Electricity consumption dataset of a local energy cooperative.

Real-world data collections are generally not easily available. Energy measurements from buildings, houses and other devices can be used within different areas of research while being employed to plan or train models, allowing the improvement of power grid energy efficiency or providing more insight on how an energy community can work. This paper provides a dataset concerning a Portuguese community of 172 households that are geographically close to each other, enabling the establishment of relationships among buildings and the analysis of a community's power consumption. In addition to the consumed energy values, the related local weather information is included in the data. The intersection of weather data and energy measurements can be helpful to train AI models, contributing to explain variations in energy consumption and the absolute values of the energy readings. The inclusion of these weather parameters aims to unveil features that can correlate to the energy measurements, enabling them to be used in multiple areas of research. Hence, it will provide added value to the data as it can be reused to explore Machine Learning algorithms or community energy planning by grid operators.

Coronary atherosclerotic burden in veteran athletes: The relationship between cardiovascular risk and volume of exercise.

INTRODUCTION AND OBJECTIVES: The association between exercise and coronary atherosclerosis still remains unclarified. We aimed to analyze the prevalence of high coronary atherosclerotic burden in veteran athletes, considering cardiovascular (CV) risk and volume of exercise. METHODS: A total of 105 asymptomatic male veteran athletes (48±5.6 years old) were studied. A high coronary atherosclerotic burden was defined as one of the following characteristics in coronary computed tomography angiography: calcium score >100, >75th percentile, obstructive plaques, involving left main, three-vessels or two-vessels including proximal anterior descending artery, segment involvement score >5 or CT-adapted Leaman score ≥5. CV risk was stratified by SCORE2 and volume of exercise by metabolic equivalent task score. RESULTS: Most athletes (n=88) were engaged in endurance sports for 17.1±9.8 years, with a median exercise volume of 66 [IQR 44-103] metabolic equivalent of tasks/hour/week. The mean Systematic Coronary Risk Evaluation 2 was 2.8±1.5%; 76.9% of athletes had a low-moderate risk and none a very high risk. High coronary atherosclerotic burden was present in 25.7% athletes. Athletes with high cardiovascular risk and high exercise volume (above the median) showed significantly high coronary atherosclerotic burden compared to those with low-moderate risk and high volume (50.0% vs. 15.6%; p=0.017). Among athletes with low to moderate risk, a high volume of exercise tended to be protective, while in those with low volume, there was similar rate of high coronary atherosclerotic burden, regardless of CV risk. CONCLUSIONS: A combination of higher volume of exercise and high cardiovascular risk revealed the worst association with coronary atherosclerosis in veteran athletes. The relationship between these variables is controversial, but integrating exercise characteristics and risk assessment into preparticipation evaluation is essential.

Exploring the Potential of Machine Learning Algorithms Associated with the Use of Inertial Sensors for Goat Kidding Detection.

The autonomous identification of animal births has a significant added value, since it enables for a prompt timely human intervention in the process, protecting the young and the mothers' health, without requiring continuous human surveillance. Wearable inertial sensors have been employed for a variety of animal monitoring applications, thanks to their low cost and the fact that they allow less invasive monitoring process. Alarms triggered by the occurrence of events must be generated close to the events to avoid delays caused by communication latency, which is why this type of mechanism is typically implemented at the network's edge and integrated with existing auxiliary mechanisms on the Internet. Although the detection of births in cattle has been carried out commercially for some years, there is no solution for small ruminants, especially goats, where the literature does not even report any attempts. The current work consisted of a first attempt at developing an automatic birth monitor using inertial sensing, as well as detection techniques based on Machine Learning, implemented in a network edge device to assure real-time alarm triggering. Thus, two concept drift detection techniques and seven kidding detection mechanisms were developed using data classification models. The work also includes the testing and comparison of learning results, both in terms of accuracy and of computational costs of the detection module, for algorithms implemented. The results revealed that, despite their simplicity, concept drift algorithms do not allow kidding detection, whereas classification-algorithm-based static learning models do, despite the unbalanced character of the dataset and its reduced size. The learning findings are quite promising in terms of computational cost and its suitability for deployment on edge devices. The algorithm demonstrates behavior changes four hours before kidding and allows for the identification of the kidding hour with an accuracy of 61%, as well as the capacity to improve the overall learning process with a larger dataset.

Kidney failure secondary to hereditary xanthinuria due to a homozygous deletion of the XDH gene, in the absence of overt kidney stone disease.

Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN. Several pathogenic variants in the XDH gene have so far been identified in patients with HXAN type I, but the clinical phenotype associated with the whole deletion of the human XDH gene is unknown. Herein, we report the case of a woman diagnosed with HXAN, whose molecular genetic testing revealed a homozygous microdeletion involving the XDH gene. Distinctive features of her medical history were the diagnosis of arterial hypertension and microalbuminuria at 22 years of age; a single pregnancy, at the age of 25, complicated by proteinuria and transient kidney function deterioration in the third trimester; unexplained severe hypouricaemia incidentally discovered during pregnancy; inability to breastfeed her newborn daughter due to primary agalactia; chronic kidney disease (CKD) stage 3 diagnosed at age 35; and progression to end-stage kidney disease over the next 12 years. Protocol non-invasive laboratory and imaging investigation was not informative as to the cause of CKD. This is the first description of the clinical phenotype associated with a natural knockout of the human XDH gene. Despite the lack of kidney histopathology data, the striking similarities with the phenotypes exhibited by comparable murine models validates the latter as useful sources of mechanistic insights for the pathogenesis of the human disease, supporting the hypothesis that the absence of xanthine dehydrogenase activity might represent a susceptibility factor for chronic tubulointerstitial nephritis, even in patients without kidney stones.

Perioperative Management of a Frail Patient With Bernard-Soulier Syndrome.

Bernard-Soulier syndrome (BSS) is an autosomal recessive inherited bleeding disorder characterized by prolonged bleeding time, thrombocytopenia, and giant platelets. Patients with BSS are at an increased risk of bleeding, especially during traumatic injury and surgical procedures. The literature on the anesthetic management of patients with BSS is limited. In this report, we detail the successful management of a frail patient with BSS who underwent a major surgical procedure. Despite comprehensive clinical monitoring and an extended pharmacological strategy, a hemorrhagic complication occurred in the later postoperative phase, emphasizing the necessity for continued support and vigilant clinical monitoring due to the ongoing bleeding risk associated with these patients. In this case, a combined strategy involving antifibrinolytics, recombinant factor VII, and platelet transfusions proved effective.

Prediction of the development of new coronary atherosclerotic plaques with radiomics.

BACKGROUND: Radiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA). METHODS: From a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV â€‹≥ â€‹1 â€‹mm3, at follow-up CCTA in each segment. RESULTS: In total, 9583 normal coronary segments were identified from 1162 patients (60.3 â€‹± â€‹9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow-up CCTA, 9.8% of the segments developed new coronary plaque. The predictive power of Models 1 and 2 was not different in both the training and test sets (C-index [95% confidence interval (CI)] of Model 1 vs. Model 2: 0.701 [0.690-0.712] vs. 0.699 [0.0.688-0.710] and 0.696 [0.671-0.725] vs. 0.0.691 [0.667-0.715], respectively, all p â€‹> â€‹0.05). The addition of radiomic features to clinical risk factors improved the predictive power of the Cox model in both the training and test sets (C-index [95% CI] of Model 3: 0.772 [0.762-0.781] and 0.767 [0.751-0.787], respectively, all p â€‹< â€‹00.0001 compared to Models 1 and 2). CONCLUSION: Radiomic features can improve the identification of segments that would develop new coronary atherosclerotic plaque. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT0280341.

Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.

PURPOSE: Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. METHODS: Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. RESULTS: Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1 kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. CONCLUSIONS: In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.

Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

OBJECTIVES: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. METHODS: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. RESULTS: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. CONCLUSIONS: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. CLINICAL RELEVANCE STATEMENT: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. KEY POINTS: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Dysbiosis and Associated Stool Features Improve Prediction of Response to Biological Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Dysbiosis of the gut microbiota is considered a key contributor to inflammatory bowel disease (IBD) etiology. Here, we investigated potential associations between microbiota composition and the outcomes to biological therapies. METHODS: The study prospectively recruited 296 patients with active IBD (203 with Crohn's disease, 93 with ulcerative colitis) initiating biological therapy. Quantitative microbiome profiles of pretreatment and posttreatment fecal samples were obtained combining flow cytometry with 16S amplicon sequencing. Therapeutic response was assessed by endoscopy, patient-reported outcomes, and changes in fecal calprotectin. The effect of therapy on microbiome variation was evaluated using constrained ordination methods. Prediction of therapy outcome was performed using logistic regression with 5-fold cross-validation. RESULTS: At baseline, 65.9% of patients carried the dysbiotic Bacteroides2 (Bact2) enterotype, with a significantly higher prevalence among patients with ileal involvement (76.8%). Microbiome variation was associated with the choice of biological therapy rather than with therapeutic outcome. Only anti-tumor necrosis factor-α treatment resulted in a microbiome shift away from Bact2, concomitant with an increase in microbial load and butyrogen abundances and a decrease in potentially opportunistic Veillonella. Remission rates for patients hosting Bact2 at baseline were significantly higher with anti-tumor necrosis factor-α than with vedolizumab (65.1% vs 35.2%). A prediction model, based on anthropometrics and clinical data, stool features (microbial load, moisture, and calprotectin), and Bact2 detection predicted treatment outcome with 73.9% accuracy for specific biological therapies. CONCLUSION: Fecal characterization based on microbial load, moisture content, calprotectin concentration, and enterotyping may aid in the therapeutic choice of biological therapy in IBD.

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.

Background: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. Objectives: The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. Design and methods: This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. Result: Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable. Limitations: Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants. Conclusions: Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families. Future work: Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives. Study registration: This study is registered as PROSPERO CRD42018117445 and CRD42019125775. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information.

Familial hypercholesterolaemia is an inherited condition that causes raised cholesterol levels from birth and increases risk of heart disease if left untreated. After someone in a family is found to have familial hypercholesterolaemia (called an index case), their close relatives need to be contacted and checked to see if they have familial hypercholesterolaemia, using genetic or cholesterol testing. This is called 'cascade testing'. We planned to find the most cost-effective and acceptable way to do this. The relatives could be contacted for testing by the index case (indirect approach), by a health-care professional (direct approach) or by a combination of both approaches. We found, based on looking at hospital records, that more relatives were tested if health-care professionals directly contacted relatives. In previous studies, slightly more relatives were tested for familial hypercholesterolaemia with a combination approach. Interviews with patients also suggested that the direct approach was the most effective, but the most acceptable and successful approach depends on family relationships: using one approach for some families and using both for other families. Furthermore, by looking at the health-care records of large numbers of patients, we confirmed that people with a recorded diagnosis of familial hypercholesterolaemia in general practice records have a much higher risk of heart disease than the general population, and this was especially so for those with previous heart disease and/or raised cholesterols levels when diagnosed. However, one-quarter of new patients with familial hypercholesterolaemia recorded in their records were not treated within 2 years, with less than one-third reaching recommended cholesterol levels. We used what we had learned to help us estimate the most cost-effective way to do cascade testing. This showed that if the health service directly contact all relatives simultaneously for further assessment, rather than the current approach whereby close (first-degree) relatives are contacted first, this was cost-effective and good value for money.

How early can atherosclerosis be detected by coronary CT angiography? Insights from quantitative CT analysis of serial scans in the PARADIGM trial.

BACKGROUND: Non-obstructing small coronary plaques may not be well recognized by expert readers during coronary computed tomography angiography (CCTA) evaluation. Recent developments in atherosclerosis imaging quantitative computed tomography (AI-QCT) enabled by machine learning allow for whole-heart coronary phenotyping of atherosclerosis, but its diagnostic role for detection of small plaques on CCTA is unknown. METHODS: We performed AI-QCT in patients who underwent serial CCTA in the multinational PARADIGM study. AI-QCT results were verified by a level III experienced reader, who was blinded to baseline and follow-up status of CCTA. This retrospective analysis aimed to characterize small plaques on baseline CCTA and evaluate their serial changes on follow-up imaging. Small plaques were defined as a total plaque volume <50 â€‹mm3. RESULTS: A total of 99 patients with 502 small plaques were included. The median total plaque volume was 6.8 â€‹mm3 (IQR 3.5-13.9 â€‹mm3), most of which was non-calcified (median 6.2 â€‹mm3; 2.9-12.3 â€‹mm3). The median age at the time of baseline CCTA was 61 years old and 63% were male. The mean interscan period was 3.8 â€‹± â€‹1.6 years. On follow-up CCTA, 437 (87%) plaques were present at the same location as small plaques on baseline CCTA; 72% were larger and 15% decreased in volume. The median total plaque volume and non-calcified plaque volume increased to 18.9 â€‹mm3 (IQR 8.3-45.2 â€‹mm3) and 13.8 â€‹mm3 (IQR 5.7-33.4 â€‹mm3), respectively, among plaques that persisted on follow-up CCTA. Small plaques no longer visualized on follow-up CCTA were significantly more likely to be of lower volume, shorter in length, non-calcified, and more distal in the coronary artery, as compared with plaques that persisted at follow-up. CONCLUSION: In this retrospective analysis from the PARADIGM study, small plaques (<50 â€‹mm3) identified by AI-QCT persisted at the same location and were often larger on follow-up CCTA.

Designing a youth-led Dialogue Forum tool: The CO-CREATE experience.

While obesity prevention represents an established field of research, the inclusion of young people, who are regularly cited as an important priority group, are rarely actioned in long-term studies. This paper focuses on the development of a dialogue tool intended to tackle this issue, engaging, and eliciting insights on the theme of obesity prevention, by young people and for young people. As part of the CO-CREATE project, this tool was co-developed by designers, public health, and youth participation experts, researchers, and young people. Co-creation is a key methodology in the design of the dialogue tool, as young people were involved in all stages of the development process. This paper elaborates on the process of co-designing a dialogue tool that helps explore obesity prevention policy ideas from multiple perspectives, and describes the design principles that informed the process and the final versions of the tool. The purpose of the Dialogue Forum tool is for youth to engage policymakers and other relevant stakeholders to discuss and refine co-created and youth-initiated ideas for healthier food and physical activity environments. We analyze how specific design principles were integrated into different prototypes and the value of this within the project and the field.

Effects of renin-angiotensin-aldosterone-system inhibitors on coronary atherosclerotic plaques: The PARADIGM registry.

BACKGROUND AND AIMS: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA). METHODS: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model. RESULTS: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient -0.100, adjusted p = 0.038) with higher levels of baseline PAV. CONCLUSIONS: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating.

Influence of Age on the Diagnostic Value of Coronary Artery Calcium Score for Ruling Out Obstructive Coronary Disease in Symptomatic Patients.

Concerns have been raised about the added diagnostic value of coronary artery calcium score (CACS) of 0 for reducing the likelihood of obstructive coronary artery disease (CAD) in younger patients. Our study aimed to assess the influence of age on the value of CAC = 0 in symptomatic patients who underwent coronary computed tomography angiography (CCTA). We conducted a 2-center retrospective study assessing symptomatic patients with suspected CAD who underwent CACS and CCTA. Pretest probability was calculated according to the Juarez-Orozco method and obstructive CAD was defined as ≥50% luminal stenosis. The diagnostic likelihood ratios and negative predictive values were used to assess the diagnostic value of a CACS of 0 to rule out obstructive CAD. A total of 2,043 patients (mean age 60 ± 11 years, 60% women, 48.5% CACS of 0) were analyzed. The pretest probability of obstructive CAD increased with age, whereas the proportion of patients with a CACS of 0 decreased with age. The added diagnostic value of a CACS of 0 was lower in younger patients (negative likelihood ratios ranging from 0.36 for <50 years to 0.10 for ≥70 years). However, the prevalence of obstructive CAD in patients with a CACS of 0 was low in all age groups. In a cohort of symptomatic patients who underwent CCTA for suspected CAD, the added diagnostic value of a CACS of 0 decreases significantly at younger ages. However, it is offset by their lower pretest probabilities, yielding high negative predictive values independently of age.

Cholesteryl hemiazelate identified in CVD patients causes in vitro and in vivo inflammation.

Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl hemiesters (ChEs), the oxidation end products of these esters, have not been studied. Through lipidomics analyses, we identified and quantified two ChE types in the plasma of CVD patients and identified four ChE types in human endarterectomy specimens. Cholesteryl hemiazelate (ChA), the ChE of azelaic acid (n-nonane-1,9-dioic acid), was the most prevalent ChE identified in both cases. Importantly, human monocytes, monocyte-derived macrophages, and neutrophils exhibit inflammatory features when exposed to subtoxic concentrations of ChA in vitro. ChA increases the secretion of proinflammatory cytokines such as interleukin-1ß and interleukin-6 and modulates the surface-marker profile of monocytes and monocyte-derived macrophage. In vivo, when zebrafish larvae were fed with a ChA-enriched diet, they exhibited neutrophil and macrophage accumulation in the vasculature in a caspase 1- and cathepsin B-dependent manner. ChA also triggered lipid accumulation at the bifurcation sites of the vasculature of the zebrafish larvae and negatively impacted their life expectancy. We conclude that ChA behaves as an endogenous damage-associated molecular pattern with inflammatory and proatherogenic properties.

Upstream anticoagulation in patients with ST-segment elevation myocardial infarction: a systematic review and meta-analysis.

BACKGROUND AND AIM: Parenteral anticoagulation is recommended for all patients presenting with ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (PPCI). Whether upstream anticoagulation improves clinical outcomes is not well established. We conducted a systematic review and meta-analysis of contemporary evidence on parenteral anticoagulation timing for STEMI patients. METHODS: We performed a systematic search of electronic databases (PubMed, CENTRAL, and Scopus) until December 2022. Studies were eligible if they (a) compared upstream anticoagulation with administration at the catheterization laboratory and (b) enrolled patients with STEMI undergoing PPCI. Efficacy outcomes included in-hospital or 30-day mortality, in-hospital cardiogenic shock (CS), and TIMI flow grade pre- and post-PPCI. Safety outcome was defined as in-hospital or 30-day major bleeding. RESULTS: Overall, seven studies were included (all observational), with a total of 69,403 patients. Upstream anticoagulation was associated with a significant reduction in the incidence of in-hospital or 30-day all-cause mortality (OR 0.61; 95% CI 0.45-0.81; p < 0.001) and in-hospital CS (OR 0.68; 95% CI 0.58-0.81; p < 0.001) and with an increase in spontaneous reperfusion (pre-PPCI TIMI > 0: OR 1.46; 95% CI 1.35-1.57; p < 0.001). Pretreatment was not associated with an increase in major bleeding (OR 1.02; 95% CI 0.70-1.48; p = 0.930). CONCLUSIONS: Upstream anticoagulation was associated with a significantly lower risk of 30-day all-cause mortality, incidence of in-hospital CS, and improved reperfusion of the infarct-related artery (IRA). These findings were not accompanied by an increased risk of major bleeding, suggesting an overall clinical benefit of early anticoagulation in STEMI. These results require confirmation in a dedicated randomized clinical trial.

Implications of three different testing strategies in the diagnostic approach to patients with stable chest pain and low pretest probability of obstructive coronary artery disease.

INTRODUCTION: The clinical implications of a widespread adoption of guideline recommendations for patients with stable chest pain and low pretest probability (PTP) of obstructive coronary artery disease (CAD) remain unclear. We aimed to assess the results of three different testing strategies in this subgroup of patients: A) defer testing; B) perform coronary artery calcium score (CACS), withholding further testing if CACS â€‹= â€‹0 and proceeding to coronary computed tomography angiography (CCTA) if CACS>0; C) perform CCTA in all. METHODS: Two-center cross-sectional study assessing 1328 symptomatic patients undergoing CACS and CCTA for suspected CAD. PTP was calculated based on age, sex and symptom typicality. Obstructive CAD was defined as any luminal stenosis ≥50% on CCTA. RESULTS: The prevalence of obstructive CAD was 8.6% (n â€‹= â€‹114). In the 786 patients (56.8%) with CACS â€‹= â€‹0, 8.5% (n â€‹= â€‹67) had some degree of CAD [1.9% (n â€‹= â€‹15) obstructive, and 6.6% (n â€‹= â€‹52) nonobstructive]. Among those with CACS>0 (n â€‹= â€‹542), 18.3% (n â€‹= â€‹99) had obstructive CAD. The number of patients needed to scan (NNS) to identify one patient with obstructive CAD was 13 for strategy B vs. A, and 91 for strategy C vs. B. CONCLUSIONS: Using CACS as gatekeeper would decrease CCTA use by more than 50%, at the cost of missing obstructive CAD in one in 100 patients. These findings may help inform decisions on testing, which will ultimately depend on the willingness to accept some diagnostic uncertainty.

Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.