tbuckley/cabot-search huggingface dataset:
IMPROVED QUALITY OF LIFE WITH AUTOMATIC POSITIVE AIRWAY PRESSURE FOR OBSTRUCTIVE SLEEP APNEA IN HEART FAILURE WITH REDUCED EJECTION FRACTION: A RANDOMISED CONTROLLED TRIAL
Authors: Olaf Oldenburg, Henrik Fox, Birgit Wellmann, Ulrich Thiem, Dieter Horstkotte, Thomas Bitter
Journal: Journal of the American College of Cardiology (2018)
ACHIEVEMENT OF NORMOKALEMIA IN HEART FAILURE PATIENTS NOT ON RENIN:ANGIOTENSIN:ALDOSTERONE SYSTEM INHIBITORS: POOLED ANALYSIS FROM TWO PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE:BLIND, PLACEBO:CONTROLLED TRIALS OF SODIUM ZIRCONIUM CYCLOSILICATE FOR TREATMENT OF HYPERKALEMIA
Authors: Mikhail Kosiborod, Bhupinder Singh, Jose Menoyo, Henrik Rasmussen
Journal: Journal of the American College of Cardiology (2016)
Identification of mechanisms of immune regulation and exhaustion generated by tumor-derived exosomes in patients with advanced non-small cell lung cancer using the trans-vivo DTH assay.
Authors: Diego Lema, Ewa Jankowska-Gan, William Burlingham, Ticiana A.B. Leal
Journal: Journal of Clinical Oncology (2018)

175 Background: The success of PD-1/PD-L1 inhibition is clearly dependent on optimal patient selection. Developing validated biomarkers that identify patients with an increased probability of response to these antibodies remains a challenge. DTH responses are a standard method to evaluate cellular immune responses in animal and human immunotherapy trials. The trans-vivo delayed-type hypersensitivity (tvDTH) methodology, using the SCID mouse footpad swelling response to human PBMC (peripheral blood mononuclear cells) + antigen injection, and using antibodies to block the regulatory pathways, was developed in our laboratory and has been used to characterize regulation systems in tolerant transplant recipients and more recently in prostate cancer. Methods: In this pilot project we aim to investigate the mechanisms of regulatory immune responses in patients with advanced NSCLC receiving anti-cancer therapies using the tvDTH, and to correlate tvDTH results with responses to checkpoint inhibitor blockade therapy. So far we have enrolled 4 NSCLC patients. PBMCs are obtained by blood draw and lung cancer antigen (LCA) is prepared from malignant pleural effusion cellular pellet or fresh frozen tumor. 1 of 4 patients’ sample was negative for malignancy. Results: Our preliminary data suggests that all NSCLC patients with pleural effusions positive for malignancy had a PD-1-dependent exhausted immune response towards their LCA. Remarkably, 1 of these patients not only showed PD-1-dependent exhaustion, but also PD-1-dependent bystander suppression, whereby a positive control immune response was reduced by co-injection of LCA, suggesting the existence of immunosuppressive mechanisms. Unlike our previous results with prostate cancer, no patient showed CTLA-4-dependent exhaustion or suppression. Importantly, an antigen preparation from a NSCLC that showed no malignant cells by cytology did not induce a swelling response. Conclusions: We plan to expand our study patient population and follow up our patients in order to correlate tvDTH results with clinical outcomes.
Heat targeted drug delivery (COMBAT) in superficial TCC : First midterm results in a cohort of high-risk patients scheduled for cystectomy.
Authors: Thomas Alexander Voegeli, Eric Frank, Christian Bach, Catejan Nzeh
Journal: Journal of Clinical Oncology (2018)

442 Background: Due to the suboptimal outcomes in recurrent superficial TCC over the last 30 years the search for new treatments continues. We report the first mid term results of a high risk cohort of heavily pretreated patients by a circulating device for intravesical thermochemotherapy.It is known that the effect of mitomycin increases at a temperature over 40 C. Methods: 58 patients with different failed methods of former intravesical therapy and recurrent TCC (21 intermediate risk and 37 high risk patients) were treated with the COMBAT device which facilitates irrigation of the bladder with mitomycin 40 mg at exactly 43 degree Celsius for 1 hour/6 courses weekly.Side effects were monitored prospectively and success of the treatment was controlled by ReTUR whenever possible and afterwards by 3 monthly cystoscopy and cytology. Results: 22 patients had dysuria during treatment and 9/58 suffered from hematuria but without intervention. In 6 cases urinary tract infection occured and 3 patients had allergic reaction. In one patient thermochemotherapy must be terminated due to pain and discomfort, no long term morbidity was recorded over the whole period. The FU was 14 month (3-29) for the entire cohort, 17 patients had a FU of over 2 years. One Patient had recurrent pTaGIII Tumor managed successfully by TUR. 2 patients underwent cystectomy because of invasive recurrence early after intravesical therapy, one patient developed bone metastasis 2 years after therapy without intravesical tumor. Conclusions: Thermochemotherapy with heated mitomycin is a well tolerated new option for patients with superficial TCC who are at high risk of recurrence or progression.The toxicity is acceptable and no long term morbidity was obeserved. The rate of cystectomies in this heavily pretreated group of patients including 18 BCG failures was very low with N= 2 respective 1,9%. Intravesical thermochemotherapy seems to be a new therapeutic bladder preserving option in high risk patients with superficial TCC. It is of note that thermochemotherapy has now been included in the European Guidelines.
RISK OF ARRHYTHMIA AND CONDUCTION DISEASE IN FORMER NATIONAL FOOTBALL LEAGUE PLAYERS
Authors: Philip Aagaard, Shishir Sharma, David McNamara, Elizabeth Hill, Colby Ayers, James Gentry, Andrew E. Lincoln, Alexander Kezia, Reginald Dunn, Andrew Tucker, Parag Joshi, Dermot Phelan
Journal: Journal of the American College of Cardiology (2018)
Tumor-Derived TGFβ Alters the Ability of Plasmacytoid Dendritic Cells to Respond to Innate Immune Signaling
Authors: Mariana Terra, Marine Oberkampf, Catherine Fayolle, Pierre Rosenbaum, Camille Guillerey, Gilles Dadaglio, Claude Leclerc
Journal: Cancer Research (2018)

Abstract A growing number of observations has suggested that plasmacytoid dendritic cells (pDC) play a critical role in tumor biology. In patients, infiltration of tumors by pDCs generally correlates with a poor prognosis, suggesting that pDCs may play an important role in the host–tumor relationship. Here, we analyze the influence of pDCs in solid tumor development using two different tumor models: TC-1 and B16-OVA. Phenotypic and functional gene profiling analysis of tumor-associated pDCs showed that the tumor microenvironment affected their activation status and ability to produce cytokines and chemokines. In addition, tumor cells secreted factors that inhibit the ability of pDCs to produce type I IFN. Among the various cytokines and chemokines produced by the tumor cells, we demonstrate that TGFβ is the main factor responsible for this inhibition. Using a mouse model deficient for pDCs, we also show that pDCs promote TC-1 tumor growth and that natural killer (NK) cells and regulatory T cells are involved in the protumoral effect of pDCs. Overall, our results evidence the cross-talk among pDCs, NK, and regulatory T cells in the promotion of tumor growth and their role in the development of antitumor immune responses. Significance: These findings highlight the importance of pDCs in the cross-talk between tumor cells and the immune system. Cancer Res; 78(11); 3014–26. ©2018 AACR.
DIAGNOSTIC IMAGING FOR ACUTE AORTIC DISSECTION: IMAGING SENSITIVITY AND PREFERENCE REVISITED
Authors: Erika C. Mauban, Reed Pyeritz, Stuart Hutchison, Takeyoshi Ota, Gilbert Upchurch, Khaled Nour, Bradley Taylor, Alan Braverman, Daniel Montgomery, Christoph Nienaber, Eric Isselbacher, Patroklos Pappas, Anthony DiScipio, Kim Eagle, Linda Pape, Dan Gilon
Journal: Journal of the American College of Cardiology (2018)
Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout
Authors: William B. White, Kenneth G. Saag, Michael A. Becker, Jeffrey S. Borer, Philip B. Gorelick, Andrew Whelton, Barbara Hunt, Majin Castillo, Lhanoo Gunawardhana
Journal: New England Journal of Medicine (2018)

Cardiovascular risk is increased in patients with gout. We compared cardiovascular outcomes associated with febuxostat, a nonpurine xanthine oxidase inhibitor, with those associated with allopurinol, a purine base analogue xanthine oxidase inhibitor, in patients with gout and cardiovascular disease.We conducted a multicenter, double-blind, noninferiority trial involving patients with gout and cardiovascular disease; patients were randomly assigned to receive febuxostat or allopurinol and were stratified according to kidney function. The trial had a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point (a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with urgent revascularization).In total, 6190 patients underwent randomization, received febuxostat or allopurinol, and were followed for a median of 32 months (maximum, 85 months). The trial regimen was discontinued in 56.6% of patients, and 45.0% discontinued follow-up. In the modified intention-to-treat analysis, a primary end-point event occurred in 335 patients (10.8%) in the febuxostat group and in 321 patients (10.4%) in the allopurinol group (hazard ratio, 1.03; upper limit of the one-sided 98.5% confidence interval [CI], 1.23; P=0.002 for noninferiority). All-cause and cardiovascular mortality were higher in the febuxostat group than in the allopurinol group (hazard ratio for death from any cause, 1.22 [95% CI, 1.01 to 1.47]; hazard ratio for cardiovascular death, 1.34 [95% CI, 1.03 to 1.73]). The results with regard to the primary end point and all-cause and cardiovascular mortality in the analysis of events that occurred while patients were being treated were similar to the results in the modified intention-to-treat analysis.In patients with gout and major cardiovascular coexisting conditions, febuxostat was noninferior to allopurinol with respect to rates of adverse cardiovascular events. All-cause mortality and cardiovascular mortality were higher with febuxostat than with allopurinol. (Funded by Takeda Development Center Americas; CARES ClinicalTrials.gov number, NCT01101035 .).
GET WITH THE GUIDELINES-HEART FAILURE RISK SCORE IS USEFUL FOR THE PREDICTION OF MODE OF DEATH IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE
Authors: Shunsuke Tamaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Jun Nakamura, Makoto Abe, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
Considerations in Assessing Disability Trajectories Before and After Stroke and Myocardial Infarction
Authors: Daniel Pan, Liqun Zhang, Anthony C. Pereira
Journal: JAMA Neurology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Large study is “robust” evidence of link between chronic heavy drinking and dementia
Authors: Jacqui Wise
Journal: BMJ (2018)

Chronic heavy drinking should be recognised as a major risk factor for dementia, especially early onset dementia, say researchers. Doctors should screen patients for heaving drinking and offer brief interventions to help reduce alcohol consumption if necessary, they wrote in Lancet Public Health .1

The French retrospective cohort study, which included data from over 31 million people, found a strong association between alcohol use disorders and all types of dementia, even after they controlled for potential confounding risk factors.

The relation between alcohol and dementia has been widely studied, with some studies showing a possible benefit of light to moderate drinking, while others have found a detrimental effect of heavy drinking on dementia risk. The World Health Organization defines chronic heavy drinking as consuming more than 60 …
Abstract 3558: Waist Circumference and Body Mass Index Powerful Predictors of Metabolic Syndrome in a Population of Healthy Men
Authors: Maud Scemama, Frederique Thomas, Bruno Panier, Patrick Henry
Journal: Circulation (2007)

Background : Metabolic syndrome (MS) is a public health problem that is linked to a high risk of diabetes and cardiovascular disease. Little is known about its natural history. We aimed to find the best predictors of MS in a general healthy population of men in France.  Method: We studied a population of 10 264 consecutive healthy men (mean age 49.7 ± 0.2 y.) who had two routine health examinations between 1997 and 2007 and were free of MS at the first visit. Men with known ischemic cardiac disease and treatment for diabetes, hypertension or lipids were excluded. MS parameters were assessed at both the first and second visits (mean time between both visits: 4.85 [1–14] y.) using NCEP ATP-III criteria. A ROC curve analysis was performed for each parameter at first visit to assess its power to predict MS at the second visit using a cut-off value with a maximal sensitivity and a specificity greater than 0.50.  Results: In this population of 10 264 men, 524 (5.1%) had developed MS by the second visit whereas 9 740 remained free of MS. The table shows the percentage of abnormal parameters of MS at first visit in each group (MS-free or subjects with MS at second visit) plus BMI, the best cut-off value and its sensitivity and specificity.  Conclusion: Waist circumference and BMI are the most powerful parameters to predict MS in a population of healthy men.
Drug Delivery: Cell‐Based Drug Delivery and Use of Nano‐and Microcarriers for Cell Functionalization (Adv. Healthcare Mater. 3/2018)
Authors: Alexander S. Timin, Maxim M. Litvak, Dmitry A. Gorin, Elena N. Atochina‐Vasserman, Dmitriy N. Atochin, Gleb B. Sukhorukov
Journal: Advanced Healthcare Materials (2018)

In article number 1700818, Gleb B. Sukhorukov and co-workers present a fresh outlook on the advance in the design of cell-based drug vehicles as a biological transporter platform for targeted delivery of different drugs. An overview of the current strategies of cell functionalization by nano- and microcarriers are provided for the first time. Authors also discuss animal models for studying cell assisted drug delivery. The cover image represents cells carrying the nanoparticles across the blood vessel wall to the inflammation site, where therapeutic nanoparticles are then released. Cover illustration by Jessica A. Vasserman.
Development of a conversation aid tool for patients with localized renal cell carcinoma at high risk of recurrence.
Authors: Grant Stewart, Danielle Bargo, Sarah Kilgariff, Claire Trennery, Bryan Bennett, Dena Battle, Jochen Casper, Michael D. Staehler
Journal: Journal of Clinical Oncology (2018)

608 Background: Approximately 15% of nephrectomised patients who are diagnosed with loco-regional renal cell carcinoma (RCC) are considered to be at high risk of recurrence according to the postoperative UCLA Integrated Staging System (UISS) and 60% of these patients are expected to recur within five years of diagnosis. This study aimed to develop a conversation aid tool to improve knowledge about RCC for post-nephrectomy RCC patients who are at high-risk of recurrence. Specifically, to enable patients to make an informed decision about whether to proceed/not proceed with adjuvant therapy, should adjuvant therapy become standard-of-care in the future. Methods: A review of existing evidence relating to the development of conversation aid tools and previously developed tools was undertaken. Following the review, a focus group with a steering committee (RCC patients, caregivers and a clinician), and semi-structured interviews were conducted with clinicians to identify information currently provided as standard of care. Additional interviews were conducted with post-nephrectomy patients, to identify information patients would prefer to have been given post-nephrectomy. Results: The evidence review of 10 articles provided a framework for the development of a tool to enable better patient/clinician communication. Clinicians described a typical post-nephrectomy consultation and highlighted key topics of discussion, which included recovery, risk of relapse and ongoing care. The research highlighted that patients are expected to absorb a significant amount of information during consultations in order to take an active role in their care. Findings from the focus group and clinician/patient interviews led to the development of a conversation aid tool providing patients with key questions to ask their clinicians to increase knowledge of RCC post-nephrectomy and also the information they may require when considering adjuvant therapy, including: prognosis, risk of relapse, and the risk/benefit profile of available treatment options. Conclusions: The conversation aid tool may be useful for patients to improve knowledge of RCC and help make informed decisions about their future treatment and care.
Fitting mSMART Into the Current Clinical Management of Waldenström Macroglobulinemia
Authors: Jorge J. Castillo, Joshua N. Gustine, Steven P. Treon
Journal: JAMA Oncology (2018)

To the Editor We read with interest the article outlining the 2016 mSMART guidelines for the diagnosis and management of Waldenström macroglobulinemia (WM).1 We believe that this is a unique opportunity to emphasize important differences that exist with WM therapy.
Phase 2 multicenter study of the EZH2 inhibitor tazemetostat in adults with INI1 negative epithelioid sarcoma (NCT02601950).
Authors: Mrinal M. Gounder, Silvia Stacchiotti, Patrick Schöffski, Steven Attia, Antoine Italiano, Robin Jones, George D. Demetri, Stephen Blakemore, Alicia Clawson, Scott Daigle, Scott Ribich, Maria Roche, Jill Rodstrom, Peter T.C. Ho, Gregory Michael Cote
Journal: Journal of Clinical Oncology (2017)

11058 Background: Epithelioid sarcoma (ES) is a rare soft tissue sarcoma (STS) typically seen in young adults accounting for &lt; 1% of all STS. While local disease may be indolent, ES can rapidly spread and patients (pts) with distant metastasis are often resistant to systemic treatment with 1 year survival of &lt; 50%. The defining molecular feature of ES is the absence of tumor expression of INI1, a SWI/SNF subunit member involved in chromatin remodeling. Tazemetostat, a potent and selective EZH2 inhibitor, has demonstrated tumor regressions in INI1 negative preclinical malignant rhabdoid tumors (MRT) models and phase 1 clinical activity in MRT and ES pts. The proposed mechanism of tazemetostat sensitivity is INI1 loss inducing compromised SWI/SNF activity and tumor dependence on PRC2 activity (of which EZH2 is the catalytic subunit). Preliminary phase 2 safety and efficacy of tazemetostat in ES pts is reported here. Methods: This is a phase 2 multicenter open-label single arm study of tazemetostat (800 mg po BID) in adult pts with ES whose tumors harbor evidence of INI1 loss. Pts enroll into 1 of 5 cohorts of different tumor types with INI1 loss/reduction, up to 30 pts each, using a 2-stage Green-Dahlberg design. For the ES cohort, primary endpoint is disease control rate (DCR) defined as objective response of any duration or stable disease (SD) lasting ≥32 wks. Success at stage 2 required DCR in ≥5/30 treated pts. Key secondary endpoints include safety/tolerability, ORR, PFS, OS, PK and response biomarkers e.g. H3K27me3. Results: In 31 ES pts with a median of 1 prior systemic therapy, stage 2 DCR criteria was surpassed with a RECIST confirmed PR (4 pts) and SD ≥32 wks (2 pts) observed to date. 13 pts are still on treatment therefore DCR and ORR will be updated. Tazemetostat was well tolerated with grade 1/2 fatigue (39%), nausea (26%) and vomiting (19%) as the most frequently reported AEs regardless of attribution. Conclusions: In the largest prospective clinical trial of ES to date, tazemetostat monotherapy shows promising antitumor activity, including confirmed responses and long-term SD, with favorable safety/tolerability in ES. Enrollment has been expanded to 60 ES pts given the clinical activity described here. Clinical trial information: NCT02601950.
Egg-specific IgE and basophil activation but not egg-specific T-cell counts correlate with phenotypes of clinical egg allergy
Authors: M.Cecilia Berin, Alexander Grishin, Madhan Masilamani, Donald Y.M. Leung, Scott H. Sicherer, Stacie M. Jones, A.Wesley Burks, Alice K. Henning, Peter Dawson, Joanna Grabowska, Charuta Agashe, Wendy F. Davidson, Robert A. Wood, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2018)
Government cites high public sector pay to bolster case for local pay variation
Authors: Helen Jaques
Journal: BMJ (2012)

The government has laid out its case for regional variation in pay in the public sector, citing research showing that public sector staff in the United Kingdom earn on average 8% more than people employed in similar jobs in the private sector.

In his 2012 Budget announcement this week the chancellor, George Osborne, reaffirmed his commitment to making public sector pay more responsive to local pay rates to better reflect regional labour markets and to make the government’s pay bill more affordable. 

NHS workers covered by the Agenda for Change …
ASSOCIATION OF PRE-ACTIVATION OF THE CARDIAC CATHETERIZATION LABORATORY ON REPERFUSION TIMING METRICS FOR PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION: A REPORT FROM ACTION REGISTRY®
Authors: Jay Shavadia, Anita Y. Chen, Joseph Lucas, Alexander Fanaroff, Ajar Kochar, Christopher Fordyce, James Jollis, Jacqueline E. Tamis-Holland, Timothy Henry, Akshay Bagai, Tracy Wang, Michael C. Kontos, Christopher Granger, Matthew Roe
Journal: Journal of the American College of Cardiology (2018)
Computer based test to be piloted for selection to specialty training
Authors: Helen Jaques
Journal: BMJ (2013)

Health Education England is to pilot a computer based clinical problem solving and situational judgment test for applicants to the first year of specialty and core training.

The pilot of the two hour computerised test will take place in 2014, and any decision on whether to introduce an entry test for specialty training will be based on the results of the pilot.

Health Education England hopes that the test will make the process of shortlisting applicants for entry to specialty training more consistent and transparent. The BMA is concerned that a single …