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As advancements in care improve longevity in patients with congenital heart disease (CHD), it is crucial to further characterize this rapidly growing adult population. It is also essential that equitable care is offered across demographic groups. Hospitalizations for adults with CHD in the National Inpatient Sample were identified to describe trends in overall and cause-specific rates of admission per 1,000 adults with CHD from 2000 to 2018. Primary admission causes were then analyzed and stratified by race. An aggregate rate of left-ventricular assist device placements and heart transplants was calculated for each group and trended over the years. A total of 1,562,001 weighted hospitalizations were identified. Overall, annual rates of hospital admissions increased from 39 per 1,000 adults with CHD in 2000 to 74 per 1,000 in 2018, as did rates of cardiovascular admissions (16 of 1,000 to 34 of 1,000, p0.001 for both). Transient ischemic attack/stroke (2.5 of 1,000 to 10.7 of 1,000), coronary artery disease (4.1 of 1,000 to 5.6 of 1,000), arrhythmias (2.8 of 1,000 to 4.6 of 1,000), and heart failure (2.8 of 1,000 to 5.0 of 1,000) were the most common cardiovascular primary causes of admission (other than CHD itself), and each significantly increased over time (p0.001 for each). Mean age at all-cause and primary heart failure hospitalization increased for all races but remained 7 to 9 years younger for Black and Hispanic adults than White adults. In conclusion, hospitalization rates of adults with CHD in the United States increased from 2000 to 2018, largely driven by an increase in adults ≥55 years. Although the age at hospitalization increased overall, Black and Hispanic patients were substantially younger at presentation for advanced heart failure. Anticoagulation guidelines in this population may need revisiting as transient ischemic attack/stroke hospitalizations were frequent.

Numerous algorithms are available to predict short-term mortality in ST elevation myocardial infarction (STEMI) but none are focused on elderly patients or include invasive hemodynamics. A simplified risk score (LASH score) including left ventricular end diastolic pressure > 20 mm Hg, age > 75 years, systolic blood pressure < 100 mm Hg and heart rate > 100 bpm was tested in a retrospective, single-center study of 346 patients ≥ 60 years old who underwent primary percutaneous coronary intervention (PPCI). The median age was 70 years [IQR: 64, 79], 60.1% were men, and 77.8% identified as White. In-hospital all-cause mortality was 10.1%. Patients with a LASH score ≥ 3 (n = 34) had an in-hospital mortality rate of 44.1% compared to 6.4% for LASH score ≤ 2 (p < 0.0001). The odds ratio for in-hospital mortality for patients with LASH score ≥ 3 was 13.2 (95% CI 5.3-33.1) compared to patients with a LASH score ≤ 2 when adjusted for sex, cardiac arrest, heart failure, and prior cerebrovascular event. The LASH score had an area under the ROC curve for predicting in-hospital mortality of 0.795 [CI 0.716-0.872], as compared to TIMI-STEMI (0.881, CI 0.829-0.931; p = 0.01), GRACE (0.849, CI 0.778-0.920; p = 0.19), shock index (0.769, CI 0.667-0.871; p = 0.51) and modified shock index (0.765, CI 0.716-0.873; p = 0.48). In summary, a simplified, easy to calculate risk score that incorporates age and invasive hemodynamics predicts in-hospital mortality in patients ≥ 60 years old undergoing PPCI for STEMI.

The formation of a thrombus in the left ventricle (LV) in patients with normal systolic function is very rare. We report a case and identified 31 other adult patients who had an LV thrombus with normal LV systolic function. The median (IQR) age of these patients was 43 [37,59] years with a slight male predominance (59%). The vast majority of patients presented with embolic complications (28; 88%) with 3 of the other patients presenting with a febrile illness. Most of the cases occurred in the setting of an identifiable medical condition that carries an increased risk of thrombosis including inflammatory diseases, malignancies or hypereosinophilia. Treatment generally included anticoagulation with or without surgical removal or systemic thrombolysis. Recurrence of LV thrombus and/or embolic events have been reported in patients with LV thrombus and normal LV systolic function suggesting that long term anticoagulation may be needed.

The difficulty associated with screening and treating colorectal polyps alongside other gastrointestinal pathology presents an opportunity to incorporate computer-aided systems. This paper develops a deep learning pipeline that accurately segments colorectal polyps and various instruments used during endoscopic procedures. To improve transparency, we leverage the Attention U-Net architecture, enabling visualisation of the attention coefficients to identify salient regions. Moreover, we improve performance by incorporating transfer learning using a pre-trained encoder, together with test-time augmentation, softmax averaging, softmax thresholding and connected component labeling to further refine predictions.

OBJECTIVE To determine whether the use of invasively measured hemodynamics improves the prognostic ability of a shock index (SI). BACKGROUND SI such as Admission-SI, Age-SI, Modified SI (MSI), and Age-MSI predict short-term mortality in ST-elevation myocardial infarction (STEMI). METHODS Single-center study of 510 patients who underwent primary percutaneous coronary intervention. STEMI SI was defined as age × heart rate (HR) divided by coronary perfusion pressure (CPP). RESULTS The mean age was 62 ± 14 years, 66% were males with hypertension (69%), tobacco use (38%), diabetes (28%) and chronic kidney disease (6%). The mean HR, systolic blood pressure (SBP), and CPP were 81 ± 18 bpm, 124 ± 28 mmHg, and 52.8 ± 16.3 mmHg, respectively. Patients with STEMI SI ≥182 (n = 51) were more likely to experience a cardiac arrest in the catheterization laboratory (9.8% vs. 2.0%; p = .001), require mechanical circulatory support (47.1% vs. 8.5%; p

We found that the pseudospectral time-domain (PSTD) formulation discussed in the literature exhibits long-time instability when applied to problems with curvilinear geometry. To overcome this problem, we have developed a provably stable PSTD formulation in curvilinear coordinates. In this article, we discuss the new PSTD formulation and present a rigorous proof of stability. Numerical results are given to validate the new formulation. The new formulation requires only a simple change in the form of the spatial-derivative operators in curvilinear coordinates and so can easily be implemented in the existing PSTD codes.

The Dice similarity coefficient (DSC) is both a widely used metric and loss function for biomedical image segmentation due to its robustness to class imbalance. However, it is well known that the DSC loss is poorly calibrated, resulting in overconfident predictions that cannot be usefully interpreted in biomedical and clinical practice. Performance is often the only metric used to evaluate segmentations produced by deep neural networks, and calibration is often neglected. However, calibration is important for translation into biomedical and clinical practice, providing crucial contextual information to model predictions for interpretation by scientists and clinicians. In this study, we provide a simple yet effective extension of the DSC loss, named the DSC++ loss, that selectively modulates the penalty associated with overconfident, incorrect predictions. As a standalone loss function, the DSC++ loss achieves significantly improved calibration over the conventional DSC loss across six well-validated open-source biomedical imaging datasets, including both 2D binary and 3D multi-class segmentation tasks. Similarly, we observe significantly improved calibration when integrating the DSC++ loss into four DSC-based loss functions. Finally, we use softmax thresholding to illustrate that well calibrated outputs enable tailoring of recall-precision bias, which is an important post-processing technique to adapt the model predictions to suit the biomedical or clinical task. The DSC++ loss overcomes the major limitation of the DSC loss, providing a suitable loss function for training deep learning segmentation models for use in biomedical and clinical practice. Source code is available at https://github.com/mlyg/DicePlusPlus.

BACKGROUND: Acutely ill and frail older adults have complex social and health care needs. It is important to understand how this complexity affects acute outcomes for admission to hospital. We validated a frailty index using routine admission laboratory tests with outcomes after patients were admitted to hospital. METHODS: In a prospective cohort of older adults admitted to a large tertiary hospital in the United Kingdom, we created a frailty index from routine admission laboratory investigations (FI-Laboratory) linked to data comprising hospital outcomes. We evaluated the association between the FI-Laboratory and total days spent in hospital, discharge to a higher level of care, readmission and mortality. RESULTS: Of 2552 admissions among 1750 older adults, we were able to generate FI-Laboratory values for 2254 admissions (88.3% of the cohort). More than half of admitted patients were women (55.3%) and the mean age was 84.6 (SD 14.0) years. We found that the FI-Laboratory correlated weakly with the Clinical Frailty Scale (CFS; r2 = 0.09). An increase in the CFS and the equivalent of 3 additional abnormal laboratory test results in the FI-Laboratory, respectively, were associated with an increased proportion of inpatient days (rate ratios [RRs] 1.43, 95% confidence interval [CI] 1.35–1.52; and 1.47, 95% CI 1.41–1.54), discharge to a higher level of care (odd ratios [ORs] 1.39, 95% CI 1.27–1.52; and 1.30, 95% CI 1.16–1.47) and increased readmission rate (hazard ratios [HRs] 1.26, 95% CI 1.17–1.37; and 1.18, 95% CI 1.11–1.26). Increases in the CFS and FI-Laboratory were associated with increased mortality HRs of 1.39 (95% CI 1.28–1.51) and 1.45 (95% CI 1.37–1.54), respectively. INTERPRETATION: We determined that FI-Laboratory, distinct from baseline frailty, could be used to predict risk of many adverse outcomes. The score is therefore a useful way to quantify the degree of acute illness in frail older adults.

The Amplatzer Vascular Plug Type II™ (AVPII) has been considered and used for the percutaneous closure of certain cases of persistent patent ductus arteriosus. Certain institutions use this device preferentially over the Amplatzer Duct Occluder Type I (ADOI). We present a series of three cases that highlight the versatility and applicability of this device, particularly in cases of adult congenital heart disease. This device is particularly useful when ductal anatomy cannot be precisely elucidated, or in adults with abnormal or difficult to define ductal anatomy. Two of the three cases presented were percutaneous interventions that were performed in Leon, Nicaragua, highlighting the use of the AVPII in resource-limited settings where device adaptability and cost are paramount.

Background Colonoscopy remains the gold-standard screening for colorectal cancer. However, significant miss rates for polyps have been reported, particularly when there are multiple small adenomas. This presents an opportunity to leverage computer-aided systems to support clinicians and reduce the number of polyps missed. Method In this work we introduce the Focus U-Net, a novel dual attention-gated deep neural network, which combines efficient spatial and channel-based attention into a single Focus Gate module to encourage selective learning of polyp features. The Focus U-Net incorporates several further architectural modifications, including the addition of short-range skip connections and deep supervision. Furthermore, we introduce the Hybrid Focal loss, a new compound loss function based on the Focal loss and Focal Tversky loss, designed to handle class-imbalanced image segmentation. For our experiments, we selected five public datasets containing images of polyps obtained during optical colonoscopy: CVC-ClinicDB, Kvasir-SEG, CVC-ColonDB, ETIS-Larib PolypDB and EndoScene test set. We first perform a series of ablation studies and then evaluate the Focus U-Net on the CVC-ClinicDB and Kvasir-SEG datasets separately, and on a combined dataset of all five public datasets. To evaluate model performance, we use the Dice similarity coefficient (DSC) and Intersection over Union (IoU) metrics. Results Our model achieves state-of-the-art results for both CVC-ClinicDB and Kvasir-SEG, with a mean DSC of 0.941 and 0.910, respectively. When evaluated on a combination of five public polyp datasets, our model similarly achieves state-of-the-art results with a mean DSC of 0.878 and mean IoU of 0.809, a 14% and 15% improvement over the previous state-of-the-art results of 0.768 and 0.702, respectively. Conclusions This study shows the potential for deep learning to provide fast and accurate polyp segmentation results for use during colonoscopy. The Focus U-Net may be adapted for future use in newer non-invasive colorectal cancer screening and more broadly to other biomedical image segmentation tasks similarly involving class imbalance and requiring efficiency., Graphical abstract Image 1, Highlights • Automatic polyp segmentation can support clinicians to reduce polyp miss rates. • Focus U-Net combines efficient spatial and channel attention into a Focus Gate. • Focus Gate uses tunable focal parameter to control degree of background suppression. • Deep supervision and new Hybrid Focal loss function further improve performance. • Focus U-Net outperforms state-of-the-art results across five public polyp datasets.

We sought to test the hypothesis that patients undergoing ultrasound-assisted catheter-directed thrombolysis (USAT) with standard alteplase and heparin dosing would not develop significant depletion of systemic fibrinogen, which may account for the lower risk of bleeding seen in contemporary trials. We also sought to compare the relative outcomes of individuals with submassive pulmonary embolism (PE) undergoing USAT and anticoagulation alone.Utilizing a single-center prospective registry, we identified 102 consecutive adult patients with submassive PE who were considered for USAT based on a standardized treatment algorithm between November 2016 and May 2019. Patients not receiving USAT therapy were treated with anticoagulation alone.Baseline characteristics were generally similar between groups (n = 51 in each group). Major bleeding rates were not significantly different between groups (2.0% vs 5.9% in USAT vs control, respectively; P=.62). Notably, no USAT patient experienced clinically significant hypofibrinogenemia (mean trough fibrinogen, 369.8 ± 127.1 mg/dL; minimum, 187 mg/dL). The mean trough fibrinogen of patients experiencing any bleeding event (major or minor) was 306.6 mg/dL (SE, 23.9 mg/dL) vs 380.3 mg/dL (SE, 20.4 mg/dL) in those without a bleeding event (P=.02).In this cohort analysis of patients undergoing USAT, there was no evidence for clinically significant depletion of fibrinogen or intracranial hemorrhage. Although our data suggest an association between lower fibrinogen levels and bleeding events, our results are not clear enough to suggest a clinically useful fibrinogen cut-off value. Further study is needed to determine the utility of routine fibrinogen monitoring in this population.

Automatic segmentation methods are an important advancement in medical image analysis. Machine learning techniques, and deep neural networks in particular, are the state-of-the-art for most medical image segmentation tasks. Issues with class imbalance pose a significant challenge in medical datasets, with lesions often occupying a considerably smaller volume relative to the background. Loss functions used in the training of deep learning algorithms differ in their robustness to class imbalance, with direct consequences for model convergence. The most commonly used loss functions for segmentation are based on either the cross entropy loss, Dice loss or a combination of the two. We propose the Unified Focal loss, a new hierarchical framework that generalises Dice and cross entropy-based losses for handling class imbalance. We evaluate our proposed loss function on five publicly available, class imbalanced medical imaging datasets: CVC-ClinicDB, Digital Retinal Images for Vessel Extraction (DRIVE), Breast Ultrasound 2017 (BUS2017), Brain Tumour Segmentation 2020 (BraTS20) and Kidney Tumour Segmentation 2019 (KiTS19). We compare our loss function performance against six Dice or cross entropy-based loss functions, across 2D binary, 3D binary and 3D multiclass segmentation tasks, demonstrating that our proposed loss function is robust to class imbalance and consistently outperforms the other loss functions. Source code is available at: https://github.com/mlyg/unified-focal-loss., Graphical Abstract ga1, Highlights • Loss function choice is crucial for class-imbalanced medical imaging datasets. • Understanding the relationship between loss functions is key to inform choice. • Unified Focal loss generalises Dice and cross-entropy based loss functions. • Unified Focal loss outperforms various Dice and cross-entropy based loss functions.

Background Hospital readmissions following transcatheter aortic valve replacement (TAVR) are associated with higher costs and worse outcomes. Purpose Identify causes and risk factors for readmissions after TAVR Methods Hospitalizations of adults aged ≥50, with aortic stenosis and undergoing elective TAVR between 2012 and 2016 in the National Readmission Database were analyzed. Multivariable generalized logistic regression, adjusting for age, sex, Charleson Comorbidity Index, primary insurance type, median household income, hospital type and size, were used to assess the effect of inpatient complications, length of stay (LOS), discharge disposition, and TAVR hospital volume on 30-day cardiovascular (CV) and non-cardiovascular (non-CV) readmission. Results Between January 2012 and November 2016, 56,858 weighted TAVR hospitalizations were included. The most common causes of readmissions after TAVR were heart failure (23%), infection (17%), gastrointestinal (11%), respiratory (8%), and “other” non-CV causes (8%). The adjusted odds of both CV and non-CV readmissions were significantly higher in patients with acute kidney injury, inpatient LOS ≥5 days, those discharged to skilled nursing facility (SNF) and those treated at medium volume compared with high volume hospitals, Table 1. Conclusion Heart failure is the most common cause of readmissions after TAVR. Inpatient incidence of acute kidney injury, as well as longer LOS, SNF discharge and lower hospital TAVR volume were associated with higher odds of 30-day readmissions. Funding Acknowledgement Type of funding source: None

Background Although readmissions after transcatheter aortic valve replacement (TAVR) were frequent in initial experiences, it is unknown if the incidence of readmission has changed with technological advances and other factors. Purpose Assess temporal trends in 30-day readmission after TAVR Methods Hospitalizations of adults aged ≥50, with aortic stenosis and undergoing elective TAVR or SAVR between 2012 and 2016 in the National Readmission Database were analyzed. Causes of 30-day readmission were classified as cardiovascular (CV) and non-cardiovascular (non-CV). Poisson regression was used to assess quarterly trends in TAVR and SAVR readmissions. Results Overall, 29,031 TAVR and 72,412 SAVR hospitalizations were included (weighted N 56,858 TAVR and 151,899 SAVR), and 14% were readmitted within 30-days (TAVR: 15%; SAVR: 13%). Of all the readmissions, 38% were cardiovascular (TAVR: 35%; SAVR: 40%). Between January 2012 and November 2016, the incidence of overall 30-day readmission significantly declined from 20% to 13% (CIE −0.13, 95% CI: −0.13, −0.13, p Conclusion Readmissions after TAVR have declined over the last several years, likely due to improvements in technology and operator experience, greater attention to comorbidities, and reductions in inpatient complications. More work is needed to reduce further inpatient complications and the incidence of readmission. Figure 1 Funding Acknowledgement Type of funding source: None

It is recognised that delirium is common among older adult inpatients and correlated with negative outcomes. The gold standard care for delirium management is achieved using multicomponent interventions. Which components work best is not yet well defined. During the COVID-19 outbreak, a paediatric ward was repurposed to treat adult patients. Paediatric nurses and play specialists remained on the ward. It was observed that the paediatric ward aesthetic and the team’s dedicated approach to cognitive stimulation and sleep promotion improved well-being among older adult patients. We propose that elements of paediatric care, primarily deployment of a play specialist, could be incorporated into a multicomponent intervention for delirium prevention and management.

Handover has long been identified as a potential source for error that can have direct consequences for patient care. The current weekend handover system at University College Hospital, London, involved a verbal handover meeting with a variety of methods used to collate information. A new handover system was introduced that involved the pre-population of a spreadsheet before attending the handover meeting. Doctors involved in the handover process were canvassed for opinion before and after the introduction of the new system, and logistical data were collected. The new system reduced the amount of time spent preparing for, and delivering, handover, and was deemed to be safer and to improve adherence to the Royal College of Physicians’ guidelines for handover, including specification of level of doctor to perform handover and prioritisation of handover.

Multiple sclerosis (MS) is a chronic disease which usually begins in young adulthood and is a lifelong condition. Individuals with MS experience physical and cognitive disability resulting from inflammation and demyelination in the central nervous system. Over the past decade, several disease-modifying therapies (DMTs) have been approved for the management of relapsing-remitting MS (RRMS), which is the most prevalent phenotype. The chronic nature of the disease and the multiple treatment options make benefit-risk-based sequencing of therapy essential to ensure optimal care. The efficacy and short- and long-term risks of treatment differ for each DMT due to their different mechanism of action on the immune system. While transitioning between DMTs, in addition to immune system effects, factors such as age, disease duration and severity, disability status, monitoring requirements, preference for the route of administration, and family planning play an important role. Determining a treatment strategy is therefore challenging as it requires careful consideration of the differences in efficacy, safety and tolerability, while at the same time minimizing risks of immune modulation. In this review, we discuss a sequencing approach for treating RRMS, with importance given to the long-term risks and individual preference when devising a treatment plan. Evidence-based strategies to counter breakthrough disease are also addressed.

Purpose Advancements in care of children with congenital heart disease (CHD) has led to an increasing adult population living with CHD that frequently requires hospitalizations and procedural interventions. We aim to describe temporal trends in hospitalizations and heart failure (HF)-related procedural volume in adults with CHD stratified by race. Methods Hospitalizations for adults ≥18 years with a diagnosis of CHD from January 1, 2000 to December 31, 2017 in the Nationwide Inpatient Sample were identified. Hospitalizations were trended over years using Poisson regression and expressed as average annual percent change (AAPC), stratified by race. A yearly aggregate sum of HF-related procedures (valvular interventions, heart transplants, and left ventricular assist device implants) similarly trended by race. Results Overall, 1,472,565 hospitalizations were identified. Total as well as primary cardiovascular hospitalizations significantly increased across all races (AAPC: White 8% and 7%, respectively; Black 9% and 9%, Hispanic 8% and 8%, other 7% and 8%). Rates of HF-related procedures were 145 per 1000 hospitalizations in White patients, 57 per 1000 in Black patients, 103 per 1000 in Hispanic patients, and 138 per 1000 in patients of other races. From 2000 to 2017, procedural rates increased in patients of all races: White (130 per 1000 to 163, p Conclusion Rate of hospitalizations and HF-related procedures increased in patients with CHD from 2000 to 2017. Black and Hispanic patients had significantly fewer procedures compared to White patients regardless of insurance type. Further studies are needed to better ascertain the causes behind demographic disparities in procedural volumes in patients with CHD and to raise awareness among patients and providers.

Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.

Patients with calcific aortic stenosis (AS) often have diffuse cardiac calcification involving the mitral valve apparatus and coronary arteries. We examined the association between global cardiac calcification quantified by a previously validated echocardiographic calcium score (eCS) with the severity of mitral stenosis (MS) and coronary artery disease (CAD) in patients with a clinical diagnosis of severe calcific AS. In this sample of 147 patients (mean age 81 ± 9 years, 50% male), 81 patients (55%) were determined by echocardiography to have some degree of MS. Higher mean eCS was observed in patients with more severe MS (r = 0.54, p 0.0001). Higher eCS was also inversely associated with mitral valve area (r = -0.31, p = 0.001) and positively associated with mitral valve mean pressure gradient (r = 0.46, p 0.0001) and mitral valve peak flow velocity (r = 0.55, p 0.0001). The area under the receiver operating characteristic curve for using eCS to predict the presence of MS was 0.76. An eCS ≥ 8 predicted MS with a sensitivity of 68%, specificity of 76%, positive predictive value of 77%, and negative predictive value of 66%. High eCS, relative to low eCS, was associated with 2.70 times the adjusted odds of CAD (odds ratio = 2.70, 95% confidence interval 1.02 to 7.17). In conclusion, global cardiac calcification is associated with MS and CAD in patients with severe calcific AS, and eCS shows ability to predict the presence of MS. This study suggests that a simple eCS may be used as part of a risk-stratification tool in patients with severe calcific aortic valve stenosis.

To solve the defect problem during the exposure process of EUV lithography (EUVL), an EUV pellicle is suggested as a solution. Even though use of an EUV pellicle is considered an essential solution for defect control during the exposure process, it is not ready for application in real commercial processes due to how difficult it is to manufacture. Due to tight requirements for an EUV pellicle, flawless fabrication is impossible and deformations such as a wrinkle would result in serious patterning problems. These deformations lead to critical dimension (CD) non-uniformity due to the non-uniform transmission distribution caused by a pellicle wrinkle. In this paper, we discuss the impact of transmission non-uniformity caused by a wrinkled pellicle. When we treat the effects of a wrinkled pellicle, we considered off-axis-illumination, which is a promising resolution enhancement technology. By shrinking the target pattern size down to 7 nm nodes (N7) or 5 nm nodes (N5), a flexible illumination system is required to enhance the resolution ability. With dipole illuminations, resolution is varied by partial coherence and by not only the beam size at the pellicle, but also by the incident angle distribution. For these reasons, a non-uniform intensity distribution caused by a wrinkled pellicle is modified with changes in off-axis illumination conditions, including spatial coherence and the aperture shape. For N5 patterning, the CD non-uniformity of 0.2 nm occurs at 1.7% transmission variation (2-pass). However, the intensity distribution is varied under various illumination conditions in spite of the same pellicle conditions. The intensity non-uniformity goes up with increasing spatial coherence. Even though feature conditions of the wrinkled pellicle are the same, the transmission non-uniformity is changed with illumination conditions. Thus, the allowable feature conditions of the wrinkled pellicle may be changed. For achieving good CD uniformity, the allowable limit of the pellicle wrinkle is carefully studied because the impact of the wrinkled pellicle varies with the illumination conditions.