Validation of a commercially available CAD-system for lung nodule detection and characterization using CT-scans.

OBJECTIVES: This study aims to externally validate a commercially available Computer-Aided Detection (CAD)-system for the automatic detection and characterization of solid, part-solid, and ground-glass lung nodules (LN) on CT scans. METHODS: This retrospective study encompasses 263 chest CT scans performed between January 2020 and December 2021 at a Dutch university hospital. All scans were read by a radiologist (R1) and compared with the initial radiology report. Conflicting scans were assessed by an adjudicating radiologist (R2). All scans were also processed by CAD. The standalone performance of CAD in terms of sensitivity and false-positive (FP)-rate for detection was calculated together with the sensitivity for characterization, including texture, calcification, speculation, and location. The R1's detection sensitivity was also assessed. RESULTS: A total of 183 true nodules were identified in 121 nodule-containing scans (142 non-nodule-containing scans), of which R1 identified 165/183 (90.2%). CAD detected 149 nodules, of which 12 were not identified by R1, achieving a sensitivity of 149/183 (81.4%) with an FP-rate of 49/121 (0.405). CAD's detection sensitivity for solid, part-solid, and ground-glass LNs was 82/94 (87.2%), 42/47 (89.4%), and 25/42 (59.5%), respectively. The classification accuracy for solid, part-solid, and ground-glass LNs was 81/82 (98.8%), 16/42 (38.1%), and 18/25 (72.0%), respectively. Additionally, CAD demonstrated overall classification accuracies of 137/149 (91.9%), 123/149 (82.6%), and 141/149 (94.6%) for calcification, spiculation, and location, respectively. CONCLUSIONS: Although the overall detection rate of this system slightly lags behind that of a radiologist, CAD is capable of detecting different LNs and thereby has the potential to enhance a reader's detection rate. While promising characterization performances are obtained, the tool's performance in terms of texture classification remains a subject of concern. CLINICAL RELEVANCE STATEMENT: Numerous lung nodule computer-aided detection-systems are commercially available, with some of them solely being externally validated based on their detection performance on solid nodules. We encourage researchers to assess performances by incorporating all relevant characteristics, including part-solid and ground-glass nodules. KEY POINTS: Few computer-aided detection (CAD) systems are externally validated for automatic detection and characterization of lung nodules. A detection sensitivity of 81.4% and an overall texture classification sensitivity of 77.2% were measured utilizing CAD. CAD has the potential to increase single reader detection rate, however, improvement in texture classification is required.

18F-FDG/PET-CT imaging findings after sternotomy.

BACKGROUND: The clinical diagnosis of deep sternal wound infection (DSWI) is supported by imaging findings including 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT). To avoid misinterpretation due to normal post-surgery inflammation we assessed normal imaging findings in non-infected patients after sternotomy. METHODS: This is a prospective cohort study including non-infectious patients with sternotomy. All patients underwent 18F-FDG-PET/CT at either 5 weeks (group 1), 12 weeks (group 2) or 52 weeks (group 3) post-surgery. 18F-FDG uptake was scored visually in five categories and assessed quantitatively. RESULTS: A total of 44 patients were included. Sternal mean SUVmax was 7.34 (± 1.86), 5.22 (± 2.55) and 3.20 (± 1.80) in group 1, 2 and 3, respectively (p < 0.01). Sternal mean SUVmean was 3.84 (± 1.00), 2.69 (± 1.32) and 1.71 (± 0.98) in group 1, 2 and 3 (p < 0.01). All patients in group 1 had elevated uptake whereas group 2 and 3 showed 2/15 (13%) and 11/20 (55%) patients respectively with no elevated uptake. Group 3 still showed an elevated uptake pattern in in 9/20 (45%) and in 3/9 (33%) with a high-grade diffuse uptake pattern. CONCLUSION: This study shows significant lower sternal 18F-FDG at 55 weeks compared to 5 weeks post-sternotomy however elevated uptake patterns may persist.

Normal imaging findings after ascending aorta prosthesis implantation on 18F-Fluorodeoxyglucose Positron Emission Tomography with computed tomography.

BACKGROUND: To diagnose abnormal 18F-Fluorodeoxyglucose (18F-FDG) uptake in suspected endocarditis after aortic root and/or ascending aorta prosthesis (ARAP) implantation, it is important to first establish the normal periprosthetic uptake on positron emission tomography with computed tomography (PET/CT). METHODS: Patients with uncomplicated ARAP implantation were prospectively included and underwent 18F-FDG-PET/CT at either 12 (± 2) weeks (group 1) or 52 (± 8) weeks (group 2) after procedure. Uptake on three different locations of the prosthesis ("cranial anastomosis (CA)," "prosthetic heart valve (PHV)," "ascending aorta prosthesis (AAP)") was scored visually (none/low/intermediate/high) and quantitatively (maximum standardized uptake value (SUVmax) and target-to-background ratio (SUVratio). RESULTS: In total, 20 patients (group 1: n = 10, group 2: n = 10) (mean age 64±7 years, 70% male) were included. Both groups had similar visual uptake intensity for all measured areas (CA: mostly low-intermediate (16/20 (80%)), p = .17; PHV: low-intermediate (16/20 (80%)), p = .88; AAP: low-intermediate (19/20 (95%)), p = .48). SUVmax for CA was 5.6 [4.1-6.1] and 3.8 [3.1-5.9] (median [IQR], p = .19), and around PHV 5.0 [4.1-5.7] and 6.3 [4.6-7.1] (p = .11) for groups 1 and 2, respectively. SUVratio for CA was 2.8 [2.3-3.2] and 2.0 [1.7-2.6] (median [IQR], p = .07) and around PHV 2.5 [2.4-2.8] and 2.9 [2.3-3.5] (median [IQR], p = .26) for groups 1 and 2, respectively. CONCLUSION: No significant differences were observed between PET/CT findings at 3 months and 1 year after ARAP implantation, warranting caution in interpretation of PET/CT in the first year after implantation.

Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease.

INTRODUCTION: There is discussion about incorporating a family history (FamHis) of premature coronary artery disease (CAD) in risk score algorithms. However, FamHis provides information on individual risk. Coronary artery calcification score (CACS) is a metric of atherosclerosis that may determine the individual risk within families at high risk of premature CAD. METHODS: In asymptomatic individuals (n = 704), we assessed the association between FamHis of CAD and elevated CACS. To assess the predictive value of CACS in individuals with a FamHis of CAD, we performed a post-hoc analysis on the St. Francis Heart Study (n = 834). We assessed, in a case control design, the risk of future CAD in individuals with a FamHis of CAD and either CACS >80th percentile or no CACS at all. RESULTS: Individuals with a FamHis for CAD had an increased risk for elevated CACS (adjusted odds ratio (OR) 2.23 (95% CI 1.48-3.36); p < 0.05), compared to those without a FamHis. In the prospective study (3.5 years follow-up), the event rate equally low in those with a positive FamHis and a negative FamHis (0% vs. 1%), if they had a CAC of 0. However, in those with CACS >80(th) percentile, a FamHis of CAD doubled the CAD event rate (positive FamHis 12.5% vs. negative FamHis 6.8%; adjusted HR 2.08 (95% CI 1.09-3.87; p < 0.05). CONCLUSION: CAC scoring leads to risk discrimination among those with a positive FamHis for premature CAD. These results support testing CAC score in asymptomatic individuals with a positive FamHis to identify a high risk population.

[18F]Fluorodeoxyglucose PET/Computed Tomography in Gastrointestinal Malignancies.

This article discusses the current state-of-the-art application of 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG)-PET and FDG-PET/computed tomography (CT) in the management of patients with gastrointestinal malignancies. Gastrointestinal malignancies include many different cell types, several common malignancies of which may be imaged by FDG-PET/CT. This review focuses on gastric carcinoma, pancreatic carcinoma, hepatocellular carcinoma, cholangiocarcinoma, colorectal carcinoma, and stroma cell tumors. The role of FDG-PET/CT in staging these malignancies is discussed, in addition to (re)staging, detection of recurrent disease, patient selection/prognostication, and response assessment, using the currently available literature.

Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study.

OBJECTIVES: The goal of this study was to evaluate whether individuals with a positive family history for premature coronary artery disease (CAD) and coronary calcium scoring (CCS) above the 80th percentile might benefit from preventive treatment. BACKGROUND: First-degree relatives of patients with premature CAD have an increased risk for cardiovascular disease (CVD), whereas events are poorly predicted in these individuals. Surrogate markers, such as CCS, might refine risk scoring. Nevertheless, the outcome of the St. Francis Heart trial, which investigated the effect of atorvastatin 20 mg/day in asymptomatic individuals with CCS above the 80th percentile, did not reach statistical significance. METHODS: We performed a post hoc analysis on the database of the St. Francis trial to assess efficacy of treatment with atorvastatin 20 mg/day in those with CCS above the 80th percentile and presence (n = 543) or absence (n = 462) of a positive family history for premature CAD. All participants received aspirin 81 mg/day. Primary outcome included coronary death, myocardial infarction, coronary revascularization, stroke, and arterial surgery. RESULTS: A total of 1,005 individuals, with a mean age of 59.0 ± 5.9 years and a median absolute CCS of 370 Agatston units (interquartile range: 183 to 662) participated in the trial. After a follow-up of 4.3 (interquartile range: 3.5 to 4.5) years, 7.2% of the treated individuals with a positive family history had a cardiovascular event versus 12.5% of the placebo group (hazard ratio [HR]: 0.55; 95% confidence intervals [CI]: 0.31 to 0.97; p = 0.040). This is comparable with a number needed to treat of 18.9. In individuals without a family history, events were minimally reduced: 6.6% in the treated versus 6.8% in the placebo group (HR: 1.04; 95% CI: 0.51 to 2.13; p = 0.912). CONCLUSIONS: The combination of a positive family history and CCS above the 80th percentile identifies a subgroup within the primary prevention population that receives greater benefit from statin treatment than the population at large. These results have important implications for future guidelines concerning individuals with a positive family history for premature CAD.

Arterial stiffness is increased in families with premature coronary artery disease.

OBJECTIVE: A positive family history of premature coronary artery disease (CAD) is a risk factor for cardiovascular disease (CVD), independent of traditional risk factors. Therefore, currently used risk algorithms poorly predict risk in these individuals. Novel methods are thus needed to assess cardiovascular risk. Pulse-wave velocity (PWV) might be such a method, but it is unknown whether PWV is increased in first-degree relatives of patients with premature CAD. DESIGN: Observational case-control study. SETTING: Academic hospital. PATIENTS: Patients with premature CAD and a positive family history of premature CVD (n=50), their first-degree relatives without CVD (n=50) and unrelated controls (n=50). INTERVENTIONS: None. MAIN OUTCOME MEASURES: PWV was measured with using an Arteriograph system. Differences in PWV were assessed by a generalised linear model and multinomial logistic regression. RESULTS: Patients with premature CAD had a higher PWV compared with first-degree relatives and controls (9.69±2.90 m/s vs 8.15±1.96 m/s and 7.38±1.08 m/s; p<0.05 patients vs all groups). Linear regression showed all groups related to PWV, with patients having the highest PWV and controls the lowest (p<0.0001). Furthermore, PWV was associated with first-degree relatives (OR 1.32, 95% CI 1.02 to 1.72; p<0.05) and premature CAD (OR 1.72, 95% CI 1.32 to 2.24; p<0.05) compared with controls. These findings were independent of blood pressure and other traditional risk factors. CONCLUSIONS: Patients with premature CAD and their first-degree relatives had higher PWV compared with controls, independent of other risk factors. This holds promise for the future, in which arterial stiffness might play a role in risk prediction within families with premature CAD.

A positive family history for premature cardiovascular disease identifies patients prone to recurrent arterial thrombotic events.

BACKGROUND: Cardiovascular disease (CVD) is characterized by slow progressive atherosclerosis and arterial thrombotic events, leading to occlusions. Whether either of these presentations is more likely in patients with a genetic predisposition for CVD is still unknown. We suggest that a genetic predisposition for CVD is related to recurrent events of the same nature. METHODS: We retrospectively investigated 275 patients with premature CVD and divided them in two groups according to their first event: an arterial thrombotic event or stable atherosclerosis. We used a Cox proportional-hazards model to estimate the effect of a positive family history for CVD on recurrent events of the same nature. This was tested in the entire cohort and in patients with coronary artery disease only. RESULTS: Patients with a first arterial thrombotic event and a positive family history had a threefold increased risk for a recurrent event of the same nature, compared to patients with a negative family history (hazard ratio 3.00, 95% confidence interval 1.32-6.81); p < 0.05). In contrast, a positive family history was not associated with an increased risk for a recurrent stable atherosclerosis (hazard ratio 0.98 (95% confidence interval 0.59-1.63). These findings were similar analysing the patients with coronary artery disease only. Additional adjustments for other risk factors did not change these associations. CONCLUSIONS: Patients with a first premature arterial thrombotic event and a positive family history for CVD have an increased risk for a second event of the same nature. This might be due to unknown hereditary mechanisms leading to recurrent acute events.

Patients with premature cardiovascular disease and a positive family history for cardiovascular disease are prone to recurrent events.

BACKGROUND: Premature cardiovascular disease (CVD) is treated in the same way as CVD of advanced age. However, in patients with premature CVD and a family history of CVD, different -possibly genetic- mechanisms may underlie this disease, which current medical treatment is not targeted to. This suggests that subjects with a genetic predisposition to CVD are more likely to have recurrent cardiovascular events. METHODS: We retrospectively investigated 291 patients with premature CVD and assessed the amount of recurrent events according to family history in a follow-up period of 31 years. Premature CVD was defined as an event <51 years for men or <56 for women. We used a Cox proportional hazards model to estimate the relationship between a positive family history and recurrence of cardiovascular events. RESULTS: Patients with recurrent events had more often a positive family history (60.0% vs. 47.1%; p<0.05), were more often smokers (85.2% vs. 70.7%; p<0.05), had more often hypertension (36.3% vs. 23.6%; p<0.05) and had a longer follow-up period (10.0 years vs. 5.4 years; p<0.001) than patients without recurrent events. After adjusting for these differences and modelling time to events, a positive family history was independently associated with recurrent events (Hazard ratio 1.31 (95% confidence intervals (CI) 1.01-1.72; p<0.05)). CONCLUSIONS: Patients with a genetic predisposition for CVD are at risk for recurrent events, after adjusting for risk factors and other confounders. This might imply that in subjects with a genetic predisposition for CVD different pathophysiological mechanisms are active, leading to recurrent events.

Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. CONCLUSION/SIGNIFICANCE: Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.