tbuckley/cabot-search huggingface dataset:
Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells
Authors: Roger Sun, Nora Sundahl, Markus Hecht, Florian Putz, Andrea Lancia, Angela Rouyar, Marina Milic, Alexandre Carré, Enzo Battistella, Emilie Alvarez Andres, Stéphane Niyoteka, Edouard Romano, Guillaume Louvel, Jérôme Durand-Labrunie, Sophie Bockel, Rastilav Bahleda, Charlotte Robert, Celine Boutros, Maria Vakalopoulou, Nikos Paragios, Benjamin Frey, Jean-Charles Soria, Christophe Massard, Charles Ferté, Rainer Fietkau, Piet Ost, Udo Gaipl, Eric Deutsch
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions. Methods Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient’s response. Results A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables. Conclusions These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.
Abstract 214: Cardiac Arrest and Extracorporeal Cardiopulmonary Resuscitation Impairs Left Ventricle Hemodynamic Function in a Ventricular Fibrillation Cardiac Arrest Model in Rats
Authors: Alexandra Maria Warenits, Matthias Müller, Ingrid Anna Maria Magnet, Florian Ettl, Ouafa Hamza, Felix Kottbauer, Sandra Högler, Bruno Podesser, Michael Holzer, Wolfgang Weihs, Attila Kiss
Journal: Circulation (2020)

Introduction: Extracorporeal Cardiopulmonary Resuscitation (ECPR) may achieve ROSC after prolonged CA when conventional cardiopulmonary resuscitation fails. We investigated the impact of ECPR on cardiac hemodynamic recovery and hypothesized, that left ventricular hemodynamic function is impaired in resuscitated hearts. Methods: Adult male Sprague-Dawley rats (500 g, n=36) were subjected to 6 or 8 min of ventricular fibrillation CA, thereafter resuscitated with ECPR (open reservoir, roller pump, membrane oxygenator, draining catheter in the right jugular vein, inflow catheter in the right femoral artery; custom made bypass system), mechanical ventilation and drugs (epinephrine, bicarbonate, heparin). After defibrillation and ROSC, rats survived for 14 days and were compared to 7 sham animals. The hearts were isolated and mounted onto an erythrocyte-perfused, isolated working heart (WH) system. Cardiac output, left ventricular systolic pressure (LVSP), coronary flow and pressure-volume (P-V) relationships (by increasing the afterload in 10 mmHg increments) were measured. Myocardium of all rats was evaluated pathohistological in hematoxylin-eosin staining. Results: ROSC was achieved in 18 animals after 6 min of CA, of which 10 survived 14 d and 7 were investigated in WH, in 8 min CA group 15 achieved ROSC of which 5 survived to 14 d and 2 were investigated in WH and compared to the hearts of 7 sham animals. At defined afterload (60 mm Hg; baseline) there was no difference in cardiac hemodynamics between sham and 6 min CA group. In contrast, 8 min CA rats showed a tendency towards decrease in cardiac output and LVSP compared to sham animals. Notably, both CA groups showed impaired P-V loop relationship and subsequently less tolerance to hemodynamic stress. Histologically all 8 min CA rats showed multiple foci of myocardial scarring. Conclusions: CA led to impaired left ventricular hemodynamics in 8 min CA rats resuscitated with ECPR. In addition, hearts were more vulnerable to hemodynamic stress after successful resuscitation. For investigating the effects of future therapy approaches during and after resuscitation from CA on the heart function, isolated WH might be a promising approach in resuscitation research.
Local steroid activation is a critical mediator of the anti-inflammatory actions of therapeutic glucocorticoids
Authors: Chloe Fenton, Claire Martin, Rachel Jones, Adam Croft, Joana Campos, Amy J Naylor, Angela E Taylor, Myriam Chimen, Mark Cooper, Gareth G Lavery, Karim Raza, Rowan S Hardy
Journal: Annals of the Rheumatic Diseases (2020)

The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a well-characterised role in the metabolism and activation of endogenous glucocorticoids (GCs). However, despite its potent upregulation at sites of inflammation, its role in peripheral metabolism and action of therapeutic GCs remains poorly understood. We investigated the contribution of 11β-HSD1 to the anti-inflammatory properties of the active GC corticosterone, administered at therapeutic doses in murine models of polyarthritis.Using the tumour necrosis factor-tg and K/BxN serum-induced models of polyarthritis, we examined the anti-inflammatory properties of oral administration of corticosterone in animals with global, myeloid and mesenchymal targeted transgenic deletion of 11β-HSD1. Disease activity and joint inflammation were scored daily. Joint destruction and measures of local and systemic inflammation were determined by histology, micro-CT, quantitative RT-PCR, fluorescence activated cell sorting and ELISA.Global deletion of 11β-HSD1 resulted in a profound GC resistance in animals receiving corticosterone, characterised by persistent synovitis, joint destruction and inflammatory leucocyte infiltration. This was partially reproduced with myeloid, but not mesenchymal 11β-HSD1 deletion, where paracrine GC signalling between cell populations was shown to overcome targeted deletion of 11β-HSD1.We identify an entirely novel component of therapeutic GC action, whereby following their systemic metabolism, they require peripheral reactivation and amplification by 11β-HSD1 at sites of inflammation to deliver their anti-inflammatory therapeutic effects. This study provides a novel mechanistic understanding of the anti-inflammatory properties of therapeutic GCs and their targeting to sites of inflammation in polyarthritis.
Retraction: Preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome and glycaemic control in adults with raised blood glucose levels (British Journal of Sports Medicine (2009) 43 (840-844)
Authors: X. Liu, Y. D. Miller, N. W. Burton, Wendy Brown
Journal: British Journal of Sports Medicine (2010)

This article has been updated and replaced by X Liu, Y D Miller, N W Burton, et al. A preliminary study of the effects of Tai Chi and Qigong medical exercise on indicators of metabolic syndrome, glycaemic control, health related quality of life, and psychological health in adults with elevated blood glucose Br J Sports Med Published Online First 16 October 2008 doi:10.1136/bjsm.2008.051144.
Core Outcome Sets for Studies of Diabetes in Pregnancy: A Review
Authors: Aoife M. Egan, Delia Bogdanet, Linda Biesty, Oratile Kgosidialwa, Carmel McDonagh, Christine O’Shea, Paula M. O’Shea, Declan Devane, Fidelma P. Dunne
Journal: Diabetes Care (2020)

Core Outcome Sets (COS) contain an agreed minimum set of outcomes to be measured and reported in all studies in a specific area, with the objective of standardizing outcome reporting. COS may minimize research waste by identifying outcomes important to key stakeholders, allowing for improved evidence synthesis, and facilitating translation of research findings to clinical practice. Over the past 5 years, there has been significant progress in developing COS relevant to studies of diabetes in pregnancy. This review summarizes work in this area, reviews the role of patient and public involvement in COS development, and suggests areas for future research.
Abstract 192: Comparative Clinical Effectiveness of Population-based Atrial Fibrillation Screening Using Wearable Devices: A Decision-Analytic Model
Authors: Shaan Khurshid, Wanyi Chen, Daniel Singer, Steven Atlas, Jeffrey M Ashburner, Patrick T Ellinor, David D McManus, Jagpreet Chhatwal, Steven A Lubitz
Journal: Circulation (2020)

Introduction: Early diagnosis of AF via screening might prevent strokes. AF screening is endorsed in certain guidelines for individuals aged ≥65 years, yet many modalities and strategies exist. Determining the comparative effectiveness of contemporary screening strategies is critical to inform population-based screening interventions. Methods: We developed a decision-analytic model to evaluate 45 distinct AF screening strategies (defined using different modalities and screening intervals), and compared them to no screening within 50 million individuals matching the United States population aged ≥65 years. The primary outcome was quality-adjusted life-years (QALYs), with incident stroke, major bleeding, and AF true and false positive rates as secondary outcomes. Results: A total of 11 AF screening strategies were effective when compared to no screening (100-1200 QALYs gained per 100,000 individuals screened, Figure ). Of 11 effective strategies, 7 (63.6%) utilized wrist-worn wearables. Effective strategies reduced stroke incidence by 0.1-0.2/1,000 person-years [PY] (number needed to screen to prevent stroke 5,000-10,000), but increased major bleeding by 0.2-0.6/1,000 PY (number needed to screen to cause major bleed 1,667-5,000). Repeated screening with discrete modalities tended to reduce effectiveness by accruing false positives without substantial gain in true AF diagnoses, while increasing the monitoring duration using wrist-worn wearables increased effectiveness as long as a confirmatory test was utilized. Sensitivity analyses identified test specificity as a highly influential parameter on screening effectiveness. Conclusions: Population-based AF screening is likely effective when specific strategies are utilized. Wrist-worn wearables appear to be an important modality for effective clinician-guided AF screening. Future technological development should focus on maximizing specificity for AF detection.
Abstract 15652: Cell Therapy in Heart Failure With Preserved Ejection Fraction (CELLpEF)
Authors: Bojan VRTOVEC, Sabina Frljak, Gregor Poglajen, Gregor Zemljic, Andraz Cerar, Matjaz Sever, Francois Haddad, Joseph C Wu
Journal: Circulation (2020)

Introduction: Previous studies have demonstrated that cell therapy may improve diastolic parameters in heart failure. Hypothesis: We sought to investigate the effects of transendocardial CD34 + cell therapy in patients with heart failure with preserved ejection fraction (HFpEF). Methods: In a prospective crossover study, we enrolled 30 patients with HFpEF (LVEF&gt;50%, E/e'&gt;15, NT-proBNP &gt;300 pg/ml). In Phase 1, patients were treated with stable medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34 + cell transplantation. They received bone marrow stimulation with filgrastim (10 mcg/kg, 5 days); CD34 + cells were collected by apheresis. We performed electroanatomical mapping of the left ventricle, and injected the cells transendocardialy in the areas of local diastolic dysfunction (80 million CD34 + cells divided into 20 injections). Patients were followed for 6 months after the procedure (Phase 2). Results: Our cohort included 23 male and 7 female patients aged 62±10 years, with LVEF of 58.7±7.3%, creatinine of 93±35 μmol/L, and bilirubin of 14.3±6.8 μmol/L. In Phase 1 (medical therapy), we found no change in E/e' (from 18.0±3.5 to 17.4±3.0, P=0.97), global systolic strain (from -12.5±2.4% to -12.8±2.6%, P=0.77), NT-proBNP levels (from 1463±1247 pg/mL to 1298±931 pg/mL, P=0.31), or 6-minute walk test distance (from 391±75 m to 402±93 m, P=0.42). In contrast, in Phase 2 (cell therapy), we found a significant improvement in E/e' (from 17.4±3.0 to 11.9±2.6, P=&lt;0.0001), a decrease in NT-proBNP levels (from 1298±931 pg/ml to 887±809 pg/ml, P=0.02), and an improvement in 6-minute walk test distance (from 402±93 m to 438±72 m, P=0.02). Although global systolic strain did not change significantly in Phase 2 (from -12.8±2.6% to -13.8±2.7%, P=0.36), we found a significant improvement of local systolic strain in myocardial segments that were injected with stem cells (-3.4±6.8%, P=0.005). Conclusion: In patients with HFpEF, transendocardial CD34 + cell therapy appears to be associated with improved left ventricular diastolic parameters, better exercise capacity, a decrease in NT-proBNP levels, and improved local systolic strain at cell injection sites.
Abstract 14569: Direct Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism in Obese Patients: A Systematic Review With Meta-analysis
Authors: Vicky Mai, Emmanuelle Marceau-Ferron, Laurent BERTOLETTI, Yves Lacasse, Sebastien Bonnet, Jean-Christophe Lega, Steeve Provencher
Journal: Circulation (2020)

Background: Obesity is a real burden and its prevalence is constantly increasing. High body weight is a risk factor for developing venous thromboembolism (VTE). Direct oral anticoagulants’ (DOAC) pharmacokinetics and pharmacodynamics are affected by obesity. Their efficacy and safety in obese (BMI ≥30kg/m 2 ) and morbidly obese (BMI ≥40kg/m 2 ) patients are still unclear in the treatment of VTE. Objectives: To compare the efficacy and safety of DOAC with vitamin K antagonist (VKA)/low molecular weight heparin (LMWH) in the acute treatment of VTE in obese and morbidly obese patients. The primary efficacy outcome was VTE recurrences. The safety outcomes were major bleeding (MB) and clinically relevant non-MB (CRNMB). All-cause mortality was also assessed. Hypothesis: We hypothesized that DOAC would present the same efficacy and safety for the treatment of acute VTE in obese and morbidly obese patients compared to VKA/LMWH. Methods: A systematic literature search (MEDLINE, EMBASE, CENTRAL, Web of Science) was conducted from inception to April 15 th 2020, identifying trials studying DOAC in the treatment of acute VTE in obese patients. Studies were included if one of the outcomes was reported. Two independent reviewers performed the study selection, data extraction, risk of bias assessment and strength of body evidence evaluation using the GRADE methodology. Analyses were conducted using the Mantel-Haenszel method based on a random-effect model. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals. Results: From 1240 citations screened, we included 21 studies (58,590 patients). VTE recurrences was similar with DOAC compared to VKA/LMWH in obese patients (risk ratio (RR): 1.03; 95%CI 0.93-1.15; p=0.55) and morbidly obese patients (RR 1.06; 95CI 0.94-1.19; p=0.35). DOAC was associated with a reduction in MB in obese patients (RR 0.57; 95%CI 0.34-0.94; p=0.03) and morbidly obese patients (RR 0.71; 95%CI 0.50-1.00; p=0.05) compared to VKA/LMWH. In obese patients, no difference was observed in CRNMB with DOAC compared to VKA/LMWH. Conclusion: DOAC is as effective in reducing VTE and is associated with less MB compared to VKA/LMWH in obese and morbidly obese patients.
Abstract 13808: Implementation of Cardiopulmonary Exercise Testing and Its Impact on 2-year Outcomes in Acute Coronary Syndrome From Mie ACS Registry
Authors: Hiroaki Murakami, Naoki Fujimoto, Akihiro Takasaki, Tairo Kurita, Kozo Hoshino, Toshiki Sawai, Atsushi Kambara, Tetsuya Kitamura, Takehiko Ichikawa, Masaaki Ito, Kaoru Dohi
Journal: Circulation (2020)

Introduction: Cardiopulmonary exercise testing (CPET) determines intensity for exercise rehabilitation which may improve outcomes in patients with acute coronary syndrome (ACS). However, it is unclear how many patients are given exercise education based on CPET around hospital discharge. Purposes: To assess the implementation of CPET and to evaluate the impacts of clinical parameters including CPET variables on 2-year outcomes in ACS patients. Methods: We enrolled 3146 ACS patients without hemodialysis (age, 68±12 yrs; 78% male) 30 days after onset using data from Mie ACS registry, a prospective and multicenter registry, between 2013 and 2017. We compared clinical characteristics in patients with and without CPET at hospital discharge. Prognostic factors including CPET variables during the 2-year follow-up were determined. Results: Forty percent of the hospitals had CPET equipment. Out of 3146, 431 patients (12%) underwent CPET and were given CPET-based exercise education. Implementation of CPET was associated with younger age, male, ST-elevation myocardial infraction, and higher peak creatine phosphokinase (p≤0.03). While, hospitalization length &lt;7 days or &gt;21 days was inversely associated with CPET. During the 2-year follow-up, 198 all-cause deaths (6%) and 103 heart failure (HF) hospitalization were observed. Multivariate Cox regression analysis demonstrated that age, male, hospitalization length &gt;21 days, Killip ≥2, mechanical circulatory and/or ventilator support were positive predictors of all-cause death. While, CPET around hospital discharge (hazard ratio, 0.52; 95%CI, 0.27-0.99, p&lt;0.05) and hemoglobin level were independent negative predictors of all-cause death. Although patients with CPET tended to have greater myocardial damage, they did not have increased rate of HF hospitalization or major adverse cardiovascular events (MACE). When analyzed only in patients with CPET, peak oxygen uptake was the only independent predictor for all-cause death. Conslusions: The number of patients who underwent CPET at discharge was small in our registry. Although the rate of HF hospitalization and MACE were similar in patients with and without CPET, CPET and CPET-based exercise education did reduce all-cause mortality in ACS patients.
Abstract 13773: Applied Behavior Change Techniques in Self-care Interventions for Patients With a Chronic Condition
Authors: Barbara Riegel, Heleen Westland, Paolo Iovino, Ingrid Barelds, Joyce Bruins Slot, Michael A Stawnychy, Onome H Osokpo, Elise Tarbi, Jaap Trappenburg, Ercole Vellone, Anna Stromberg, Tiny JAARSMA
Journal: Circulation (2020)

Introduction: Self-care requires behavior change in patients and healthcare providers play a pivotal role in supporting those changes. Examination of the behavior change techniques used by providers in self-care interventions can provide insights into how self-care behavior is enhanced in patients with a chronic condition. Objective: To quantify the behavior change techniques used to enhance healthy behavior in self-care interventions for patients with a chronic condition. Methods: Studies from a scoping review (n=233) were reviewed to identify behavior change techniques used in studies testing self-care interventions in adults with nine chronic conditions, most of which were CVDs. All studies were published between January 2008 and January 2019. Nine techniques from the Behavior Change Technique Taxonomy V1 (with 93 consensually agreed, distinct techniques) were selected for review because they are commonly used by a broad range of disciplines and have previously been shown to influence behavior change. Results: The 233 studies represent 59,950 patients, mean age 59.5 (±8.3) years, 44% female. Study sample sizes ranged from 24 to 2,445 patients. Most studies focused on DM2 (n=85; 36%), HTN (n=32; 14%) or HF (n=27; 12%). Most interventions targeted only patients (n=207; 89%). Goal setting (n=113; 48%) and problem solving (n=92; 40%) were the behavior change techniques used predominantly. Action planning, feedback and review of behavioral goals were used in 46-60 (20%-26%) studies and most commonly in patients with DM2 or CAD and rarely in patients with HTN or HF. Information about health consequences was used in 46 (20%) studies. Social support (n=17; 7%) and reminders (n=13; 6%) were rarely used. Conclusions: Few behavior change techniques were specified in the published self-care intervention trials. In future research, behavior change techniques and the associated mechanisms of actions need to be specified to support self-care intervention research.
Long-term survival of patients with stage III colon cancer treated with VRP-CEA(6D), an alphavirus vector that increases the CD8+ effector memory T cell to Treg ratio
Authors: Erika J Crosby, Amy C Hobeika, Donna Niedzwiecki, Christel Rushing, David Hsu, Peter Berglund, Jonathan Smith, Takuya Osada, William R Gwin III, Zachary C Hartman, Michael A Morse, Herbert Kim Lyerly
Journal: Journal for ImmunoTherapy of Cancer (2020)

There remains a significant need to eliminate the risk of recurrence of resected cancers. Cancer vaccines are well tolerated and activate tumor-specific immune effectors and lead to long-term survival in some patients. We hypothesized that vaccination with alphaviral replicon particles encoding tumor associated antigens would generate clinically significant antitumor immunity to enable prolonged overall survival (OS) in patients with both metastatic and resected cancer.OS was monitored for patients with stage IV cancer treated in a phase I study of virus-like replicon particle (VRP)-carcinoembryonic antigen (CEA), an alphaviral replicon particle encoding a modified CEA. An expansion cohort of patients (n=12) with resected stage III colorectal cancer who had completed their standard postoperative adjuvant chemotherapy was administered VRP-CEA every 3 weeks for a total of 4 immunizations. OS and relapse-free survival (RFS) were determined, as well as preimmunization and postimmunization cellular and humoral immunity.Among the patients with stage IV cancer, median follow-up was 10.9 years and 5-year survival was 17%, (95% CI 6% to 33%). Among the patients with stage III cancer, the 5-year RFS was 75%, (95%CI 40% to 91%); no deaths were observed. At a median follow-up of 5.8 years (range: 3.9-7.0 years) all patients were still alive. All patients demonstrated CEA-specific humoral immunity. Patients with stage III cancer had an increase in CD8 +TEM (in 10/12) and decrease in FOXP3 +Tregs (in 10/12) following vaccination. Further, CEA-specific, IFNγ-producing CD8+granzyme B+TCM cells were increased.VRP-CEA induces antigen-specific effector T cells while decreasing Tregs, suggesting favorable immune modulation. Long-term survivors were identified in both cohorts, suggesting the OS may be prolonged.