Long COVID exhibits clinically distinct phenotypes at 3-6 months post-SARS-CoV-2 infection: results from the P4O2 consortium.

BACKGROUND: Four months after SARS-CoV-2 infection, 22%-50% of COVID-19 patients still experience complaints. Long COVID is a heterogeneous disease and finding subtypes could aid in optimising and developing treatment for the individual patient. METHODS: Data were collected from 95 patients in the P4O2 COVID-19 cohort at 3-6 months after infection. Unsupervised hierarchical clustering was performed on patient characteristics, characteristics from acute SARS-CoV-2 infection, long COVID symptom data, lung function and questionnaires describing the impact and severity of long COVID. To assess robustness, partitioning around medoids was used as alternative clustering. RESULTS: Three distinct clusters of patients with long COVID were revealed. Cluster 1 (44%) represented predominantly female patients (93%) with pre-existing asthma and suffered from a median of four symptom categories, including fatigue and respiratory and neurological symptoms. They showed a milder SARS-CoV-2 infection. Cluster 2 (38%) consisted of predominantly male patients (83%) with cardiovascular disease (CVD) and suffered from a median of three symptom categories, most commonly respiratory and neurological symptoms. This cluster also showed a significantly lower forced expiratory volume within 1 s and diffusion capacity of the lung for carbon monoxide. Cluster 3 (18%) was predominantly male (88%) with pre-existing CVD and diabetes. This cluster showed the mildest long COVID, and suffered from symptoms in a median of one symptom category. CONCLUSIONS: Long COVID patients can be clustered into three distinct phenotypes based on their clinical presentation and easily obtainable information. These clusters show distinction in patient characteristics, lung function, long COVID severity and acute SARS-CoV-2 infection severity. This clustering can help in selecting the most beneficial monitoring and/or treatment strategies for patients suffering from long COVID. Follow-up research is needed to reveal the underlying molecular mechanisms implicated in the different phenotypes and determine the efficacy of treatment.

The relationship of fat and muscle measurements with emphysema and bronchial wall thickening in smokers.

Introduction: Differences in body composition in patients with COPD may have important prognostic value and may provide opportunities for patient-specific management. We investigated the relation of thoracic fat and muscle with computed tomography (CT)-measured emphysema and bronchial wall thickening. Methods: Low-dose baseline chest CT scans from 1031 male lung cancer screening participants from one site were quantified for emphysema, bronchial wall thickening, subcutaneous fat, visceral fat and skeletal muscle. Body composition measurements were performed by segmenting the first slice above the aortic arch using Hounsfield unit thresholds with region growing and manual corrections. COPD presence and severity were evaluated with pre-bronchodilator spirometry testing. Results: Participants had a median age of 61.5 years (58.6-65.6, 25th-75th percentile) and median number of 38.0 pack-years (28.0-49.5); 549 (53.2%) were current smokers. Overall, 396 (38.4%) had COPD (256 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 140 GOLD 2-3). Participants with COPD had less subcutaneous fat, visceral fat and skeletal muscle (p<0.001 for all). With increasing GOLD stages, subcutaneous (p=0.005) and visceral fat values (p=0.004) were higher, and skeletal muscle was lower (p=0.004). With increasing severity of CT-derived emphysema, subcutaneous fat, visceral fat and skeletal muscle values were lower (p<0.001 for all). With increasing CT-derived bronchial wall thickness, subcutaneous and visceral fat values were higher (p<0.001 for both), without difference in skeletal muscle. All statistical relationships remained when adjusted for age, pack-years and smoking status. Conclusion: COPD presence and emphysema severity are associated with smaller amounts of thoracic fat and muscle, whereas bronchial wall thickening is associated with fat accumulation.

Pulmonary Computed Tomography Screening Frequency in Primary Antibody Deficiency.

BACKGROUND: Patients with primary antibody deficiency (PAD) frequently suffer from pulmonary complications, associated with severe morbidity and mortality. Hence, regular pulmonary screening by computed tomography (CT) scanning is advised. However, predictive risk factors for pulmonary morbidity are lacking. OBJECTIVE: To identify patients with PAD at risk for pulmonary complications necessitating regular CT screening. METHODS: A retrospective, longitudinal cohort study of patients with PAD (median follow-up 7.4 [2.3-14.8] years) was performed. CTs were scored using the modified Brody-II scoring system. Clinical and laboratory parameters were retrospectively collected. Potential risk factors were identified by univariate analysis when P < .2 and confirmed by multivariable logistic regression when P < .05. RESULTS: The following independent risk factors for progression of airway disease (AD) were identified: (1) diagnosis of X-linked agammaglobulinemia (XLA), (2) recurrent airway infections (2.5/year), and (3) the presence of AD at baseline. Signs of AD progression were detected in 5 of 11 patients with XLA and in 17 of 80 of the other patients with PAD. Of the 22 patients who progressed, 17 had pre-existent AD scores ≥7.0%. Increased AD scores were related to poorer forced expiratory volume in 1 second values and chronic cough. Common variable immunodeficiency and increased CD4 effector/memory cells were risk factors for an interstitial lung disease (ILD) score ≥13.0%. ILD ≥13.0% occurred in 12 of 80 patients. Signs of ILD progression were detected in 8 of 80 patients, and 4 of 8 patients showing progression had pre-existent ILD scores ≥13.0%. CONCLUSION: We identified risk factors that distinguished patients with PAD at risk for AD and ILD presence and progression, which could guide future screening frequency; however, independent and preferably prospective validation is needed.

Comparison of Commercial AI Software Performance for Radiograph Lung Nodule Detection and Bone Age Prediction.

Background Multiple commercial artificial intelligence (AI) products exist for assessing radiographs; however, comparable performance data for these algorithms are limited. Purpose To perform an independent, stand-alone validation of commercially available AI products for bone age prediction based on hand radiographs and lung nodule detection on chest radiographs. Materials and Methods This retrospective study was carried out as part of Project AIR. Nine of 17 eligible AI products were validated on data from seven Dutch hospitals. For bone age prediction, the root mean square error (RMSE) and Pearson correlation coefficient were computed. The reference standard was set by three to five expert readers. For lung nodule detection, the area under the receiver operating characteristic curve (AUC) was computed. The reference standard was set by a chest radiologist based on CT. Randomized subsets of hand (n = 95) and chest (n = 140) radiographs were read by 14 and 17 human readers, respectively, with varying experience. Results Two bone age prediction algorithms were tested on hand radiographs (from January 2017 to January 2022) in 326 patients (mean age, 10 years ± 4 [SD]; 173 female patients) and correlated strongly with the reference standard (r = 0.99; P < .001 for both). No difference in RMSE was observed between algorithms (0.63 years [95% CI: 0.58, 0.69] and 0.57 years [95% CI: 0.52, 0.61]) and readers (0.68 years [95% CI: 0.64, 0.73]). Seven lung nodule detection algorithms were validated on chest radiographs (from January 2012 to May 2022) in 386 patients (mean age, 64 years ± 11; 223 male patients). Compared with readers (mean AUC, 0.81 [95% CI: 0.77, 0.85]), four algorithms performed better (AUC range, 0.86-0.93; P value range, <.001 to .04). Conclusions Compared with human readers, four AI algorithms for detecting lung nodules on chest radiographs showed improved performance, whereas the remaining algorithms tested showed no evidence of a difference in performance. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Omoumi and Richiardi in this issue.

Added value of an artificial intelligence algorithm in reducing the number of missed incidental acute pulmonary embolism in routine portal venous phase chest CT.

OBJECTIVES: The purpose of this study was to evaluate the incremental value of artificial intelligence (AI) compared to the diagnostic accuracy of radiologists alone in detecting incidental acute pulmonary embolism (PE) on routine portal venous contrast-enhanced chest computed tomography (CT). METHODS: CTs of 3089 consecutive patients referred to the radiology department for a routine contrast-enhanced chest CT between 27-5-2020 and 31-12-2020, were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The diagnostic performance of the AI was compared to the initial report. To determine the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, another experienced cardiothoracic radiologist with knowledge of the initial report and the AI output adjudicated. RESULTS: The prevalence of acute incidental PE in the reference standard was 2.2% (67 of 3089 patients). In 25 cases, AI detected initially unreported PE. This included three cases concerning central/lobar PE. Sensitivity of the AI algorithm was significantly higher than the outcome of the initial report (respectively 95.5% vs. 62.7%, p < 0.001), whereas specificity was very high for both (respectively 99.6% vs 99.9%, p = 0.012). The AI algorithm only showed a slightly higher amount of false-positive findings (11 vs. 2), resulting in a significantly lower PPV (85.3% vs. 95.5%, p = 0.047). CONCLUSION: The AI algorithm showed high diagnostic accuracy in diagnosing incidental PE, detecting an additional 25 cases of initially unreported PE, accounting for 37.3% of all positive cases. CLINICAL RELEVANCE STATEMENT: Radiologist support from AI algorithms in daily practice can prevent missed incidental acute PE on routine chest CT, without a high burden of false-positive cases. KEY POINTS: • Incidental pulmonary embolism is often missed by radiologists in non-diagnostic scans with suboptimal contrast opacification within the pulmonary trunk. • An artificial intelligence algorithm showed higher sensitivity detecting incidental pulmonary embolism on routine portal venous chest CT compared to the initial report. • Implementation of artificial intelligence support in routine daily practice will reduce the number of missed incidental pulmonary embolism.

Bronchiectasis is associated with lower lung function in lung cancer screening participants.

BACKGROUND AND OBJECTIVE: Bronchiectasis is a frequent incidental finding on chest computed tomography (CT), but its relevance in lung cancer screening is not fully understood. We investigated the association between bronchiectasis and respiratory symptoms, pulmonary function, and emphysema in lung cancer screening participants with and without chronic obstructive pulmonary disease (COPD). METHODS: We included 3260 (ex-)smokers from the Dutch-Belgian lung cancer screening trial (NELSON). Bronchiectasis was scored by chest radiologists. The relationship with pulmonary function (FEV1%predicted, FEV1/FVC), respiratory complaints (cough, dyspnea, wheezing, mucus hypersecretion), and CT-quantified emphysema (15th percentile) was examined with independent t-tests and multivariate regression. RESULTS: Bronchiectasis was present in 5.4% (n = 175/3260). There was no difference in prevalence between subjects with and without COPD (68/1121 [5.9%] vs. 109/2139 [5.1%]; p = .368). COPD subjects with bronchiectasis had a lower FEV1%predicted (76.2% vs. 85.0%; p < .001), lower FEV1/FVC (0.58 vs. 0.62; p < .001), and more emphysema (- 938 HU vs. - 930 HU; p = .001) than COPD subjects without bronchiectasis. In COPD subjects, bronchiectasis was independently associated with a lower FEV1%predicted (B = - 7.7; CI [- 12.3, - 3.3]), lower FEV1/FVC (B = - 2.5; CI [- 4.3, - 0.8]), more cough (OR 2.4; CI [1.3, 4.3]), more mucus hypersecretion (OR 1.8; CI [1.0, 3.1]) and more dyspnea (OR 2.3; CI [1.3, 3.9]). In those without COPD (n = 2139), bronchiectasis was associated with more cough, mucus hypersecretion, and wheezing, but not with deteriorating lung function. CONCLUSION: Bronchiectasis was present in 5.4% of our lung cancer screening participants and was associated with more respiratory symptoms and, in those with COPD, with lower lung function and more emphysema. CLINICAL RELEVANCE STATEMENT: In a lung cancer screening population, bronchiectasis has a prevalence of 5.4% with a mainly mild severity. This finding is of little clinical relevance unless mild COPD is also present. In those subjects, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema. KEY POINTS: • Bronchiectasis was found in 5.4% of lung cancer screening participants, consisting of (ex-)smokers with and without mild COPD. • In those with mild COPD, bronchiectasis was associated with a lower lung function, more respiratory symptoms, and more emphysema. • Incidental findings of mild bronchiectasis are not very relevant in a lung cancer screening population, unless COPD is also present.

Acute and early-onset cardiotoxicity in children and adolescents with cancer: a systematic review.

BACKGROUND: Cardiotoxicity is among the most important adverse effects of childhood cancer treatment. Anthracyclines, mitoxantrone and radiotherapy involving the heart are its main causes. Subclinical cardiac dysfunction may over time progress to clinical heart failure. The majority of previous studies have focused on late-onset cardiotoxicity. In this systematic review, we discuss the prevalence and risk factors for acute and early-onset cardiotoxicity in children and adolescents with cancer treated with anthracyclines, mitoxantrone or radiotherapy involving the heart. METHODS: A literature search was performed within PubMed and reference lists of relevant studies. Studies were eligible if they reported on cardiotoxicity measured by clinical, echocardiographic and biochemical parameters routinely used in clinical practice during or within one year after the start of cancer treatment in ≥ 25 children and adolescents with cancer. Information about study population, treatment, outcomes of diagnostic tests used for cardiotoxicity assessment and risk factors was extracted and risk of bias was assessed. RESULTS: Our PubMed search yielded 3649 unique publications, 44 of which fulfilled the inclusion criteria. One additional study was identified by scanning the reference lists of relevant studies. In these 45 studies, acute and early-onset cardiotoxicity was studied in 7797 children and adolescents. Definitions of acute and early-onset cardiotoxicity prove to be highly heterogeneous. Prevalence rates varied for different cardiotoxicity definitions: systolic dysfunction (0.0-56.4%), diastolic dysfunction (30.0-100%), combinations of echocardiography and/or clinical parameters (0.0-38.1%), clinical symptoms (0.0-25.5%) and biomarker levels (0.0-37.5%). Shortening fraction and ejection fraction significantly decreased during treatment. Cumulative anthracycline dose proves to be an important risk factor. CONCLUSIONS: Various definitions have been used to describe acute and early-onset cardiotoxicity due to childhood cancer treatment, complicating the establishment of its exact prevalence. Our findings underscore the importance of uniform international guidelines for the monitoring of cardiac function during and shortly after childhood cancer treatment.

Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci are related to bone mineralization, phosphate catabolism and hormone metabolic pathways. Several new loci harbor candidate causal genes supported by multiple lines of functional evidence and are regulators of smooth muscle cell-mediated calcification ex vivo and in vitro. Together, these findings help refine the genetic architecture of CAC and extend our understanding of the biological and potential druggable pathways underlying CAC.

Precision Medicine for More Oxygen (P4O2)-Study Design and First Results of the Long COVID-19 Extension.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to the death of almost 7 million people, however, with a cumulative incidence of 0.76 billion, most people survive COVID-19. Several studies indicate that the acute phase of COVID-19 may be followed by persistent symptoms including fatigue, dyspnea, headache, musculoskeletal symptoms, and pulmonary functional-and radiological abnormalities. However, the impact of COVID-19 on long-term health outcomes remains to be elucidated. Aims: The Precision Medicine for more Oxygen (P4O2) consortium COVID-19 extension aims to identify long COVID patients that are at risk for developing chronic lung disease and furthermore, to identify treatable traits and innovative personalized therapeutic strategies for prevention and treatment. This study aims to describe the study design and first results of the P4O2 COVID-19 cohort. Methods: The P4O2 COVID-19 study is a prospective multicenter cohort study that includes nested personalized counseling intervention trial. Patients, aged 40-65 years, were recruited from outpatient post-COVID clinics from five hospitals in The Netherlands. During study visits at 3-6 and 12-18 months post-COVID-19, data from medical records, pulmonary function tests, chest computed tomography scans and biological samples were collected and questionnaires were administered. Furthermore, exposome data was collected at the patient's home and state-of-the-art imaging techniques as well as multi-omics analyses will be performed on collected data. Results: 95 long COVID patients were enrolled between May 2021 and September 2022. The current study showed persistence of clinical symptoms and signs of pulmonary function test/radiological abnormalities in post-COVID patients at 3-6 months post-COVID. The most commonly reported symptoms included respiratory symptoms (78.9%), neurological symptoms (68.4%) and fatigue (67.4%). Female sex and infection with the Delta, compared with the Beta, SARS-CoV-2 variant were significantly associated with more persisting symptom categories. Conclusions: The P4O2 COVID-19 study contributes to our understanding of the long-term health impacts of COVID-19. Furthermore, P4O2 COVID-19 can lead to the identification of different phenotypes of long COVID patients, for example those that are at risk for developing chronic lung disease. Understanding the mechanisms behind the different phenotypes and identifying these patients at an early stage can help to develop and optimize prevention and treatment strategies.

Retrospective batch analysis to evaluate the diagnostic accuracy of a clinically deployed AI algorithm for the detection of acute pulmonary embolism on CTPA.

PURPOSE: To generate and extend the evidence on the clinical validity of an artificial intelligence (AI) algorithm to detect acute pulmonary embolism (PE) on CT pulmonary angiography (CTPA) of patients suspected of PE and to evaluate the possibility of reducing the risk of missed findings in clinical practice with AI-assisted reporting. METHODS: Consecutive CTPA scan data of 3316 patients referred because of suspected PE between 24-2-2018 and 31-12-2020 were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The output of the AI was compared with the attending radiologists' report. To define the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, an experienced cardiothoracic radiologist adjudicated. RESULTS: According to the reference standard, PE was present in 717 patients (21.6%). PE was missed by the AI in 23 patients, while the attending radiologist missed 60 PE. The AI detected 2 false positives and the attending radiologist 9. The sensitivity for the detection of PE by the AI algorithm was significantly higher compared to the radiology report (96.8% vs. 91.6%, p < 0.001). Specificity of the AI was also significantly higher (99.9% vs. 99.7%, p = 0.035). NPV and PPV of the AI were also significantly higher than the radiology report. CONCLUSION: The AI algorithm showed a significantly higher diagnostic accuracy for the detection of PE on CTPA compared to the report of the attending radiologist. This finding indicates that missed positive findings could be prevented with the implementation of AI-assisted reporting in daily clinical practice. CRITICAL RELEVANCE STATEMENT: Missed positive findings on CTPA of patients suspected of pulmonary embolism can be prevented with the implementation of AI-assisted care. KEY POINTS: The AI algorithm showed excellent diagnostic accuracy detecting PE on CTPA. Accuracy of the AI was significantly higher compared to the attending radiologist. Highest diagnostic accuracy can likely be achieved by radiologists supported by AI. Our results indicate that implementation of AI-assisted reporting could reduce the number of missed positive findings.

Real-time myocardial landmark tracking for MRI-guided cardiac radio-ablation using Gaussian Processes.

Objective.The high speed of cardiorespiratory motion introduces a unique challenge for cardiac stereotactic radio-ablation (STAR) treatments with the MR-linac. Such treatments require tracking myocardial landmarks with a maximum latency of 100 ms, which includes the acquisition of the required data. The aim of this study is to present a new method that allows to track myocardial landmarks from few readouts of MRI data, thereby achieving a latency sufficient for STAR treatments.Approach.We present a tracking framework that requires only few readouts of k-space data as input, which can be acquired at least an order of magnitude faster than MR-images. Combined with the real-time tracking speed of a probabilistic machine learning framework called Gaussian Processes, this allows to track myocardial landmarks with a sufficiently low latency for cardiac STAR guidance, including both the acquisition of required data, and the tracking inference.Main results.The framework is demonstrated in 2D on a motion phantom, andin vivoon volunteers and a ventricular tachycardia (arrhythmia) patient. Moreover, the feasibility of an extension to 3D was demonstrated byin silico3D experiments with a digital motion phantom. The framework was compared with template matching-a reference, image-based, method-and linear regression methods. Results indicate an order of magnitude lower total latency (<10 ms) for the proposed framework in comparison with alternative methods. The root-mean-square-distances and mean end-point-distance with the reference tracking method was less than 0.8 mm for all experiments, showing excellent (sub-voxel) agreement.Significance.The high accuracy in combination with a total latency of less than 10 ms-including data acquisition and processing-make the proposed method a suitable candidate for tracking during STAR treatments. Additionally, the probabilistic nature of the Gaussian Processes also gives access to real-time prediction uncertainties, which could prove useful for real-time quality assurance during treatments.

Radiological and long-term clinical response to elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease.

INTRODUCTION: A triple combination of CFTR modulators ELE/TEZ/IVA (elexacaftor/tezacaftor/ivacaftor, Trikafta™) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. During registration and settling reimbursement in Europe, it could be requested on a compassionate use basis, for patients with advanced lung disease (ppFEV1 < 40). AIM: The aim of this study is to evaluate 2 years of experience with the clinical and radiological response of ELE/TEZ/IVA in pwCF in a compassionate use setting. METHODS: pwCF who started ELE/TEZ/IVA in a compassionate use setting were prospectively followed with assessment of spirometry, BMI, chest CT, CFQ-R and sweat chloride concentration (SCC) before start and after 3 months. Furthermore, spirometry, sputum cultures, and BMI were repeated after 1, 6, 12, 18, and 24 months. RESULTS: Eighteen patients were eligible for this evaluation, nine with F508del/F508del genotype (eight of whom were using dual CFTR modulators) and nine with F508del/minimal function mutation. After 3 months, mean change in SCC was -44.9 (p ≤ 0.001), together with significant improvement in CT (change in Brody score: -28.27 p ≤ 0.001) and CFQ-R results (change in respiratory domain: +18.8, p = 0.002). After 24 months, ppFEV1 change was +8.89 (p = 0.002), BMI had improved by +1.53 kg/m2 (p ≤ 0.001) and exacerbation rate declined from 5.94 in 24 months before start to 1.17 (p ≤ 0.001) in the 24 months after. CONCLUSION: pwCF with advanced lung disease experience relevant clinical benefit after 2 years of treatment with ELE/TEZ/IVA in a compassionate use setting. Structural lung damage, quality of life, exacerbation rate, and BMI improved significantly with treatment. Gain in ppFEV1 is lower compared to the phase III trials that included younger patients with moderately affected lung function.

Multi-source data approach for personalized outcome prediction in lung cancer screening: update from the NELSON trial.

Trials show that low-dose computed tomography (CT) lung cancer screening in long-term (ex-)smokers reduces lung cancer mortality. However, many individuals were exposed to unnecessary diagnostic procedures. This project aims to improve the efficiency of lung cancer screening by identifying high-risk participants, and improving risk discrimination for nodules. This study is an extension of the Dutch-Belgian Randomized Lung Cancer Screening Trial, with a focus on personalized outcome prediction (NELSON-POP). New data will be added on genetics, air pollution, malignancy risk for lung nodules, and CT biomarkers beyond lung nodules (emphysema, coronary calcification, bone density, vertebral height and body composition). The roles of polygenic risk scores and air pollution in screen-detected lung cancer diagnosis and survival will be established. The association between the AI-based nodule malignancy score and lung cancer will be evaluated at baseline and incident screening rounds. The association of chest CT imaging biomarkers with outcomes will be established. Based on these results, multisource prediction models for pre-screening and post-baseline-screening participant selection and nodule management will be developed. The new models will be externally validated. We hypothesize that we can identify 15-20% participants with low-risk of lung cancer or short life expectancy and thus prevent ~140,000 Dutch individuals from being screened unnecessarily. We hypothesize that our models will improve the specificity of nodule management by 10% without loss of sensitivity as compared to assessment of nodule size/growth alone, and reduce unnecessary work-up by 40-50%.

Real world impact of added FFR-CT to coronary CT angiography on clinical decision-making and patient prognosis - IMPACT FFR study.

OBJECTIVES: The addition of CT-derived fractional flow reserve (FFR-CT) increases the diagnostic accuracy of coronary CT angiography (CCTA). We assessed the impact of FFR-CT in routine clinical practice on clinical decision-making and patient prognosis in patients suspected of stable coronary artery disease (CAD). METHODS: This retrospective, single-center study compared a cohort that received CCTA with FFR-CT to a historical cohort that received CCTA before FFR-CT was available. We assessed the clinical management decisions after FFR-CT and CCTA and the rate of major adverse cardiac events (MACEs) during the 1-year follow-up using chi-square tests for independence. Kaplan-Meier curves were used to visualize the occurrence of safety outcomes over time. RESULTS: A total of 360 patients at low to intermediate risk of CAD were included, 224 in the CCTA only group, and 136 in the FFR-CT group. During follow-up, 13 MACE occurred in 12 patients, 9 (4.0%) in the CCTA group, and three (2.2%) in the FFR-CT group. Clinical management decisions differed significantly between both groups. After CCTA, 60 patients (26.5%) received optimal medical therapy (OMT) only, 115 (51.3%) invasive coronary angiography (ICA), and 49 (21.9%) single positron emission CT (SPECT). After FFR-CT, 106 patients (77.9%) received OMT only, 27 (19.9%) ICA, and three (2.2%) SPECT (p < 0.001 for all three options). The revascularization rate after ICA was similar between groups (p = 0.15). However, patients in the CCTA group more often underwent revascularization (p = 0.007). CONCLUSION: Addition of FFR-CT to CCTA led to a reduction in (invasive) diagnostic testing and less revascularizations without observed difference in outcomes after 1 year. KEY POINTS: • Previous studies have shown that computed tomography-derived fractional flow reserve improves the accuracy of coronary computed tomography angiography without changes in acquisition protocols. • This study shows that use of computed tomography-derived fractional flow reserve as gatekeeper to invasive coronary angiography in patients suspected of stable coronary artery disease leads to less invasive testing and revascularization without observed difference in outcomes after 1 year. • This could lead to a significant reduction in costs, complications and (retrospectively unnecessary) usage of diagnostic testing capacity, and a significant increase in patient satisfaction.

A Systematic Review of Chest Imaging Findings in Long COVID Patients.

Long COVID is the persistence of one or more COVID-19 symptoms after the initial viral infection, and there is evidence supporting its association with lung damage. In this systematic review, we provide an overview of lung imaging and its findings in long COVID patients. A PubMed search was performed on 29 September 2021, for English language studies in which lung imaging was performed in adults suffering from long COVID. Two independent researchers extracted the data. Our search identified 3130 articles, of which 31, representing the imaging findings of 342 long COVID patients, were retained. The most common imaging modality used was computed tomography (CT) (N = 249). A total of 29 different imaging findings were reported, which were broadly categorized into interstitial (fibrotic), pleural, airway, and other parenchymal abnormalities. A direct comparison between cases, in terms of residual lesions, was available for 148 patients, of whom 66 (44.6%) had normal CT findings. Although respiratory symptoms belong to the most common symptoms in long COVID patients, this is not necessarily linked to radiologically detectable lung damage. Therefore, more research is needed on the role of the various types of lung (and other organ) damage which may or may not occur in long COVID.

Prospective of 31 P MR Spectroscopy in Hepatopancreatobiliary Cancer: A Systematic Review of the Literature.

BACKGROUND: The incidence of liver and pancreatic cancer is rising. Patients benefit from current treatments, but there are limitations in the evaluation of (early) response to treatment. Tumor metabolic alterations can be measured noninvasively with phosphorus (31 P) magnetic resonance spectroscopy (MRS). PURPOSE: To conduct a quantitative analysis of the available literature on 31 P MRS performed in hepatopancreatobiliary cancer and to provide insight into its current and potential for therapy (non-) response assessment. POPULATION: Patients with hepatopancreatobiliary cancer. FIELD STRENGTH/SEQUENCE: 31 P MRS. ASSESSMENT: The PubMed, EMBASE, and Cochrane library databases were systematically searched for studies published to 17 March 17, 2022. All 31 P MRS studies in hepatopancreatobiliary cancer reporting 31 P metabolite levels were included. STATISTICAL TESTS: Relative differences in 31 P metabolite levels/ratios between patients before therapy and healthy controls, and the relative changes in 31 P metabolite levels/ratios in patients before and after therapy were determined. RESULTS: The search yielded 10 studies, comprising 301 subjects, of whom 132 (44%) healthy volunteers and 169 (56%) patients with liver cancer of various etiology. To date, 31 P MRS has not been applied in pancreatic cancer. In liver cancer, alterations in levels of 31 P metabolites involved in cell proliferation (phosphomonoesters [PMEs] and phosphodiesters [PDEs]) and energy metabolism (ATP and inorganic phosphate [Pi]) were observed. In particular, liver tumors were associated with elevations of PME/PDE and PME/Pi compared to healthy liver tissue, although there was a broad variety among studies (elevations of 2%-267% and 21%-233%, respectively). Changes in PME/PDE in liver tumors upon therapy were substantial, yet very heterogeneous and both decreases and increases were observed, whereas PME/Pi was consistently decreased after therapy in all studies (-13% to -76%). DATA CONCLUSION: 31 P MRS has great potential for treatment monitoring in oncology. Future studies are needed to correlate the changes in 31 P metabolite levels in hepatopancreatobiliary tumors with treatment response. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

On the feasibility of cardiac substructure sparing in magnetic resonance imaging guided stereotactic lung radiotherapy.

BACKGROUND: Lung stereotactic body radiotherapy (SBRT) has proven an effective treatment for medically inoperable lung tumors, even for (ultra-)central tumors. Recently, there has been growing interest in radiation-induced cardiac toxicity in lung radiotherapy. More specifically, dose to cardiac (sub-)structures (CS) was found to correlate with survival after radiotherapy. PURPOSE: Our goal is first, to investigate the percentage of patients who require CS sparing in an magnetic resonance imaging guided lung SBRT workflow, and second, to quantify how successful implementation of cardiac sparing would be. METHODS: The patient cohort consists of 34 patients with stage II-IV lung cancer who were treated with SBRT between 2017 and 2020. A mid-position computed tomography (CT) image was used to create treatment plans for the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) following clinical templates. Under guidance of a cardio-thoracic radiologist, 11 CS were contoured manually for each patient. Dose constraints for five CS were extracted from the literature. Patients were stratified according to their need for cardiac sparing depending on the CS dose in their non-CS constrained MR-linac treatment plans. Cardiac sparing treatment plans (CSPs) were then created and dosimetrically compared with their non-CS constrained treatment plan counterparts. CSPs complied with the departmental constraints and were considered successful when fulfilling all CS constraints, and partially successful if some CS constraints could be fulfilled. Predictors for the need for and feasibility of cardiac sparing were explored, specifically planning target volume (PTV) size, cranio-caudal (CC) distance, 3D distance, and in-field overlap volume histograms (iOVH). RESULTS: 47% of the patients (16 out of 34) were in need of cardiac sparing. A successful CSP could be created for 62.5% (10 out of 16) of these patients. Partially successful CSPs still complied with two to four CS constraints. No significant difference in dose to organs at risk (OARs) or targets was identified between CSPs and the corresponding non-CS constrained MR-linac plans. The need for cardiac sparing was found to correlate with distance in the CC direction between target and all of the individual CS (Mann-Whitney U-test p-values <10-6 ). iOVHs revealed that complying with dose constraints for CS is primarily determined by in-plane distance and secondarily by PTV size. CONCLUSION: We demonstrated that CS can be successfully spared in lung SBRT on the MR-linac for most of this patient cohort, without compromising doses to the tumor or to other OARs. CC distance between the target and CS can be used to predict the need for cardiac sparing. iOVHs, in combination with PTV size, can be used to predict if cardiac sparing will be successful for all constrained CS except the left ventricle.

Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications.

Objectives: DISH has been associated with increased coronary artery calcifications and incident ischaemic stroke. The formation of bone along the spine may share pathways with calcium deposition in the aorta. We hypothesized that patients with DISH have increased vascular calcifications. Therefore we aimed to investigate the presence and extent of DISH in relation to thoracic aortic calcification (TAC) severity. Methods: This cross-sectional study included 4703 patients from the Second Manifestation of ARTerial disease cohort, consisting of patients with cardiovascular events or risk factors for cardiovascular disease. Chest radiographs were scored for DISH using the Resnick criteria. Different severities of TAC were scored arbitrarily from no TAC to mild, moderate or severe TAC. Using multivariate logistic regression, the associations between DISH and TAC were analysed with adjustments for age, sex, BMI, diabetes, smoking status, non-high-density lipoprotein cholesterol, cholesterol lowering drug usage, renal function and blood pressure. Results: A total of 442 patients (9.4%) had evidence of DISH and 1789 (38%) patients had TAC. The prevalence of DISH increased from 6.6% in the no TAC group to 10.8% in the mild, 14.3% in the moderate and 17.1% in the severe TAC group. After adjustments, DISH was significantly associated with the presence of TAC [odds ratio (OR) 1.46 [95% CI 1.17, 1.82)]. In multinomial analyses, DISH was associated with moderate TAC [OR 1.43 (95% CI 1.06, 1.93)] and severe TAC [OR 1.67 (95% CI 1.19, 2.36)]. Conclusions: Subjects with DISH have increased TACs, providing further evidence that patients with DISH have an increased burden of vascular calcifications.

Diffuse idiopathic skeletal hyperostosis of the cervical spine causing dysphagia and airway obstruction: an updated systematic review.

BACKGROUND AND CONTEXT: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by growing ossifications of spinal entheses and tendons, which may cause trachea and esophagus compression when located anteriorly in the cervical spine. PURPOSE: Our previous systematic review on the epidemiological and clinical knowledge of dysphagia and airway obstruction caused by cervical DISH was updated, with a focus on (surgical) treatment and outcomes. STUDY DESIGN: A systematic review of the literature was performed. METHODS: Publications in Medline and EMBASE from July 2010 to June 2021 were searched. Two investigators performed data extraction and study specific quality assessment. RESULTS: A total of 138 articles (112 case reports and 26 case series) were included, describing 419 patients with dysphagia and/or airway obstruction. The mean age of the patient group was 67.3 years (range: 35-91 years), and 85.4% was male. An evident increase of published cases was observed within the last decade. Surgical treatment was chosen for 66% of patients with the anterolateral approach most commonly used. The total complication rate after surgery was 22.1%, with 12.7% occurring within 1 month after intervention. Improvement of dysphagia was observed in 95.5% of operated patients. After a mean follow-up of 3.7 years (range: 0.4-9.0 years), dysphagia recurred in 12 surgically treated patients (4%), of which five patients had osteophyte regrowth. CONCLUSIONS: The number of published cases of dysphagia in patients with DISH has doubled in the last decade compared to our previous review. Yet, randomized studies or guidelines on the treatment or prevention on recurrence are lacking. Surgical treatment is effective and has low (major) complication rates. Common trends established across the cases in our study may help improve our understanding and management of dysphagia and airway obstruction in cervical DISH.

Feasibility of cardiac-synchronized quantitative T1 and T2 mapping on a hybrid 1.5 Tesla magnetic resonance imaging and linear accelerator system.

Background and Purpose: The heart is important in radiotherapy either as target or organ at risk. Quantitative T1 and T2 cardiac magnetic resonance imaging (qMRI) may aid in target definition for cardiac radioablation, and imaging biomarker for cardiotoxicity assessment. Hybrid MR-linac devices could facilitate daily cardiac qMRI of the heart in radiotherapy. The aim of this work was therefore to enable cardiac-synchronized T1 and T2 mapping on a 1.5 T MR-linac and test the reproducibility of these sequences on phantoms and in vivo between the MR-linac and a diagnostic 1.5 T MRI scanner. Materials and methods: Cardiac-synchronized MRI was performed on the MR-linac using a wireless peripheral pulse-oximeter unit. Diagnostically used T1 and T2 mapping sequences were acquired twice on the MR-linac and on a 1.5 T MR-simulator for a gel phantom and 5 healthy volunteers in breath-hold. Phantom T1 and T2 values were compared to gold-standard measurements and percentage errors (PE) were computed, where negative/positive PE indicate underestimations/overestimations. Manually selected regions-of-interest were used for in vivo intra/inter scanner evaluation. Results: Cardiac-synchronized T1 and T2 qMRI was enabled after successful hardware installation on the MR-linac. From the phantom experiments, the measured T1/T2 relaxation times had a maximum percentage error (PE) of -4.4%/-8.8% on the MR-simulator and a maximum PE of -3.2%/+8.6% on the MR-linac. Mean T1/T2 of the myocardium were 1012 ± 34/51 ± 2 ms on the MR-simulator and 1034 ± 42/51 ± 1 ms on the MR-linac. Conclusions: Accurate cardiac-synchronized T1 and T2 mapping is feasible on a 1.5 T MR-linac and might enable novel plan adaptation workflows and cardiotoxicity assessments.