11 research outputs found

    Assessing the role of an artificial intelligence assessment tool for thoracic aorta diameter on routine chest CT

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    OBJECTIVE: To assess the diagnostic accuracy and clinical impact of automated artificial intelligence (AI) measurement of thoracic aorta diameter on routine chest CT. METHODS: A single-centre retrospective study involving three cohorts. 210 consecutive ECG-gated CT aorta scans (mean age 75 ± 13) underwent automated analysis (AI-Rad Companion Chest CT, Siemens) and were compared to a reference standard of specialist cardiothoracic radiologists for accuracy measuring aortic diameter. A repeated measures analysis tested reporting consistency in a second cohort (29 patients, mean age 61 ± 17) of immediate sequential pre-contrast and contrast CT aorta acquisitions. Potential clinical impact was assessed in a third cohort of 197 routine CT chests (mean age 66 ± 15) to document potential clinical impact. RESULTS: AI analysis produced a full report in 387/436 (89%) and a partial report in 421/436 (97%). Manual vs AI agreement was good to excellent (ICC 0.76-0.92). Repeated measures analysis of expert and AI reports for the ascending aorta were moderate to good (ICC 0.57-0.88). AI diagnostic performance crossed the threshold for maximally accepted limits of agreement (&gt;5 mm) at the aortic root on ECG-gated CTs. AI newly identified aortic dilatation in 27% of patients on routine thoracic imaging with a specificity of 99% and sensitivity of 77%. CONCLUSION: AI has good agreement with expert readers at the mid-ascending aorta and has high specificity, but low sensitivity, at detecting dilated aortas on non-dedicated chest CTs. ADVANCES IN KNOWLEDGE: An AI tool may improve the detection of previously unknown thoracic aorta dilatation on chest CTs vs current routine reporting.</p

    Assessing the role of an artificial intelligence assessment tool for thoracic aorta diameter on routine chest CT

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    OBJECTIVE: To assess the diagnostic accuracy and clinical impact of automated artificial intelligence (AI) measurement of thoracic aorta diameter on routine chest CT. METHODS: A single-centre retrospective study involving three cohorts. 210 consecutive ECG-gated CT aorta scans (mean age 75 ± 13) underwent automated analysis (AI-Rad Companion Chest CT, Siemens) and were compared to a reference standard of specialist cardiothoracic radiologists for accuracy measuring aortic diameter. A repeated measures analysis tested reporting consistency in a second cohort (29 patients, mean age 61 ± 17) of immediate sequential pre-contrast and contrast CT aorta acquisitions. Potential clinical impact was assessed in a third cohort of 197 routine CT chests (mean age 66 ± 15) to document potential clinical impact. RESULTS: AI analysis produced a full report in 387/436 (89%) and a partial report in 421/436 (97%). Manual vs AI agreement was good to excellent (ICC 0.76-0.92). Repeated measures analysis of expert and AI reports for the ascending aorta were moderate to good (ICC 0.57-0.88). AI diagnostic performance crossed the threshold for maximally accepted limits of agreement (&gt;5 mm) at the aortic root on ECG-gated CTs. AI newly identified aortic dilatation in 27% of patients on routine thoracic imaging with a specificity of 99% and sensitivity of 77%. CONCLUSION: AI has good agreement with expert readers at the mid-ascending aorta and has high specificity, but low sensitivity, at detecting dilated aortas on non-dedicated chest CTs. ADVANCES IN KNOWLEDGE: An AI tool may improve the detection of previously unknown thoracic aorta dilatation on chest CTs vs current routine reporting.</p

    Deep-Learning for Epicardial Adipose Tissue Assessment with Computed Tomography: Implications for Cardiovascular Risk Prediction

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    Background: Epicardial adipose tissue (EAT) volume is a marker of visceral obesity that can be measured in coronary computed tomography angiograms (CCTA). The clinical value of integrating this measurement in routine CCTA interpretation has not been documented./ Objectives: This study sought to develop a deep-learning network for automated quantification of EAT volume from CCTA, test it in patients who are technically challenging, and validate its prognostic value in routine clinical care./ Methods: The deep-learning network was trained and validated to autosegment EAT volume in 3,720 CCTA scans from the ORFAN (Oxford Risk Factors and Noninvasive Imaging Study) cohort. The model was tested in patients with challenging anatomy and scan artifacts and applied to a longitudinal cohort of 253 patients post-cardiac surgery and 1,558 patients from the SCOT-HEART (Scottish Computed Tomography of the Heart) Trial, to investigate its prognostic value./ Results: External validation of the deep-learning network yielded a concordance correlation coefficient of 0.970 for machine vs human. EAT volume was associated with coronary artery disease (odds ratio [OR] per SD increase in EAT volume: 1.13 [95% CI: 1.04-1.30]; P = 0.01), and atrial fibrillation (OR: 1.25 [95% CI:1.08-1.40]; P = 0.03), after correction for risk factors (including body mass index). EAT volume predicted all-cause mortality (HR per SD: 1.28 [95% CI: 1.10-1.37]; P = 0.02), myocardial infarction (HR: 1.26 [95% CI:1.09-1.38]; P = 0.001), and stroke (HR: 1.20 [95% CI: 1.09-1.38]; P = 0.02) independently of risk factors in SCOT-HEART (5-year follow-up). It also predicted in-hospital (HR: 2.67 [95% CI: 1.26-3.73]; P ≀ 0.01) and long-term post–cardiac surgery atrial fibrillation (7-year follow-up; HR: 2.14 [95% CI: 1.19-2.97]; P ≀ 0.01). Conclusions: Automated assessment of EAT volume is possible in CCTA, including in patients who are technically challenging; it forms a powerful marker of metabolically unhealthy visceral obesity, which could be used for cardiovascular risk stratification

    Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro

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    Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∌30-minutes, with blood samples collected pre-, immediately post-, and 30-minutes post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p &lt; 0.001), owing to an increased frequency of CD3−CD56+CD16+ NK-cells (+348%), HLA-DR+CD14dimCD16+ monocytes (+125%), and HLA-DR+CD14+CD32+ monocytes (+41%) in blood (p &lt; 0.01). However, overall, total plasma cells (CD38+CD138+) nor clonal plasma cells (CD38brightCD138+CD45−/dimCD19− with light-chain restriction) increased in blood (p &gt; 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis

    ‘Super Rehab’: can we achieve coronary artery disease regression? A feasibility study protocol

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    Introduction Patients diagnosed with coronary artery disease (CAD) are currently treated with medications and lifestyle advice to reduce the likelihood of disease progression and risk of future major adverse cardiovascular events (MACE). Where obstructive disease is diagnosed, revascularisation may be considered to treat refractory symptoms. However, many patients with coexistent cardiovascular risk factors, particularly those with metabolic syndrome (MetS), remain at heightened risk of future MACE despite current management.Cardiac rehabilitation is offered to patients post-revascularisation, however, there is no definitive evidence demonstrating its benefit in a primary prevention setting. We propose that an intensive lifestyle intervention (Super Rehab, SR) incorporating high-intensity exercise, diet and behavioural change techniques may improve symptoms, outcomes, and enable CAD regression.This study aims to examine the feasibility of delivering a multicentre randomised controlled trial (RCT) testing SR for patients with CAD, in a primary prevention setting.Methods and analysis This is a multicentre randomised controlled feasibility study of SR versus usual care in patients with CAD. The study aims to recruit 50 participants aged 18–75 across two centres. Feasibility will be assessed against rates of recruitment, retention and, in the intervention arm, attendance and adherence to SR. Qualitative interviews will explore trial experiences of study participants and practitioners. Variance of change in CAD across both arms of the study (assessed with serial CT coronary angiography) will inform the design and power of a future, multi-centre RCT.Ethics and dissemination Ethics approval was granted by South West—Frenchay Research Ethics Committee (reference: 21/SW/0153, 18 January 2022). Study findings will be disseminated via presentations to relevant stakeholders, national and international conferences and open-access peer-reviewed research publications.Trial registration number ISRCTN14603929

    Safety and Feasibility of a 16-Week Progressive Exercise Intervention in Treatment NaĂŻve Chronic Lymphocytic Leukaemia

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    A growing body of evidence from preclinical and human epidemiology studies of multiple cancer types indicate that physical activity can delay or avert the outgrowth of cancer, in a mechanistic process that may involve exercise-induced alterations to anti-cancer immunity. Many Chronic Lymphocytic leukaemia (CLL) patients present with asymptomatic, early-stage disease that is monitored until disease progression. Thus, exercise may be an effective way to manage disease burden and delay progression in treatment naĂŻve CLL. The primary objective of this pilot study was to investigate the safety and feasibility of an exercise programme in people with treatment naĂŻve CLL, and preliminarily explore the effects of exercise training on CLL counts, body composition, cardiorespiratory fitness, and immune cell phenotypes including T-cells. We approached N = 100 treatment naĂŻve CLL patients (Binet stage A and B) (Figure 1). Trial uptake was 40%, thus n = 40 participants with treatment naĂŻve CLL were screened. After assessing suitability for exercise (e.g., resting electrocardiogram and other safety tests), n = 11 participants were excluded - the majority of these, n = 9, were due to the presence of cardiac abnormalities. Consequently, n = 28 participants were randomised into a 16-week, home-based, supervised, personalised, progressive exercise intervention ( n = 14: mean ± SD: age = 62 ± 12 years) or 16-weeks of usual care, control group ( n = 14: mean ± SD: age = 61 ± 10 years). The overall retention rate was 86%, with 79% of the exercise group and 93% of the control group completing the trial. Adherence to the exercise intervention was 92 ± 8%. One serious adverse event was reported (hospitalisation for pneumonia) that was unrelated to the trial and one adverse event was reported (syncope following exercise) that was related to the trial. Together, this evidence indicates that exercise training is both safe and feasible in people with treatment naĂŻve CLL who passed pre-trial screening. The exercise intervention elicited a 2% increase in DEXA-derived lean mass in the exercise group compared to a 0.4% decrease in the control group ( p = .01) (Table 1). DEXA-derived total body fat percentage decreased by 4% and 1% and fat mass decreased by 3% and 2% ( p 0.05). Resting systolic and diastolic blood pressure was lower at post-intervention in both groups ( p 0.05) suggesting the observed changes could be the result of “white coat hypertension” pre-intervention. Additionally, no changes were observed for whole-body mass, BMI, bone mineral density, resting heart rate, or measures of cardiorespiratory fitness (all p>0.05). This trial provided a unique opportunity to investigate the effects of regular exercise on neoplastic activity in humans (i.e., CLL counts) without the confounding presence of anti-cancer therapy. Resting blood samples collected pre- and post-intervention were analysed by flow cytometry to enumerate CD5 +CD19 + CLL cells clonally restricted to kappa or lambda. No differences were observed for clonal CLL cells over time or between conditions ( p>0.05) (Table 1). We also analysed resting blood samples collected pre- and post-intervention by flow cytometry to enumerate T cell subsets. No statistically significant changes were observed between conditions pre-intervention to post-intervention for CD4 + or CD8 + T-cell subsets including, naĂŻve (CD27 +CD45RA +), stem cell-like memory (CD27 +CD45RA +CD127 +CD95 +), central memory (CD27 +CD45RA -), effector memory (CD27 -CD45RA -), EMRAs (CD27 -CD45RA +) or exhausted T-cells (PD1 +, Tim3 +) or FoxP3 T-regulatory cells (CD4 +CD127 lowCD25 +FoxP3 +) (all p>0.05). Our results show that exercise is safe and feasible in people with treatment naĂŻve CLL who passed pre-trial screening. In addition, exercise training increased lean mass. No changes were observed to CLL cells. The latter finding is unsurprising given the poorly immunogenic profile of CLL

    A single bout of vigorous intensity exercise enhances the efficacy of rituximab against human chronic lymphocytic leukaemia B-cells ex vivo

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    Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts induce a transient relocation of NK-cells and B-cells into peripheral blood, which could be harnessed to enhance the efficacy of rituximab in CLL by relocating both target and effector cells together with rituximab in blood. In this pilot study, n = 20 patients with treatment-naĂŻve CLL completed a bout of cycling 15 % above anaerobic threshold for ∌ 30-minutes, with blood samples collected pre-, immediately post-, and 1-hour post-exercise. Flow cytometry revealed that exercise evoked a 254 % increase in effector (CD3−CD56+CD16+) NK-cells in blood, and a 67 % increase in CD5+CD19+CD20+ CLL cells in blood (all p < 0.005). NK-cells were isolated from blood samples pre-, and immediately post-exercise and incubated with primary isolated CLL cells with or without the presence of rituximab to determine specific lysis using a calcein-release assay. Rituximab-mediated cell lysis increased by 129 % following exercise (p < 0.001). Direct NK-cell lysis of CLL cells – independent of rituximab – was unchanged following exercise (p = 0.25). We conclude that exercise improved the efficacy of rituximab-mediated ADCC against autologous CLL cells ex vivo and propose that exercise should be explored as a means of enhancing clinical responses in patients receiving anti-CD20 immunotherapy
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