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Background Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score >= 15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs >= 20 kPa; FIB-4: <13 vs 13 to <= 267 vs >267; NFS: <-1455 vs -1455 to <= 0676 vs >0676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was regist, Funding Agencies|Innovative Medicines Initiative 2 (IMI2) Joint Undertaking [777377]; EU; EFPIA; Fonds de Recherche du Quebec-Sante [296306]; Wellcome Trust [221805/Z/20/Z]; Royal Society [221805/Z/20/Z]; KHIDI - Ministry of Health Welfare, Korea [HI14C1135]; Newcastle NIHR Biomedical Research Centre

Background: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. Methods: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. Findings: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a me

Background and aims: Detecting NASH remains challenging, while at-risk NASH (steatohepatitis and F≥ 2) tends to progress and is of interest for drug development and clinical application. We developed prediction models by supervised machine learning techniques, with clinical data and biomarkers to stage and grade patients with NAFLD. Approach and results: Learning data were collected in the Liver Investigation: Testing Marker Utility in Steatohepatitis metacohort (966 biopsy-proven NAFLD adults), staged and graded according to NASH CRN. Conditions of interest were the clinical trial definition of NASH (NAS ≥ 4;53%), at-risk NASH (NASH with F ≥ 2;35%), significant (F ≥ 2;47%), and advanced fibrosis (F ≥ 3;28%). Thirty-five predictors were included. Missing data were handled by multiple imputations. Data were randomly split into training/validation (75/25) sets. A gradient boosting machine was applied to develop 2 models for each condition: clinical versus extended (clinical and biomarkers). Two variants of the NASH and at-risk NASH models were constructed: direct and composite models.Clinical gradient boosting machine models for steatosis/inflammation/ballooning had AUCs of 0.94/0.79/0.72. There were no improvements when biomarkers were included. The direct NASH model produced AUCs (clinical/extended) of 0.61/0.65. The composite NASH model performed significantly better (0.71) for both variants. The composite at-risk NASH model had an AUC of 0.83 (clinical and extended), an improvement over the direct model. Significant fibrosis models had AUCs (clinical/extended) of 0.76/0.78. The extended advanced fibrosis model (0.86) performed significantly better than the clinical version (0.82). Conclusions: Detection of NASH and at-risk NASH can be improved by constructing independent machine learning models for each component, using only clinical predictors. Adding biomarkers only improved the accuracy of fibrosis.

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), two-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) are proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH). METHODS: PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model. RESULTS: We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and four 2DSWE studies, and for diagnosing NASH in four MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs. CONCLUSIONS: When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking. LAY SUMMARY: Non-invasive tests that meas, ReviewFunding agencies:Innovative Medicines Initiative 2 Joint Undertaking 777377Europen Federation of Pharmaceutical Industries and Associations (efpia.eu)

[Background and Aims] Vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2-dimensional shear wave elastography (2DSWE), magnetic resonance elastography (MRE), and magnetic resonance imaging (MRI) have been proposed as non-invasive tests for patients with non-alcoholic fatty liver disease (NAFLD). This study evaluated their diagnostic accuracy for liver fibrosis and non-alcoholic steatohepatitis (NASH)., [Methods] PubMED/MEDLINE, EMBASE and the Cochrane Library were searched for studies examining the diagnostic accuracy of these index tests, against histology as the reference standard, in adult patients with NAFLD. Two authors independently screened and assessed methodological quality of studies and extracted data. Summary estimates of sensitivity, specificity and area under the curve (sAUC) were calculated for fibrosis stages and NASH, using a random effects bivariate logit-normal model., [Results] We included 82 studies (14,609 patients). Meta-analysis for diagnosing fibrosis stages was possible in 53 VCTE, 11 MRE, 12 pSWE and 4 2DSWE studies, and for diagnosing NASH in 4 MRE studies. sAUC for diagnosis of significant fibrosis were: 0.83 for VCTE, 0.91 for MRE, 0.86 for pSWE and 0.75 for 2DSWE. sAUC for diagnosis of advanced fibrosis were: 0.85 for VCTE, 0.92 for MRE, 0.89 for pSWE and 0.72 for 2DSWE. sAUC for diagnosis of cirrhosis were: 0.89 for VCTE, 0.90 for MRE, 0.90 for pSWE and 0.88 for 2DSWE. MRE had sAUC of 0.83 for diagnosis of NASH. Three (4%) studies reported intention-to-diagnose analyses and 15 (18%) studies reported diagnostic accuracy against pre-specified cut-offs., [Conclusions] When elastography index tests are acquired successfully, they have acceptable diagnostic accuracy for advanced fibrosis and cirrhosis. The potential clinical impact of these index tests cannot be assessed fully as intention-to-diagnose analyses and validation of pre-specified thresholds are lacking., [Lay summary] Non-invasive tests that measure liver stiffness or use magnetic resonance imaging (MRI) have been suggested as alternatives to liver biopsy for assessing the severity of liver scarring (fibrosis) and fatty inflammation (steatohepatitis) in patients with non-alcoholic fatty liver disease (NAFLD). In this study, we summarise the results of previously published studies on how accurately these non-invasive tests can diagnose liver fibrosis and inflammation, using liver biopsy as the reference. We found that some techniques that measure liver stiffness had a good performance for the diagnosis of severe liver scarring.

ObjectiveMethodsThis study aimed to investigate the value of imaging-based multivariable body composition profiling by describing its association with coronary heart disease (CHD), type 2 diabetes (T2D), and metabolic health on individual and population levels. The first 6,021 participants scanned by UK Biobank were included. Body composition profiles (BCPs) were calculated, including abdominal subcutaneous adipose tissue, visceral adipose tissue (VAT), thigh muscle volume, liver fat, and muscle fat infiltration (MFI), determined using magnetic resonance imaging. Associations between BCP and metabolic status were investigated using matching procedures and multivariable statistical modeling. ResultsConclusionsMatched control analysis showed that higher VAT and MFI were associated with CHD and T2D (Pamp;lt;0.001). Higher liver fat was associated with T2D (Pamp;lt;0.001) and lower liver fat with CHD (Pamp;lt;0.05), matching on VAT. Multivariable modeling showed that lower VAT and MFI were associated with metabolic health (Pamp;lt;0.001), and liver fat was nonsignificant. Associations remained significant adjusting for sex, age, BMI, alcohol, smoking, and physical activity. Body composition profiling enabled an intuitive visualization of body composition and showed the complexity of associations between fat distribution and metabolic status, stressing the importance of a multivariable approach. Different diseases were linked to different BCPs, which could not be described by a single fat compartment alone., Funding Agencies|Pfizer Inc.

Udgivelsesdato: 2009-Jun, RATIONALE AND OBJECTIVES: Inhaled hyperpolarized (3)He magnetic resonance (MR) imaging has been used to measure alveolar size in patients with emphysema. The aim of this study was to test the hypothesis that (3)He MR images could be used to develop a biomarker of emphysema progression. MATERIALS AND METHODS: Twelve healthy controls and 18 patients with emphysema (eight current smokers, 10 ex-smokers) were imaged at baseline and 6 and 12 months. An additional nine subjects with alpha-1 antitrypsin deficiency (four with emphysema, six without symptoms) were also imaged at baseline and at 6 months. Each subject was imaged at two lung volumes: functional residual capacity (FRC) and FRC plus 15% of total lung capacity. Means and standard deviations of apparent diffusion coefficients (ADCs) were calculated from coronal images of the entire lung and correlated with pulmonary function test results. The lacunarity hypothesis was tested and calculated from the data using a range of 2 x 2 x 2 to 6 x 6 x 6 voxels, and the average was calculated. RESULTS: There was no change in the mean ADC at either lung volume in any subject over the 6- or 12-month period. FRC and residual volume increased over the 12 months, suggesting air trapping. The lacunarity of images collected at FRC increased at 6 and 12 months in smokers only (P = .063 and P = .023, respectively). CONCLUSIONS: The mean ADC calculated from MR images of the lungs with helium was not sufficiently sensitive to detect changes over a 12-month period. However, lacunarity captured more of the spatial information in the images and detected emphysema progress in the smokers.

This report reviews a technical effort that accomplished computer simulations and experimental demonstrations of piston-type micromirror arrays for laser beam steering, shaping, and aberration correction. especially simulations and demonstrations with possible relevance for communication applications. The effort successfully investigated the use of micromirror arrays for laser beam manipulations and illustrated both their potential advantages in terms of small size, high ruggedness and low cost and their potential limitations in terms of small beam steering range and, in particular low optical efficiency due to inactive inter-micromirror space, lack of tilt control, and diffraction into undesired orders. The report concludes that micromirror arrays could be useful in applications where high optical efficiency is not a priority; otherwise continuous mirrors with micromechanical actuation are likely to provide the best fine beam steering and beam shaping or aberration correction performance while retaining the potential advantages of small size, high ruggedness. and low cost.

Corrosion damage in aging aircraft is an increasingly critical concern for the U. S. Air Force. Effective, but inexpensive, techniques are needed to identify and evaluate corrosion damage to aircraft structures. The extent of material loss due to corrosion can be reliably measured from x-ray data, but x-ray measurements are costly, slow, and usually require significant aircraft disassembly. Corrosion by-products, which typically occupy more volume than uncorroded material, often causes slight aircraft surface deformations, or 'pillowing.' Pillowing can be measured with various inexpensive, rapid, and nondestructive optical imaging techniques. However, the relationship between percent material loss and 'pillowing' surface deformation is complex, and conventional methods for quantifying the relationship typically lead to unacceptably low correct-detection rates or unacceptably high false-alarm rates. Neural net technology offers a potentially more accurate approach for establishing this relationship. This paper describes the results of a study applying neural net technology to evaluate the percent of material loss and pillowing surface deformation measured with optical imaging techniques.