1590TiPSafety, tolerability and activity of autologous T-cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non-small cell lung cancer: A phase Ib/IIa randomised pilot study
AbstractBackgroundNY-ESO-1 and LAGE-1a are antigens expressed in several tumours, including non-small cell lung cancer (NSCLC). Previous clinical trials using autologous T cells directed against NY-ESO-1/LAGE-1a have shown objective responses between 40% and 60% in synovial sarcoma, metastatic melanoma and multiple myeloma. Pembrolizumab (PEM) is a monoclonal antibody that blocks PD-1/PD-L1 interaction and increases anti-tumour activity in anti-tumour T cells. Here, PEM will be used in combination with NY-ESO-1/LAGE-1a T-cell receptor engineered patient T cells (GSK3377794) to potentially improve clinical benefit in this p...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1589TiPKEYNOTE-495/KeyImPaCT: A randomized, biomarker-directed, phase II trial of pembrolizumab-based therapy for non –small cell lung cancer (NSCLC)
AbstractBackgroundKEYNOTE-495 is a randomized, open-label, phase II trial (NCT03516981) evaluating the clinical activity and safety of pembrolizumab (pembro)-based combination (combo) therapy in patients (pts) with treatment-naive, advanced NSCLC in biomarker-defined response groups. This biomarker-based approach is based on 2 validated, independent, next-generation biomarkers (T cell –inflamed gene expression profile [GEP] and tumor mutational burden [TMB]) and can help determine the differential efficacy of pembro-based combo therapy, based on the composite biomarker profile, and inform precision immunotherapy in the f...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1588TiPThe elderly patient individualized chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer
AbstractBackgroundNon-small cell lung cancer (NSCLC) is one of the commonest disease worldwide and the leading cause of cancer-related death. Incidence increases with age and reaches a peak in senility, when patients ’ (pts) comorbidities may limit the efficacy of treatments. At this time, no homogeneous indications are available for elderly NSCLC pts and the optimization of treatment, with the lowest side effects, is still an unmet need, also after the introduction of innovative drugs. The ribonucleotide redu ctase catalytic subunit M1(RRM1), the DNA-excision repair protein ERCC1 and the thymidylate synthetase (TS) are ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1587TiPCANOPY phase III program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
AbstractBackgroundThe presence of inflammatory mediators in the tumor microenvironment may have pro or antitumorigenic effects. The cytokine interleukin-1 β (IL-1β) affects multiple aspects of the tumor microenvironment promoting carcinogenesis, tumor invasiveness, and immunosuppression. Canakinumab is a human monoclonal antibody with high affinity and specificity for IL-1β. Results of the phase III Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) have shown that IL-1β inhibition with canakinumab was associated with reduced lung cancer incidence and mortality, providing a rationale to investigate the po...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1586TiPPhase III ALTA-3 study of brigatinib (BRG) vs alectinib (ALC) in patients (pts) with advanced anaplastic lymphoma kinase (ALK) −positive non–small cell lung cancer (NSCLC) that progressed on crizotinib (CRZ)
AbstractBackgroundThe second-generation ALK tyrosine kinase inhibitor (TKI) ALC has demonstrated efficacy and acceptable safety in ALK+ NSCLC pts who have progressed on CRZ. However, resistance to ALC eventually develops, with secondary resistance mutations detected in approximately 50% of pts and a median progression-free survival (PFS)<1 year. BRG is a next-generation ALK TKI designed to have potent and broad activity against ALK mutants. Post-CRZ, BRG demonstrated high systemic and central nervous system (CNS) objective response rates (ORRs) and the longest reported median PFS of any ALK inhibitor in this setting (16...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
464PPharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours
ConclusionsBT1718 is a first in class BTC which is generally well tolerated at the present dose level. Current plasma and tumor PK data are consistent with proposed preclinical mechanism of tumor targeted toxin delivery.Clinical trial identificationNCT03486730.Legal entity responsible for the studyCancer Research UK.FundingCancer Research UK and BicycleRD Limited.DisclosureN. Cook: Advisory / Consultancy: Tarveda Therapeutics; Advisory / Consultancy: Epigene Therapeutics. U. Banerji: Advisory / Consultancy: Astellas; Advisory / Consultancy: Novartis; Advisory / Consultancy: Karus Therapeutics; Advisory / Consultancy: Phoen...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
457PFirst-in-human study of ABBV-621 in patients (pts) with previously treated sold tumours: Dose-optimization cohorts
ConclusionsAdministration of ABBV-621 in pts with R/R CRC and pancreatic cancer shows an acceptable safety profile at all DL and evidence of antitumor activity.Clinical trial identificationNCT03082209.Editorial acknowledgementMedical writing support was provided by Yanci M. Baker, PhD, from Aptitude Health, Atlanta, GA, and funded by AbbVie.Legal entity responsible for the studyAbbVie Inc.FundingAbbVie Inc.DisclosureE. Calvo: Honoraria (self): HM Hospitales Group; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Nanobiotix; Advisory / Consu...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
La parentalité des personnes handicapées mentales sous vigilance : comment les professionnels construisent-ils leur expertise ?
Publication date: Available online 18 September 2019Source: AlterAuthor(s): Adeline ParentelliRésuméLa parentalité est aujourd’hui érigée en compétence, ce qui accentue la responsabilité des parents. L’expertise/conseil se développe dans divers champs scientifiques et produit des normes de parentalité utilisées par les pouvoirs publics pour construire leurs dispositifs destinés à des parents catégorisés comme vulnérables. Au niveau de la loi, les personnes handicapées mentales sont considérées comme vulnérables sur appréciation du juge et, de ce fait, plus ou moins capables juridiquement de se protÃ...
Source: ALTER - European Journal of Disability Research - September 19, 2019 Category: Disability Source Type: research
Factors associated with the non-use of telehealth consultancy by physicians of the Family Health Strategy
This study sought to evaluate the frequency and factors associated with non-use of telehealth consultancy by physicians who work in the Family Health Strategy (FHS) in the North of the State of Minas Gerais. It is a cross-sectional study that used a previously-tested self-administered questionnaire. Poisson regression analysis with robust variance was used after bivariate analysis to identify the factors associated with non-use of telehealth consultancy. A total of 385 physicians from 73 municipalities participated in the study. The frequency of non-use of telehealth consultancy by physicians in the FHS was 55.8%. After mu...
Source: Ciencia e Saude Coletiva - August 5, 2019 Category: Occupational Health Source Type: research
How to Achieve an Accurate Anatomical Femoral Tunnel Technique in ACL Reconstruction in the Early Years of Your Consultancy? Femoral Offset Aimer Technique: Consistent and Reproducible Technique
J Knee Surg DOI: 10.1055/s-0039-1692993Femoral tunnel malposition is the most common reason for failure of primary anterior cruciate ligament reconstruction. There are several methods to identify the anatomical location of femoral footprint. Femoral offset aimer technique is one such technique which is easy to use and reliable. It is an ideal technique for junior and inexperienced surgeons to recreate the femoral tunnel in its anatomical footprint. The senior author (P.E.) has been using this technique for 30 consecutive cases in his first year of independent practice during his consultancy without any major intraoperative...
Source: Journal of Knee Surgery - August 1, 2019 Category: Orthopaedics Authors: Ellapparadja, Pregash Joseph, Ignatius Selvaratnam, Veenesh Tags: Original Article Source Type: research
Are Traditional Forms of Exercise Feasible and Acceptable for Chronic Heart Failure Patients in China? A Mixed-Method Pilot Study
Baduanjin (eight silken movements), a traditional Chinese exercise, is a promising solution to the poor uptake of cardiac rehabilitation due to low availability and unaffordability in China. The Baduanjin Eight-Silken-Movements wIth Self- Efficacy building for Heart Failure (BESMILE-HF) program is the first to apply Baduanjin in a multi-component rehabilitation program (exercise-education-evaluation-consultancy-adherence strategies). (Source: Journal of Cardiac Failure)
Source: Journal of Cardiac Failure - July 31, 2019 Category: Cardiology Authors: Xiankun Chen, Huiying Zhu, Zehuai Wen, Gaetano Marrone, Wei Jiang, Weihui Lu Tags: 272 Source Type: research
The effects of amniotic fluid and foetal cord blood cotinine concentrations on pregnancy complications and the anthropometric measurements of newborns.
This study was conducted as a case-control study, in Turkey. A total of 250 pregnant women with amniocentesis indication were recruited into the study and the cotinine levels in the AF and FCB were determined. A smoking habit did not statistically affect the incidence of pregnancy complications (p>.05). The birth weights of the newborns were negatively correlated with the AF cotinine levels. The incidences of low birth weight, low Apgar scores and RDS were positively correlated with higher levels of cotinine in AF and FCB. It is important for healthcare staff to provide training and consultancy services for the health i...
Source: Journal of Obstetrics and Gynaecology - June 21, 2019 Category: OBGYN Tags: J Obstet Gynaecol Source Type: research
Oligonucleotide Microarrays Identified Potential Regulatory Genes Related to Early Outward Arterial Remodeling Induced by Tissue Plasminogen Activator
This study was supported by National Institutes of Health grant HL-62836 to BB, by NHLBI funds for exchanges of scientists under the auspices of the United States–Russia Joint Agreement in Cardiopulmonary Research, by NATO LST. CLG.979209, by Grants of the Russian Science Foundation (No. 14-24-00086 in part of gene expression profiling induced by tPA; No. 19-75-30007 in part of vessel and tissue remodeling processes).
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of inter...
Source: Frontiers in Physiology - April 29, 2019 Category: Physiology Source Type: research
Harnessing the Four Elements for Mental Health
DiscussionAs detailed above, the “elements” in both a classical and a contemporary sense have effects on our mental health and are potentially modifiable aspects that can be harnessed as therapeutic interventions. The most robust interventional evidence currently available shows tentative support for several use of the elements via horticultural and nature-exposure therapy, green exercise/physical activity, sauna and heat therapy, balneotherapy, and breathing exercises. It should be noted that, in many cases, these interventions were not studied in definitive diagnosed psychiatric disorders and thus it is pre...
Source: Frontiers in Psychiatry - April 23, 2019 Category: Psychiatry Source Type: research
Beta Amyloid Deposition Is Not Associated With Cognitive Impairment in Parkinson's Disease
In this study, we used a well-validated visual assessment to clinically rate scans as being amyloid positive or negative (38). As there is not an accepted threshold based on standardized centiloid reference regions, we defined an amyloid positivity centiloid cut-off threshold in our sample. Our cut-off (CL = 31.3, SUVR = 1.21) corresponds well to the estimated value proposed by Rowe and colleagues (34) in the context of AD (CL = 25–30), however our estimated threshold may be biased by the low number of Aβ positive patients.
Our results suggest a lower prevalence of amyloid-positive PDD individuals than in ...
Source: Frontiers in Neurology - April 23, 2019 Category: Neurology Source Type: research
