bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of ARIC heart failure risk score in the Asian population: The CORE-Thailand cohort study
Authors: Phrommintikul A , Osataphan N , Chichareon P , Suwannasom P , Leemasawat K , Prasertwittayakij N , Gunaparn S , Wongcharoen W
Published: November 2023

Background

The Atherosclerotic Risk in Communities (ARIC) heart failure (HF) score was developed from population in the United States to predict HF. However, it has not been validated in Asian population.

Purpose

To validate the ARIC HF score and develop the new ARIC-CORE score to predict HF in Asian population in the Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand).

Methods

The CORE-Thailand registry was a prospective study that enrolled Thai patients with high atherosclerotic risk. Patients were followed for the occurrence of cardiovascular events including HF. The ARIC HF score comprised nine variables (age, race, heart rate, systolic blood pressure, BP-lowering medication use, diabetes, coronary heart disease, smoking status, and body mass index) to predict the occurrence of HF. Original coefficients of the full ARIC HF model were used to calculate the original ARIC HF score. The new ARIC-CORE score was developed by re-estimating the coefficients of all ARIC score variables in the study population using ridge regression analysis. The polynomial function was applied to the continuous variables with non-linear association with HF, which included heart rate, systolic blood pressure, and body mass index. Discrimination of the models was determined using C-index and calibration was assessed by plotting the observed outcomes versus the predicted probabilities of the outcomes. Net reclassification index (NRI) was used to compare the prediction performance between the ARIC HF and the ARIC-CORE risk score. Clinical utility of the scores were assessed with decision curve analysis.

Results

From a total of 8919 patients who had no history of HF, 199 (2.23%) developed HF. The ARIC HF score provided a good discrimination at C-statistics of 0.71 (95% confidence interval (CI) 0.67-0.75) with good calibration. (Figure 1 A). The ARIC-CORE risk score had a C-statistics of 0.75 (95%CI;0.71-0.76) with good calibration. (Figure 1B) Using the ARIC-CORE was associated with an improved classification of HF risk (NRI 0.32, 95%CI:0.18-0.44) compared to the ARIC HF score. The net benefit of using the ARIC-CORE score was higher than the original ARIC HF score in the decision curve analysis (Figure 2).

Conclusion

The ARIC HF score had acceptable discrimination and calibration in the CORE cohort. Interestingly, the ARIC-CORE score performed better in classifying HF risk and could be a suitable model to be used in Asian populations.Calibration plotDecision curve analysis
Development and validation of risk score for patients in primary care setting in Poland
Authors: Banach M , Osadnik T , Lejawa M , Golawski M , Gierlotka M , Jozwiak J
Published: November 2023

Background

Suitable, optimal risk prediction in primary care is still a large challenge. Current tools enable the creation of risk scales based on data for specific populations, which can be a large support to recognized risk scales used in primary and secondary prevention.

Purpose

Therefore, we decided to suggest a new risk score generated with the machine-learning tools based on the data from consecutive patients in the family physicians’ practices within the LIPIDOGRAM cohort study 2015.

Methods

The LIPIDOGRAM 2015 study was carried out in 2015 and 2016 in the primary care setting all 16 administrative regions of Poland. 438 physicians participating in the study were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the detailed questionnaire on chronic diseases, treatment, and lifestyle. The primary outcome, based on the data from the National Health Fund, was all-cause mortality. A machine learning-based framework AutoScore was used to generate risk score basing on the variables obtained from questionnaires. Dataset was divided into training, validation, and test cohort in the proportion of 0.6, 0.1 and 0.3 respectively. Performance of the risk score was evaluated using ROC analysis in the test set Kaplan-Meier analysis of survival according to quartiles of the score was carried out.

Results

13 611 patients were finally recruited. 5 years follow-up data was available for 13 419 patients (98.6%). A score based on age, sex, body mass index (BMI), alcohol consumption, smoking, presence of comorbidities - hypertension, diabetes mellitus, atrial fibrillation, chronic kidney disease, hypertension, history of myocardial infarction, self-declared physical activity, place of residence and education level that is presented in detail in Table 1, achieved an AUC of 0.825 (95% CI - 0.794-0.856) (Figure 1).

Conclusions

Risk scales created based on data representative of primary care patients can be easily created thanks to modern statistical tools. Such scores may include variables that better describe local communities, such as education level, place of residence, physical activity, or alcohol consumption, and in the consequence may better predict and monitor (in case of intervention) the risk of all-cause and cause-specific mortality.Developed predictive model.Test set results. 5-year prognosis.
The RAPID-10 score: a new risk score from the retrospective analysis of maximal workload predictors of survival in ischemic heart disease at 10 years
Authors: Braganca B , Campos I G , Cruz I , Lopes R G , Oliveira I , Monteiro J P , Queiros C , Pinto P , Andrade A
Published: November 2023

Background

Cardiac stress testing (CST) is valuable in the management of ischemic heart disease (IHD). The FIT Treadmill Score from the largest study of physical fitness - the Henry Ford Exercise Testing Project– is among the most accurate model in predicting survival. Recent data from our group showed that workload-indexed blood pressure (WPBR) is a strong and independent predictor of survival in IHD, a variable not included in the FIT score.

Purpose

Therefore, our purpose was to create a new score that includes WBPR and other maximal exercise variables and compare with the FIT score.

Methods

The study comprised 713 patients with IHD that performed CST on treadmill between 2009-2010. The follow-up period was 10±2 years. WBPR (systolic blood pressure / (metabolic equivalent of task(met)-1)) and the FIT score were calculated at baseline as previously described 1,2. Continuous variables were fitted using linear and nonlinear regressions. Time-to-event (death and major adverse cardiovascular events (MACE)) were correlated with baseline variables through logistic regression models. The new score was built using a backward stepwise regression of clinical and CST variables. Score accuracy was assessed with receiver operating characteristic (ROC) curves. Event-free survival analyses used Cox regression models. Data are: mean ± standard deviation; 95% confidence interval (CI) for hazard ratios (HR); significance level p<0.05.

Results

Relevant baseline characteristics were: age 59±10 years, 87% male, 74% dyslipidemia, 65% hypertension,body mass index 29±4 kg/m2, 31% diabetes, 16% chronic kidney disease, 45% smokers, 5% stroke, 76% myocardial infarction. During follow-up, 109 patients died (16%), 342 (49%) had MACE, 183 (26%) de novo heart failure (HF) and 100 (14%) myocardial infarction (MI). The final score (RAPID-10) combines four predictive variables of survival: binary WBPR (1 if ≥ 5.15 mmHg/met) and sex (1 if female); continuous maximal predicted heart rate (MPHR) and age-squared. The adjusted final model is: 4WPBR + 0.008age^2 + 20MPHR + 6sex. The median score was 11 points, ranging from -13 to 40 points. After adjusting for comorbidities and medication, each 10-point increase in RAPID-10 was associated with mortality (HR 1.85, CI 1.42-2.42, p<0.0001), MACE (HR 1.26, CI 1.42-2.42, p<0.0001), and HF (HR 1.4, CI 1.19-1.56, p<0.0001) but not MI (HR 0.91, CI 0.77-1.01, p=0.239). Discriminative power of RAPID-10 was good in ROC curves (AUC = 0.75), and slightly higher than FIT score (AUC = 0.73).

Conclusions

The RAPID-10 score is a robust tool, with good discriminative power to predict 10-year survival in IHD patients. Further studies are needed to validate the model in other populations.
Utility of a polygenic risk score for incident CHD: interplay with lifestyle in a multi-ethnic cohort of more than 60,000 individuals
Authors: Iribarren C , Lu M , Elosua R , Rana J S
Published: November 2023

Background

The degree to which benefits of healthy eating, physical activity and not smoking are protective for coronary heart disease (CHD) based on levels of polygenic risk remains an important question. We set out to investigate whether and to what degree a favorable lifestyle could reduce the effect of high genetic risk.

Methods

We utilized data from the Genetic Epidemiology Resource in Adult Health and Aging (GERA) Multi-Ethnic cohort of 60,682 (mean ± SD age = 59 ± 9 years; 67% female; 18% non-European ancestry) Kaiser Permanente of Northern California (KPNC) members. We characterized the cohort at baseline in 2003-2007 by smoking status (never, former or current smoker), Mediterranean-pattern diet (MedDiet) and meeting current AHA physical activity recommendations (PAR) of at least 150 min of moderate activity or 75 min of vigorous activity per week. We stratified the cohort into three groups of CHD genetic risk (low: quintile 1, intermediate: quintiles 2, 3 and 4 combined, and high: quintile 5) using a validated 12-SNP Polygenic Risk Score (PRS) for CHD (CARDIO inCode-Score, GENinCode Plc). Incident CHD consisted of primary in-patient codes for angina pectoris, myocardial infarction, revascularization procedures or CHD death (n=2,220) through 12/31/2014; mean follow-up was 9.5 years.

Results

Age-adjusted CHD rates per 10,000 person-years were estimated using Poisson regression (accounting for death and health plan disenrollment) by number of favorable lifestyle factors (LF) and, within each level, by genetic risk groups (see Figure below). Genetic background provided further CHD risk stratification within each lifestyle group. The most favorable lifestyle (never smoking, MedDiet, meeting PAR) reduced the effect of high genetic risk by 59% (age-adjusted rates per 10,000 person-years 40 vs. 99) and similar reductions were observed at intermediate or low genetic risk.

Conclusions

Our results are consistent with an additive model of genetic risk and lifestyle as determinants of CHD. These results underscore the importance of favorable lifestyle and the need to prioritize those individuals with the highest CHD risk (most unfavorable lifestyle and high genetic risk), who will benefit the most from lifestyle advice.
External Validation of HASBLED and ORBIT bleeding risk scores in Wales-AF population
Authors: Torabi F A T E M E , Harris D , Lacey A , Akbari A , Gravenor M , Halcox J
Published: November 2023

Background

Anticoagulant therapy (AC) is recommended for Atrial Fibrillation (AF) patients when formal assessment of thromboembolic and bleeding risk suggests a net benefit of AC treatment. Recent UK National Institute of Health and Care Excellence guidelines consider that the ORBIT bleeding risk score(1) provides a more accurate assessment of bleeding risk with AC than the HASBLED score(2) and is recommended for routine clinical use in the UK.

Purpose

To compare the performance of HASBLED and ORBIT scores to predict hospitalisations for bleeding (HB) in a large population of UK patients with AF receiving AC.

Methods

We conducted a retrospective longitudinal analysis using linked primary and secondary care health records in the All-Wales SAIL databank. Patients with a diagnosis of AF treated with AC were identified between 2012 and 2018. Both HASBLED and ORBIT scores were calculated for each patient annually based on identified comorbidities, demographics and prescription data. All HB were evaluated. Logistic regression models were used to compare sensitivity and specificity of each score for HB prediction. The Area Under Curve for the Receiver operating Characteristic plot (AUC) was generated for each score to illustrate the risk discrimination ability of each prediction schemes.

Results

A total of 107,137 (45% female, mean age=74) AF patients were evaluated over the study period. The number of anticoagulated AF patients increased from 27,959 in 2012 (49.3% of cohort) to 48,595 in 2018 (66.8%), providing a total of 265,410 patient years of AC therapy for analysis. There were 710 HB (2.5% of AC patients) in 2012 increasing to 1,146 (2.4%) in 2018. The predictive power of HASBLED and ORBIT increased slightly over the period of study: with observed HASBLED AUC of 60.8 and ORBIT AUC of 64.8 in 2018 (Figure 1). Over the period of study, the observed HB rates for AC AF patients with HAS BLED scores of 0-3 and ORBIT scores of 0-5 were similar to those observed in the original studies, but observed HB for patients with higher HASBLED and ORBIT scores were less consistent (Fig. 2)

Conclusion

Our findings demonstrated that HASBLED and ORBIT were relatively limited in their predictive performance for HB in a large, real-world AC AF population, with ORBIT providing more accurate prediction across the overall risk range. This highlights the need to develop and validate new bleeding risk scores from the wide range of clinical and demographic factors in AF patients to improve effectiveness of risk communication and AC prescribing in AF.Figure 1Figure 2
Association of random glucose to albumin ratio with post-contrast acute kidney injury and clinical outcomes in patients with ST-elevation myocardial infarction
Authors: Liu Y H , Lai P , Zhang Y S , Dai Y N , Zhen C E , Lin Z J , He P C , Tang N
Published: November 2023

Background

Both glucose and albumin are associated with chronic inflammation, which plays a vital role in post-contrast acute kidney injury (PC-AKI). However, the relationship between the combination of random glucose and albumin in PC-AKI patients remains elusive. Current study aims to explore the relationship between random glucose to albumin ratio (RAR) and the incidence of PC-AKI after percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI).

Methods

We consecutively enrolled STEMI patients who underwent PCI from January,01 2010 to February,28 2020. All patients were categorized into Q1, Q2, and Q3 groups, respectively, based on RAR value ( RAR<8.62; 8.62≤ RAR ≤ 9

.04; 9.04≤ RAR ≤ 9.45). The primary outcome was the incidence of PC-AKI, which is defined as an increase in serum creatinine (SCr) of more than 44.2 mol/L (0.5 mg/dL) from baseline during the inital 48 to 72 hours after contrast exposure. The incidence of major adverse clinical events (MACE) was the second endpoint, which included all-cause mortality, recurrent of myocardial infarction, renal replacement therapy, stroke, and revascularization of target vessel during hospitalization. The association between RAR and PC-AKI was assessed by multivariate logistic regression analysis.

Results

A total of 2924 patients with STEMI were finally included. The incidence of PC-AKI increased in a stepwise manner with the increasing tertile of RAR (3.2% vs 4.8% vs 10.6%, P<0.001). Multivariate regression analyses demonstrated that RAR(as a continuous variable) was associated with the incidence of PC-AKI (adjusted odds ratio (OR) =1.10, 95% confdence interval (CI) =1.04–1.16, P=0.000) and in-hospital MACE (OR=1.07, 95% CI=1.02–1.14, P=0.012); When RAR was a categorical variable, RAR was related to PC-AKI (Q3 vs. Q1, OR=1.70, 95% CI=1.08–2.67, P=0.021), and in-hospital MACE (Q3 vs. Q1, OR=1.63, 95% CI=1.02-2.60, P=0.041) when analyzed by multivariate regression analyses. Receiver operating characteristic curve analysis showed that RAR exhibited a predictive value for PC-AKI(area under the curve (AUC)=0.666, 95% CI=0.625-0.708, P<0.001), and in-hospital MACE (AUC= 0.662, 95% CI =0.619 - 0.706) . In addition, the AUC of RAR for predicting PC-AKI in the no diabetes subgroup was significantly higher compared to that in the diabetes subgroup (AUC: 0.640 vs. 0.611, P=0.021).

Conclusions

The high value of RAR was significantly associated with the incidence of PC-AKI and in-hospital MACE after PCI in STEMI patients, and RAR offers a robust predictive value for these outcomes.Figure 1Figure 2
Sex-specific associations of the difference between 2-hour post-load and fasting plasma glucose with cardiovascular risk in a normoglycemic population
Authors: Abdi A , Kohansal K , Khalili D , Hadaegh F
Published: November 2023

Background

Elevated levels of fasting plasma glucose (FPG) and 2-hour post-load glucose (2hPG) have been established as individual risk factors for cardiovascular disease (CVD), coronary heart disease (CHD), and stroke. However, it is unclear whether the difference between 2hPG and FPG (2hPG-FPG) within normoglycemic influences the cardiovascular risk in women and men.

Purpose

To investigate the association between 2hPG-FPG and the incidence of CVD, CHD, and stroke among normoglycemic women and men in a large population-based cohort.

Methods

In this prospective cohort study, a total of 7224 participants with the normoglycemic state (mean age 37±11; women, 57.4%) that had baseline measurements of both FPG and 2hPG values and did not have prior CVD, CHD, or stroke were included and were followed for incidence of outcomes annually until March 2018. The normoglycemic range was defined as FPG< 5.55 and 2 h-PG< 7.77 mmol/L and not taking anti-diabetic medications. CHD was defined as either positive ECG findings and biomarkers, cardiac symptoms accompanied by either positive ECG or biomarker, or angiographic-proven CHD. Stroke was defined based on the WHO criteria. Also, CVD was defined as a composite of CHD and stroke. A Multivariable Cox­-regression model adjusted for age, body mass index, hypertension, hyperlipidemia, FPG, education level, and smoking status was used to assess the association between 2hPG-FPG and incident CVD, CHD, and stroke in women and men. We also used a cumulative incidence curve to illustrate the cumulative sex-specific incidence of CVD, CHD, and stroke during the follow-up time (Figure 1).

Results

During a median follow-up of 17.9 years (IQR: 13.75-18.46), 487 CVD (174 women), 427 CHD (140 women), and 76 stroke (37 women) events occurred. Among men, 2hPG-FPG was associated with an increased risk of CVD (hazard ratio [HR]:1.11, 95% confidence interval [CI]:1.01-1.22, p=0.03) and CHD (HR:1.11, 95% CI:1.00-1.22, p=0.04 ), but not stroke (HR:1.14, 95% CI:0.88-1.50, p= 0.33). No significant associations among women were found between 2hPG-FPG and the incidence of outcomes, with adjusted HRs of 1.02 (95% CI, 0.88-1.18, p=0.82), 1.00 (0.85-1.17, p=0.99), and 1.10 (0.80-1.52, p=0.54) for incident CVD, CHD, and stroke, respectively (Table 1).

Conclusion

A greater difference between 2hPG and FPG (2hPG-FPG) within the normoglycemic range was associated with an increased risk for incidence of CVD and CHD in men but not women. Further studies are warranted to explore the potential use of 2hPG-FPG for cardiovascular risk stratification, particularly among those with normal glucose parameters.Association of 2hPG-FPG with CV riskCumulative incidence of CVD, CHD, stroke
Reference intervals for carotid artery intima-media thickness measurements in the multi-ethnic Asian population: relationship with cardiometabolic risk factors
Authors: Dalan R , Mina T H M , Nur Azizah N A , Loh M L , Gervais W G , Chambers J C C
Published: November 2023

Background

Carotid artery intima-media thickness (cIMT) is an intermediate surrogate marker for cardiovascular disease (CVD). It has been reported that although the distribution of cIMT values is very heterogeneous and values vary widely between different ethnicity, geographic location, and ultrasound protocol, the prediction of vascular events with study-specific cIMT values is consistent across all ethnicities and regions (1). Hence, Consensus Statement from the American Society of Echocardiography suggests that cIMT greater than or equal to 75th percentile for the patient’s age, sex, and ethnicity is indicative of increased CVD risk (2).

Aims

We aimed to establish age, sex, and ethnic-specific reference intervals in the multi-ethnic Asian population comprising Chinese, Malays, and Indians.

Methods

We analysed data from 8762 healthy individuals who had a 3D carotid ultrasonography done as part of the Health for Life in Singapore study. Carotid ultrasonography measurements were taken from the distal common carotid artery (CCA) at both the lateral and posterior angles bilaterally during the end-diastolic phase. The mean of all 4 measurements were taken as average cIMT (avgcIMT). For this analysis, we excluded individuals on treatment for diabetes, hypertension, hyperlipidemia, and ischemic heart disease to derive a healthy population subset comprising of 6522 individuals (Chinese: 69%, Malays: 14%, Indians: 17%). We then assessed the 75th percentile as a marker of cardiovascular risk in all individuals, by testing associations with Framingham risk scores (locally adapted) and with cardiometabolic risk factors (3).

Results

Ethnic- and sex-specific 75th percentiles (95% CI) of CIMT for our Asian populations are summarised in Table 1. Compared to reference intervals reported in European and African American populations, the 75th centiles are lower in all Asian ethnic subgroups (p<0.05). Framingham risk score, BMI, LDL-C, HbA1c and systolic blood pressure were higher in Asians with cIMT more than 75th percentile (p<0.001), compared to Asians with normal cIMT.

Conclusions

We estimated race- and sex-specific 75th percentiles of avgcIMT across age in the multi-ethnic Asian population. The thresholds for Asian populations are substantially lower than reported in European and African populations. The 75th centiles identify people with raised cardiovascular risk factors, supporting the validity of cIMT as marker of vascular risk in the population. The 75th centiles will be useful in interpretation of cIMT measures obtained both in research and clinical settings in different ethnic populations in Asia. Longitudinal evaluation is needed to determine the prediction of our Asian specific thresholds for predicting hard cardiovascular outcomes.
Feature-based clustering of left ventricular strain curve for risk stratification in the general population
Authors: Ntalianis E , Sabovcik F , Cauwenberghs N , Kuznetsova T
Published: November 2023

Objective

Global left ventricular (LV) strain has been identified as an important predictor of adverse cardiovascular (CV) events. However, currently only the peak strain is used from the LV deformation curve, neglecting the temporal information hidden in all phases of cardiac cycle. Therefore, we employed unsupervised machine learning methods on time-series-derived features from LV strain to identify distinct clinical phenogroups associated with the risk of developing adverse events in the general population.

Design and Method

We prospectively studied 1185 community-dwelling individuals (mean age, 53.2 years; 51.3% women), in whom we acquired clinical and echocardiographic data including LV strain traces at baseline and collected CV events (n=116) on average 8.7 years later. We utilised Gaussian Mixture Model (GMM) on different features derived from LV strain curve, including slope during systole and early diastole, peak strain, slope during late diastole and the duration and height of diastasis (Figure, left panel). We evaluated the clinical significance of the clusters (k) by comparing the clinical characteristics and CV adverse outcome.

Results

Based on inertia and BIC scores the optimal number of clusters (k) was 4. The first two clusters had differences in heart rate, but had similar low CV risk profiles. Cluster 4 had the worst CV risk factors combination, and higher prevalence of LV remodelling and diastolic dysfunction (i.e. lowest e’ velocity and highest E/e’) compared to other clusters. Kaplan–Meier showed an increased cumulative incidence risk for all CV events across clusters (Figure, right panel). After adjustment for traditional risk factors, the risk was significantly higher in clusters 3 (HR: 1.28; 95% CI: 1.01-1.61; P=0.038) and 4 (HR: 1.20; 95% CI: 1.02-1.43; P=0.034) compared to the average population, while the risk of adverse events did not reach the significant level in subjects with an abnormal peak LV strain (<17%) (HR 1.12; P=0.66).

Conclusion

Unsupervised machine learning algorithm employed on features derived from time series LV strain curves identifies clinically meaningful clusters, and provides important prognostic information over the peak LV strain.
Lipid assessment and achievement of secondary prevention european society of cardiology guideline targets in patients with atherosclerotic cardiovascular disease with and without depression
Authors: Summers R , Halcox J P , Ellins E A
Published: November 2023

Background

Patients who have a diagnosis of atherosclerotic cardiovascular disease (aCVD) who also have depression (Dep) have a worse CV prognosis than those without Dep. Appropriate secondary prevention greatly improves CVD outcomes. The European Society of Cardiology (ESC) provide guideline targets for lipid levels (2016 & 2019). It is unknown how well these targets are achieved and maintained over time in patients with aCVD at a population level and whether this differs in those with and without Dep.

Purpose

To investigate the assessment of lipid levels and/or achievement of guideline targets in patients with aCVD with and without Dep over an 11-year period.

Methods

A retrospective observational cohort study of patients with aCVD was conducted on individual-level linked electronic health record data between 2009 &2019 using the all-Wales SAIL databank. Clinical codes were used to identify aCVD and Dep diagnoses, lipid assessments and lipid-lowering therapy (LLT) from GP data. The proportions of those having lipid assessments during each calendar year, lipid levels achieving ESC 2016 guideline targets and current LLT were documented.

Results

In 2009, the aCVD cohort comprised of 183,275 patients (44% female) with a mean age (70.6 ±12.3 years), of whom 22% had a Dep diagnosis (56.6% female). In 2009, lipid levels were assessed in 63.1% of patients, dropping to 48.3% by 2019 (68.06% Dep, 61.65% non-Dep in 2009 and 51.7% Dep, 46.84% non-Dep in 2019. Table and Figure).

Over the period of study an increasing proportion of patients were prescribed High intensity statins (HIS) and a decreasing proportion were prescribed low intensity statin (LIS) and/or Ezetimibe. Dep patients were more likely to be treated with HIS and/or Ezetimibe and less likely to receive LIS throughout compared with non-Dep (table).

An increasing trend for lipid targets being achieved was observed between 2009 and 2019 in those being tested (Table and Figure). However, a significantly smaller proportion of those with Dep met the ESC targets vs non-Dep over the period of study (Table and Figure).

Conclusion

The proportion of aCVD patients having their lipids checked fell progressively between 2009 and 2019, although a greater proportion of those "checked" patients had achieved LDL-C and non-HDL-C targets, although the proportion who met these targets remained low. Despite patients with aCVD and Dep being more likely to have their lipids assessed and to be prescribed more intensive LLT those without Dep, with the "gap" widening over time. Considerable additional effort will be required in the future to meet the more intensive 2019 targets in these very high risk patients.
Remnant cholesterol predicts major cardiovascular events in cardiovascular disease patients with NAFLD
Authors: Larcher B , Mader A , Sprenger L , Vonbank A , Maechler M , Plattner T , Leiherer A , Muendlein A , Drexel H , Saely C H
Published: November 2023

Remnant cholesterol has attracted interest as a marker of cardiovascular event risk.

The purpose of this study was to assess the power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD).

We enrolled a high-risk cohort of 1420 consecutive patients with established cardiovascular disease (1183 patients with stable coronary artery disease and 237 patients with peripheral artery disease). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.6±5.0 years.

At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=683) than in patients who did not have NAFLD (29±26 mg/dl vs. 19±16 mg/dl; p<0.001). During follow-up, 570 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.15 [1.06-1.24], p<0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.16 [1.03-1.30], p=0.012 and 1.14 [1.02-1.27], p=0.028, respectively).

From our data we conclude that remnant cholesterol is a predictor of MACE in cardiovascular disease patients with NAFLD.
An in vitro investigation of the effects of Urolithins A and B on low-density lipoprotein uptake and its regulatory genes
Authors: Ganjali S , Riahi M M , Mahboobnia K , Iranshahy M , Banach M , Jangjoo A , Ashari S , Tayarani-Najaran Z , Sahebkar A
Published: November 2023

Background

Elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) is a causal risk factor for atherosclerosis. A major pathway of LDL-C clearance from bloodstream is its uptake by hepatic LDL receptors (LDLRs), which is mainly restricted by proprotein convertase subtilisin/kexin type-9 (PCSK9).

Purpose

This study aimed to evaluate the possible role of Urolithin A (UA) and Urolithin B (UB) on the induction of LDL uptake and the expression of its regulatory genes.

Methods

Curcumin (20 uM), berberine (50 uM), UA (80 uM) and UB (80 uM) were used as the treatments in the experimental tests. LDL uptake in HepG2 cells was detected by LDL uptake cell-based assay kit and the degrees of LDL uptake as well as the distribution of cell surface LDLR were assessed using fluorescent microscopy. Moreover, the mRNA expression levels of LDLR and PCSK9 genes in HepG2 cells were assessed using qPCR.

Results

The LDL uptake as well as cell-surface LDLR were higher in cells treated with UA in comparison with cells treated with UB, and even in relation to the cells treated with curcumin and berberine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression level compared with curcumin (FC: 2.144, P=0.013) and berberine (FC: 2.761, P=0.006). However, UA treatment resulted in a significantly lower expression levels of LDLR compared with curcumin (FC: 0.274, P<0.001) and berberine (FC: 0.352, P=0.009). UB demonstrated approximately 8 times greater LDLR expression levels when compared with UA (FC:7.835, P=0.001) (Figure 1A). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it illustrated higher levels of PCSK9 expression when compared with UA group (FC: 3.694, P<0.001) (Figure 1B).

Conclusion

The present results support that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the suppression of PCSK9 expression but not induction of LDLR expression.

Figure 1. HepG2 (A) LDLR and (B) PCSK9 fold change expression in treatment groups. All data were normalized to control group (PBS).
Bronchus compression is a predictor for reobstruction in coarctation with hypoplastic arch repair
Authors: Hui Chengyi , Ren Qiushi , Zhuang Jian , Chen Jimei , Li Xiaohua , Cui Hujun , Cen Jianzheng , Xu Gang , Wen Shusheng
Published: November 2023

OBJECTIVES

The surgical treatment of coarctation of aorta with hypoplastic aortic arch (CoA/HAA) was challenging to achieve long-lasting arch patency. We reviewed early and late outcomes in our centre and identified predictors for arch reobstruction.

METHODS

A retrospective analysis of medical records was performed to identify CoA/HAA patients who underwent primary arch reconstruction via median sternotomy between 2011 and 2020. Preoperative aortic arch geometry was analysed with cardiac computed tomographic angiography. Bedside flexible fibre-optic bronchoscopy was routinely performed after surgery in intensive care unit.

RESULTS

There were 104 consecutive patients (median age 39.5 days) who underwent extended end-to-end anastomosis, extended end-to-side anastomosis and autograft patch augmentation. Early mortality was 3.8% and overall survival was 94.1% [95% confidence interval (CI) 89.6–98.8%] at 1, 3 and 5 years. Reobstruction-free survival was 85.1% (95% CI 78.4–92.3%) at 1 year, 80.6% (95% CI 73.1–88.9%) at 3 years and 77.4% (95% CI 69.2–86.6%) at 5 years. Preoperative aortic arch geometric parameters were not important factors for reobstruction. Nineteen patients (18.3%) were detected with left main bronchus compression (LMBC) on flexible fibre-optic bronchoscopy. Cardiopulmonary bypass time [P < 0.001, hazard ratio (95% CI): 1.02 (1.01–1.03)] and postoperative LMBC [P = 0.034, hazard ratio (95% CI): 2.99 (1.09–8.23)] were independent predictive factors on multivariable Cox regression analysis of reobstruction-free survival.

CONCLUSIONS

Aortic arch can be satisfactorily repaired by extended end-to-end anastomosis, extended end-to-side anastomosis and autograft patch augmentation via median sternotomy in CoA/HAA. Cardiopulmonary bypass time and postoperative LMBC detected by flexible fibre-optic bronchoscopy are significant predictors for long-term arch reobstruction.
AI is a Catalyst for Global Innovation
Authors: Burnett Sarah
Published: November 2023

Industry analyst and author Sarah Burnett FBCS examines the impact of AI on our business and personal lives, and explains the wealth of potential it affords.
The Role of AI, Technology and Education in Gender Equality
Authors: Martin Nicole
Published: November 2023

The 67th session of the United Nations' Commission on the Status of Women took place in March 2023. Three BCS members were delegates and reported on some of the sessions. Nicola Martin MBCS reports on the role of AI, technology and education in gender equality.
Aviation: Cyber Security in the Skies
Authors: Mansha Ilyas
Published: November 2023

Ilyas Mansha, Managing Director of LeapTronx, explores the challenges facing aviation and explains the importance of aligning boards, organisations and suppliers to help mitigate cyber risk.
Practical Digital Ethics
Authors: Rogerson Simon
Published: November 2023

Simon Rogerson FBCS explores recent ethical issues surrounding digital technology, illustrating the need to ensure everyone's digital ethics awareness.
Navigating Data Scarce Environments in Computer Vision
Authors: Datar Sumedh
Published: November 2023

Sumedh Datar FBCS is a senior software engineer with expertise in computer vision. He explores ways in which an absence of data may not necessarily result in AI being unable to identify new objects correctly.
Business Analysis
Authors: Lovelock Christina
Published: November 2023

Christina Lovelock MBCS recently contributed to in-depth industry research looking at the adoption of AI in business analysis and requirements management.
Does comorbidity index predict OPAT readmission?
Authors: Stubbs Ryan D , Shorten Robert J , Benedetto Valerio , Muir Alison
Published: November 2023

Objectives

To determine if the Charlson comorbidity index (CCI) is an accurate predictor of unplanned readmissions for patients using outpatient parenteral antimicrobial therapy (OPAT) services.

Methods

Retrospective analysis of patients >16 years of age who had received OPAT at Lancashire Teaching Hospitals between 2019 and 2021. The number of unplanned hospitalizations was measured and categorized as OPAT related or non-OPAT related. The CCI for each patient group was calculated using an online tool, and logistic regression was used to assess the association between risk factors and risk of being readmitted.

Results

The cohort consisted of 741 patients. Unplanned readmission was seen in 112 patients (15.1%). The mean CCI score for patients with OPAT-related readmissions was 4.22, 0.92 higher than the mean for patients who were not readmitted (3.30). The mean CCI score for patients with non-OPAT-related readmissions was higher still at 4.89. The logistic regression showed that increased CCI, age, male gender and home location compared with clinic were associated with increased odds of readmission, although these effects did not meet statistical significance.

Conclusions

These results suggest that a higher CCI score is associated with a non-statistically significant increased risk of unplanned hospitalization. We concluded that the CCI may therefore be used in future decision-making regarding the acceptance of patients to OPAT and requires further investigation.
ASAS-NANP symposium: mathematical modeling in animal nutrition—Making sense of big data and machine learning: how open-source code can advance training of animal scientists
Authors: Brennan Jameson R , Menendez Hector M , Ehlert Krista , Tedeschi Luis O
Published: November 2023

Advancements in precision livestock technology have resulted in an unprecedented amount of data being collected on individual animals. Throughout the data analysis chain, many bottlenecks occur, including processing raw sensor data, integrating multiple streams of information, incorporating data into animal growth and nutrition models, developing decision support tools for producers, and training animal science students as data scientists. To realize the promise of precision livestock management technologies, open-source tools and tutorials must be developed to reduce these bottlenecks, which are a direct result of the tremendous time and effort required to create data pipelines from scratch. Open-source programming languages (e.g., R or Python) can provide users with tools to automate many data processing steps for cleaning, aggregating, and integrating data. However, the steps from data collection to training artificial intelligence models and integrating predictions into mathematical models can be tedious for those new to statistical programming, with few examples pertaining to animal science. To address this issue, we outline how open-source code can help overcome many of the bottlenecks that occur in the era of big data and precision livestock technology, with an emphasis on how routine use and publication of open-source code can help facilitate training the next generation of animal scientists. In addition, two case studies are presented with publicly available data and code to demonstrate how open-source tutorials can be utilized to streamline data processing, train machine learning models, integrate with animal nutrition models, and facilitate learning. The National Animal Nutrition Program focuses on providing research-based data on animal performance and feeding strategies. Open-source data and code repositories with examples specific to animal science can help create a reinforcing mechanism aimed at advancing animal science research.
ASAS-NANP symposium: mathematical modeling in animal nutrition: agent-based modeling for livestock systems: the mechanics of development and application
Authors: Kaniyamattam Karun , Tedeschi Luis O
Published: November 2023

Over the last three decades, agent-based modeling/model (ABM) has been one of the most powerful and valuable simulation-based decision modeling techniques used to study the complex dynamic interactions between animals and their environment. ABM is a relatively new modeling technique in the animal research arena, with immense potential for routine decision-making in livestock systems. We describe ABM’s fundamental characteristics for developing intelligent modeling systems, exemplify its use for livestock production, and describe commonly used software for designing and developing ABM. After that, we discuss several aspects of the developmental mechanics of an ABM, including (1) how livestock researchers can conceptualize and design a model, (2) the main components of an ABM, (3) different statistical methods of analyzing the outputs, and (4) verification, validation, and replication of an ABM. Then, we perform an overall analysis of the utilities of ABM in different subsystems of the livestock systems ranging from epidemiological prediction to nutritional management to livestock market dynamics. Finally, we discuss the concept of hybrid intelligent models (i.e., merging real-time data streams with intelligent ABM), which have applications in artificial intelligence-based decision-making for precision livestock farming. ABM captures individual agents’ characteristics, interactions, and the emergent properties that arise from these interactions; thus, animal scientists can benefit from ABM in multiple ways, including understanding system-level outcomes, analyzing agent behaviors, exploring different scenarios, and evaluating policy interventions. Several platforms for building ABM exist (e.g., NetLogo, Repast J, and AnyLogic), but they have unique features making one more suitable for solving specific problems. The strengths of ABM can be combined with other modeling approaches, including artificial intelligence, allowing researchers to advance our understanding further and contribute to sustainable livestock management practices. There are many ways to develop and apply mathematical models in livestock production that might assist with sustainable development. However, users must be experienced when choosing the appropriate modeling technique and computer platform (i.e., modeling development tool) that will facilitate the adoption of mathematical models by certifying that the model is field-ready and versatile enough for untrained users.
Diffuse large B-cell lymphoma associated with papillary thyroid carcinoma: a case report and systematic review on management and outcomes
Authors: Lincango Eddy P , Serrano Luis F , Vallejo Sebastian , Solis-Pazmino Paola , Garcia-Bautista Andrea , Acosta William , Ponce Oscar J , Salazar-Vega Jorge , Garcia Cristhian
Published: November 2023

Primary thyroid lymphoma is a rare thyroid cancer, comprising ˂5% of thyroid neoplasms. Most cases are diffuse large B-cell lymphoma (DLBCL). Coexistence with papillary thyroid cancer (PTC) is extremely rare. This study presents a case of a 55-year-old woman with DLBCL and micropapillary thyroid cancer who underwent lobectomy, chemotherapy, and radiotherapy. Additionally, we performed a systematic review of 10 cases, including the reported case. The risk of bias in case reports varied. DLBCL diagnoses were mainly made after surgery, with total thyroidectomy being the most common surgical procedure. Chemotherapy was administered in most cases, and radiotherapy was used in some cases. Long-term outcomes indicated a low recurrence rate. While some debate the role of surgery in thyroid lymphoma, this study suggests that surgery should be considered in selected cases. Further research is needed to determine optimal treatment strategies for DLBCL with PTC.
Generation of renal tubular organoids from adult SOX9+ kidney progenitor cells
Authors: Zhou Dewei , Li Dandan , Nie Hao , Duan Jun , Liu Sarah , Wang Yujia , Zuo Wei
Published: November 2023

The pathogenesis of several kidney diseases results in the eventual destruction of the renal tubular system, which can progress to end-stage renal disease. Previous studies have demonstrated the involvement of a population of SOX9-positive cells in kidney regeneration and repair process following kidney injury. However, the ability of these cells to autonomously generate kidney organoids has never been investigated. Here, we isolated SOX9+ kidney progenitor cells (KPCs) from both mice and humans and tested their differentiation potential in vitro. The data showed that the human SOX9+ KPC could self-assemble into organoids with kidney-like morphology. We also used single-cell RNA sequencing to characterize the organoid cell populations and identified four distinct types of renal tubular cells. Compared to the induced pluripotent stem cell-derived kidney organoids, KPC demonstrated more tubular differentiation potential but failed to differentiate into glomerular cells. KPC-derived organoid formation involved the expression of genes related to metanephric development and followed a similar mechanism to renal injury repair in acute kidney injury patients. Altogether, our study provided a potentially useful approach to generating kidney tubular organoids for future application.
The metallicity dependence of the stellar initial mass function
Authors: Tanvir Tabassum S , Krumholz Mark R
Published: November 2023

During star formation, dust plays the crucial role of coupling gas to stellar radiation fields, allowing radiation feedback to influence gas fragmentation and thus the stellar initial mass function (IMF). Variations in dust abundance therefore provide a potential avenue by which variation in galaxy metallicity might affect the IMF. In this paper, we present a series of radiation-magnetohydrodynamic simulations in which we vary the metallicity and thus the dust abundance from 1 per cent of solar to 3× solar, spanning the range from the lowest metallicity dwarfs to the most metal-rich early-type galaxies (ETGs) found in the local Universe. We design the simulations to keep all dimensionless parameters constant so that the interaction between feedback and star-forming environments of varying surface density and metallicity is the only factor capable of breaking the symmetry between the simulations and modifying the IMF, allowing us to isolate and understand the effects of each environmental parameter cleanly. We find that shifts in the IMF with varying metallicity at a fixed surface density are smaller than the shifts in varying surface density at a fixed surface metallicity. We also find that metallicity-induced IMF variations are too small to explain the mass-to-light ratio shifts seen in the ETGs. We therefore conclude that metallicity variations are much less important than variations in surface density in driving changes in the IMF and that the latter rather than the former are most likely responsible for the IMF variations found in ETGs.
Pulse profile modelling of thermonuclear burst oscillations – II. Handling variability
Authors: Kini Yves , Salmi Tuomo , Vinciguerra Serena , Watts Anna L , Choudhury Devarshi , Bogdanov Slavko , Buchner Johannes , Meisel Zach , Suleimanov Valery
Published: November 2023

Pulse profile modelling is a relativistic ray-tracing technique that can be used to infer masses, radii, and geometric parameters of neutron stars. In a previous study, we looked at the performance of this technique when applied to thermonuclear burst oscillations from accreting neutron stars. That study showed that ignoring the variability associated with burst oscillation sources resulted in significant biases in the inferred mass and radius, particularly for the high count rates that are nominally required to obtain meaningful constraints. In this follow-on study, we show that the bias can be mitigated by slicing the bursts into shorter segments where variability can be neglected, and jointly fitting the segments. Using this approach, the systematic uncertainties on the mass and radius are brought within the range of the statistical uncertainty. With about 106 source counts, this yields uncertainties of approximately 10 per cent for both the mass and radius. However, this modelling strategy requires substantial computational resources. We also confirm that the posterior distributions of the mass and radius obtained from multiple bursts of the same source can be merged to produce outcomes comparable to that of a single burst with an equivalent total number of counts.