tbuckley/cabot-search huggingface dataset:
Abstract 11771: Health Self-efficacy is Associated With Increased Physical Activity in Patients With Coronary Heart Disease
Authors: Justin M Bachmann, Kenneth A Wallston, Christianne L Roumie, Daniel Munoz, Niral Patel, Sunil Kripalani
Journal: Circulation (2015)

Introduction: Physical inactivity is strongly associated with morbidity and mortality, especially in patients with coronary heart disease (CHD). Low levels of health self-efficacy, or a patient’s belief in his ability to engage in behaviors to improve his health, may serve as a barrier to regular physical activity in CHD patients. We evaluated the association of health self-efficacy with physical activity in the Mid-South Coronary Heart Disease Cohort Study (MCHDCS). Methods: The MCHDCS is a prospective cohort of outpatients with CHD. Participants complete a set of validated demographic, psychological, social, behavioral, and functional measures. Health self-efficacy is assayed using two items from the Perceived Health Competence Scale (PHCS-2) that comprise a ten point scale with higher scores indicating better self-efficacy. Physical activity is evaluated with the International Physical Activity Questionnaire, which measures activity in metabolic equivalent (MET)-minutes/week. Less than 600 MET-minutes/week is considered to be a low physical activity level. We used negative binomial and ordinal logistic regression to evaluate the association of self-efficacy with physical activity. Results: A total of 1612 MCHDCS participants (31% female, 9% minority, mean age 67.5 + 10.6 years) were included in the analysis. The majority of participants had low physical activity levels, with a median of 540 (interquartile range 100 to 1600) MET-minutes/week. Each one point increase on the PHCS-2 scale was associated with an 8.7% increase (95% confidence interval 2.9%-14.9%, p=0.003) in MET-minutes/week after adjustment for socioeconomic status as well as depression, health literacy, social support and other factors (Table). Conclusions: Health self-efficacy is associated with physical activity in patients with CHD. Further study is needed to determine whether interventions to increase self-efficacy will raise levels of physical activity in this population.
Re-induction using whole cell melanoma vaccine genetically modified to melanoma stem cells-like beyond recurrence extends long term survival of high risk resected patients - updated results
Authors: Jacek Mackiewicz, Tomasz Burzykowski, Dariusz Iżycki, Andrzej Mackiewicz
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> AGI-101H is an allogeneic gene modified whole cell therapeutic melanoma vaccine, evaluated in over 400 melanoma patients in the adjuvant and therapeutic settings. We present updated long-term survival results from two single-arm, phase II adjuvant trials (Trial 3 and Trial 5) with the focus on treatment beyond recurrence of the disease. <h3>Methods</h3> Patients with resected high-risk melanoma (stage IIIB-IV) were enrolled to Trial 3 (<i>n</i>&nbsp;= 99) and Trial 5 (<i>n</i>&nbsp;= 97). The primary endpoint was disease-free survival (DFS), and the secondary was overall survival (OS). In the induction phase, the vaccine was administered every 2 weeks (eight times), followed by the maintenance phase every month until progression. At progression, maintenance was continued or re-induction was applied with or without surgery. <h3>Results</h3> In Trial 3, the 10-year DFS was equal to 33.0% overall and to 52.4, 25.0, and 8.7% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the overall 10-year DFS was equal to 24.2%, and to 37.5, 18.0, and 17.6% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 3, the 10-year OS was equal to 42.3% overall, and to 59.5, 37.5, and 17.4% for stage IIIB, IIIC, and stage IV patients, respectively. In Trial 5, the 10-year OS was equal to 34.3% overall and to 46.9, 28.0, and 29.4% for stage IIIB, IIIC, and stage IV patients, respectively. Among the 65 patients of Trial 3 who developed progression, 43 received re-induction with (<i>n</i>&nbsp;= 22) or without (<i>n</i>&nbsp;= 21) surgery. Two patients received surgery without re-induction. All the 22 progressing patients, who did not receive re-induction, died. Among the 75 patients of Trial 5 who experienced progression, 39 received re-induction with (<i>n</i>&nbsp;= 21) or without (<i>n</i>&nbsp;= 18) surgery. Among the 36 progressing patients who did not receive the re-induction, 35 died. Surgery and re-induction reduced (independently) the increase of mortality after progression in both trials, with the effect of re-induction reaching statistical significance in Trial 5. <h3>Conclusions</h3> Vaccination beyond recurrence of the disease with additional re-induction combined with surgery or alone increased long term survival of melanoma patients. However, further studies on larger patient cohorts are required. <h3>Trial registration</h3> Central Evidence of Clinical Trials (EudraCT Number 2008–003373-40)
Surgeons call for compulsory registers of all new medical devices
Authors: Rebecca Coombes
Journal: BMJ (2018)

The government must act urgently to reform the lax regulation system governing medical devices, including a compulsory registry of all new implants, says the Royal College of Surgeons.

The call comes after a global investigation by journalists from 36 countries, including The BMJ , BBC Panorama , and the Guardian , into the medical device industry, which unearthed thousands of documents to reveal rising numbers of malfunctions and injuries.

The government said that it would work with the UK regulator to see what changes were required.

The investigation also provides new evidence of devices being implanted in humans after tests only in pigs or after small scale studies of just tens of patients. The lack of transparency and available data means that the scale of problems remains hidden from doctors and patients. Unlike with drugs, many devices are introduced rapidly onto the market without clinical trial data or centrally held evidence.

The president of the Royal College of Surgeons, …
The Direct Antiglobulin Test for Evaluating Anemia
Authors: Corbin Eule, Arjun Gupta, Srikanth Nagalla
Journal: JAMA (2018)

A 68-year-old woman with chronic lymphocytic leukemia (CLL) presents with dyspnea on exertion, conjunctival pallor and scleral icterus, and moderate anemia with elevated reticulocytes and LDH and a 3+ anti-IgG direct antiglobulin test (DAT). How do you interpret the results?
Arg1 expression defines immunosuppressive subsets of tumor-associated macrophages
Authors: Sean P Arlauckas, Seth B Garren, Chris S Garris, Rainer H Kohler, Juhyun Oh, Mikael J Pittet, Ralph Weissleder
Journal: Theranostics (2018)

Tumor-associated macrophages (TAM) have attracted attention as they can modulate key cancer-related activities, yet TAM represent a heterogenous group of cells that remain incompletely characterized. In growing tumors, TAM are often referred to as M2-like macrophages, which are cells that display immunosuppressive and tumorigenic functions and express the enzyme arginase 1 (Arg1). Methods: Here we combined high resolution intravital imaging with single cell RNA seq to uncover the topography and molecular profiles of immunosuppressive macrophages in mice. We further assessed how immunotherapeutic interventions impact these cells directly in vivo. Results: We show that: i) Arg1+ macrophages are more abundant in tumors compared to other organs; ii) there exist two morphologically distinct subsets of Arg1 TAM defined by previously unknown markers (Gbp2b, Bst1, Sgk1, Pmepa1, Ms4a7); iii) anti-Programmed Cell Death-1 (aPD-1) therapy decreases the number of Arg1+ TAM while increasing Arg1- TAM; iv) accordingly, pharmacological inhibition of arginase 1 does not synergize with aPD-1 therapy. Conclusion: Overall, this research shows how powerful complementary single cell analytical approaches can be used to improve our understanding of drug action in vivo.
Abstract 14780: The First Hundred Days: Gender Differences in Psychosocial Distress After Heart Transplant
Authors: Lynn Doering, Belinda Chen, Kathleen Hickey, Erik Carter, Carmen Castillo, David Pickham, Donna Mancini, Mario Deng, Jon Kobashigawa, Barbara Drew
Journal: Circulation (2015)

Early psychological distress after heart transplant (HTx) is associated with adverse outcomes (e.g. poorer medical compliance, higher risk of infection). In the HTx population, gender effects of depression and anxiety symptoms are controversial. Our objective was to examine gender differences in psychosocial measures early after HTx. Methods: We enrolled 91 adult HTx patients (29% female, mean age=51 ± 14 years) who completed measures of depression (Patient Health Questionnaire [PHQ]-9), anxiety (Brief Symptom Inventory [BSI]), perceived control (Control Attitudes Scale-Revised) and quality of life (QOL) (RAND-36 Health Survey) in the first 100 days after HTx (mean time from HTx = 50 ± 24 days). Hierarchical multiple linear regression models were used to examine gender influences on depression, anxiety, control, and QOL. Results: Compared to men, women are more likely to experience high depressive symptoms (15% vs. 39%, p=0.02), high levels of anxiety (46% vs.77%, p=0.008), and low perceived control (average score 33 vs. 29, p=0.007). For both men and women, anxiety is more prevalent than depressive symptoms (Figure). Compared to men, women had lower QOL due to pain (p=0.045) and limitations from emotional problems (p=0.02). In linear regression analyses, the effect of gender remained significant on depression (p=0.003), anxiety (p=0.03), and perceived control (p=0.02), but not QOL, after controlling for demographics (age, marital status, race, time between HTx and questionnaire completion, and Charlson Comorbidity Index). Conclusion: In the first 100 days after HTx, women experience more depressive and anxiety symptoms and less control over their heart health than men. Clinicians should monitor these symptoms early after HTx, especially in women. Development of gender-specific interventions aimed at a smooth post-HTx transition are warranted. Future research is needed to evaluate the relationship of anxiety and depressive symptoms before and after HTx.
Annals Story Slam - Chocolate Mousse
Authors: Dhruv Nayyar
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - Chocolate MousseFREEDhruv Nayyar, MDDhruv Nayyar, MDUniversity of Toronto, Toronto, Ontario, Canada (D.N.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0033 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Chocolate Mousse "Chocolate Mousse," by Dhruv Nayyar, MD (Duration 5:50)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto, Toronto, Ontario, Canada (D.N.)Current Author Address: Dhruv Nayyar, MD; e-mail, dhruv.[email protected]utoronto.ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1KeywordsChocolate ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer
Authors: T.Y. Seiwert, C.C. Foster, E.A. Blair, T.G. Karrison, N. Agrawal, J.M. Melotek, L. Portugal, R.J. Brisson, A. Dekker, S. Kochanny, Z. Gooi, M.W. Lingen, V.M. Villaflor, D.T. Ginat, D.J. Haraf, E.E. Vokes
Journal: Annals of Oncology (2018)

BackgroundPatients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.Patients and methodsPatients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%–50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity.ResultsSixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001).ConclusionsInduction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified.Clinical trial registrationClinical trials.gov identifier: NCT02258659.
Abstract 16474: Arrhythmic Events in Patients With Cardiac Channelopathies Submitted to Local Dental Anesthesia. A Randomized Pilot Study
Authors: Ana Carolina Guimaraes Oliveira, Itamara Neves, Mauricio Scanavacca, Luciana Sacilotto, Natalia Olivetti, Denise Hachul, Silvio Barbosa, Cesar Grupi, Ricardo Neves, Francisco Darrieux
Journal: Circulation (2017)

Ion channels disorders, such as Brugada Syndrome (BS), long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) may account for at least one-third of the unexplained...
Molecular remission and response patterns in patients with mutant-IDH2 acute myeloid leukemia treated with enasidenib
Authors: Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Daniel A. Pollyea, Richard M. Stone, Jessica K. Altman, Gail J. Roboz, Manish R. Patel, Robert Collins, Ian W. Flinn, Mikkael A. Sekeres, Anthony S. Stein, Hagop M. Kantarjian, Ross L. Levine, Paresh Vyas, Kyle J. MacBeth, Alessandra Tosolini, Jason VanOostendorp, Qiang Xu, Ira Gupta, Thomas Lila, Alberto Risueno, Katharine E. Yen, Bin Wu, Eyal C. Attar, Martin S. Tallman, Stéphane de Botton
Journal: Blood (2018)
Prediction of Acute Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation Using a Machine Learning Algorithm
Authors: Yasuyuki Arai, Tadakazu Kondo, Kyoko Fuse, Yasuhiko Shibasaki, Masayoshi Masuko, Junichi Sugita, Takanori Teshima, Naoyuki Uchida, Takahiro Fukuda, Kazuteru Ohashi, Yukiyasu Ozawa, Tatsuo Ichinohe, Yoshinobu Kanda, Yoshiko Atsuta
Journal: Blood (2018)
David Oliver: Preventing a Gosport repeat
Authors: David Oliver
Journal: BMJ (2018)

In the wake of this June’s inquiry report on the sometimes preventable or needlessly distressing deaths of 451 patients at Gosport War Memorial Hospital in the 1990s,1 a November Commons statement by the health secretary set out policies aiming to prevent a repeat and to improve wider healthcare safety.2

I broadly welcome such government attention, but the devil is in the detail. Ultimately, the only way to improve safety and prevent further scandals is through the culture and solutions of local organisations.3 Reports on other recent mass care failings have shown that external regulation can be late in recognising them.456 A recent King’s Fund report on the Care Quality Commission questioned its record in improving safety rather than describing or rating …
Growth Hormone’s Links to Cancer
Authors: Cesar Luiz Boguszewski, Margaret Cristina da Silva Boguszewski
Journal: Endocrine Reviews (2018)

Several components of the GH axis are involved in tumor progression, and GH-induced intracellular signaling has been strongly associated with breast cancer susceptibility in genome-wide association studies. In the general population, high IGF-I levels and low IGF-binding protein-3 levels within the normal range are associated with the development of common malignancies, and components of the GH-IGF signaling system exhibit correlations with clinical, histopathological, and therapeutic parameters in cancer patients. Despite promising findings in preclinical studies, anticancer therapies targeting the GH-IGF signaling system have led to disappointing results in clinical trials. There is substantial evidence for some degree of protection against tumor development in several animal models and in patients with genetic defects associated with GH deficiency or resistance. In contrast, the link between GH excess and cancer risk in acromegaly patients is much less clear, and cancer screening in acromegaly has been a highly controversial issue. Recent studies have shown that increased life expectancy in acromegaly patients who attain normal GH and IGF-I levels is associated with more deaths due to age-related cancers. Replacement GH therapy in GH deficiency hypopituitary adults and short children has been shown to be safe when no other risk factors for malignancy are present. Nevertheless, the use of GH in cancer survivors and in short children with RASopathies, chromosomal breakage syndromes, or DNA-repair disorders should be carefully evaluated owing to an increased risk of recurrence, primary cancer, or second neoplasia in these individuals.
CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells
Authors: Gang Liu, Kangmao Huang, Zhiwei Jie, Yizheng Wu, Junxin Chen, Zizheng Chen, Xiangqian Fang, Shuying Shen
Journal: Molecular Cancer (2018)

There is an urgent need to identify new molecular targets for treatment of osteosarcoma. Circular RNAs are a class of endogenous RNAs that are extensively found in mammalian cells and exert critical functions in the regulation of gene expression, but in osteosarcoma the underlying molecular mechanism of circular RNAs remain poorly understood. Here we assessed the tumorigenesis properties of a circular RNA, circFAT1 in osteosarcoma. The effects of circFAT1/miR-375/YAP1 was evaluated on human osteosarcoma cells growth, apoptosis, migration, invasion and tumorigenesis. Signaling pathways were analyzed by western blotting, qRT-PCR, fluorescence in situ hybridization, chromogenic in situ hybridization,RNA Binding Protein Immunoprecipitation and immunofluorescence. The consequence of circFAT1 short hairpin RNA combined or not with miR-375 sponge was evaluated in mice bearing 143B xenografts on tumor growth. In this study, we observed significant upregulation of circFAT1 originating from exon 2 of the FAT1 gene in human osteosarcoma tissues and cell lines. Inhibition of circFAT1 effectively prevented the migration, invasion, and tumorigenesis of osteosarcoma cells in vitro and repressed osteosarcoma growth in vivo. Mechanistic studies revealed that circFAT1 contains a binding site for the microRNA-375 (miR-375) and can abundantly sponge miR-375 to upregulate the expression of Yes-associated protein 1. Moreover, inhibition of miR-375 reversed attenuation of cell proliferation, migration, and invasion, which was induced by circFAT1 knockdown, and therefore promoted tumorigenesis. Our findings demonstrate a novel function of circFAT1 in tumorigenesis and suggest a new therapeutic target for the treatment of osteosarcoma.
Ibudilast Inhibits Chemokine Expression in Rheumatoid Arthritis Synovial Fibroblasts and Exhibits Immunomodulatory Activity in Experimental Arthritis
Authors: Felix I. L. Clanchy, Richard O. Williams
Journal: Arthritis & Rheumatology (2018)

Ibudilast is a well-tolerated, orally available phosphodiesterase 4 (PDE4) inhibitor used to treat asthma and stroke. Since PDE4 inhibition suppresses inflammatory mediator production and cell proliferation in leukocytes, ibudilast may be a valuable therapy for the treatment of inflammatory autoimmune diseases such as rheumatoid arthritis (RA). This study was undertaken to assess the therapeutic potential of ibudilast by measuring its capacity to modulate inflammation in human leukocytes and RA synovial fibroblasts (RASFs) and in experimental arthritis.Using standard curve quantitative polymerase chain reaction, the effect of ibudilast on gene expression in activated human leukocytes and RASFs was measured. Ibudilast was used to treat DBA/1 mice with collagen-induced arthritis, and an adoptive transfer model was used to assess its tolerogenic capacity.Ibudilast inhibited the expression of TNF, IL12A, and IL12B and the secretion of tumor necrosis factor (TNF) and interleukin-12 (IL-12)/23p40 from leukocytes, and reduced the expression of CCL5 and CCL3 in activated RASFs. Treatment of experimental arthritis with ibudilast resulted in a reduction in IL-17-producing cells and inhibition of disease progression. When combined with a TNF inhibitor, ibudilast caused marked suppression of active disease. Exposure of leukocytes from type II collagen-immunized DBA/1 mice to ibudilast in vitro attenuated their ability to adoptively transfer arthritis to DBA/1J-PrkdcSCID mice, providing evidence of an immunomodulatory effect.Our findings indicate that ibudilast reduces the expression and/or secretion of inflammatory mediators from activated human leukocytes and RASFs, inhibits Th17 cell responses in vivo, and improves established arthritis. Given the established safety profile of ibudilast in humans, its clinical evaluation in RA, either alone or in combination with a TNF inhibitor, should be considered.