Surrogate Criteria Research Articles

Acute-on-chronic inflammation in acute myocardial infarction.

Acute myocardial infarction (AMI) is heralded by chronic inflammation and entails an excessive burst of acute-on-chronic inflammation (AoCI). This review describes the evolution from understanding atherosclerosis as a chronic inflammatory disease, to recent efforts in optimizing anti-inflammatory therapy to patients with AMI. It highlights the challenges and opportunities in selecting the optimal patient with AMI to derive maximal benefit from early anti-inflammatory therapy. The causal role of inflammation in atherosclerosis has been proven in large outcome trials. Since then, several smaller trials have sought to translate the concept of anti-inflammatory therapy targeting residual inflammatory risk to the dynamic early phase of AoCI after AMI. Current evidence highlights the importance of selecting patients with a high inflammatory burden. Surrogate criteria for large AMI (e.g., angiographic or electrocardiographic), as well as novel point-of-care biomarker testing may aid in selecting patients with particularly elevated AoCI. Additionally, patients presenting with AMI complicated by pro-inflammatory sequelae (e.g., atrial fibrillation, acute heart failure, left ventricular thrombosis) may dually profit from anti-inflammatory therapy. Improved understanding of the mechanisms and dynamics of acute and chronic inflammatory processes after AMI may aid the strive to optimize early anti-inflammatory therapy to patients with AMI.

Directly selecting cell-type marker genes for single-cell clustering analyses

In single-cell RNA sequencing (scRNA-seq) studies, cell types and their marker genes are often identified by clustering and differentially expressed gene (DEG) analysis. A common practice is to select genes using surrogate criteria such as variance and deviance, then cluster them using selected genes and detect markers by DEG analysis assuming known cell types. The surrogate criteria can miss important genes or select unimportant genes, while DEG analysis has the selection-bias problem. We present Festem, a statistical method for the direct selection of cell-type markers for downstream clustering. Festem distinguishes marker genes with heterogeneous distribution across cells that are cluster informative. Simulation and scRNA-seq applications demonstrate that Festem can sensitively select markers with high precision and enables the identification of cell types often missed by other methods. In a large intrahepatic cholangiocarcinoma dataset, we identify diverse CD8+ Tcell types and potential prognostic marker genes.

Surrogate markers in assessment of bisphosphonate effectiveness in osteoporosis treatment (bone mineral density, bone turnover markers)

A review of the literature which summarizes our knowledge on the use of surrogate markers of the osteoporosis treatment effectiveness when on bisphosphonate (BP) therapy. Bone mineral density (BMD) and markers of bone turnover, which have been shown to be associated with the clinical fracture end point, have been used as surrogate criteria for the effectiveness of treatment of osteoporosis in randomized controlled trials. When prescribing BP for the treatment of osteoporosis, BMD measurement every 12 months by dual-energy x-ray absorptiometry (DXA) is the well-described surrogate marker of BP efficacy. At the same time, stabilization of BMD is also a criterion for the treatment effectiveness since changes in BMD determined only 16% of the anti-fracture effectiveness of BP. Markers of bone remodeling can be used as surrogate markers after 3 (bone resorption) or 6 (bone formation) months from the start of BP therapy. A decrease of 30% or more is considered to be prognostically effective for both antifracture and BMD gain. There is a direct relationship between the degree of bone remodeling markers decrease and the antifracture effectiveness of BP therapy. The decrease in markers persists throughout the entire period of therapy and, accordingly, they can be used as surrogate markers of effectiveness and adherence to BP therapy throughout the entire treatment period. However, the presence of pathological fractures is a key clinical manifestation of osteoporosis and should be considered first in every decision making compared to any surrogate marker.Thus, when prescribing BP treatment, surrogate markers of changes in BMD and/or markers of bone remodeling can be used to monitor the effectiveness of treatment throughout the entire period of treatment and patients’ monitoring.

Критерии оценки эффективности антикоагулянтной терапии: роль суррогатных критериев

The article is devoted to the problem of using indirect indicators, or surrogate criteria, both in randomized clinical and observational studies. The reasons for the increasing frequency of using surrogate criteria in assessing the results of clinical trials are considered. The possible negative consequences of the widespread use of proxy measures and the need to educate clinicians to obtain evidence-based information using surrogate criteria rather than true clinical outcomes are discussed. Data from analyzes aimed at identifying the most important problems in the use of surrogate criteria in assessing the effectiveness of certain interventions are presented. The problem of using surrogate criteria in assessing the effectiveness and safety of the use of anticoagulants in patients with atrial fibrillation or venous thromboembolic complications is separately considered. The necessary conditions are provided to ensure the possibility of using surrogate criteria in studies assessing the effectiveness of interventions. Examples of the use of both justified and insufficiently justified use of surrogate criteria for assessing the effectiveness of anticoagulants in various clinical situations are considered. The results of a randomized clinical trial evaluating the effectiveness of an anticoagulant based on identifying surrogate criteria for atrial fibrillation using devices implanted in the heart are discussed. The problem of using surrogate criteria when assessing the risk of bleeding in studies assessing the effects of anticoagulants is discussed separately. The opinions of experts are presented, emphasizing the need for careful use of surrogate criteria when assessing the incidence of both venous thromboembolic complications and bleeding, since in such cases the results of comparing the benefits and risks of the intervention can be significantly distorted.

Design of control systems with multiple memoryless nonlinearities for inputs restricted in magnitude and slope

This paper develops a methodology for designing a control system composed of a linear time-invariant system interconnecting with multiple decoupled time-invariant memoryless nonlinearities. The design problem is to determine parameters of the system such that its outputs and the nonlinearity inputs always remain within prescribed bounds for all exogenous inputs whose magnitude and slope satisfy certain bounding conditions. By using Schauder fixed point theorem, we show that a design associated with a linear system is also a solution of the problem. Based on this, we further develop surrogate design criteria in the form of the inequalities that can readily be solved in practice. Sufficient conditions for the solvability of such inequalities are given for deadzone and saturation. To show the usefulness and the effectiveness of the methodology, a design example of a load frequency control system with time delay is carried out where deadzone and saturation are taken into account.

Differential diagnosis of small hepatocellular nodules incirrhosis: surrogate histological criteria of TERT promotermutations.

The differential diagnosis of small hepatocellular nodules in cirrhosis between dysplastic nodules and hepatocellular carcinoma (HCC) remains challenging on biopsy. As TERT promoter (pTERT) mutations may indicate the nodules already engaged in the malignant process, the aim of this study was to identify histological criteria associated with pTERT mutations by detecting these mutations by ddPCR in small formalin-fixed paraffin-embedded (FFPE) hepatocellular nodules arising in cirrhosis. We built a bicentric cohort data set of 339 hepatocellular nodules < 2 cm from cirrhotic samples, divided into a test cohort of 299 resected samples and a validation cohort of 40 biopsies. Pathological review, based on the evaluation of 14 histological criteria, classified all nodules. pTERT mutations were identified by ddPCR in FFPE samples. Among the 339 nodules, ddPCR revealed pTERT mutations in 105 cases (31%), including 90 and 15 cases in the test and validation cohorts, respectively. On multivariate analysis, three histological criteria were associated with pTERT mutations in the test cohort: increased cell density (P = 0.003), stromal invasion (P = 0.036) and plate-thickening anomalies (P < 0.001). With the combination of at least two of these major criteria, the AUC for predicting pTERT mutations was 0.84 in the test cohort (sensitivity: 86%, specificity: 83%) and 0.81 in the validation cohort (sensitivity: 87%, specificity: 76%). We identified three histological criteria as surrogate markers of pTERT mutations that may be used in routine biopsy to more clearly classify small hepatocellular nodules arising in cirrhosis.

Evaluation of full-face, open-face, and airbag-equipped helmets for facial impact protection

ObjectiveTwo-wheeler riders frequently sustain injuries to the head and face in real-world crashes, including traumatic brain injury, basilar skull fracture, and facial fracture. Different types of helmets exist today, which are recognized as preventing head injuries in general; however, their efficacy and limitations in facial impact protection are underexplored. Biofidelic surrogate test devices and assessment criteria are lacking in current helmet standards. This study addresses these gaps by applying a new, more biofidelic test method to evaluate conventional full-face helmets and a novel airbag-equipped helmet design. Ultimately, this study aims to contribute to better helmet design and testing standards. MethodsFacial impact tests at two locations, mid-face and lower face, were conducted with a complete THOR dummy. Forces applied to the face and at the junction of the head and neck were measured. Brain strain was predicted by a finite element head model taking both linear and rotational head kinematics as input. Four helmet types were evaluated: full-face motorcycle and bike helmets, a novel design called a face airbag (an inflatable structure integrated into an open-face motorcycle helmet), and an open-face motorcycle helmet. The unpaired, two-sided student’s t-test was performed between the open-face helmet and the others, which featured face-protective designs. ResultsA substantial reduction in brain strain and facial forces was found with the full-face motorcycle helmet and face airbag. Upper neck tensile forces increased slightly with both full-face motorcycle (14.4%, p >.05) and bike helmets (21.7%, p =.039). The full-face bike helmet reduced the brain strain and facial forces for lower-face impacts, but not for mid-face impacts. The motorcycle helmet reduced mid-face impact forces while slightly increasing forces in the lower face. Significance of resultsThe chin guards of full-face helmets and the face airbag protect by reducing facial load and brain strain for lower face impact; however, the full-face helmets’ influence on neck tension and increased risk for basilar skull fracture need further investigation. The motorcycle helmet’s visor re-directed mid-face impact forces to the forehead and lower face via the helmet’s upper rim and chin guard: a thus-far undescribed protective mechanism. Given the significance of the visor for facial protection, an impact test procedure should be included in helmet standards, and the use of helmet visors promoted. A simplified, yet biofidelic, facial impact test method should be included in future helmet standards to ensure a minimum level of protection performance.

Exploring the quantitative genetics of traits associated with drought tolerance and yield in Pimpinella anisum L. under different water regimes

Genetic improvement of seed yield and drought resistance could be simultaneously gained in anise when breeding for drought resistance. Improving the water use efficiency of anise is a primary objective of anise breeding programs aimed at mitigating the impacts of drought stress. This study aimed to determine the predominant mechanisms involved in drought tolerance and investigate the genetic control of associated traits with drought tolerance and higher grain yield. According to these aims, 10 half-diallel hybrids and their five parents were evaluated in both field and greenhouse lysimetric experiments under well-watered and water deficit stress conditions. The results indicated that the inheritance of grain yield is complex and affected by water deficit stress. Similar heritability and genetic architecture were detected for flowering time and percentages of photosynthate partitioned to grain (PPPG) in both well-watered and water deficit stress treatments. Significant negative genetic correlations were observed between grain yield and flowering time, root dry mass, root diameter, root volume, root number, percentages of photosynthate partitioned to shoot, and percentages of photosynthate partitioned to root. Therefore, the selection of low values of these attributes can be used to improve grain yield under drought conditions. In contrast, a positive significant genetic linkage between grain yield and PPPG, chlorophyll content, cell membrane stability, and leaf relative water content reveal selection for high values of these attributes is favored. These attributes could be used as surrogate selection criteria in the early segregating generations. The P1 parent (early ripening parent) contained key genes associated with PPPG and drought escape. It was concluded that improvement of drought tolerance and grain yield could be simultaneously achieved in anise breeding programs.

Analysis of multi-objective vehicle routing problem with flexible time windows: The implication for open innovation dynamics

Renewable energy has been a worldwide interest due to a growing energy demand as well as a mounting concern over the hostile impacts from traditional fuels. One of a direction for future renewable energy is the use of biofuel. In this research, we initially apply the K-means algorithm to evaluate the possible locations of collection sites at the upstream of the biofuel supply chain. Next, we propose the multi-objective vehicle routing problem model, in which flexible time windows are synchronized in the model. Additionally, our integrated model evaluates the perspective of socioeconomic by considering total cost – the surrogate criterion for economic aspect as well as the lateness for delivery and the maximum delivery time – the surrogate criteria for social aspect, into account. Finally, we apply a model to a regional case study based on the wood-biomass data of the biofuel supply chain in Thailand, in which the geographic information system is applied.

Head injury criteria assessment using head kinematics from crash tests and accident reconstructions

Objective The aim of this study was to assess head injury criteria based on their correlation to brain strain in a Finite Element (FE) head model (the KTH Royal Institute of Technology model), by simulation of head kinematics data from frontal and side crash tests with Anthropomorphic Test Devices (ATDs), and from Human Body Model (HBM) accident reconstructions. Methods Six Degrees of Freedom (DoF) head kinematic data was extracted from 221 crash tests, consisting of frontal impacts with the THOR-50M ATD, near-side and far-side impacts with the WorldSID-50M ATD, and from 19 FE HBM accident reconstructions. The head injury criteria HIC15, HIP, BrIC, UBrIC, DAMAGE and CIBIC were calculated, and FE head model simulations were conducted using the six DoF kinematics data. The 100th, 99th, and 95th percentile Maximum Principal Strains (MPS) of the brain were extracted and linear regression models with respect to the injury criteria were created. The injury criteria were then evaluated based on the coefficient of determination, R2, and the Normalized Root Mean Square Error (NRMSE) of each regression model. Results For all the data sets combined and for the WorldSID far-side data, CIBIC had the best goodness of fit, with R2 of 0.76 and 0.85. For frontal impacts with THOR and the combined ATD data set, DAMAGE had highest R2, 0.83 and 0.78, respectively. Injury criteria including translational accelerations were ranked lower, and BrIC were among the three lowest ranked for most data sets evaluated. UBrIC generally ranked after DAMAGE and CIBIC with respect to the goodness of fit but had the lowest NRMSE for all data sets. Conclusions The two mass-spring-damper brain surrogate model criteria, DAMAGE and CIBIC, were best in capturing the head model MPS response for both the THOR and WorldSID data sets. BrIC had lower correlation to the head model MPS and performed marginally better than the linear acceleration only criteria for all the data sets combined. This study supports the suitability of DAMAGE and CIBIC as brain injury criteria to be used with THOR-50M and WorldSID-50M in vehicle crash test conditions, as they outperform BrIC.

Chronic Pain Increases the Risk of Dementia: A Nationwide Population-Based Cohort Study

Chronic pain (CP) may increase the risk of cognitive impairment; however, the association between CP and dementia is still unclear. Therefore, we conducted this study to clarify the association between CP and dementia. Retrospective cohort study. Nationwide population based. This study recruited 27,792 patients (>= 50 years) with CP from the Taiwan National Health Insurance Research Database between January 1, 2000, and December 31, 2015, as the study cohort. The comparison cohort consists of patients without CP who were matched 1:1 for age, gender, and index date with the study cohort. A comparison of the risk of dementia between the two cohorts was performed by following up until 2015. The prevalence of CP was 13.4% in the population aged >= 50 years. Patients with CP had a higher risk of dementia than those without CP (adjusted hazard ratio [AHR]: 1.21; 95% confidence interval [CI]: 1.15-1.26). Compared with the other age subgroups, the 50-64 years age group with CP had the highest risk of dementia (AHR: 1.28; 95% CI: 1.14-1.43). The impact of CP on the increased risk of dementia was more prominent in the younger age subgroup and decreased with aging. The increased risk of dementia in patients with CP was persistent, even following up for more than 5 years (AHR: 1.19; 95% CI: 1.12-1.26). Using "analgesics use at least 3 months" as the surrogate criteria of CP may underestimate the diagnosis of CP. CP was associated with a higher risk of dementia, especially in the 50-64 years age group. Early treatment of CP for the prevention of dementia is suggested.

Which is the best alternative to estimate muscle mass for sarcopenia diagnosis when DXA is unavailable?

BackgroundDual x-ray absorptiometry (DXA) is widely adopted to estimate muscle mass for research, but for daily practice is only available in a limited number of facilities. AimTo elucidate if it is anthropometry or bioelectrical impedance analysis (BIA) the method more concordant with DXA in estimating muscle mass for sarcopenia diagnosis among older adults, and to investigate the impact of several cut-off points in sarcopenia frequency. Methods159 older adults (≥65 years) were included in a cross-sectional analysis. Sarcopenia was identified using the 2018 EWGSOP2 definition, plus previous definitions for muscle mass. Estimation of muscle mass by DXA (appendicular skeletal muscle mass (ASM) and ASM/height2), by BIA (skeletal muscle mass/height2 (SMM/height2) and skeletal muscle mass index (SMI)), and anthropometry (calf and mid-arm muscle circumferences (CC and MAMC, respectively)) was carried out, as well as measurements of handgrip strength and gait speed. ResultsSarcopenia frequency varied from 5.0 to 42.1% depending on the method and cut-off point applied. All surrogate diagnostic criteria had a higher agreement with the DXA defined criterion ASM over ASM/height2. A substantial agreement was also found with BIA SMM/height2 (κ= 0.67), and with BIA SMI (κ= 0.65), and a moderate agreement with MAMC (κ= 0.42), p<0.001. Using the DXA ASM and ASM/height2 criteria as reference, CC showed a specificity of 100% and 94%, respectively. ConclusionsBIA is a suitable method to evaluate muscle mass in sarcopenia diagnosis when DXA is unavailable. Furthermore, CC showed to be a valid indicator to rule in the presence of sarcopenia.

Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights.

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

Outcome assessment using estimation of left ventricular filling pressure in asymptomatic patients at risk for heart failure with preserved ejection fraction

AimsHigh prevalence and lack of pharmacological treatment are making heart failure with preserved ejection fraction (HFpEF) a growing public health problem. No algorithm for the screening of asymptomatic patients with risk for HFpEF exists to date. We assessed whether HFA/ESC 2007 diagnostic criteria for HFpEF are helpful to investigate the cardiovascular outcome in asymptomatic patients. Methods and resultsWe performed an analysis of the Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST-CHF) that recruited patients with cardiovascular risk factors. All patients underwent a comprehensive diagnostic workup at baseline. Asymptomatic patients with preserved LVEF (>50%) were selected and classified according to HFA/ESC surrogate criteria for left ventricular elevated filling pressure (mean E/e’ >15 or E/e’ >8 and presence of either NT-proBNP > 220 ng/l, BNP > 200 ng/l or atrial fibrillation) into elevated filling pressure (FPe) or controls. Cardiovascular hospitalizations and all-cause death were assessed for both groups over a 10-year-follow-up.851 asymptomatic patients (age 65.5 ± 7.6 years, 44% female) were included in the analysis. FPe-patients were significantly older (p < 0.001), more often female (p = 0.003) and more often had a history of coronary artery disease, atrial fibrillation and renal dysfunction (p < 0.001, respectively) compared to controls. Incidence of death was significantly higher in the FPe group after a 10-year follow-up (p < 0.001), whereas cardiovascular hospitalization did not differ between groups. ConclusionAsymptomatic patients that fulfill HFA/ESC diagnostic criteria for HFpEF are at higher risk of symptomatic HFpEF and have a worse 10-year-outcome than those who do not fulfill criteria.

Habitat selection of an old‐growth forest specialist in managed forests

AbstractOld‐growth forest specialists are among the species most affected by commercial forestry. However, it is often unclear whether such species can persist and what their habitat needs are in managed forests. We investigated habitat selection of one such old‐growth forest specialist, the white‐backed woodpecker Dendrocopos leucotos, a species highly dependent on dead wood and typically found in primeval forests. Our aim was to understand factors affecting occupancy probability in managed forests in Central Europe, based on detection/non‐detection data in 62 squares of 1 km2 in 2015 and 2016. We used occupancy models to compare a priori expectations about the relationships between occupancy and habitat characteristics at two spatial scales while accounting for imperfect detection. Occupancy was best explained by a proxy for food availability at a large (1 km2) scale and increased with the abundance of emergence holes produced by saproxylic beetles on standing and lying dead wood. Furthermore, occupancy was positively related to the mean diameter at breast height of live trees and standing dead wood at a small scale (0.25 km2 with high amounts of dead wood). Detection probability was negatively related to time of day, date and number of accessible survey points, and positively related to the number of observers. Our results demonstrate that detailed knowledge about a species’ foraging ecology is important for its effective conservation as surrogate criteria such as dead wood availability might not reflect the key factors required. For white‐backed woodpeckers, it is important that the available dead wood is sufficiently colonized by saproxylic beetles, and for the conservation of the species, the habitat requirements of saproxylic beetles thus have to be taken into account as well.

Sex-Specific 99th Percentile Upper Reference Limits for High Sensitivity Cardiac Troponin Assays Derived Using a Universal Sample Bank.

How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (>URL 6.5%), NT-proBNP (>URL 125 ng/L) and eGFR (<60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.

On the individual surrogate paradox.

When the primary outcome is difficult to collect, a surrogate endpoint is typically used as a substitute. It is possible that for every individual, the treatment has a positive effect on the surrogate, and the surrogate has a positive effect on the primary outcome, but for some individuals, the treatment has a negative effect on the primary outcome. For example, a treatment may be substantially effective in preventing the stroke for everyone, and lowering the risk of stroke is universally beneficial for life expectancy; however, the treatment may still cause death for some individuals. We define such paradoxical phenomenon as the individual surrogate paradox. The individual surrogate paradox is proposed to capture the treatment effect heterogeneity, which is unable to be described by either the surrogate paradox based on average causal effect or that based on distributional causal effect. We investigate the existing surrogate criteria in terms of whether the individual surrogate paradox could manifest. We find that only the strong binary surrogate can avoid such paradox without additional assumptions. Utilizing the sharp bounds, we propose novel criteria to exclude the individual surrogate paradox. Our methods are illustrated in an application to determine the effect of the intensive glycemia on the risk of development or progression of diabetic retinopathy.

Efficient Design Optimization Assisted by Sequential Surrogate Models

The paper proposes a global optimization algorithm employing surrogate modeling and adaptive infill criteria. The surrogates are exploited to screen the design space and provide lower-fidelity predictions across it; on the other hand, specific criteria are designed to suggest new points for high-fidelity evaluation so as to enrich the optimizer database. Both Kriging and radial basis function network are used as surrogates with different training strategies. Sequential design is achieved by introducing several infill criteria according to the realization of the exploration-exploitation trade-off. Optimization results are provided both for scalable and analytical test functions and for a practical aerodynamic shape optimization problem.

Varices on computed tomography are surrogate of clinically significant portal hypertension and can predict survival in compensated cirrhosis patients.

To investigate prognostic value of varices on computed tomography (CT) and redefine surrogate criteria for clinically significant portal hypertension (CSPH). We retrospectively enrolled 241 patients with compensated cirrhosis who underwent hepatic venous pressure gradient (HVPG) measurement from 2008 to 2013. Using CT and upper endoscopy findings obtained within 3months from HVPG measurement, patients were classified into three groups: presence of standard surrogate for CSPH, defined as presence of varices on upper endoscopy and/or splenomegaly associated with thrombocytopenia (Group 1, n=139); varices on CT without standard surrogate for CSPH (Group 2, n=41); and free from both (Group 3, n=61). HVPG value and overall survival (OS) rates were compared among three patient groups. Revised surrogate for CSPH was defined as presence of standard surrogate and/or presence of varices on CT (i.e. both Group 1 and Group 2). Mean HVPG value in Group 2 was significantly higher than that in Group 3 (10.3mmHg vs 6.5mmHg, P<0.001), but significantly lower than that in Group 1 (10.3mmHg vs 13.1mmHg, P<0.001). Seven-year OS rates in Group 2 was similar to those in Group 1 (57.0% vs 62.7%, P=0.591), but significantly poorer than those in Group 3 (57.0% vs 84.0%, P=0.015). The presence of revised surrogate for CSPH was a significant predictive factor for OS (P=0.025, Hazard ratio=2.71 [1.14-6.45]) on multivariate analysis whereas standard surrogate for CSPH was not (P=0.849). The presence of varices on CT was a significant sign for CSPH, predicting poor OS outcome in patients with compensated cirrhosis.

Electrocardiographic and electrophysiologic differentiation between atriofascicular, long atrioventricular, and short atrioventricular decrementally conducting accessory pathways.

We aimed to examine the electrocardiographic and electrophysiologic characteristics of anterograde-conducting decremental accessory pathways (DAP) and to identify surrogate criteria to distinguish short atrioventricular (SAV) DAP from atriofascicular (AF) AP and long atrioventricular (LAV) DAP. We identified all patients with DAPs and analysed electrocardiographic and electrophysiologic characteristics. Distal insertion sites were examined using existing criteria, including V-H interval, ventricular activation at the right ventricular apex, and around tricuspid annulus during antidromic atrioventricular re-entrant tachycardia (A-AVRT) or complete pre-excitation and evaluated the AV node-like properties according to the response to adenosine and radiofrequency ablation. Out of 45 patients with DAPs, 28 (62.2%) had SAV-DAP (13 with definite AF-AP, 2 with definite LAV-DAP, 2 indeterminate). In all, 50% of SAV-DAPs and 53.3% of AF-AP/LAV-DAPs had 'rS' pattern in lead III. Longer QRS duration (159.9 ± 17.4 ms vs. 139.2 ± 14.3 ms, P < 0.0001) during full pre-excitation or A-AVRT differentiated SAV-DAP from AF-AP. The QRS-V(His) interval was longer for those with SAV-DAP compared vs. AF-AP/LAV-DAP (45.3 ± 2.4 ms vs. 22.9 ± 2.5 ms, P < 0.0001) and a cut-off value of 33.0 ms differentiated the two (sensitivity 81.3%, specificity 87.5%). The majority of the SAV-DAPs are located at the TA free wall. An 'rS' pattern in lead III is frequently seen in SAV-DAP as well as AF-AP/LAV-DAPs. Measuring the QRS-V(His) interval would be helpful to distinguish SAV-DAP from AF-AP/LAV-DAP.