tbuckley/cabot-search huggingface dataset:
Reservoir of Genetic Data Related to Cardiovascular Disease
Authors: Tracy Hampton
Journal: JAMA (2016)

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PATRIOT Trial: Randomized phase II study of prostate stereotactic body radiotherapy comparing 11 versus 29 days overall treatment time.
Authors: Harvey Charles Quon, Aldrich Ong, Patrick Cheung, William Chu, Hans T. Chung, Danny Vesprini, Amit Chowdhury, Dilip Panjwani, Geordi Pang, Renee Korol, Melanie Davidson, Ananth Ravi, Boyd McCurdy, Liying Zhang, Oliver Bucher, Alexandre Mamedov, Andrea Deabreu, Elizabeth Lylyk, D. Andrew Loblaw
Journal: Journal of Clinical Oncology (2015)

6 Background: Stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer is rapidly increasing. Reported regimens differ in time, dose, and fractionation. We report the results of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL) and toxicity. Methods: Men with cT1-2b, Gleason &lt;=7, and PSA &lt;= 20 ng/mL prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered every other day (11 days) vs. once per week (29 days) using gantry-based SBRT. QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) at baseline, weeks 2, 4, 6, 12, months 6 and 12, then annually. Toxicity was graded according to RTOG Criteria. The primary end point was the proportion of patients with a minimum clinically important change (MCIC) in bowel QOL at any time during the acute (&lt;=12 week) period and was analyzed by Fisher’s exact test with a two-sided p &lt; 0.05 considered significant. MCIC was defined as a decrease in EPIC score of &gt;0.5 standard deviation of the baseline value. ClinicalTrials.gov NCT01423474. Results: 152 men from 3 centres were randomized with a median follow-up of 13.1 months. Baseline characteristics were similar in both arms except for the International Prostate Symptom Score with medians of 4 vs. 7 in the 11 and 29 day groups, respectively (p=0.02). There were significant differences between the 11 and 29 day groups in the proportion of patients with acute MCIC in bowel (90.0% vs. 69.6%, p&lt;0.01) and urinary (95.7% vs. 74.6%, p&lt;0.01) scores, respectively. No differences were found in acute sexual (p=0.38) or hormonal (p=0.48) QOL. Worst acute grade 1, 2, 3 toxicities were 64, 18, 0% vs. 41, 11, 0% (p&lt;0.01) for GI and 38, 32, 1% vs. 30, 34, 3% (p=0.69) for GU in the 11 and 29 day groups, respectively. There were no late grade 3+ GI toxicities. Late grade 3 GU toxicity occurred in 1 vs. 0 patients in the 11 and 29 day arms (p=0.32). Conclusions: Prostate SBRT delivered over 29 days was associated with superior bowel and urinary QOL compared to 11 days in the first 3 months of treatment. There were few severe (grade 3+) toxicities in either group. Follow-up is continuing to compare long-term outcomes. Clinical trial information: NCT01423474.
Diverse and Targetable Kinase Alterations Drive Histiocytic Neoplasms
Authors: Benjamin Heath Durham, Eli L. Diamond, Julien Haroche, Zhan Yao, Jing Ma, Sameer A. Parikh, John Choi, Eunhee Kim, Fleur Cohen-Aubart, Stanley Chun-Wei Lee, Yijun Gao, Jean-Baptiste Micol, Patrick Campbell, Michael P. Walsh, Brooke Sylvester, Igor Dolgalev, Aminova Olga, Adriana Heguy, Paul Zappile, Joy Nakitandwe, James Dalton, David W Ellison, Juvianee Estrada-Veras, Mario Lacouture, William A. Gahl, Phil Stephens, Vincent A. Miller, Jeffrey Ross, Siraj Ali, Sebastien Héritier, Jean Donadieu, David Solit, David M. Hyman, Jose Baselga, Filip Janku, Barry S. Taylor, Christopher Y. Park, Ahmet Dogan, Zahir Amoura, Jean-Francois Emile, Raajit K. Rampal, Neal Rosen, Tanja A. Gruber, Omar Abdel-Wahab
Journal: Blood (2015)
Clonal Evolution and Therapy Related Selection Of TP53 Mutations In Chronic Lymphocytic Leukemia Patients
Authors: Karla Plevova, Jitka Malcikova, Martin Trbusek, Sarka Pavlova, Ludmila Sebejova, Boris Tichy, Michael Doubek, Yvona Brychtova, Jiri Mayer, Sarka Pospisilova
Journal: Blood (2013)
Isotype-selective histone deacetylase (HDAC) inhibitor MGCD0103 demonstrates clinical activity and safety in patients with relapsed/refractory classical Hodgkin Lymphoma (HL)
Authors: R. G. Bociek, J. Kuruvilla, B. Pro, A. Wedgwood, Z. Li, M. Drouin, T. Patterson, R. Ward, R. E. Martell, A. Younes
Journal: Journal of Clinical Oncology (2008)

8507 Background: With no approved post-transplant therapies, HL patients (pts) with relapsed or refractory disease have poor prognosis. MGCD0103 is an oral isotype-selective inhibitor of histone deacetylases (HDACs) with significant preclinical and clinical activity in hematopoietic cancers. Methods: Open-label, Phase II trial in adults with relapsed/refractory HL (Trial 010); most with prior transplant. Pts received MGCD0103 at 110 or 85 mg 3x per week in 4-week cycles. Plasma Thymus and Activation Regulated Chemokine (TARC) levels were determined by ELISA. Responses were assessed by CT and PET. Results: 33 pts have been enrolled to date (median age, 31 yrs; range, 19–62 yrs) of which 29 (88%) had prior transplant. Among 23 pts in the 110 mg cohort, 21 were evaluable, of whom 2 (10%) had a complete response (CR) and 6 (29%) had a partial response (PR) for an overall response (OR) rate of 38% (median time to response, 2 cycles). The 2 pts with CR had progression free survival lasting >270 and >420 days with both responses ongoing. One additional pt (5%) had SD >6 cycles. Among 10 pts in the 85 mg cohort, 5 were evaluable for efficacy, all of whom had tumor reductions of ≥30%, including 1 PR and 2 SDs (45% and 49% tumor reduction). Comparison between 85 and 110 mg revealed 20% and 39% of pts respectively with ≥ grade 3 toxicity. Decrease in Day 8 plasma TARC levels correlated with clinical response (PR+CR). Conclusions: MGCD0103 demonstrated significant anti-tumor activity in relapsed/refractory post-transplant HL. The 85 mg dose exhibited meaningful activity and may be better tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MethylGene Inc., Pharmion Corporation MethylGene Inc. MethylGene Inc.
Should We Abandon Routine Visits?
Authors: Thomas J. Poulton
Journal: Annals of Internal Medicine (2016)

Letters4 October 2016Should We Abandon Routine Visits?Thomas J. Poulton, MDThomas J. Poulton, MDFrom The Creighton University School of Medicine, Phoenix, Arizona.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0322 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Himmelstein and Phillips' exhortation to continue thoughtful routine visits (1) arrived in the mail, appropriately, on the same day that I received 3 reminders to attend to necessary care in my own life. My optometrist wants to see me: It has been 1 year since my last visit. My automobile repair shop wants me to bring my car in for a “routine checkup to prevent problems before they happen.” My dentist helpfully reminded me that it has been 6 months since my last visit and that I should “invest in a great smile by scheduling a checkup ...Reference1. Himmelstein DU, Phillips RS. Should we abandon routine visits? There is little evidence for or against. Ann Intern Med. 2016;164:498-9. [PMID: 26747523]. doi:10.7326/M15-2097 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From The Creighton University School of Medicine, Phoenix, Arizona.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0322. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoShould We Abandon Routine Visits? There Is Little Evidence for or Against David U. Himmelstein and Russell S. Phillips Should We Abandon Routine Visits? William R. Phillips Should We Abandon Routine Visits? Daniel Pomerantz Should We Abandon Routine Visits? Stephen J. Gluckman Should We Abandon Routine Visits? David U. Himmelstein and Russell S. Phillips Metrics 4 October 2016Volume 165, Issue 7Page: 529KeywordsBehaviorCheesesConflicts of interestDisclosureOptometrists ePublished: 4 October 2016 Issue Published: 4 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Japanese cellular biologist wins Nobel prize for study of autophagy
Authors: Michael McCarthy
Journal: BMJ (2016)

Yoshinori Ohsumi, a Japanese cellular biologist, has been awarded the Nobel prize in physiology or medicine for his work elucidating how cells break down and recycle obsolete or damaged macromolecules and organelles. The process—called autophagy, from the Greek words auto and phagein, meaning “self eating”—has a vital role in cellular metabolism in health and disease.

“Autophagy has been known for over 50 years,” the Nobel committee noted in its announcement of the award, “but its fundamental importance in physiology and medicine was only recognised after Yoshinori Ohsumi’s paradigm shifting research in the 1990s.” The award, …
Long-Term Health Outcomes in Women With Silicone Gel Breast Implants
Authors: Tim Brown
Journal: Annals of Internal Medicine (2016)

Letters4 October 2016Long-Term Health Outcomes in Women With Silicone Gel Breast ImplantsTim Brown, MChirTim Brown, MChirFrom Berwick, Victoria, Australia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0195 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Balk and colleagues' review systematically examines the literature on use of silicone breast implants over the past 50 years and their possible effect on women's health (1, 2). Not surprisingly, it concludes that (as does almost every meta-analysis in the history of medical publication) further work needs to be undertaken, the evidence is inconclusive, and the study design is poor in many cases.These conclusions undoubtedly will be used to further the particular agendas of any interested party: the universities to set up (well-funded) implant registries, the surgeons to convince patients that implants are safe, and the ...References1. Balk EM, Earley A, Avendano EA, Raman G. Long-term health outcomes in women with silicone gel breast implants. A systematic review. Ann Intern Med. 2016;164:164-75. [PMID: 26550776]. doi:10.7326/M15-1169 LinkGoogle Scholar2. Nanayakkara PW, de Blok CJ. Silicone gel breast implants: what we know about safety after all these years [Editorial]. Ann Intern Med. 2016;164:199-200. [PMID: 26551242]. doi:10.7326/M15-2427 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Berwick, Victoria, Australia.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L16-0195. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoLong-Term Health Outcomes in Women With Silicone Gel Breast Implants Ethan M. Balk , Amy Earley , Esther A. Avendano , and Gowri Raman Long-Term Health Outcomes in Women With Silicone Gel Breast Implants Ethan M. Balk and Gowri Raman Metrics 4 October 2016Volume 165, Issue 7Page: 527KeywordsConflicts of interestDatabasesDisclosureObstetrics and gynecologyPatientsSurgeonsSystematic reviews ePublished: 4 October 2016 Issue Published: 4 October 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
How should doctors be employed?
Authors: Fiona Godlee
Journal: BMJ (2016)

After last week’s question about whether GPs should retain their gatekeeper role (doi:10.1136/bmj.i5272), this week we ask whether all GPs should become NHS employees in the same way hospital doctors are. With the bitter dispute between junior doctors in England and the government now entering a “cold war” (doi:10.1136/bmj.i5213), opting for direct NHS employment may seem like recklessness.

In our latest Head to Head debate Azeem Majeed is more positive about the proposition (doi:10.1136/bmj.i5064). Over a quarter of GPs in England are already salaried, but most of …
The impact of physical activity on fatigue and quality of life in lung cancer patients: A randomised controlled trial (RCT).
Authors: Janette L. Vardy, Melanie Bell, Hidde van der Ploeg, Jane Turner, Michael Kabourakis, Lissa Spencer, Craig R. Lewis, Rina Hui, Prunella Louise Blinman, Stephen John Clarke, Michael J. Boyer, Haryana M. Dhillon
Journal: Journal of Clinical Oncology (2015)

9507 Background: Physical activity (PA) has been shown to improve fatigue and quality of life (QOL) in a range of cancer populations. Little research has been done in the advanced lung cancer setting. This RCT evaluated a 2-month PA intervention in patients with unresectable lung cancer. Methods: Participants were stratified (disease stage, performance status [PS] 0-1 vs 2, center) and randomized (1:1) to usual care (UC) (general nutrition and PA education materials) or UC plus 2-month program of supervised weekly PA and behaviour change sessions and home-based PA. Assessments were completed at baseline, 2, 4 and 6 months. The primary endpoint was fatigue (FACT-F subscale) at 2-months. Secondary endpoints included: QOL, functional abilities, physical fitness, activity (accelerometers), mood, dyspnea, survival and blood results. Intention-to-treat analysis using linear mixed models was done. Results: 111 patients were randomized: male 55%, median age 62 (35-80); 95% NSCLC, 5% SCLC; 95% Stage IV. At baseline 77% were on active treatment. Baseline characteristics, including PA levels, comorbidities and Glasgow Prognostic Score (GPS) were well balanced between groups. Attrition was 22, 36 and 50% at 2, 4 and 6 months respectively; no difference between groups. Adherence to intervention sessions: behavioral 77%, PA 69%. There were no significant differences in fatigue, QOL, symptoms, mood, distress, sleep, dyspnea, activities of daily living, GPS between groups at 2, 4 or 6 months. Patients over report PA levels compared to accelerometer data. Using accelerometer data, PA increased only in the PA group from 0 – 2 months, but the difference in PA between groups was not significant. Median survival (months): PA 13.7 vs UC 12.6 (p= 0.76): 38 participants remain alive. Conclusion: Adherence to the 8-week intervention was good but did not increase PA levels compared to education materials alone. No difference was seen in fatigue, QOL, symptom control or functional status. Clinical trial information: ACTRN12609000971235. PA n=55 UC n=56 P-value FACT-F Fatigue: 0 38.4 36.3 2 37.5 36.3 0.61 4 39.6 35.4 0.10 6 36.6 34.5 0.44 EORTC Global QOL 0 63.8 58.9 2 63.2 64.3 0.81 4 64.2 60.2 0.45 6 60.8 54.2 0.26 Performance Status 0 0.8 0.9 2 0.8 1.0 0.30 4 0.8 1.0 0.16 6 0.7 1.2 0.01
A multicenter open-label phase II study of the efficacy and safety of palbociclib a cyclin-dependent kinases 4 and 6 inhibitor in patients with recurrent ovarian cancer.
Authors: Gottfried E. Konecny, Andrea Elisabeth Wahner Hendrickson, Aminah Jatoi, Jill K. Burton, Jill Paroly, John A. Glaspy, Sean Christopher Dowdy, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2016)

5557 Background: Deregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6) – p16 – Rb signaling pathway is commonly found in ovarian cancer (OC). Palbociclib is an inhibitor of CDK4/6 and was recently shown to delay disease progression in postmenopausal women with advanced breast cancer. Here we study the safety and efficacy of palbociclib in patients (pts) with recurrent OC. Methods: Asymptomaticpts with RECIST and/or CA125 measurable disease failing chemotherapy or anti-hormonal therapy were given oral palbociclib 125 mg once daily for 3 weeks followed by 1 week off over 28-day cycles. Response was assessed every 8 wks. The primary endpoint was proportion of patients progression-free at 6 months. Secondary endpoints included ORR (RECIST or GCIG CA125 criteria), PFS and safety. Tumor was collected for targeted next generation sequencing (NGS). NCT01536743 Results: As of January 28, 2016, 37 of 40 pts were accrued from 2 centers. Safety and efficacy data are available for 37 and 30 pts, respectively. Pt characteristics were: Serous (78%), RECIST measurable disease (87%), elevated CA125 (100%) and ECOG PS 0 (67%). Median age was 61 years (range 42-78). Median number of prior chemotherapy regimens was 3 (range 1-12). The proportion of patients who were progression-free at 6 months were 9/30 (30%). Using RECIST median PFS was 3.7 months (95%CI, 1.2-6.2), and 1/26 PR (4%), 17/26 SD (65%) and 8/26 PD (31%) were seen. Using GCIG CA125 criteria median PFS was 4 months (95%CI, 0.3-7.6), 1/30 CR (3%), 3/30 PR (10%), 18/30 SD (60%) and 8/30 PD (27%) were seen. Toxicity was minimal; grade 2 events included anemia (2), nausea (1) abdominal pain (1), grade 3/4 events included neutropenia (5), thrombocytopenia (4), hypokalemia (1) and emesis (1). 1 pt experienced a bowel obstruction and 1 pt died due to disease progression within 30 days of treatment discontinuation. Efficacy is being correlated with targeted NGS data including CDKN2A, RB or CCNE. Conclusions: CDK4/6 inhibition with palbociclib was well tolerated and demonstrated single-agent activity in heavily pretreated unselected OC patients. Ongoing predictive biomarker analyses may facilitate patient selection. Clinical trial information: NCT01536743.
ExTRaマッピングと呼ばれる新しく開発された(準)リアルタイムフェーズマッピングシステムを用いた心房細動(AF)時におけるRotorの検出
Authors: Fukui Akira, Yamaguchi Takanori, Nagamoto Yasutsugu, Inada Shin, Nakazawa Kazuo, Ashihara Takashi, Tsuchiya Takeshi
Journal: Circulation (2015)
Liposomal Targeted Delivery Overcomes Immunostimulatory Effects of Oligonucleotide Based Therapy In Chronic Lymphocytic Leukemia.
Authors: Bo Yu, Yicheng Mao, Li-Yuan Bai, Sarah E.M. Herman, Asha Ramanunni, Yan Jin, Xiaokui Mo, Carolyn Cheney, Kenneth K. Chan, David Jarjoura, Guido Marcucci, Robert Lee, L.James Lee, John C. Byrd, Natarajan Muthusamy
Journal: Blood (2010)
Symptomatic treatment of pollen-related allergic rhinoconjunctivitis in children: randomized controlled trial
Authors: J. B. Wartna, A. M. Bohnen, G. Elshout, M. W. H. Pijnenburg, D. H. J. Pols, R. R. Gerth van Wijk, P. J. E. Bindels
Journal: Allergy (2016)

Background About 12% of children are affected by allergic rhinoconjunctivitis (AR). Although the main symptomatic treatments are intranasal corticosteroids (INCS) (daily or on demand) and oral antihistamines, it remains unclear which treatment provides the best relief of symptoms. Therefore, this study examines whether daily use of INCS is superior to on-demand use or to oral antihistamines on demand. Methods A single-blinded randomized controlled trial in children (aged 6–18 years) with pollen-related AR. Patients received either INCS daily (fluticasone propionate), INCS on demand (fluticasone propionate) or oral antihistamine on demand (levocetirizine) for 3 months during the grass pollen season. A daily online symptom diary on both nose and eye symptoms was completed. The primary outcome was the percentage of symptom-free days. Results A total of 150 children were randomized. The percentage symptom-free days was in favour of INCS on demand (30%) compared with INCS daily (22%), that is 8% difference (95% CI −5 to +21%; not significant). The antihistamine on-demand group had 15% symptom-free days, that is 7% difference compared to INCS daily (95% CI −6 to +19%;, not significant). Patients in the INCS on-demand group used on average 61% less fluticasone than patients in the INCS daily group during the study period (P < 0.0001). Conclusions This trial with three parallel treatment groups shows that INCS daily was not superior to INCS on demand or to antihistamine on demand regarding the number of symptom-free days. An on-demand INCS strategy has the advantage of a lower overall corticosteroid exposure and less costs.
Relative quantification of protein expression in metastatic renal cell carcinoma using iTRAQ LC-MS/MS analysis reveals galectin-1 as a potential prognostic marker and therapeutic target.
Authors: Nicole M.A. White, Olena Masui, Leroi DeSouza, Olga Krakovska, Ajay Matta, Georg A. Bjarnason, K.W. Michael Siu, George M. Yousef
Journal: Journal of Clinical Oncology (2013)

412 Background: Metastatic renal cell carcinoma (RCC) is one of the most treatment-resistant cancers. Identification of proteins involved in tumor progression will help gain a better understanding of the disease and will form the basis for the identification of novel therapeutic targets. Methods: Using six fresh-frozen primary and six unmatched metastatic RCC tumors, we used iTRAQ labeling and LC-MS/MS analysis to identify proteins differentially expressed in metastatic versus primary RCC. We verified protein expression by western blot and immunohistochemical analyses and the measured the effect of dysregulated protein expression on biological processes with RCC cell line models. Results: After analysis, we identified 29 proteins differentially expressed in metastatic versus primary RCC. We verified expressions of profilin-1, 14-3-3 zeta/delta, and galectin-1 (Gal-1) on two independent tissue sets by western blot (10 primary and 10 metastatic RCC tissues) and immunohistochemistry (22 primary and 23 metastatic tissues). Overexpression of Gal-1 in CAKI-1 cells lead to decreased actin, increased vimentin expression, and increased cellular migration. Additionally, when Gal-1 was decreased via siRNA, cells showed decreased cellular migration. Protein array analysis showed expression of cell motility-related proteins HSP27, JNK, and RSK, were altered after siRNA transfection. We also showed that Gal-1 expression was increased in response to HIF-1alpha. Furthermore, we analyzed the expression of Gal-1 mRNA in 404 RCC patients using the Cancer Genome Anatomy Project, and found that patients who had higher Gal-1 expression in the primary RCC had significantly decreased overall survival (41 vs. 78 months; p &lt; 0.01). Conclusions: Gal-1 is increased in metastatic RCC and can effect cell migration by targeting proteins involved in cell motility. This may be a downstream effect of HIF-1α dysregulation. Decreased Gal-1 significantly decreased cellular migration suggesting Gal-1 may serve as a potential therapeutic target. Additionally, we showed that increased Gal-1 expression was associated with decreased overall survival.