tbuckley/cabot-search huggingface dataset:
Evaluation of biological activity of PCK3145 in metastatic hormone resistant prostatic cancer (HRPC) using serum markers
Authors: L. Daigneault, H. Dulude, C. Panchal, S. Garde, A. Armstrong, R. Cowan, R. Hawkins
Journal: Journal of Clinical Oncology (2004)

4692 Background: Evaluation of efficacy for new treatment of HRPC is both challenging and rewarding as new targets are elucidated. Biological activity of PCK3145, a synthetic 15-mer peptide derived from the prostate secretory protein (PSP94) sequence was assessed by the analysis of several serum markers in the PCK3145-UK-2001 clinical trial. Tumor markers alone are not accepted by regulatory agency as a basis for marketing approval of oncology drugs, but may be used as elements in composite end points. With this first in man study, an attempt was made to find preliminary tumor markers correlation in this dose finding study with PCK3145 in HRPC patients. Methods: PCK3145 was administered i.v. in 4 cohorts of 4 patients with a dosage of 5, 20, 40 and 80 mg/m2. One cycle consist of an administration of PCK3145 three times a week for 4 weeks. Additional cycles may be proposed to patients in absence of toxicity and disease progression. Blood samples were collected prior and after each cycle. Serum markers includes hemoglobin, alkaline phosphatase, FSH, LH, tPSA, fPSA, PAP, Chromogranin A, Neuron-Specific Enolase, MMP-2, MMP-9, TIMP-1. Results: Patients received in average 2 cycles of PCK3145. One patient with a prostatectomy demonstrated an elevated level of FSH (over 60 IU/L) and had a 35 % reduction of the FSH level after the PCK3145 treatment. MMP-9 level was elevated (over 100 ug/L) in approximately 50 % of our patient population. Patients who had an elevated MMP-9 levels before treatment showed reductions by 72% (34% to 90%) after the very first cycle. Patients who had normal MMP-9 level (below 100 ug/L) remained normal after two cycles. PCK3145 seems to normalize the MMP-9 production. Evaluation of the MMP-9, PAP, Chromogranin A and PSA demonstrates clinical utility to monitor the disease status. Conclusions: The marked reduction in plasma MMP-9 levels of patients receiving PCK3145 treatment indicates a biological effect, and provides a potentially novel mechanism of action of this small molecule in these patients. These clinical results suggest the potential role of PCK3145 in the intervention of the metastatic process. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Procyon Biopharma, Inc. Procyon Biopharma, Inc. Procyon Biopharma, Inc. Procyon BioPharma, Inc.
Frequency of BRAF V600E variant in circulating free DNA compared with the single melanoma biopsy.
Authors: Lorenza Di Guardo, Viviana Vallacchi, Simona Frigerio, Agata Cova, Paola Squarcina, Felicetta Giardino, Paola Frati, Valentina Colonna, Roberto Patuzzo, Filippo G. De Braud, Mario Santinami, Licia Rivoltini, Monica Rodolfo
Journal: Journal of Clinical Oncology (2013)

9092 Background: To select melanoma patients for treatment with BRAF inhibitors, the BRAF mutational status is determined in the most recent tumor biopsy. However, tumor specimens are not always available for the analysis, and relying on a single biopsy specimen can potentially exclude from treatment patients with heterogeneity among metastatic tumors due to polyclonality of BRAF mutation, which appears as a rather common condition. As an alternative approach we explored a blood-based mutation detection assay. Methods: We developed a method including enrichment for the BRAV600E variant by selective elimination of the wild type allele by TspRI digestion and BRAFV600E detection by TaqMan Mutation Detection Assay (BRAF_476_mu, Life Technologies). Sensitivity testing showed that BRAFV600E variant was detected starting from 6.25X10 -5 ng of DNA, and specificity testing showed that the variant can be detected when diluted in 8X10 5 copies of wild-type alleles. Results: Mutational analysis performed by Sanger sequencing of exon15 in 114 melanoma biopsies showed that 4 (3%) harbored the c.1798_1799GT&gt;AA (V600K) mutation, 1 (1%) the c.1799_1800TG&gt;AA mutation (V600E), and 56 (49%) the most common c.1799T&gt;A mutation (V600E), while by the novel method the latter mutation was detected in 9 additional specimens (8% increment) and confirmed by sequencing the PCR product after TspRI digestion. Pre-surgery plasma was available for 50/114 patients at advanced stages, 26/50 (52%) showing a mutated specimen, including 4 with a double nucleotide substitution (V600K and V600E). The matched plasma samples resulted mutated in 25/26 cases with mutated biopsy and in further 14/25 samples with biopsy resulting wild type; in contrast, plasma of 50 healthy controls tested negative. Taken together, these results indicate that V600E circulating variant was detectable in 39/50 (78%) plasma samples and in 22/50 (44%) tumor specimens. Conclusions: Detection of BRAF V600E variant in circulating free DNA may represent a more sensitive approach for patient selection and decision making process during the treatment with BRAF inhibitors.
Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial
Authors: Emmanuelle Cambau, Isabelle Durand-Zaleski, Stéphane Bretagne, Christian Brun-Buisson, Catherine Cordonnier, Xavier Duval, Stéphanie Herwegh, Julien Pottecher, René Courcol, Sylvie Bastuji-Garin
Journal: Intensive Care Medicine (2017)
A phase II study of vinorelbine (VNR) and letrozole (LTZ) in aged women with metastatic breast cancer (MBC)
Authors: G. Perez Manga, J. M. Garcia Bueno, H. Palombo, S. Morales, M. Méndez, B. Esteban
Journal: Journal of Clinical Oncology (2004)

756 Background: To evaluate the efficacy and toxicity profile of VNR and LTZ in aged women with MBC. Methods: Between April 2001 and August 2003, fifty-three women with measurable MBC, no prior chemotherapy for advanced disease, ECOG performance status (PS) 0–1, and adequate bone marrow, renal and hepatic function were included. Twenty-four pts had been treated with neo/adjuvant therapy, 16 of them with chemotherapy. Only five patients had received hormonal therapy as first line treatment for MBC. Treatment consists in VNR 30 mg/m2 i.v. on days 1 and 8 every 21 days for a maximum of 8 cycles, and LTZ 2.5 mg/day continuous. Tumor evaluation was done every 3 cycles. Results: : Of 53 pts included, 48 are fully evaluable for response and toxicity. Median age was 73.0 years (range 56–82); ECOG PS 0/1: 26/22 pts; patients had metastases in bone (14 pts), liver (12 pts), lung (9 pts), nodes (12 pts), cutaneous (11 pts), other sites (3 pts). Fourteen pts have two o more metastatic localization. A total of 279 cycles of VNR were administered (median 6, range 2–8). Toxicity was generally mild: grade 3–4 toxicity consisted of leukopenia in 3 pts (2.2% cycles), neutropenia in 12 pts (7,2% cycles), anemia in 3 pts (1.1% cycles), asthenia in 4 pts (1.8% cycles) and liver toxicity in 1 pt (0,7% cycles). Efficacy: To date, 4 (8%) pts achieved a complete response and 20 (42%) pts a partial response, 16 (33%) pts had stable disease and 8 (17%) pts had progressive disease. The median time to progression was 11.6 months. Conclusions: The combination of VNR and LTZ in aged women with MBC appears to be active regimen with a favorable toxicity profile. No significant financial relationships to disclose.
Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial
Authors: Jørgen Vestbo, Alberto Papi, Massimo Corradi, Viktor Blazhko, Isabella Montagna, Catherine Francisco, Géraldine Cohuet, Stefano Vezzoli, Mario Scuri, Dave Singh
Journal: The Lancet (2017)
DISECCIÓN SUBMUCOSA ENDOSCÓPICA (DSE): MODELO MULTIVARIANTE PARA PREDECIR LA CONVERSIÓN A RESECCIÓN MUCOSA FRAGMENTADA (RME-F)
Authors: JC Marín-Gabriel, J Díaz-Tasende, P Cancelas-Navia, S Rodríguez-Muñoz, AJ Del Pozo-García, M Pérez-Carreras, M Alonso-Riaño, Y Rodríguez-Gil, G Castellano-Tortajada
Journal: Endoscopy (2015)

Introducción: Conocer los factores que pueden dificultar la DSE y requerir la conversión a RMEf puede ser de utilidad para los grupos que deseen implantar la técnica en su medio.
Lingering Questions Concerning Specific Dietary Fats and Mortality
Authors: Grant Schofield, George Henderson
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative
Authors: Lisa G. Rider, Rohit Aggarwal, Angela Pistorio, Nastaran Bayat, Brian Erman, Brian M. Feldman, Adam M. Huber, Rolando Cimaz, Rubén J. Cuttica, Sheila Knupp de Oliveira, Carol B. Lindsley, Clarissa A. Pilkington, Marilynn Punaro, Angelo Ravelli, Ann M. Reed, Kelly Rouster‐Stevens, Annet van Royen‐Kerkhof, Frank Dressler, Claudia Saad Magalhaes, Tamás Constantin, Joyce E. Davidson, Bo Magnusson, Ricardo Russo, Luca Villa, Mariangela Rinaldi, Howard Rockette, Peter A. Lachenbruch, Frederick W. Miller, Jiri Vencovsky, Nicolino Ruperto
Journal: Arthritis & Rheumatology (2017)

Objective To develop response criteria for juvenile dermatomyositis (DM). Methods We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Results Consensus was reached for a conjoint analysis–based continuous model with a total improvement score of 0–100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91–98% for minimal improvement, 92–94% and 94–99% for moderate improvement, and 91–98% and 85–86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement ( P = 0.009–0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement ( P &lt; 0.006). Conclusion The response criteria for juvenile DM consisted of a conjoint analysis–based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.
Assessment of management capacity to improve the value of health-care systems: a survey
Authors: Rebecca L Weintraub, Keri Wachter, Jennifer Goldsmith, Marie J Teichman, Eda Algur, Julie D Rosenberg
Journal: The Lancet Global Health (2017)

BackgroundStrong management is important for high-value health-care systems if returns on global health investments are to be delivered and the Sustainable Development Goals met by 2030. Managers are responsible for care delivery systems and strategies, making sure that health services benefit the population they intend to serve. Most managers in resource-limited settings work at the district level and below, with little training in non-clinical skills. They are often health care providers who have been promoted into management roles. Here, we aimed to understand the most challenging aspects of the health-care management role in resource-constrained settings and to identify gaps in managers' skills and knowledge in order to better design programmes and tools to support managers in their delivery of care.MethodsWe sent a web-based branching survey to frontline global health managers via Devex between October, 2014, and January, 2015. The survey used multiple-choice and Likert-scale questions about skills within five categories of management in global health: finance; human resources; facility/supply chain or inventory management; clinical, field, or laboratory team management; and relationships with community and partners. Before the survey, we did a literature review, held a virtual discussion with experts, and piloted the survey to refine areas of management and enable targeted training. The pilot survey was also completed by mid-career professionals attending the Global Health Delivery Intensive at the Harvard T H Chan School of Public Health in July, 2013.FindingsWe included data from from 350 survey respondents in 44 low-income countries, the virtual discussion panel with 131 experts from five continents, and responses from 33 Global Health Delivery Intensive attendees from 11 countries. Our findings indicated that health-care managers are short on time, are required to multitask without an understanding of priorities, and that they lack management skills, motivation, and information. We refined our intensive global health delivery course to meet what were identified as the most pressing challenges, and we offer an online community of practice to facilitate peer-to-peer learning and expert guidance to these areas. In 2016, 52 professionals from 24 countries participated in the eighth annual Global Health Delivery Summer Intensive. More than 90% of respondents (n=49) said they planned to incorporate their learning to make changes to their professional approach or practice.InterpretationUniversities can play an important role in convening managers and helping them to facilitate knowledge dissemination and translation. Future investments are needed to ensure global health professionals can access continuous professional development opportunities.FundingThe Abundance Foundation.
Spherical Polyelectrolyte Brushes as a Novel Platform for Paramagnetic Relaxation Enhancement and Passive Tumor Targeting
Authors: Qin Zhu, Zhenyu Yuan, Weiqiao Qian, Yuanyuan Li, Zhiqiang Qiu, Weijun Tang, Jie Wang, Yun Ding, Aiguo Hu
Journal: Advanced Healthcare Materials (2017)

A novel platform for the development of highly efficient magnetic resonance imaging (MRI) contrast agents has been demonstrated. New contrast agents are designed and produced through electrostatic self‐assembly of cationic gadolinium(III) complexes onto anionic spherical polyelectrolyte brushes (SPB). The structurally well‐defined SPB are composed of polystyrene core and polyacrylic acid brush layer, where numerous binding sites and confined microenvironments are available for the embedment of the gadolinium(III) contrast agents. Both in vitro and in vivo experiments show excellent biocompatibility and relaxometric performance of these SPB‐based gadolinium hybrid materials. The enhanced relaxivity value is up to 86.2 mM −1 s −1 per Gd, a remarkably high record value at 1.5 T magnetic field. In vivo imaging displays a prolonged blood circulation time and massive accumulation of the contrast agents at the tumor region due to the enhanced permeability and retention effect. The SPB‐based gadolinium hybrid materials not only broaden the horizons of new MRI contrast agents, but also have a great potential for tumor diagnosis.
Late myocardial perfusion defects in left versus right-sided radiotherapy (RT) for breast cancer
Authors: C. Correa, W.-T. Hwang, V. A. Ferrari, H. I. Litt, L. J. Solin, E. E. Harris
Journal: Journal of Clinical Oncology (2004)

563 Background: Recent studies show a higher incidence of nuclear perfusion defects in left vs. right-side irradiated patients. This study compares the late incidence of myocardial perfusion defects in left vs. right-side RT for breast cancer. Methods: The medical records of patients treated from 1977–1990 for stage I-II breast cancer were reviewed for results of stress tests. A total of 17 right and 23 left-side patients presented with chest pain and underwent either stress echocardiogram (5), exercise (30), or pharmacological (5) SPECT Tc-99m sestimibi testing. Results: Univariate analysis showed that left-side RT was significantly correlated with perfusion defects (p=0.008). Time since RT, age at RT, use of any chemotherapy at diagnosis or subsequently, use of any cardiotoxic chemotherapy, use of any tamoxifen, smoking history, and family cardiac history did not significantly correlate with perfusion defects (all p≥0.11). Based on the Framingham model (Grundy, J Am Coll Cardiol 1999), both left and right-side patients had the same risk of developing coronary artery disease at 10 and 20 years post-RT (7% and 11%, respectively). At 10 year follow-up there was no significant difference in the incidence of perfusion defects in left vs. right-side patients (8.7% vs. 0%, p=0.50). However, at 20 year follow-up there was a trend towards a higher incidence of defects in left vs. right-side patients (79% vs. 40%, p=0.26), and a higher percentage of left-side patients had perfusion defects than predicted (79% vs. 11%, p<0.0001). Furthermore, 10 of the 14 left-side perfusion defects were in the left anterior descending artery territory. The percentage of perfusion defects in right-side patients was also higher than predicted, although not significant (p=0.097). Conclusions: Stress testing in irradiated breast cancer patients demonstrates an excess of very late cardiac perfusion defects in left-side patients. No significant financial relationships to disclose.
Supportive care in cancer. Who does what?
Authors: J. Sussman
Journal: Journal of Clinical Oncology (2004)

8267 Background: The provision of supportive cancer care remains problematic. 40% of patients report unmet needs for information, emotional/psychological supports, social and physical/symptom needs. Patients consistently identify physicians as coordinators of supportive care. Given this perspective, we were interested in exploring how physicians and nurses viewed their roles and responsibilities in the assessment of supportive care needs. Methods: Survey of all practicing oncologists, surgeons and oncology nurses as well as a random sample of family physicians in 3 regions of Ontario Canada. The survey instrument was specifically designed to measure level of assessment of supportive care needs( 5 point likert scale), awareness of services( 27 items) and perception of role responsibility in needs assessment. The survey was conducted using a modified Dilman approach to maximize responses in March 2003. Results: Unadjusted response rate was 45% (511/1129). 98 respondents indicated that they did not care for cancer patients and were not included in the final analysis. There was no difference in responses by practitioner type. Mean assessment scores were higher for nurses than for physicians for information, emotional, social and physical/symptom needs (p<.001 ANOVA). In terms of awareness of available resources, nurses and family physicians had higher awareness scores compared with oncologists (10 vs. 8) although this was not statistically significant. Finally nurses appeared to identify themselves as primarily responsible for coordination of care more consistantly in all 4 domains of practice. Conclusions: Some of the barriers to meeting the supportive care needs of patients with cancer may be as a result of divergence of perspective of responsibility by practitioners and patients. Perception of role responsibility by practitioners could also be a factor that may limit access to needed services. Nurses may be in the best position to coordinate supportive care. These results are important in informing potential interventions to improve the supportive care of cancer patients that might include education of patients and interventions to improve practitioner awareness of needs and available resources. No significant financial relationships to disclose.
Reviewing deaths within 30 days of systemic anti-cancer therapy: Driving quality in a regional chemotherapy service.
Authors: Caroline Forde, Paula Scullin, Lynne Edgar, James J McAleer, Victoria M Coyle
Journal: Journal of Clinical Oncology (2017)

112 Background: Systemic anti-cancer therapy (SACT) administration rate at the end of life has been deemed a key metric for assessing quality of cancer care. A structured peer review process has been developed within the Cancer Centre, Belfast City Hospital, to discuss all patient deaths occurring within 30 days of SACT across Northern Ireland at a monthly, multidisciplinary, educational mortality meeting. We aimed to review cases discussed, characterising patients, causes of death and the role of SACT in patients’ deaths. Methods: A retrospective analysis was undertaken of 282 solid tumour patients, whose deaths were discussed at the mortality meetings from January 2013 to August 2016. Results: The 30-day mortality rate for the Cancer Centre was 4.5%. Most commonly represented tumour sites were gastrointestinal (39%), lung (22%) and breast (17%) with 96% receiving palliative treatments. WHO Performance Status (PS) was 0-2 at final SACT cycle in 83% (8% PS 3, unknown 9%). 43% of patients were receiving their first cycle and 56% receiving first line treatment for advanced disease. 77% of deaths occurred in hospital with 57% attributed to progressive disease. Other causes of death included infection (7% neutropenic, 11% non-neutropenic) and thromboembolism (12%). In 10% SACT was deemed to have caused or hastened death whereas in 65% SACT was non-contributory. In 25% SACT did not play a major role, but a contributory role could not be confidently excluded. Conclusions: SACT related death rate appears comparable to other institutions’ published routine outcomes. Robust review of SACT mortality encourages service improvement and individual reflection. Prescribers are reminded of the critical importance of carefully balancing patients’ needs and concerns with realistic outcomes and treatment risks, particularly in heavily pretreated or poor PS patients. Case discussions have generated service improvements including site and regimen specific prepopulated consent forms, a standardised SACT assessment proforma and mandatory response assessments as part of SACT protocols. Neutropenic sepsis remains the leading cause of SACT related mortality and further innovative improvements in care are required.
IL-12hi Rapamycin-Conditioned Dendritic Cells Mediate IFN-γ-Dependent Apoptosis of Alloreactive CD4+ T Cells and Limit Graft-Versus-Host Diseas
Authors: Elizabeth O. Stenger, Brian R. Rosborough, Lisa Mathews, Huihui Ma, Markus Mapara, Angus W. Thomson, Heth R. Turnquist
Journal: Blood (2012)