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Abstract Background Albuminuria is considered an early and sensitive marker of kidney dysfunction, but also an independent cardiovascular risk factor. Considering the possible relationship among metabolic liver disease, cardiovascular disease and chronic kidney disease, we aimed to evaluate the risk of developing albuminuria regarding the presence of epicardial adipose tissue and the steatotic liver disease status. Methods A retrospective long-term longitudinal study including 181 patients was carried out. Epicardial adipose tissue and steatotic liver disease were assessed by computed tomography. The presence of albuminuria at follow-up was defined as the outcome. Results After a median follow up of 11.2 years, steatotic liver disease (HR 3.15; 95% CI, 1.20–8.26; p = 0.02) and excess amount of epicardial adipose tissue (HR 6.12; 95% CI, 1.69–22.19; p = 0.006) were associated with an increased risk of albuminuria after adjustment for visceral adipose tissue, sex, age, weight status, type 2 diabetes, prediabetes, hypertriglyceridemia, hypercholesterolemia, arterial hypertension, and cardiovascular prevention treatment at baseline. The presence of both conditions was associated with a higher risk of developing albuminuria compared to having steatotic liver disease alone (HR 5.91; 95% CI 1.15–30.41, p = 0.033). Compared with the first tertile of visceral adipose tissue, the proportion of subjects with liver steatosis and abnormal epicardial adipose tissue was significantly higher in the second and third tertile. We found a significant correlation between epicardial fat and steatotic liver disease (rho = 0.43 [p

Summary: Background: Tobacco is the main risk factor for developing lung cancer. Yet, while some heavy smokers develop lung cancer at a young age, other heavy smokers never develop it, even at an advanced age, suggesting a remarkable variability in the individual susceptibility to the carcinogenic effects of tobacco. We characterized the germline profile of subjects presenting these extreme phenotypes with Whole Exome Sequencing (WES) and Machine Learning (ML). Methods: We sequenced germline DNA from heavy smokers who either developed lung adenocarcinoma at an early age (extreme cases) or who did not develop lung cancer at an advanced age (extreme controls), selected from databases including over 6600 subjects. We selected individual coding genetic variants and variant-rich genes showing a significantly different distribution between extreme cases and controls. We validated the results from our discovery cohort, in which we analysed by WES extreme cases and controls presenting similar phenotypes. We developed ML models using both cohorts. Findings: Mean age for extreme cases and controls was 50.7 and 79.1 years respectively, and mean tobacco consumption was 34.6 and 62.3 pack-years. We validated 16 individual variants and 33 variant-rich genes. The gene harbouring the most validated variants was HLA-A in extreme controls (4 variants in the discovery cohort, p = 3.46E-07; and 4 in the validation cohort, p = 1.67E-06). We trained ML models using as input the 16 individual variants in the discovery cohort and tested them on the validation cohort, obtaining an accuracy of 76.5% and an AUC-ROC of 83.6%. Functions of validated genes included candidate oncogenes, tumour-suppressors, DNA repair, HLA-mediated antigen presentation and regulation of proliferation, apoptosis, inflammation and immune response. Interpretation: Individuals presenting extreme phenotypes of high and low risk of developing tobacco-associated lung adenocarcinoma show different germline profiles. Our strategy may allow the identification of high-risk subjects and the development of new therapeutic approaches. Funding: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Recent advances in computer-aided diagnosis, treatment response and prognosis in radiomics and deep learning challenge radiology with requirements for world-wide methodological standards for labeling, preprocessing and image acquisition protocols. The adoption of these standards in the clinical workflows is a necessary step towards generalization and interoperability of radiomics and artificial intelligence algorithms in medical imaging.

Abstract The main objective of this work is to develop and evaluate an artificial intelligence system based on deep learning capable of automatically identifying, quantifying, and characterizing COVID-19 pneumonia patterns in order to assess disease severity and predict clinical outcomes, and to compare the prediction performance with respect to human reader severity assessment and whole lung radiomics. We propose a deep learning based scheme to automatically segment the different lesion subtypes in nonenhanced CT scans. The automatic lesion quantification was used to predict clinical outcomes. The proposed technique has been independently tested in a multicentric cohort of 103 patients, retrospectively collected between March and July of 2020. Segmentation of lesion subtypes was evaluated using both overlapping (Dice) and distance-based (Hausdorff and average surface) metrics, while the proposed system to predict clinically relevant outcomes was assessed using the area under the curve (AUC). Additionally, other metrics including sensitivity, specificity, positive predictive value and negative predictive value were estimated. 95% confidence intervals were properly calculated. The agreement between the automatic estimate of parenchymal damage (%) and the radiologists’ severity scoring was strong, with a Spearman correlation coefficient (R) of 0.83. The automatic quantification of lesion subtypes was able to predict patient mortality, admission to the Intensive Care Units (ICU) and need for mechanical ventilation with an AUC of 0.87, 0.73 and 0.68 respectively. The proposed artificial intelligence system enabled a better prediction of those clinically relevant outcomes when compared to the radiologists’ interpretation and to whole lung radiomics. In conclusion, deep learning lesion subtyping in COVID-19 pneumonia from noncontrast chest CT enables quantitative assessment of disease severity and better prediction of clinical outcomes with respect to whole lung radiomics or radiologists’ severity score.

Abstract Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease morbimortality. However, it is not clear if NAFLD staging may help identify early or subclinical markers of cardiovascular disease. We aimed to evaluate the association of liver stiffness and serum markers of liver fibrosis with epicardial adipose tissue (EAT) and coronary artery calcium (CAC) in an observational cross-sectional study of 49 NAFLD patients that were seen at Clínica Universidad de Navarra (Spain) between 2009 and 2019. Liver elastography and non-invasive fibrosis markers were used to non-invasively measure fibrosis. EAT and CAC, measured through visual assessment, were determined by computed tomography. Liver stiffness showed a direct association with EAT (r = 0.283, p-value = 0.049) and CAC (r = 0.337, p-value = 0.018). NAFLD fibrosis score was associated with EAT (r = 0.329, p-value = 0.021) and CAC (r = 0.387, p-value = 0.006). The association of liver stiffness with CAC remained significant after adjusting for metabolic syndrome features (including carbohydrate intolerance/diabetes, hypertension, dyslipidaemia, visceral adipose tissue, and obesity). The evaluation of NAFLD severity through liver elastography or non-invasive liver fibrosis biomarkers may contribute to guide risk factor modification to reduce cardiovascular risk in asymptomatic patients. Inversely, subclinical cardiovascular disease assessment, through Visual Scale for CAC scoring, may be a simple and effective measure for patients with potential liver fibrosis, independently of the existence of other cardiovascular risk factors.

BackgroundTo better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction–associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes.MethodsCross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography.ResultsCompared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively).ConclusionMAFLD–T2D and MAFLD–OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.

Rationale Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all characterised by airflow limitation. Objectives We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood follow different trajectories to reach distinct phenotypes. Methods Using the validated Stunkard's Pictogram, 356 COPD patients chose the somatotype that best reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based trajectory modelling was used to determine somatotype trajectories. We then compared the current COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory. Measurements and main results At 18 years of age, 88% of the participants described having a lean or medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2) while the other 12% a heavier somatotype (estimated BMI between 25 and 27 kg·m−2). From age 18 onwards, five distinct trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age 40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE (BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss of tissue (MOLT) phenotype. Conclusions COPD patients have distinct somatotype trajectories throughout adulthood. Those with the MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in early adulthood deserve particular attention as they seem to develop more severe COPD.

INTRODUCTION:The prevalence of bronchiectasis in the general population and in individuals undergoing lung cancer screening with low dose computed tomography (LDCT) is unknown. The aim of this study is to estimate the prevalence and impact of bronchiectasis in a screening lung cancer program. METHODS:3028 individuals participating in an international multicenter lung cancer screening consortium (I-ELCAP) were selected from 2000 to 2012. Patients with bronchiectasis on baseline CT were identified and compared to selected controls. Detection of nodules, need for additional studies and incidence of cancer were analyzed over the follow-up period. RESULTS:The prevalence of bronchiectasis was 11.6%(354/3028). On the baseline LDCT, the number of subjects with nodules identified was 189(53.4%) in patients with bronchiectasis compared to 63(17.8%) in controls (p

Abstract Background Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients. The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients. Methods CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables. The predictive power of each parameter was explored using CV events as the main outcome. Results During a median follow up of 65 months (ICR: 36–100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%). A total of 35 CV deaths occurred during that period. Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events. Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19–1.46, p

BackgroundTo assess the relationship between lung cancer and emphysema subtypes.ObjectiveAirflow obstruction and emphysema predispose to lung cancer. Little is known, however, about the lung cancer risk associated with different emphysema phenotypes. We assessed the risk of lung cancer based on the presence, type and severity of emphysema, using visual assessment.MethodsSeventy-two consecutive lung cancer cases were selected from a prospective cohort of 3,477 participants enrolled in the Clínica Universidad de Navarra's lung cancer screening program. Each case was matched to three control subjects using age, sex, smoking history and body mass index as key variables. Visual assessment of emphysema and spirometry were performed. Logistic regression and interaction model analysis were used in order to investigate associations between lung cancer and emphysema subtypes.ResultsAirflow obstruction and visual emphysema were significantly associated with lung cancer (OR = 2.8, 95%CI: 1.6 to 5.2; OR = 5.9, 95%CI: 2.9 to 12.2; respectively). Emphysema severity and centrilobular subtype were associated with greater risk when adjusted for confounders (OR = 12.6, 95%CI: 1.6 to 99.9; OR = 34.3, 95%CI: 25.5 to 99.3, respectively). The risk of lung cancer decreases with the added presence of paraseptal emphysema (OR = 4.0, 95%CI: 3.6 to 34.9), losing this increased risk of lung cancer when it occurs alone (OR = 0.7, 95%CI: 0.5 to 2.6).ConclusionsVisual scoring of emphysema predicts lung cancer risk. The centrilobular phenotype is associated with the greatest risk.

Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers.In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival.During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03-1.12, p

Background: There is increasing interest in performing left atrial appendage (LAA) occlusion at the time of atrial fibrillation (AF) ablation procedures. However, to date there has been no description of the acute changes to the LAA immediately following pulmonary vein (PV) isolation and additional left atrium (LA) substrate modification. This study assessed changes in the size and tissue characteristics of the LAA ostium in patients undergoing PV isolation. Methods: This series included 8 patients who underwent cardiovascular magnetic resonance evaluation of the LA with delayed enhancement magnetic resonance imaging and contrast enhanced 3-D magnetic resonance angiography pre-, within 48 h of, and 3 months post ablation. Two independent cardiac radiologists evaluated the ostial LAA diameters and area at each time point in addition to the presence of gadolinium enhancement. Results: Compared to pre-ablation values, the respective median differences in oblique diameters and LAA area were +1.8 mm, +1.7 mm, and +0.6 cm2 immediately post ablation (all NS) and −2.7 mm, −2.3 mm, and −0.5 cm2 at 3 months (all NS). No delayed enhancement was detected in the LAA post ablation. Conclusion: No significant change to LAA diameter, area, or tissue characteristics was noted after PV isolation. While these findings suggest the safety and feasibility of concomitant PV isolation and LAA device occlusion, the variability in the degree and direction of change of the LAA measurements highlights the need for further study.

RationaleLow-grade inflammation and emphysema have been shown to be associated with an increased risk of lung cancer. However, the systemic inflammatory response in patients with emphysema is still unknown.ObjectiveTO COMPARE THE PLASMA CYTOKINE PROFILES IN TWO GROUPS OF CURRENT OR FORMER SMOKERS WITHOUT AIRWAY OBSTRUCTION: a control group of individuals without computed tomography (CT) detected emphysema vs. a study group of individuals with CT detected emphysema.MethodsSubjects underwent a chest CT, spirometry, and determination of EGF, IL-15, IL-1ra, IL-8, MCP-1, MIP-1β, TGFα, TNFα, and VEGF levels in plasma. Cytokine levels in each group were compared adjusting for confounding factors.Results160 current smokers and former smokers without airway obstruction participated in the study: 80 without emphysema and 80 subjects with emphysema. Adjusted group comparisons revealed significant reductions in EGF (-0.317, p = 0.01), IL-15 (-0.21, p = 0.01), IL-8 (-0.180, p = 0.02) and IL-1ra (-0.220, p = 0.03) in subjects with emphysema and normal spirometry.ConclusionsCurrent or former smokers expressing a well-defined disease characteristic such as emphysema, has a specific plasma cytokine profile. This includes a decrease of cytokines mainly implicated in activation of apoptosis or decrease of immunosurveillance. This information should be taken into account when evaluated patients with tobacco respiratory diseases.

RationaleEpicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population.ObjectivesTo assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.MethodsWe measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.ResultsCOPD patients had a higher EAT volume [143.7 (P25-75, 108.3-196.6) vs 129.1 (P25-75, 91.3-170.8) cm(3), p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, pConclusionsEAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.

Skin burns below ground pads during monopolar RF ablation are increasingly prevalent, thereby hindering the development of higher power RF generators capable of creating larger tumor ablation zones in combination with multiple or new applicators. Our goal was to evaluate reduction in skin temperatures via additional ground pads in an in vivo porcine model. Three ground pads placed on the animal's abdomen were activated either simultaneously or sequentially, where activation timing was adjusted to equilibrate skin temperature below each pad. Thirteen RF ablations (n = 4 simultaneous at 300 W, n = 5 sequential at 300 W, and n = 4 sequential at 375 W) were performed for 12 min via two internally cooled cluster electrodes placed in the gluteus maximus of domestic swine. Temperature rise at each pad and burn degree as determined via histology were compared. Ablation zone size was determined via T2-weighted MRI. Maximum temperature rise was significantly higher with simultaneous activation than with either of the sequential activation group (21.4 °C versus 8.1 °C or 9.6 °C, p < 0.01). Ablation zone diameters during simultaneous (300 W) and sequential activations (300 and 375 W) were and 6.9 ± 0.3, 5.6 ± 0.3, and 7.5 ± 0.6 cm, respectively. Sequential activation of multiple ground pads results in significantly lower skin temperatures and less severe burns, as measured by histological examination. [ABSTRACT FROM AUTHOR]

Among the broad spectrum of tumoral bone lesions that affect the sacrum are chondrosarcoma, chondroma, aneurysmal bone cyst, Ewing sarcoma, giant cell tumor, lymphoma, Paget disease, osteosarcoma, plasmacytoma, and neurogenic tumors. The clinical onset may be insidious, and sacral bone tumors may be incidental findings on conventional radiographs. Plain radiographic films are frequently obtained for the initial study of neoplastic processes involving the sacrum. In some cases, it is difficult to determine whether the tumor is benign or malignant, as well as to determine its origin and extent. Computed tomography (CT) and magnetic resonance imaging (MRI) are used to evaluate the effect of the tumor on adjacent soft tissues. Because of its multiplanar capability and superior contrast resolution, MRI is the modality of choice for evaluating bone neoplasms. This article reviews the most characteristic features of sacral neoplasms on conventional radiographs, CT scans, and MRI scans, and offers ways to differentiate among the lesions to arrive at the correct diagnosis. [ABSTRACT FROM AUTHOR]