The asbestos-asbestosis exposure-response relationship: a cohort study of the general working population.

OBJECTIVES: The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure-response relationship for asbestosis in a general working population setting. We examined the exposure-response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. METHODS: We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure-response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. RESULTS: The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15- -1.22]. The IRR was 1.94 (95% CI 1.53-2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. CONCLUSIONS: This study found exposure-response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

Commercially Available Chest Radiograph AI Tools for Detecting Airspace Disease, Pneumothorax, and Pleural Effusion.

Background Commercially available artificial intelligence (AI) tools can assist radiologists in interpreting chest radiographs, but their real-life diagnostic accuracy remains unclear. Purpose To evaluate the diagnostic accuracy of four commercially available AI tools for detection of airspace disease, pneumothorax, and pleural effusion on chest radiographs. Materials and Methods This retrospective study included consecutive adult patients who underwent chest radiography at one of four Danish hospitals in January 2020. Two thoracic radiologists (or three, in cases of disagreement) who had access to all previous and future imaging labeled chest radiographs independently for the reference standard. Area under the receiver operating characteristic curve, sensitivity, and specificity were calculated. Sensitivity and specificity were additionally stratified according to the severity of findings, number of findings on chest radiographs, and radiographic projection. The χ2 and McNemar tests were used for comparisons. Results The data set comprised 2040 patients (median age, 72 years [IQR, 58-81 years]; 1033 female), of whom 669 (32.8%) had target findings. The AI tools demonstrated areas under the receiver operating characteristic curve ranging 0.83-0.88 for airspace disease, 0.89-0.97 for pneumothorax, and 0.94-0.97 for pleural effusion. Sensitivities ranged 72%-91% for airspace disease, 63%-90% for pneumothorax, and 62%-95% for pleural effusion. Negative predictive values ranged 92%-100% for all target findings. In airspace disease, pneumothorax, and pleural effusion, specificity was high for chest radiographs with normal or single findings (range, 85%-96%, 99%-100%, and 95%-100%, respectively) and markedly lower for chest radiographs with four or more findings (range, 27%-69%, 96%-99%, 65%-92%, respectively) (P < .001). AI sensitivity was lower for vague airspace disease (range, 33%-61%) and small pneumothorax or pleural effusion (range, 9%-94%) compared with larger findings (range, 81%-100%; P value range, > .99 to < .001). Conclusion Current-generation AI tools showed moderate to high sensitivity for detecting airspace disease, pneumothorax, and pleural effusion on chest radiographs. However, they produced more false-positive findings than radiology reports, and their performance decreased for smaller-sized target findings and when multiple findings were present. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Yanagawa and Tomiyama in this issue.

Late adverse events to iodinated contrast media in patients treated with IL-2: a safety report from the Danish Renal Carcinoma Group (DaRenCa) study - 1.

BACKGROUND: A higher incidence of late adverse events (LAEs) to iodinated contrast media in interleukin-2 (IL-2)-treated patients has been reported. PURPOSE: To assess the incidence of LAEs after administration of iodinated contrast media in patients with metastatic renal cell carcinoma (mRCC) treated with IL-2. MATERIAL AND METHODS: Patients were randomized to treatment with IL-2 and interferon-α with/without bevacizumab in the Danish Renal Carcinoma Group study - 1. Patients underwent a computed tomography (CT) scan at baseline, at one month, at three months, and every third month until RECIST 1.1 defined progression. LAEs due to iodinated contrast media were systematically registered according to the Common Terminology Criteria for Adverse Events classification. RESULTS: In total, 89 patients were included and underwent a total of 507 contrast-enhanced CT scans. An overall incidence of 46 (9.1%) LAEs was observed in 38 of 89 (42.7%) patients; 3 LAEs at baseline (3.4% of all baseline scans), 39 (13.9%) LAEs during IL-2-based therapies, and 4 (2.9%) LAEs after termination of IL-based therapies. There was no difference in progression-free survival, overall survival, and treatment response in patients experiencing LAEs compared to patients without LAEs (P = 0.2, P = 0.5, and P = 0.6, respectively). CONCLUSION: Patients with mRCC demonstrated a higher incidence of LAEs after administration of iodinated contrast during ongoing IL-2 therapy, indicating that iodinated contrast media may cause a recall phenomenon of IL-2 toxicities in patients with mRCC. Treatment with IL-2 should not be a contraindication for contrast-enhanced scans in patients with mRCC but expertise and vigilance are required.

Association between Parenchymal B-Cell Follicles and CT-Proven Enlarged Mediastinal Lymph Nodes in Patients with Pulmonary Fibrosis.

BACKGROUND: Mediastinal lymph node enlargement (MLNE) is a finding described in a subset of patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) and is associated with accelerated disease progression and increased mortality. The cause of MLNE is still not known. Our hypothesis is that there is an association between MLNE and B-cell follicles in lung tissue, another aspect detectable in the lung tissue of patients with IPF and other ILDs. OBJECTIVES: The aim of this study was to assess if there is an association between MLNE and B-cell follicles in lung tissue in patients with IPF and other ILDs. METHOD: Patients having transbronchial cryobiopsies performed as part of an investigation for ILD were included in this prospective observational study. MLNE (smallest diameter ≥10 mm) were assessed in station 7, 4R, and 4L on high-resolution computed tomography scans. B-cell follicles were assessed on haematoxylin-eosin-stained specimens. Lung function, 6-minute walk test, acute exacerbation, and mortality were registered after 2 years. In addition, we investigated if the finding of B-cell follicles was consistent in patients who underwent both surgical lung biopsies (SLBs) and cryobiopsies. RESULTS: In total, 93 patients were included for analysis (46% diagnosed with IPF, 54% diagnosed with other ILDs). MLNE was found in 26 (60%) of the IPF patients and in 23 (46%) of the non-IPF patients (p = 0.164). Diffusing capacity for carbon monoxide was significantly lower (p = 0.03) in patients with MLNE compared to patients without MLNE. B-cell follicles were found in 11 (26%) of the IPF patients and in 22 (44%) of the non-IPF patients (p = 0.064). Germinal centres were not seen in any of the patients. There was no association between MLNE and B-cell follicles (p = 0.057). No significant difference in change of pulmonary function test was seen at 2-year follow-up when comparing the patients with and without MLNE or B-cell follicles. In 13 patients, both SLBs and cryobiopsies were performed. The presence of B-cell follicles was not consistent when comparing the two different methods. CONCLUSION: MLNE is evident in a substantial part of patients with ILD and is associated with lower DLCO at inclusion. We could not demonstrate an association between histological B-cell follicles in biopsies and MLNE. A possible explanation for this is that the cryobiopsies might not have captured the changes we sought.

Autonomous Chest Radiograph Reporting Using AI: Estimation of Clinical Impact.

Background Automated interpretation of normal chest radiographs could alleviate the workload of radiologists. However, the performance of such an artificial intelligence (AI) tool compared with clinical radiology reports has not been established. Purpose To perform an external evaluation of a commercially available AI tool for (a) the number of chest radiographs autonomously reported, (b) the sensitivity for AI detection of abnormal chest radiographs, and (c) the performance of AI compared with that of the clinical radiology reports. Materials and Methods In this retrospective study, consecutive posteroanterior chest radiographs from adult patients in four hospitals in the capital region of Denmark were obtained in January 2020, including images from emergency department patients, in-hospital patients, and outpatients. Three thoracic radiologists labeled chest radiographs in a reference standard based on chest radiograph findings into the following categories: critical, other remarkable, unremarkable, or normal (no abnormalities). AI classified chest radiographs as high confidence normal (normal) or not high confidence normal (abnormal). Results A total of 1529 patients were included for analysis (median age, 69 years [IQR, 55-69 years]; 776 women), with 1100 (72%) classified by the reference standard as having abnormal radiographs, 617 (40%) as having critical abnormal radiographs, and 429 (28%) as having normal radiographs. For comparison, clinical radiology reports were classified based on the text and insufficient reports excluded (n = 22). The sensitivity of AI was 99.1% (95% CI: 98.3, 99.6; 1090 of 1100 patients) for abnormal radiographs and 99.8% (95% CI: 99.1, 99.9; 616 of 617 patients) for critical radiographs. Corresponding sensitivities for radiologist reports were 72.3% (95% CI: 69.5, 74.9; 779 of 1078 patients) and 93.5% (95% CI: 91.2, 95.3; 558 of 597 patients), respectively. Specificity of AI, and hence the potential autonomous reporting rate, was 28.0% of all normal posteroanterior chest radiographs (95% CI: 23.8, 32.5; 120 of 429 patients), or 7.8% (120 of 1529 patients) of all posteroanterior chest radiographs. Conclusion Of all normal posteroanterior chest radiographs, 28% were autonomously reported by AI with a sensitivity for any abnormalities higher than 99%. This corresponded to 7.8% of the entire posteroanterior chest radiograph production. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Park in this issue.

Potential impact of texture analysis in contrast enhanced CT in non-small cell lung cancer as a marker of survival: A retrospective feasibility study.

The objective of this feasibility study was to assess computed tomography (CT) texture analysis (CTTA) of pulmonary lesions as a predictor of overall survival in patients with suspected lung cancer on contrast-enhanced computed tomography (CECT). In a retrospective pilot study, 94 patients (52 men and 42 women; mean age, 67.2 ±â€…10.8 yrs) from 1 center with non-small cell lung cancer (NSCLC) underwent CTTA on the primary lesion by 2 individual readers. Both simple and multivariate Cox regression analyses correlating textural parameters with overall survival were performed. Statistically significant parameters were selected, and optimal cutoff values were determined. Kaplan-Meier plots based on these results were produced. Simple Cox regression analysis showed that normalized uniformity had a hazard ratio (HR) of 16.059 (3.861-66.788, P < .001), and skewness had an HR of 1.914 (1.330-2.754, P < .001). The optimal cutoff values for both parameters were 0.8602 and 0.1554, respectively. Normalized uniformity, clinical stage, and skewness were found to be prognostic factors for overall survival in multivariate analysis. Tumor heterogeneity, assessed by normalized uniformity and skewness on CECT may be a prognostic factor for overall survival.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts.

We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.

Assessment of Correlation between Dual-Energy Ct (De-Ct)-Derived Iodine Concentration and Local Flourodeoxyglucose (Fdg) Uptake in Patients with Primary Non-Small-Cell Lung Cancer.

(1) The current literature contains several studies investigating the correlation between dual-energy-derived iodine concentration (IC) and positron emission tomography (PET)-derived Flourodeoxyglucose (18F-FDG) uptake in patients with non-small-cell lung cancer (NSCLC). In previously published studies, either the entire tumor volume or a region of interest containing the maximum IC or 18F-FDG was assessed. However, the results have been inconsistent. The objective of this study was to correlate IC with FDG both within the entire volume and regional sub-volumes of primary tumors in patients with NSCLC. (2) In this retrospective study, a total of 22 patients with NSCLC who underwent both dual-energy CT (DE-CT) and 18F-FDG PET/CT were included. A region of interest (ROI) encircling the entire primary tumor was delineated, and a rigid registration of the DE-CT, iodine maps and FDG images was performed for the ROI. The correlation between tumor measurements and area-specific measurements of ICpeak and the peak standardized uptake value (SUVpeak) was found. Finally, a correlation between tumor volume and the distance between SUVpeak and ICpeak centroids was found. (3) For the entire tumor, moderate-to-strong correlations were found between SUVmax and ICmax (R = 0.62, p = 0.002), and metabolic tumor volume vs. total iodine content (R = 0.91, p < 0.001), respectively. For local tumor sub-volumes, a negative correlation was found between ICpeak and SUVpeak (R = −0.58, p = 0.0046). Furthermore, a strong correlation was found between the tumor volume and the distance in millimeters between SUVpeak and ICpeak centroids (R = 0.81, p < 0.0001). (4) In patients with NSCLC, high FDG uptakes and high DE-CT-derived iodine concentrations correlated on a whole-tumor level, but the peak areas were positioned at different locations within the tumor. 18F-FDG PET/CT and DE-CT provide complementary information and might represent different underlying patho-physiologies.

Comparison of Intracranial and Extracranial Carotid Artery Calcifications between Obstructive Sleep Apnea Patients and Healthy Individuals: A Combined Cone-Beam Computed Tomography and Polysomnographic Study.

Purpose: This study aimed to compare the presence and grades of intra- and extracranial carotid artery calcifications between obstructive sleep apnea (OSA) and non-OSA patients. Methods: CBCT records of 190 patients (95 OSA patients and 95 non-OSA patients) were retrospectively collected and analyzed. Patient demographic data, including age and gender for both study groups and body mass index (BMI), and apnea-hypopnea index (AHI) for OSA patients were recorded. The presence of intra- and extracranial carotid artery calcifications and the number of calcifications were noted according to the grading scale. Results: There was a significant difference in carotid artery calcifications between OSA patients and healthy individuals. A total of 56.8% of the OSA patients showed at least one carotid artery calcification, whereas 13.8% of healthy individuals showed at least one carotid artery calcification (p < 0.05). For intracranial calcifications, OSA patients showed a significantly higher prevalence than healthy individuals (p < 0.05). The results showed that as the apnea-hypopnea index increases in OSA patients, the incidence of carotid artery calcification increases simultaneously. AHI > 30 patients showed the highest percentage of calcifications. Conclusion: In conclusion, OSA patients showed a higher prevalence of calcified carotid artery calcifications than healthy individuals. The results can be interpreted as the higher AHI, the more carotid artery calcification occurs. As these lesions can be a precursor of future strokes, 3D MDCT/CBCT images should evaluate meticulously not only extracranial but also intracranially, especially in OSA patients.

Experiences of nurses and coordinators in a childhood obesity prevention trial based on motivational interviewing within Swedish child health services.

PURPOSE: To explore the experiences of nurses and coordinators in the PRIMROSE childhood obesity prevention trial, and to understand the factors that might help to improve the outcome of future primary prevention of obesity. METHODS: Using a qualitative approach, data were obtained by interviewing nine intervention nurses and three regional study coordinators. All participants were female. The interviews were transcribed and analysed using content analysis. RESULTS: Two themes emerged: The nurses experienced that it was rewarding to participate in the trial, but challenging to combine the intervention with regular work; and The study coordinators experienced that they were in a difficult position handling the conflicting needs of the research group and the nurses' commitment to usual child health care services. The importance of support, encouragement, briefer and simpler intervention, and adaptation of the training in motivational interviewing to the setting was emphasized. Stress and lack of time were major barriers to deliver the intervention as intended. CONCLUSIONS: Although the PRIMROSE intervention was developed in collaboration with representatives from the child health services, and additional research funding was provided to compensate for time spent working with the trial, nurses experienced stress and time constraints. .

AI-based automatic segmentation of craniomaxillofacial anatomy from CBCT scans for automatic detection of pharyngeal airway evaluations in OSA patients.

This study aims to generate and also validate an automatic detection algorithm for pharyngeal airway on CBCT data using an AI software (Diagnocat) which will procure a measurement method. The second aim is to validate the newly developed artificial intelligence system in comparison to commercially available software for 3D CBCT evaluation. A Convolutional Neural Network-based machine learning algorithm was used for the segmentation of the pharyngeal airways in OSA and non-OSA patients. Radiologists used semi-automatic software to manually determine the airway and their measurements were compared with the AI. OSA patients were classified as minimal, mild, moderate, and severe groups, and the mean airway volumes of the groups were compared. The narrowest points of the airway (mm), the field of the airway (mm2), and volume of the airway (cc) of both OSA and non-OSA patients were also compared. There was no statistically significant difference between the manual technique and Diagnocat measurements in all groups (p > 0.05). Inter-class correlation coefficients were 0.954 for manual and automatic segmentation, 0.956 for Diagnocat and automatic segmentation, 0.972 for Diagnocat and manual segmentation. Although there was no statistically significant difference in total airway volume measurements between the manual measurements, automatic measurements, and DC measurements in non-OSA and OSA patients, we evaluated the output images to understand why the mean value for the total airway was higher in DC measurement. It was seen that the DC algorithm also measures the epiglottis volume and the posterior nasal aperture volume due to the low soft-tissue contrast in CBCT images and that leads to higher values in airway volume measurement.

Early reduction in spectral dual-layer detector CT parameters as favorable imaging biomarkers in patients with metastatic renal cell carcinoma.

OBJECTIVES: To associate the early change in DL-CT parameters and HU with survival outcomes and treatment response in patients with metastatic renal cell carcinoma (mRCC). METHODS: DL-CT scans were performed at baseline and after 1 month of checkpoint immunotherapy or tyrosine kinase inhibitor therapy. Scans were reconstructed to conventional CT and DL-CT series, and used for assessment of HU, iodine concentration (IC), and the effective atomic number (Zeffective) in the combined RECISTv.1.1 target lesions. The relative changes, defined as ΔIC(combined), ΔZeffective(combined), and ΔHU(combined), were associated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The reduction in the sum of diameters of target lesions ≥ 30% after 1 month was associated with OS, PFS, and ORR. RESULTS: Overall, 115 and 104 mRCC patients were included at baseline and 1 month, respectively. Median IC(combined) decreased from 2.3 to 1.2 mg/ml (p < 0.001), Zeffective(combined) from 8.5 to 8.0 (p < 0.001), and HU(combined) from 86.0 to 64.00 HU (p < 0.001). After multivariate adjustments, the largest reductions in ΔIC(combined) (HR 0.47, 95% CI: 0.24-0.94, p = 0.033) and ΔZeffective(combined) (HR = 0.43, 95% CI: 0.21-0.87, p = 0.019) were associated with favorable OS; the largest reduction in ΔZeffective(combined) was associated with higher response (OR = 2.79, 95% CI: 1.12-6.94, p = 0.027). The largest reduction in ΔHU(combined) was solely associated with OS in univariate analysis (HR 0.45, 95% CI: 0.23-0.91). Reduction in SOD ≥ 30% at 1 month was not associated with outcomes (p > 0.075). CONCLUSIONS: Early reductions at 1 month in ΔIC(combined) and ΔZeffective(combined) are associated with favorable outcomes in patients with mRCC. This information may reassure physicians and patients about treatment strategy. KEY POINTS: • Early reductions following 1 month of therapy in spectral dual-layer detector CT-derived iodine concentration and the effective atomic number (Zeffective) are independent biomarkers for better overall survival in patients with metastatic renal cell carcinoma. • Early reduction after 1 month of therapy in the effective atomic number (Zeffective) is an independent imaging biomarker for better treatment response metastatic renal cell carcinoma.

Unpacking the behavioural components and delivery features of early childhood obesity prevention interventions in the TOPCHILD Collaboration: a systematic review and intervention coding protocol.

INTRODUCTION: Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS: Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION: The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration: protocol for a systematic review with individual participant data meta-analysis of behavioural interventions for the prevention of early childhood obesity.

INTRODUCTION: Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION: Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER: CRD42020177408.

Prognostic Utility of Parameters Derived From Pretreatment Dual-Layer Spectral-Detector CT in Patients With Metastatic Renal Cell Carcinoma.

BACKGROUND. New therapies have emerged for metastatic renal cell carcinoma (mRCC), though corresponding imaging markers are lacking. Dual-layer spectral-detector CT (DLCT) can quantify iodine concentration (IC) and effective atomic number (Zeffective), providing information beyond attenuation that may indicate mRCC prognosis. OBJECTIVE. The purpose of our study was to assess the utility of the DLCT-derived parameters IC and Zeffective for predicting mRCC treatment response and survival. METHODS. This prospective study enrolled 120 participants with mRCC from January 2018 to January 2020 who underwent DLCT, with reconstruction of IC and Zeffective maps, before treatment initiation. Final analysis included 115 participants (86 men, 29 women; median age, 65.1 years), incorporating 313 target lesions that were clinically selected using RECIST version 1.1 on arterial phase acquisitions of the chest and abdomen. Semiautomatic volumetric segmentation was performed of the target lesions. Voxels from all lesions were combined to a single histogram per patient. The median IC and Zeffective of the combined histograms were recorded. Measurements above and below the cohort median values were considered high and low, respectively. Univariable associations were explored between IC and Zeffective with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariable associations were explored between IC and ORR, PFS, and OS, adjusting for treatment (tyrosine kinase inhibitor vs checkpoint immunotherapy) and significant univariable predictors (including tumor histology and International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] risk factors). RESULTS. At baseline, median IC was 2.26 mg/mL, and median Zeffective was 8.49. In univariable analysis, high IC and high Zeffective were associated with better ORR (both, odds ratio [OR] = 4.35; p = .001), better PFS (both, hazard ratio [HR] = 0.51; p = .004), and better OS (both, HR = 0.38; p < .001). In multivariable models, high IC independently predicted better ORR (OR = 4.35, p = .001), better PFS (HR = 0.51, p = .004), and better OS (HR = 0.37, p < .001); neutrophilia independently predicted worse PFS (HR = 2.10, p = .004) and worse OS (HR = 2.28, p = .003). The estimated C-index for predicting OS using IMDC risk factors alone was 0.650 versus 0.687 when incorporating high attenuation and 0.692 when incorporating high IC or high Zeffective. CONCLUSION. High IC and high Zeffective are significant predictors of better treatment response and survival in mRCC. CLINICAL IMPACT. Baseline DLCT parameters may improve current mRCC prognostic models. TRIAL REGISTRATION. ClinicalTrials.gov NCT03616951.

Economic impact of spectral body imaging in diagnosis of patients suspected for occult cancer.

BACKGROUND: Based on prior studies spectral CT has shown a higher sensitivity for malignant lesions than conventional CT at the cost of lower specificity. For the radiologists, it also offers a higher degree of certainty in the diagnosis of benign lesions. The objective of this study was to evaluate the economic impact of spectral CT in patients suspected of occult cancer in a medical center in Denmark. METHODS: This study was a secondary analysis using de-identified data from a prospective study of patients receiving a contrast-enhanced spectral CT scan. Based on suggested follow-up examinations on both spectral CT and contrast-enhanced CT, costs from a payer's perspective were determined using unit costs obtained from national databases. RESULTS: The dataset contained 400 patients. Overall, 203 follow-up procedures were eliminated based on spectral data reading. The largest reduction in suggested follow-up procedures was found for the kidney (83%), followed by the liver (66%), adrenal glands (60%), and pancreas (42%). The total estimated costs for suggested follow-up procedures based on spectral data reading were €155,219, 25.2% (€52,384) less than that of conventional CT reading. CONCLUSION: Our results provide support for spectral body imaging as an advanced imaging modality for suspected occult cancer. A substantial number of follow-up diagnostic procedures could be eliminated based on spectral data reading, which would result in significant cost savings.

Physical activity in women attending a dissonance-based intervention after Roux-en-Y Gastric Bypass: A 2-year follow-up of a randomized controlled trial.

BACKGROUND: The majority of Roux-en-Y gastric bypass (RYGB) patients are not sufficiently physically active post-surgery, yet little support from the Swedish healthcare system is offered. We investigated if a dissonance-based group intervention, aiming to increase health-related quality of life after surgery, had any effect on patients' physical activity two years post-RYGB. METHODS: Women undergoing RYGB surgery were recruited from five Swedish hospitals and randomized to intervention or control group (standard post-surgery care). The dissonance-based intervention was conducted three months post-RYGB and consisted of four group sessions, each with a specific topic, of which one addressed physical activity. ActiGraph GT3X+ accelerometers were used to measure physical activity at pre-RYGB, one- and two-years post-surgery. RESULTS: At pre-RYGB, 259 women were recruited and randomized (intervention n = 156 and control n = 103). Participants had a mean age of 44.7 years (SD 10.3) and pre-RYGB body mass index of 40.8 (SD 4.5) kg/m2. At two-years follow-up, 99 participants (63.5%) in intervention group and 68 (66.0%) in control group had valid accelerometer-measurements. Pre- to post-surgery increases were seen in all physical activity outcomes, but no statistically significant differences between the groups were observed at the two-years follow-up, and intervention effects were poor (d = 0.02-0.35). CONCLUSION: To our knowledge, this is the first dissonance-based intervention targeting women undergoing RYGB surgery. At two-years follow-up, we did not observe any differences in physical activity levels between the intervention group and control group. Trial registration number: ISRCTN16417174.

Comparison of hyoid bone morphology between obstructive sleep apnea patients and healthy individuals.

OBJECTIVE: We aimed to find morphological properties of the hyoid bone, which are predominant among the patients diagnosed with obstructive sleep apnoea (OSA), and compare them with healthy individuals. METHODS: A total of 67 cone-beam computed tomography (CBCT) image sequences of patients (44 males, 23 females) diagnosed with OSA and a total of 70 multislice computed tomography (MSCT) data of non-OSA patients (45 males, 25 females) were selected in this study. DICOM images were imported into InVivo 5.1.2 (Anatomage) software. The position of the hyoid bone relative to the C3 and C4 cervical vertebrae, as well as its morphological type (B, V, U, H, D, HK-type) and its total volume was determined. RESULTS: The volumetric values of the hyoid bone of OSA patients (2384.49 ± 682.073 mm3 ) were significantly (P < .001) lower compared to the values derived from non-OSA patients (2952.96 ± 932.5 mm3 ). The difference was independent of gender, and volumetric values showed a strong significant (P < .01) difference between male OSA and non-OSA (2709.18 ± 608.05; 3157.87 ± 926.5 mm3 ) and female OSA and non-OSA patients (1763 ± 242.51 2584; 2584.12 ± 840.21 mm3 ), as well. In the case of B and V-types, the volumetric values showed significant differences (P < .05), when the OSA (2300,77 ± 622; 2166 ± 312 mm3 ) and non-OSA patients were compared (2823,48 ± 780; 3216 ± 463 mm3 ). CONCLUSION: Our results suggest that the volume of the hyoid bone might be a potential biological marker for OSA, especially in the case of B and V hyoid bone types.

Blood Volume as a new functional image-based biomarker of progression in metastatic renal cell carcinoma.

RECIST v1.1 has limitations in evaluating progression. We assessed Dynamic Constrast Enhanced Computed Tomography (DCE-CT) identified Blood Volume (BV) for the evaluation of progressive disease (PD) in patients with metastatic renal cell carcinoma (mRCC). BV was quantified prospectively at baseline, after one month, then every three months until PD. Relative changes (ΔBV) were assessed at each timepoint compared with baseline values. The primary endpoint was Time to PD (TTP), the secondary endpoint was Time to the scan prior to PD (PDminus1). Cox proportional hazard models adjusted ΔBV for treatments and International mRCC Database Consortium factors. A total of 62 patients had analyzable scans at the PD timepoint. Median BV was 23.92 mL × 100 g-1 (range 4.40-399.04) at PD and 26.39 mL × 100 g-1 (range 8.70-77.44) at PDminus1. In the final multivariate analysis higher ΔBV was statistically significantly associated with shorter Time to PD, HR 1.11 (95% CI 1.07-1.15, P < 0.001). Also assessed at PDminus1, higher ΔBV was significantly associated with shorter time to PD, HR 1.14 (95% CI 1.01-1.28, P = 0.031). In conclusion, DCE-CT identified BV is a new image-based biomarker of therapy progression in patients with mRCC.