twelve-month follow-up data of 1242 prospective patients (enrolled October 01 2010-September 02 2015) are reported. 81% of patients had baseline comorbidities. Treatment selection was based on perceived efficacy over patient comorbidity profile. There was a predominance of imatinib-treated patients enrolled earlier in the study, with subsequent shift toward dasatinib- and nilotinib-treated patients by 2013/2014. Monitoring for either CyR/MR improved over time and was documented for 36%, 82%, and 95% of patients by 3, 6, and 12 months, respectively; 5% had no documentation of CyR/MR monitoring during the first year of therapy. Documentation of MR/CyR testing was higher in Europe than the US (P < .001) and at academic versus community practices (P = .001). Age <65 years, patients being followed at sites within Europe, those followed at academic centers and patients no longer on first-line therapy were more likely to be monitored by 12 months. SIMPLICITY demonstrates that the NCCN and ELN recommendations on response monitoring have not been consistently translated into routine clinical practice. In the absence of appropriate monitoring practices, clinical response to TKI therapy cannot be established, any needed changes to treatment strategy will thus not be implemented, and long-term patient outcomes are likely to be impacted.
Particulate Matter Exposure and Stress Hormone Levels
Authors: Huichu Li, Jing Cai, Renjie Chen, Zhuohui Zhao, Zhekang Ying, Lin Wang, Jianmin Chen, Ke Hao, Patrick L. Kinney, Honglei Chen, Haidong Kan
Journal: Circulation (2017)

Background: Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students. Methods: We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants’ dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal partial least square-discriminant analysis and mixed-effect models. Secondary outcomes include blood pressure, corticotropin-releasing hormone, adrenocorticotropic hormone, insulin resistance, and biomarkers of oxidative stress and inflammation. Results: The average personal exposure to PMs with aerodynamic diameters ≤2.5 μm was 24.3 μg/m 3 during the real purification and 53.1 μg/m 3 during the sham purification. Metabolomics analysis showed that higher exposure to PMs with aerodynamic diameters ≤2.5 μm led to significant increases in cortisol, cortisone, epinephrine, and norepinephrine. Between-treatment differences were also observed for glucose, amino acids, fatty acids, and lipids. We found significantly higher blood pressure, hormones, insulin resistance, and biomarkers of oxidative stress and inflammation among individuals exposed to higher PMs with aerodynamic diameters ≤2.5 μm. Conclusions: This study suggests that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM. Furthermore, our study demonstrated short-term reductions in stress hormone following indoor air purification. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02712333.
Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for ≥24 weeks in Europe
Authors: Johann S. de Bono, Simon Chowdhury, Susan Feyerabend, Tony Elliott, Enrique Grande, Amal Melhem-Bertrandt, Benoit Baron, Mohammad Hirmand, Patrick Werbrouck, Karim Fizazi
Journal: European Urology (2017)

Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported.To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment.Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required.Patients received enzalutamide 160mg/d orally.The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints.Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1-8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6-5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported.Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment.Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment.
A longitudinal, multimodal approach to characterizing chemotherapy-induced peripheral neuropathy.
Authors: Sabrina Ramnarine, Patrick M. Dougherty, Linda J Williams, Charlie Gourley, Marie T Fallon
Journal: Journal of Clinical Oncology (2017)

e21595 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a complex, dose-limiting toxicity impacting prognosis and quality of life. The optimal approach to identification and assessment remains unclear. This study aims to prospectively characterize the development and trajectory of CIPN using a combination of patient-reported outcomes (PROs) and objective Quantitative Sensory Testing (QST) measures in gynaecological, colorectal and lung cancer patients receiving neurotoxic platinum and/or taxane-based chemotherapy. Methods: Patients (n = 33, mean age 60.8) were evaluated at baseline prior to chemotherapy, during (every 3 weeks) and post-treatment every 3 months up to 1 year. Assessments at each time point included: PRO (EORTC QLQ-CIPN20 questionnaire) and QST measures (thermal and mechanical detection and grooved pegboard test). Statistical modelling using repeated measures analysis by patient was conducted. Results: Significant and parallel changes were observed in PROs and QST measures over time. Total EORTC score (sensory, motor and autonomic) increased in severity from baseline at all time points, peaking at 3 months post-treatment (34.8% increase; p &lt; 0.0001) and persisting at 1 year (17.9% increase; p = 0.01). Every increase by one point in EORTC sensory score over time corresponded with an elevation in QST parameters: warm detection threshold (upper limb; p = 0.02 and lower limb; p = 0.03) and mechanical detection threshold, MDT (upper limb; p = 0.04 and lower limb; p = 0.02). Equally, rising total EORTC and motor score were related to increasing MDT in the upper limb p = 0.02 and p = 0.003 respectively. A delay of one second taken to complete the grooved pegboard test (dominant hand) was linked to a proportional increase in EORTC motor score (p = 0.01). Conclusions: Associations are shown here amongst PROs and QST parameters providing an opportunity to quantify and synthesize objective with subjective measures of neuropathy in CIPN patients. This may have potentially informative implications to underlying mechanisms of CIPN symptom burden, contributing to a more comprehensive clinical picture and allow stratification of patients by phenotype severity. Additional studies are warranted.
Brief Report: Drug‐Free Long‐Term Remission in Severe Behçet's Disease Following Withdrawal of Successful Anti–Tumor Necrosis Factor Treatment
Authors: Petros P. Sfikakis, Aikaterini Arida, Stylianos Panopoulos, Kalliopi Fragiadaki, George Pentazos, Katerina Laskari, Maria Tektonidou, Nikos Markomichelakis
Journal: Arthritis & Rheumatology (2017)

Objective To test the hypothesis that remission of Behçet's disease ( BD ) in patients with severe vital organ involvement is maintained after withdrawal of successful anti–tumor necrosis factor (anti‐ TNF ) treatment. Methods This single‐center, retrospective, longitudinal outcomes study focused on consecutive patients with disease refractory to treatment with conventional immunosuppressant agents who responded to add‐on long‐term anti‐ TNF treatment that was subsequently discontinued. The end point was the proportion of patients remaining in complete remission for at least 3 years after withdrawal of anti‐ TNF treatment. Results In our BD cohort comprising 87 patients, 29 were eligible for analysis. All of these patients had disease that was refractory to conventional immunosuppressive therapy and had received successful anti‐ TNF treatment for a median of 2 years (interquartile range [ IQR ] 1.1–2.0) before treatment discontinuation. Of these patients, 12 (41%) achieved the study end point. The remaining 17 patients experienced a relapse within 1 year ( IQR 0.6–1.5) after discontinuation. Re‐treatment with anti‐ TNF was safe and effective in 14 (82%) of 17 patients; so far, 4 of these patients also achieved the study end point. Overall, 16 patients have remained in complete remission (median 6.5 years [ IQR 5.5–8]). Ten of these patients are in drug‐free remission (treated with anti‐ TNF agents, mainly for sight‐threatening disease), and 6 are in azathioprine‐maintained remission (treated with anti‐ TNF agents for ocular, intestinal, or central nervous system involvement). Notably, patients in drug‐free remission were significantly younger and had a significantly shorter duration of BD when anti‐ TNF treatment was initiated compared to patients receiving azathioprine maintenance treatment. Conclusion Drug‐free, long‐term remission after withdrawal of successful anti‐ TNF treatment is feasible in patients with severe BD . Because an anti‐ TNF agent–induced “cure” cannot be differentiated from spontaneous remission by natural history, prospective studies should examine whether anti‐ TNF agents should be used as first‐line treatment for the induction of remission in every patient with vital organ involvement.
Exertional Alternations of the QRS Complex and Cardiopulmonary Indices in Patients with Cardiac Resynchronization Therapy
Authors: Kato Jo, Takayanagi Yuta, Qin Rujie, Nagamine Arisa, Hayashi Kosuke, WU Longmei, Nishi Isao, Koike Akira, Aonuma Kazutaka
Journal: Circulation (2016)
Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma
Authors: Jeremy S Abramson, Brianne McGree, Sarah Noyes, Sean Plummer, Curtis Wong, Yi-Bin Chen, Edwin Palmer, Tina Albertson, Judith A Ferry, Isabel C Arrillaga-Romany
Journal: New England Journal of Medicine (2017)

In this case, a woman with refractory diffuse large-B-cell lymphoma had a CNS recurrence that responded completely to anti-CD19 CAR T-cell therapy. After biopsy of a subsequent skin recurrence, the lesions cleared in association with an expansion of the CAR T cells in the blood.
FRI0445 Faecal calprotectin, but not anti-saccharomyces cerevisiae antibodies, is linked to worse disease status in axial spondyloarthritis patients without inflammatory bowel disease: results from the spartakus cohort
Authors: T Olofsson, E Mogard, K Andréasson, J Marsal, M Geijer, L-E Kristensen, E Lindqvist, JK Wallman
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Inflammatory bowel disease (IBD) is a common comorbidity in axial spondyloarthritis. <h3>Objectives</h3> To study faecal calprotectin (F-calprotectin) levels and anti-<i>Saccharomyces cerevisiae</i> antibodies (ASCA) and their associations with disease status and gastrointestinal (GI) symptoms in axial spondyloarthritis. <h3>Methods</h3> Consecutive patients with a clinical axial spondyloarthritis diagnosis were examined and classified as non-radiographic axial spondyloarthritis (nr-axSpA; Assessment of SpondyloArthritis international Society [ASAS] criteria; n=26) or ankylosing spondylitis (AS; modified New York criteria; n=45). Only patients without known IBD were included. F-calprotectin and ASCA IgA and IgG antibodies in serum were measured by commercially available enzyme-linked immunosorbent assay kits (Calpro AS; ORGENTEC Diagnostika). <h3>Results</h3> Elevated levels of F-calprotectin (≥50 mg/kg) were observed in 15% of nr-axSpA and 40% of AS patients (non-significant difference, with reservation for small groups). Overall, worse mean disease activity/disability scores were observed among patients with elevated versus normal F-calprotectin levels (Table), whereas no association was seen between F-calprotectin and GI symptoms. Similar results remained after exclusion of patients with monoclonal antibody type anti-TNF therapy. Elevated levels of ASCA IgA were observed in 8%/2% of nr-axSpA/AS patients, and IgG in 28%/26%. Only 2 subjects were ASCA double positive. Neither disease activity/disability measures nor GI symptoms were associated with ASCA status. <h3>Conclusions</h3> Elevated levels of F-calprotectin and ASCA IgG antibodies are both common in axial spondyloarthritis patients without IBD, and elevated F-calprotectin may be a marker of more severe spondyloarthritis. Neither F-calprotectin nor ASCA levels were associated with self-reported GI symptoms. <h3>Disclosure of Interest</h3> T. Olofsson: None declared, E. Mogard: None declared, K. Andréasson: None declared, J. Marsal Grant/research support from: AbbVie, Ferring, Hospira, Consultant for: AbbVie, Ferring, Hospira, MSD, Pfizer, Takeda, Tillotts, UCB, M. Geijer: None declared, L.-E. Kristensen Grant/research support from: Oak Foundation, Consultant for: AbbVie, Celgene, BMS, MSD, Novartis, Pfizer, UCB, E. Lindqvist: None declared, J. Wallman Consultant for: Celgene, Novartis, UCB
PI3K/APC pathway and cyclin-dependent kinase pathway to predict complete responders in CRC patients treated with ADAPT therapy.
Authors: Edward H. Lin, Xiaowei Yan, Fang Xie, David Wu, John Dallas Scarborough, Jing Tang, Colin C. Pritchard, Raymond Sze Yeung, Leroy E. Hood, Qiang Tian
Journal: Journal of Clinical Oncology (2015)

e14642 Background: Recent studies have demonstrated that aspirin or selective COX-2 inhibitor improves overall survival in colorectal cancer (CRC) patients with PIK3CA mutations. However, routine use of anti-inflammatory agents in metastatic CRC patients remains controversial. We showed that addition of celecoxib, a selective COX-2 inhibitor coupled with capecitabine in a two step ADAPT (activating dormant tumor cells and potentiate targeting) therapy led to complete responses (CR) and long-term survival in patients with stage IV CRC. We sought to determine genetic aberrations and related pathways as predictor of CR to ADAPT therapy. Methods: We retrospectively reviewed 54 ADAPT therapy treated patients with stage IV CRC patients and tested for a panel of 199 cancer-related genes (UW Oncoplex) with Illumina deep sequencing platform between 2002-2012 including 11 CR for chemo, 12 CR for chemo-radiation, and surgical CR patients (none CR). The median overall survival in these CR patients had reached 92.7 months (95% CI, 63.2 –not yet reached) from the start of the ADAPT therapy. Results: In vitro treatment of CRC cell lines with ADAPT drugs target PI3K/stemness pathway genes. None of the single genes give rise to satisfactory classifier.for CR versus none except for lack of APC mutations and PI3K mutations. Lack APC muations is noted in CR vs none CR pts 6% vs 43.5% (p = 0.002). PI3K mutations is noted 36% of CR versus 6.5% none-CR pts. (p = 0.01). Cyclin-dependent kinases (CDK4/6/8) are upregulated more frequently in the non-CR pts with high specificity of 93.1%, but lack sensitivity (p = 0.27). Unbiased computational analysis via associations rule mining identified a panel of four genes (APC, PIK3CA, NPM1, PTPRD), which accomplishes combined sensitivity of 87.1% and specificity of 82.6% (2.71E-07).Validation study in the ongoing phase II ADAPT trial patients (20/43 enrolled to date) will be reported at the meeting. Conclusions: Lack of APC mutations and PI3K mutations predict ADAPT therapy CR. A 4 genes ADAPT panel is identiifed. Future study should explore synthetic lethaltiy targeting both PI3K and CDK in pts who progress on ADAPT therapy. Funded by R01CA190122 and Gateway for Cancer Research
Enhanced p122RhoGAP/DLC-1 Expression can be a Cause of Coronary Spasm
Authors: Kinjo Takahiko, Tanaka Makoto, Osanai Tomohiro, Shibutani Shuji, Ishida Yuji, Tanno Tomohiro, Nishizaki Kimitaka, Ichikawa Hiroaki, Kimura Yoshihiro, Tomita Hirofumi, Okumura Ken
Journal: Circulation (2016)
Abstract 17681: A Redox Dependent Mechanism for Regulation of AMPK Activation by Thioredoxin1 during Energy Starvation
Authors: Dan Shao, Shin-ichi Oka, Tong Liu, Peiyong Zhai, Tetsuro Ago, Sebastiano Sciarretta, Hong Li, Junichi Sadoshima
Journal: Circulation (2013)

Dan Shao, 2013 Finalist and Presenting Author
単量体シーケンスの影響と生分解性ポリ(lactic-co-グリコール酸)マトリックスの膨潤および侵食に及ぼす立体化学【Powered by NICT】
Authors: A Washington Michael, J Swiner Devin, R Bell Kerri, V Fedorchak Morgan, R Little Steven, Y Meyer Tara
Journal: Biomaterials (2017)
皮膚創傷治癒のための止血と接着性を用いた自己修復性創傷被覆材としての抗菌抗酸化活性注入可能ヒドロゲル【Powered by NICT】
Authors: Zhao Xin, Wu Hao, Guo Baolin, Dong Ruonan, Qiu Yusheng, X Ma Peter
Journal: Biomaterials (2017)
ナノ粒子腫瘍局在,オートファゴソーム輸送の破壊および長期薬物送達は腹膜中皮腫における生存率を改善する【Powered by NICT】
Authors: Liu Rong, H Colby Aaron, Gilmore Denis, Schulz Morgan, Zeng Jialiu, F Padera Robert, Shirihai Orian, W Grinstaff Mark, L Colson Yolonda
Journal: Biomaterials (2016)
Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial
Authors: Xavier Forns, Samuel S Lee, Joaquin Valdes, Sabela Lens, Reem Ghalib, Humberto Aguilar, Franco Felizarta, Tarek Hassanein, Holger Hinrichsen, Diego Rincon, Rosa Morillas, Stefan Zeuzem, Yves Horsmans, David R Nelson, Yao Yu, Preethi Krishnan, Chih-Wei Lin, Jens J Kort, Federico J Mensa
Journal: The Lancet Infectious Diseases (2017)
Abstract 13793: Ten-Year Clinical Follow-up After Sirolimus-Eluting Stent Implantation
Authors: Palhais Nuno, Diego Arroyo, Sonja Lehmann, Mario Togni, Urs Kaufmann, Jean-Christophe Stauffer, Jean-Jacques Goy, Stéphane Cook
Journal: Circulation (2013)

INTRODUCTION:  Little is known on the “very” long-term incidence of major adverse cardiac events (MACE), target-lesion revascularization (TLR), target-vessel revascularization (TVR) and stent thrombosis (ST) after sirolimus-eluting stent (SES) implantation. We present the first study to provide a 10-year clinical follow-up in an unselected patient population who underwent SES implantation.   Methods and Results:  We ran a systematic 10-year clinical follow-up in a series of 200 consecutive patients treated with unrestricted SES implantation between April 2002 and April 2003 in two Swiss hospitals. Outcomes and follow-up were obtained in all 200 patients. The cumulative 10-year MACE rate was 47% with all-cause death of 20%, cardiac death of 9%, myocardial infarction of 7%, TLR and TVR of 8% and 11% respectively. ARC-defined “definite and probable” stent thrombosis-rate was 2.5%. TLR risk was maximal between 3 to 6 years. New lesion revascularization increased throughout the study period.   CONCLUSION:  Incidence of TLR was maximal 3 to 6 years after SES implantation and decreased thereafter. MACE and non-TLR revascularization rates steadily increased during the complete follow-up underlining the progression of coronary artery disease.
Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial
Authors: Maria E. Cabanillas, Jonas A. de Souza, Susan Geyer, Lori J. Wirth, Michael E. Menefee, Stephen V. Liu, Komal Shah, John Wright, Manisha H. Shah
Journal: Journal of Clinical Oncology (2017)

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.