tbuckley/cabot-search huggingface dataset:
Seropositivity combined with smoking is associated with increased prevalence of periodontitis in patients with rheumatoid arthritis
Authors: Kaja Eriksson, Lena Nise, Lars Alfredsson, Anca Irinel Catrina, Johan Askling, Karin Lundberg, Lars Klareskog, Tülay Yucel-Lindberg
Journal: Annals of the Rheumatic Diseases (2017)

An association between periodontitis and rheumatoid arthritis (RA) has been proposed based on observations of increased risk of periodontitis in patients with RA as well as the presence of antibodies to citrullinated protein antigens (ACPAs) and rheumatoid factor (RF) in serum and gingiva of patients with periodontitis.1–3 Additionally, smoking is one of the most important risk factors for both periodontitis and RA, and predispose for the development of seropositive RA.4–6 We have previously reported that smokers with RA have increased prevalence of periodontitis as compared with never smokers in the Swedish population-based case–control study EIRA (Epidemiological Investigation of Rheumatoid Arthritis).7 The objective of the current study was to further investigate the effects of smoking on the risk of periodontitis in seropositive and seronegative (ACPA/RF) subsets of RA.

Data on periodontal status (years 2008–2012) were retrieved from the Swedish Dental Health Registry (DHR) for 2327 patients with established RA (1469/852 ACPA-positive/ACPA-negative and 1505/822 RF-positive/RF-negative, respectively) included in the EIRA study (years 1996–2009) as previously described.7 Periodontal diagnosis was based on diagnostic codes for periodontitis, peri-implantitis and …
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator
Authors: Paul W. Armstrong, Lothar Roessig, Mahesh J. Patel, Kevin J. Anstrom, Javed Butler, Adriaan A. Voors, Carolyn S.P. Lam, Piotr Ponikowski, Tracy Temple, Burkert Pieske, Justin Ezekowitz, Adrian F. Hernandez, Joerg Koglin, Christopher M. O'Connor
Journal: JACC Heart Failure (2017)

This trial sought to evaluate whether vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, was superior to placebo, on a background of standard of care, in increasing the time to the first occurrence of the composite endpoints of cardiovascular (CV) death and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction (HFrEF). Deficiency in sGC-derived cyclic guanosine monophosphate (cGMP) causes both myocardial dysfunction and impaired endothelium-dependent vasomotor regulation that includes the myocardial microcirculation. Experimental studies have suggested multiple potential benefits of sGC stimulators including prevention, or even reversal, of left ventricular hypertrophy and fibrosis, as well as reduction of ventricular afterload through both systemic and pulmonary vasodilation. Hence, restoration of sufficient nitric oxide (NO)-sGC-cGMP signaling has been proposed as an important treatment target in HF. Vericiguat has been shown to directly stimulate sGC and enhance sGC sensitivity to endogenous NO. Available phase IIb data in HFrEF patients indicate vericiguat is safe and well-tolerated, and exploratory analyses indicate that it results in a dose-dependent, clinically significant reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the highest tested dose. VICTORIA (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) is a randomized, placebo-controlled, parallel group, multicenter, double-blind, event-driven phase 3 trial of vericiguat in subjects with HFrEF. Approximately 4,872 subjects will be randomized to evaluate the efficacy and safety of vericiguat compared with placebo on a background of standard of care. After a screening phase of up to 30 days, eligible subjects will be treated until the required number of cardiovascular deaths is observed. The estimated median follow-up duration is approximately 18 months. All subjects will be followed until study completion to assess for the occurrence of endpoint events. VICTORIA will establish the efficacy and safety of vericiguat on cardiovascular death and HF hospitalization in patients with HFrEF. (A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction [HFrEF]-VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction [VICTORIA]; NCT02861534).
A screening test for <i>BRAF</i> mutant melanoma: Immunohistochemical (IHC) analysis of <i>BRAF</i> V600E mutation.
Authors: Tomas Lyons, Odharnaith O'Brien, Sandra Murphy, Richard Bambury, Deirdre O'Mahony, Seamus O'Reilly, Cynthia Heffron, Derek Power
Journal: Journal of Clinical Oncology (2016)

e21076 Background: Activating BRAF V600 mutations have been shown to occur in 40%–60% of melanomas, although the mutation rate among the Irish melanoma population has been reported to be lower (30%). The current standard for determining BRAF mutation status is with the use of the Cobas 4800 PCR test. IHC analysis to determine BRAF mutation status has been made possible by the development of monoclonal antibodies directed at mutant BRAF protein expression, which may be of use as an alternative to molecular testing. Methods: We identified 132 patients with metastatic melanoma between 2011 and 2014 at our institution that had tumour tested for BRAF mutation using PCR. Of these, 122 cases were suitable for IHC. Tissue samples were obtained and tested with the BRAF V600E antibody. IHC was assessed as 0 (negative), 1, 2 or 3 based on intensity of cytoplasmic staining. We assessed the incidence of BRAF mutation, investigated the sensitivity and specificity of the BRAF V600E antibody in detecting the presence of the BRAF V600E mutation. Clinical response to BRAF inhibitor therapy as per RECIST was correlated to BRAF mutation status by PCR and to IHC expression. Results: The incidence of BRAF mutation as assessed by PCR was 28.8% (38/132). The antibody showed a sensitivity of 86.1% with a specificity of 96.9%. The positive predictive value was 96.9%; the negative predictive value was 94.4%. The concordance rate between PCR and IHC was 95.1% (116/122). One false positive case and five false negative cases were observed. The results of clinical outcomes for the PCR positive cohort and the IHC level of expression cohorts are shown in the table. Conclusions: The high concordance rate of PCR and IHC methods in determining BRAF status and predicting response to therapy suggests that antibody testing is a viable and cost effective alternative to PCR testing. The BRAF V600E antibody may be suitable as a screening test for the BRAF mutation, with all negative cases being submitted for PCR testing to identify variant BRAF mutations not detected by IHC. Response Rate (%) Median Duration of Response (months) Median Overall Survival (months) PCR (n = 25) 92 7 12 IHC 3+ (n = 10) 83 9.5 12 IHC 2+ (n = 4) 100 7 10 IHC 1+ (n = 1) 100 18 31 IHC 0 (n = 5) 100 6 8
Duration of response and tumor shrinkage with first-line ribociclib + letrozole in postmenopausal women with HR+, HER2– ABC
Authors: W. Janni, E. Alba Conejo, T. Bachelot, S. Diab, M. Gil-Gil, T.J. Beck, L. Ryvo, R. López, M. Tsai, F.J. Esteva, M.P. Zamora Aunon, Z. Kral, P. Ward, P. Richards, T.J. Pluard, S. Sutradhar, M. Miller, M. Campone
Journal: Annals of Oncology (2017)
AGITG NABNEC: A randomised phase II study of nab-paclitaxel in combination with carboplatin as first line treatment of gastrointestinal neuroendocrine carcinomas
Authors: M. Khasraw, M.S. Hofman, L. Chantrill, N. Pavlakis, V. Gebski, A.J. Gill, B. Markman, S. Yip, E. Gibbs, C. Karapetis, S.F. Wong, D.T. Ransom, M. Michael, K. Wilson, J. Simes, L. Lipton
Journal: Annals of Oncology (2017)
The benefits of patient-centered patient registries.
Authors: Michelle Durborow, Kathrena Aljallad, Jerry Call, Mildred Menos, Norman J. Scherzer
Journal: Journal of Clinical Oncology (2017)

e21625 Background: Created in 2001, The Lift Raft Group GIST Patient Registry has always put the patient at the heart of its work. Those contributing data are not merely study participants but people in need of help. In 2017, the newest evolution of the Registry debuts- GIST/PRIME, an interactive desktop/mobile application that serves both the patient and doctor to track treatment efficacy and disease progression over time rather than the traditional single survey input. Methods: The Registry operates on an SQL cloud based platform under an IRB informed consent process. Incoming members provide their full disease history. Examples of data collected include: Demographic, primary tumor site, date(s) of diagnosis, initiation of treatment, dosage, and response to treatment. Outcomes are based upon response to drug therapy. Research analysis is supported by the platform’s filterable, queryable and auto-calculating fields as well as unique features such as treatment lines which chart therapy history to investigate potential correlation between mutational status, drug treatment and order of drug taken. Results: The traditional registry structure only provides a one-way benefit- from patient to registry. GIST/PRIME seeks to remedy this by providing a clear set of benefits and user-friendly features back to patients: The Dashboard displays Registry demographics and how the patient relates others within the system. Based on entered data, this dashboard can also calculate Risk of Recurrence and provide education on treatment and mutational types; Input and editing of Diagnosis, Evaluation and Treatment; push notifications; The GISTORY- An exportable, printable document that provides a comprehensive summary of a patient’s GIST medical history, helping facilitate efficient communication between patient and doctor. Conclusions: The idea of reframing a patient registry as a tool which can provide as much benefit to its members as it does to the researchers who analyze its data is overdue. By committing to a patient-centered structure and style, registry members are more deeply engaged over time, providing richer data that is not limited to a single drug or place of treatment.
Selective Androgen Receptor Modulator RAD140 Inhibits the Growth of Androgen/Estrogen Receptor–Positive Breast Cancer Models with a Distinct Mechanism of Action
Authors: Ziyang Yu, Suqin He, Dannie Wang, Hitisha K. Patel, Chris P. Miller, Jeffrey L. Brown, Gary Hattersley, Jamal C. Saeh
Journal: Clinical Cancer Research (2017)

Purpose: Steroidal androgens suppress androgen receptor and estrogen receptor positive (AR/ER+) breast cancer cells and were used to treat breast cancer, eliciting favorable response. The current study evaluates the activity and efficacy of the oral selective AR modulator RAD140 in in vivo and in vitro models of AR/ER+ breast cancer.Experimental Design: A series of in vitro assays were used to determine the affinity of RAD140 to 4 nuclear receptors and evaluate its tissue-selective AR activity. The efficacy and pharmacodynamics of RAD140 as monotherapy or in combination with palbociclib were evaluated in AR/ER+ breast cancer xenograft models.Results: RAD140 bound AR with high affinity and specificity and activated AR in breast cancer but not prostate cancer cells. Oral administration of RAD140 substantially inhibited the growth of AR/ER+ breast cancer patient-derived xenografts (PDX). Activation of AR and suppression of ER pathway, including the ESR1 gene, were seen with RAD140 treatment. Coadministration of RAD140 and palbociclib showed improved efficacy in the AR/ER+ PDX models. In line with efficacy, a subset of AR-repressed genes associated with DNA replication was suppressed with RAD140 treatment, an effect apparently enhanced by concurrent administration of palbociclib.Conclusions: RAD140 is a potent AR agonist in breast cancer cells with a distinct mechanism of action, including the AR-mediated repression of ESR1 It inhibits the growth of multiple AR/ER+ breast cancer PDX models as a single agent, and in combination with palbociclib. The preclinical data presented here support further clinical investigation of RAD140 in AR/ER+ breast cancer patients. Clin Cancer Res; 23(24); 7608-20. ©2017 AACR.
The role of hepatocyte nuclear factor 1 homeobox B (HNF1B) loss in chromophobe RCC (ChRCC) development
Authors: E. Jonasch, G. Fuller, I. McCutcheon, Z. Ding, L. Zhou, X. Liu, W. Kong, R. Powell, I.-Y. Park, N. Tannir, W.K. Rathmell, B. Dong, S. Matin, X. Tong, Y. Huang, P. Tong, J. Wang, C. Walker, M. Sun
Journal: Annals of Oncology (2017)
Recommended cancer screening and vulnerable populations: results from the EDIFICE 5 survey
Authors: J-F. Morere, F. Eisinger, J-Y. Blay, S. Couraud, L. Brignoli-Guibaudet, C. Lhomel, A. Cortot, L. Greillier, J. Viguier
Journal: Annals of Oncology (2017)
Change of patient perceptions of chemotherapy side effects in breast and ovarian cancer patients
Authors: B. Ataseven, J. Frindte, P. Harter, G. Göke, J. Holtschmidt, C. Vogt, A. Traut, B. Vincenzo, M. Vincent, H. Florian, S. Kuemmel, S. Prader, M. Sporkmann, S. Schneider, A. du Bois
Journal: Annals of Oncology (2017)
Global project to map drug resistance and tackle “superbugs” is launched
Authors: Jacqui Wise
Journal: BMJ (2017)

A project that aims to generate the largest dataset on antimicrobial resistance has been launched as part of a global effort to tackle the growing problem of drug resistant “superbugs.”

The Global Burden of Disease AMR project is a collaboration between the UK government, the UK health research charity the Wellcome Trust, the Bill and Melinda Gates Foundation, the University of Oxford, and the Institute for Health Metrics and Evaluation, an independent research centre at the University of Washington, Seattle.

Over the next four years the project will gather and publish data on the spread and effects of antimicrobial resistance around the world.

England’s chief medical …
Cancer Genetic Counseling Services (GCS) at Saint Francis Cancer Treatment Center (SFCTC).
Authors: Mehmet Sitki Copur, Kimberly Brussow, Jack Wagoner, Ryan C. Ramaekers, Mithat Gonen, Stephanie Percich, Dron Gauchan, Lata Nawal, Mary Mickey, Max Norvell, Douglas Clark, K. M Islam
Journal: Journal of Clinical Oncology (2015)

e12506 Background: Approach to cancer prevention, detection, and therapy has been revolutionized by rapid progress in genetic/genomic technology making GCS a crucial component of cancer care. Majority of cancer patients (pts) reside in the community where patient/provider awareness, resources, and utilization of GCS are limited. Optimal utilization of GCS in this setting has not been well studied. Methods: Six years of GCS data at SFCTC, a community-based cancer center in rural Nebraska, were analyzed. Data included medical/family history, genetic counseling(GC) referral source/rate, refusal/failure to show, risk assessment/management, genetic tests (GT) offered/performed, and genetic syndromes (GS) suspected/confirmed. Results: 2009 through 2015, 483 of 3107 (15%) new cancer pts were referred for GC. 29% failed to show due to lack/fear of insurance/discrimination, fear of bad news, and travel limitations. 83% was referred by medical oncologists (MO) vs 17% by primary care PCP (p = 0.001). 3% of all referrals (refs) initiated by self request. 41% of MO vs 50% of PCP refs had a GT performed (p = 0.20). 6% of MO vs 13% of PCP refs had a positive GT (p = 0.10). 6% of refs with breast/ovarian cancer and 7% of refs with colorectal cancer had confirmed hereditary breast/ovarian cancer and Lynch syndromes respectively. 10% of refs with a hereditary cancer syndrome in family but no self-cancer diagnosis had a 14% rate of confirmed hereditary cancer syndrome (p = 0.38). Post GT counseling was given to all. Conclusions: Availability of GCS enhanced its utilization. One third of pts refused/failed to show while 3% self-requested through their PCP. MO referred more than PCP. Acceptance/performance of GT and detection of positive GT were not different between MO vs PCP refs. A personal cancer diagnosis vs a known family history of hereditary cancer syndrome without cancer diagnosis detected cancer syndrome diagnoses similarly. Our data highlight the need for awareness/education in optimal utilization of GCSs in the community and may serve as a reference for current perception/utilization of GCSs in the community setting where scarce data exist. Larger studies of GCS along with evaluation of universal healthcare/telemedicine effects are needed.
Abstract 3: The Histone Methyltransferase Smyd1 is a Novel Transcriptional Regulator of Cardiac Fatty Acid Metabolism in Mice
Authors: Junko S Warren, Dane W Barton, Mickey Miller, Li Wang, James Cox, Tatiana N Yuzyuk, Alexey V Zaitsev, Sarah Franklin
Journal: Circulation Research (2016)

Epigenetic control of metabolism in the healthy and diseased heart remains poorly understood. We recently demonstrated that chromatin-bound Smyd1, a muscle-specific histone methyltransferase, is significantly upregulated in a mouse model of pressure overload-induced heart failure (HF) and that inducible, cardiac-specific Smyd1 knock-out (Smyd1-KO) mice develop cellular hypertrophy and fulminate HF. Bioinformatic analysis of transcripts differentially regulated in these mice revealed that cardiac metabolism was the most perturbed biological function in the heart. However, it was not clear whether alterations in cardiac metabolism were a direct consequence of Smyd1 deletion or were secondary to developed HF. Here we hypothesized that Smyd1 directly regulates cardiac metabolism; the effects of which should be detectable in Smyd1-KO mice before overt cardiac dysfunction. To test this hypothesis we performed unbiased metabolomic analysis of Smyd1-KO mice using GC/MS and MS/MS (n=9 control, n=10 KO) combined with targeted gene expression analysis. Our results showed significant changes in the metabolic profile of Smyd1-KO mice at the earliest time point (3 weeks after tamoxifen treatment) in which Smyd1 protein expression was significantly reduced while cardiac function remained normal. The most profound difference, in energetics-associated pathways in these mice, was found in fatty acid β-oxidation, manifested by the decreased myocardial content of carnitine and free fatty acids and downregulation of their transporters, OCTN2 and CD36. In addition, mRNA levels of the PPAR-α complex (PPAR-α;RXR-α;PGC-1α), an established regulator of fatty acid β-oxidation, and its target genes (CPT1b;CD36;Acox1;MCAD) were significantly reduced in Smyd1-KO mice prior to the onset of cardiac dysfunction (all p&lt;0.05). To identify whether Smyd1 directly controls gene expression of PPAR-α, we examined the PPAR-α loci using chromatin-immunoprecipitation followed by qPCR and observed significant binding of Smyd1 upstream of the PPAR-α transcriptional start site. Overall, this study identifies Smyd1 as a novel regulator of fatty acid metabolism and suggests that Smyd1 controls cardiac energetics directly by regulating gene expression of PPAR-α.
Improved long-term clinical outcomes and safety profile of sunitinib dosing schedule with 4/2 switched to 2/1 in patients with metastatic renal cell carcinoma
Authors: X. Zhang, G. Sun, J. Zhao, K. Shu, P. Zhao, J. Liu, Y. Yang, Q. Tang, J. Chen, P. Shen, H. Zeng
Journal: Annals of Oncology (2017)
Eurosurveillance – keeping an eye on infectious diseases
Authors: I Steffens, K Ekdahl
Journal: Eurosurveillance (2010)

Preview this article: Eurosurveillance – keeping an eye on infectious diseases, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/15/1/art19452-en-1.gif
Low-dose metronomic oral cyclophosphamide plus prednisone for castration resistant prostate cancer (CRPC): A retrospective study.
Authors: Nieves Martinez Lago, Urbano Anido Herranz, Luis Leon Mateos, Maria Vieito, Rafael Varela Ponte, Santiago Aguin Losada, Elena Brozos Vazquez, Marta Carmona Campos, Carmela Rodriguez Lopez, Alexandra Sabela Cortegoso mosquera, Sonia Candamio Folgar, Rafael López López
Journal: Journal of Clinical Oncology (2013)

e16095 Background: CRPC remains a therapeutic challenge, although in recent years the introduction of new agents has allowed an improvement in overall survival of these patients. In the literature there are few data on the use of cyclophosphamide in this context. The current study was designed to evaluate the efficacy and toxicity of the metronomic oral administration of a combination of cyclophosphamide and prednisone in patients with CRPC, not candidates for docetaxel or after progression to it. Methods: We retrospectively evaluated the medical records of all patients with metastatic CRPC who were treated with prednisone and cyclophosphamide in our institution. Patients had been previously treated with a docetaxel-containing regimen or were not considered candidates for taxanes, because of important comomorbidities or poor Performance Status (PS). Results: Data from 40 patients treated with cyclophosphamide 50 mg/day vo and prednisone 5 mg bid from January 2010 to December 2012 has been analyzed. Baseline characteristics of the patients are listed in the Table. 36 patients were evaluable for efficacy and toxicity. The PSA response rate (RR) was 30%, with partial responses in 7/40 patients. The clinical benefit (stabilization disease + RR) was 52%. Median progression-free survival was 13 weeks (95% CI 13.2 – 14.5). Median overall survival was 46 weeks (95% CI 26.4 – 65.9). The overall 1-year and 2-year survival were 32% and 8 %, respectively. The treatment was safe and well tolerated. Anemia (grade 0-3) was observed in a third of all patients. Conclusions: In this study in patients with a poor prognosis, metronomic oral cyclophosphamide plus prednisone have demonstrated efficacy with excelent tolerance. Oral cyclophosphamide is an interesting alternative to consider in patients non candidates for intravenous chemotherapy. [Table: see text]
ARIEL4: An international, randomised phase 3 study of the PARP inhibitor rucaparib vs chemotherapy for the treatment of BRCA-mutated, relapsed, high-grade ovarian cancer
Authors: R.S. Kristeleit, D. Lorusso, A. Oaknin, T. Safra, E.M. Swisher, I.M. Bondarenko, T. Huzarski, J. Klat, V. Moiseyenko, R.L. Póka, L.S. Viola, C. Tankersley, L. Maloney, S. Goble, C. Unger, A. Dowson, H. Giordano, A.M. Oza
Journal: Annals of Oncology (2017)
Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib
Authors: V. Koneti Rao, Sharon Webster, Virgil A. S. H. Dalm, Anna Šedivá, P. Martin van Hagen, Steven Holland, Sergio D. Rosenzweig, Andreas D. Christ, Birgitte Sloth, Maciej Cabanski, Aniket D. Joshi, Stefan de Buck, Julie Doucet, Danilo Guerini, Christoph Kalis, Ilona Pylvaenaeinen, Nicolas Soldermann, Anuj Kashyap, Gulbu Uzel, Michael J. Lenardo, Dhavalkumar D. Patel, Carrie L. Lucas, Christoph Burkhart
Journal: Blood (2017)