Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Exploring the Impact of Controlled Ovarian Stimulation and Non-Invasive Oocyte Assessment in ART Treatments.

Invasive and noninvasive features are normally applied to select developmentally competent oocytes and embryos that can increase the take-home baby rates in assisted reproductive technology. The noninvasive approach mainly applied to determine oocyte and embryo competence has been, since the early days of IVF, the morphological evaluation of the mature cumulus-oocyte complex at the time of pickup, first polar body, zona pellucida thickness, perivitelline space and cytoplasm appearance. Morphological evaluation of oocyte quality is one of the options used to predict successful fertilization, early embryo development, uterine implantation and the capacity of an embryo to generate a healthy pregnancy to term. Thus, this paper aims to provide an analytical revision of the current literature relating to the correlation between ovarian stimulation procedures and oocyte/embryo quality. In detail, several aspects of oocyte quality such as morphological features, oocyte competence and its surrounding environment will be discussed. In addition, the main noninvasive features as well as novel approaches to biomechanical parameters of oocytes that might be correlated with the competence of embryos to produce a healthy pregnancy and live birth will be illustrated.

A method for harvesting viable cells from wound dressings.

Wound fluid has been well studied for exploring protein biomarkers contained in it. However, cells in wound fluid have not received much attention due to the difficulty in their collection. Our study aimed to establish a method for collecting viable cells from discarded wound dressings. A protocol was designed to wash out nonadherent cells and detach adherent cells from silicone-faced foam wound dressings using trypsin-EDTA. The optimal concentration and incubation time of trypsin-EDTA for collecting equivalent proportions of different cell types to the original cell population were determined in vitro. Cell composition and gene expression changes in monocytes, lymphocytes, neutrophils, fibroblasts and keratinocytes were confirmed using immunocytochemistry and RNA-sequencing ex vivo. Full-thickness wounds were created on 9-week-old male C57BL/6J mice. Wound fluid was collected, and half of it was applied to the wound dressings. The original cell population in the wound fluid and the cell population collected from wound dressings were compared. In the in vitro study, 0.25% trypsin-EDTA and 2.5-min incubation time were considered optimal for collecting adherent cells from wound dressings. In the ex vivo study, among all cell types, only CD3+ lymphocytes showed a significantly higher cell proportion in the collected group. The relative gene expression of the five selected cells showed no significant changes (p-value >0.05, |log2 fold change| < 1.5, differential gene expression analysis). Viable nonadherent and adherent cells were collected from wound dressings without altering gene expression and could be used in future studies for cellular analysis of wound fluid.

Noninvasive Assessment of Arterial Pulse-Pressure Variation During General Anesthesia: Clinical Evaluation of a New High-Fidelity Upper Arm Cuff.

OBJECTIVES: To compare noninvasive pulse-pressure variation (PPV) measurements obtained from a new high-fidelity upper arm cuff using a hydraulic coupling technique to corresponding intraarterial PPV measurements. DESIGN: The authors used prospective multicenter comparison and development studies for the new high-fidelity upper arm cuff. SETTING: The study was performed in the departments of Anesthesiology at the Ludwig-Maximilians-Universität München Hospital, the University Hospital of Bonn, and the RoMed Hospital in Rosenheim (all Germany). PARTICIPANTS: A total of 153 patients were enrolled, undergoing major abdominal surgery or neurosurgery with mechanical ventilation. For the evaluation of PPV, 1,467 paired measurements in 107 patients were available after exclusion due to predefined quality criteria. INTERVENTIONS: Simultaneous measurements of PPV were performed from a reference femoral arterial catheter (PPVref) and the high-fidelity upper arm cuff (PPVcuff). The new device uses a semirigid conical shell. It incorporates a hydraulic sensor pad with a pressure transducer, leading to a tissue pressure-pulse contour with all characteristics of an arterial- pulse contour. MEASUREMENTS AND MAIN RESULTS: The comparative analysis of the included measurements showed that PPVref and PPVcuff were closely correlated (r = 0.92). The mean of the differences between PPVref and PPVcuff was 0.1 ± 2.0%, with 95% limits of agreement between -4.1% and 3.9%. To track absolute changes in PPV >2%, the concordance rate between the 2 methods was 93%. CONCLUSIONS: The new high-fidelity upper arm cuff method provided a clinically reliable estimate of PPV.

A methodological study of 2D shear wave elastography for noninvasive quantitative assessment of renal fibrosis in patients with chronic kidney disease.

PURPOSE: To determine the optimal measurement method of 2D shear wave elastography (2D-SWE) for noninvasive quantitative assessment of renal fibrosis in chronic kidney disease (CKD) patients. METHODS: A total of 190 CKD patients were enrolled for 2D-SWE of right kidney. The success rates, coefficients of variation (CV), and pathological correlation of different measurement sites, body positions, and depths were compared. RESULTS: (1) Measurement sites: Success rate in the middle part (100%) was higher than that in the lower pole (97.3%, P > 0.05). CV in the middle part (10.2%) was lower than that in the lower pole (16.4%, P < 0.05). Pathological correlation of the middle part (r = - 0.452, P < 0.05) was higher than that of the lower pole (r = 0.097, P > 0.05). (2) Body positions: Success rate in left lateral decubitus position (100%) was higher than that in supine (99.4%, P > 0.05) and prone position (99.4%, P > 0.05). CV was lowest (11.9%) and pathological correlation was highest (r = -0.256, P < 0.05) in prone position. (3) Measurement depths: Success rate at depth < 4 cm (100%) was higher than that at depth ≥ 4 cm (98.8%, P > 0.05). CV at depth < 4 cm (11.1%) was lower than that at depth ≥ 4 cm (14.4%, P < 0.05). Pathological correlation at depth < 4 cm (r = - 0.303, P < 0.05) was higher than that at depth ≥ 4 cm (r = - 0.156, P > 0.05). CONCLUSION: The optimal measurement method of 2D-SWE for renal fibrosis assessment was prone position, renal middle part, and measurement depth < 4 cm.

The Benefit of Bariatric Surgery on Histological Features of Metabolic Associated Fatty Liver Disease Assessed Through Noninvasive Methods.

BACKGROUND: In patients with clinically severe obesity, metabolic associated fatty liver disease (MAFLD) and steatohepatitis are highly prevalent. There is a lack of prospective studies evaluating the impact of bariatric surgery (BS) on MAFLD using both noninvasive and histological criteria. The present study aims to assess the impact of BS on MAFLD using histological and biochemical criteria. METHODS: This is a prospective study of 52 patients subjected to BS. Noninvasive fibrosis risk scores (NIFRS) along with anthropometric, clinical, and biochemical parameters were recorded pre- and 12 months post-BS. Liver biopsy was obtained in all individuals at baseline (wedge biopsy) and was repeated at 12 months (percutaneous Tru-cut) in those diagnosed with steatohepatitis. The primary outcome was the change in the degree of steatohepatitis and fibrosis. The secondary outcome was the change in scores for hepatocellular ballooning, lobular inflammation, steatosis, and fibrosis. RESULTS: One year after BS, steatohepatitis resolved in core biopsies with no worsening of fibrosis in 95.7% of individuals (n = 21, 95% CI: 87.3-100), and 13 (56.5%) exhibited complete resolution. Of 15 patients with fibrosis at baseline, 13 (86.7%) showed improvement and 12 exhibited fibrosis resolution. The values of transaminases improved, but only gamma glutamyl transferase (GGT) showed statistical significance. Among the NIFRS, NAFLD fibrosis score (NFS) and Hepamet fibrosis score (HFS) showed significant improvement. CONCLUSIONS: In the setting it was studied, BS improved or resolved steatohepatitis and fibrosis in patients with obesity. NIFRS, especially NFS and HFS, and levels of GGT could be used as markers of recovery of liver function after BS.

Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD).

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD. METHODS: Adult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort. RESULTS: 147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89). CONCLUSIONS: This cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and <65, unlikely to have cirrhosis so higher-risk patients maintain access to specialty care.

Prenatal Identification of Confined Placental Mosaicism in Pregnant Women with Fetal Growth Restriction.

We examined the influence of confined placental mosaicism (CPM) as a cause of fetal growth restriction (FGR), and whether CPM can be screened using cell-free DNA (cfDNA) analysis of the maternal plasma. We analyzed cfDNA in the maternal plasma of 40 FGR cases with an estimated fetal weight of less than - 2.0 SD using massively parallel sequencing to detect chromosomal aberrations. Fetal and placental genotyping was performed to confirm CPM cases. cfDNA analyses of maternal plasma detected suspected CPM cases with chromosomal aneuploidy or copy number variations in 5 of 40 cases (12.5%). For 4 cases in which the entire placenta consisted of cells with chromosomal abnormalities, fetal growth was severely restricted. CPM can be screened by cfDNA analysis in maternal plasma, accounting for approximately 10% of the causes of moderate or severe FGR, and the higher the proportion of abnormal karyotype cells in the placenta, the more severe the placental dysfunction and FGR.

The Assessment of Autonomic Nervous System Activity Based on Photoplethysmography in Healthy Young Men.

Noninvasive assessment of autonomic nervous system (ANS) activity is of great importance, but the accuracy of the method used, which is primarily based on electrocardiogram-derived heart rate variability (HRV), has long been suspected. We investigated the feasibility of photoplethysmography (PPG) in ANS evaluation. Data of 32 healthy young men under four different ANS activation patterns were recorded: baseline, slow deep breathing (parasympathetic activation), cold pressor test (peripheral sympathetic activation), and mental arithmetic test (cardiac sympathetic activation). We extracted 110 PPG-based features to construct classification models for the four ANS activation patterns. Using interpretable models based on random forest, the main PPG features related to ANS activation were obtained. Results showed that pulse rate variability (PRV) exhibited similar changes to HRV across the different experiments. The four ANS patterns could be better classified using more PPG-based features compared with using HRV or PRV features, for which the classification accuracies were 0.80, 0.56, and 0.57, respectively. Sensitive features of parasympathetic activation included features of nonlinear (sample entropy), frequency, and time domains of PRV. Sensitive features of sympathetic activation were features of the amplitude and frequency domain of PRV of the PPG derivatives. Subsequently, these sensitive PPG-based features were used to fit the improved HRV parameters. The fitting results were acceptable (p < 0.01), which might provide a better method of evaluating ANS activity using PPG.

Novel extraction, rapid assessment and bioavailability improvement of quercetin: A review.

Quercetin (QUR) have got the attention of scientific society frequently due to their wide range of potential applications. QUR has been the focal point for research in various fields, especially in food development. But, the QUR is highly unstable and can be interrupted by using conventional assessment methods. Therefore, researchers are focusing on novel extraction and non-invasive tools for the non-destructive assessment of QUR. The current review elaborates the different novel extraction (ultrasound-assisted extraction, microwave-assisted extraction, supercritical fluid extraction, and enzyme-assisted extraction) and non-destructive assessment techniques (fluorescence spectroscopy, terahertz spectroscopy, near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, and surface-enhanced Raman spectroscopy) for the extraction and identification of QUR in agricultural products. The novel extraction approaches facilitate shorter extraction time, involve less organic solvent, and are environmentally friendly. While the non-destructive techniques are non-interruptive, label-free, reliable, accurate, and environmental friendly. The non-invasive spectroscopic and imaging methods are suitable for the sensitive detection of bioactive compounds than conventional techniques. QUR has potential therapeutic properties such as anti-obesity, anti-diabetes, antiallergic, antineoplastic agent, neuroprotector, antimicrobial, and antioxidant activities. Besides, due to the low bioavailability of QUR innovative drug delivery strategies (QUR loaded gel, QUR polymeric micelle, QUR nanoparticles, glucan-QUR conjugate, and QUR loaded mucoadhesive nanoemulsions) have been proposed to improve its bioavailability and providing novel therapeutic approaches.

[Personalized ischemia diagnostics in chronic coronary syndrome]. / Personalisierte Ischämiediagnostik beim chronischen Koronarsyndrom.

Myocardial ischemia is triggered by a mismatch between the oxygen supply and demand of the myocardial tissue. The most common cause is coronary artery disease; however, not every coronary stenosis is hemodynamically relevant and leads to myocardial ischemia. The guidelines recommend noninvasive ischemia diagnostics prior to invasive treatment in patients with chronic coronary syndrome. Cardiac computed tomography, stress echocardiography, nuclear cardiological procedures (positron emission tomography and single photon emission computed tomography) and cardiac magnetic resonance imaging are the main diagnostic tools for this purpose and are incorporated into the clinical routine. This article provides a review of the indications, the relative advantages and disadvantages of the respective methods and their utilization in routine clinical practice.

Online Noninvasive Assessment of Human Brain Death by Near-Infrared Spectroscopy with Protocol of O2 Inspiration.

Brain death is the irreversible loss of all the functions of the brain and brainstem. Compared to traditional diagnostic methods of brain death, near-infrared spectroscopy (NIRS) is a noninvasive, objective, cost-effective, and safe way of assessment of brain death. Eighteen brain dead patients and 20 healthy subjects were studied by NIRS, with a multiple-phase protocol at varied fractions of inspired O2 (FIO2). We found that the changes in the concentration ratios of oxyhemoglobin to deoxyhemoglobin (Δ[HbO2]/Δ[Hb]) in the cerebral cortex of brain dead patients were significantly higher than those of healthy subjects, and its low-to-high FIO2 phase was most sensitive, with a recommended threshold in the range 1.40-1.50. Our study indicated that NIRS is a promising technology for assessing brain death. The success of this application potentially offers a supplementary technique for the assessment of brain death in real time in order to be able to promptly offer quality-assured donor organs.

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study.

Background: Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling. Objective: The research aims to evaluate the diagnostic accuracy of this algorithm. Methods: The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography - included retrospectively, 64 - prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland-Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman's rank correlation coefficient. Results: During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71-82.03); the specificity was 78.95% (95% CI: 56.67-91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13-84.40); the specificity was 87.50% (95% CI: 52.91-99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97-88.08), p < 0.0001. Conclusion: The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97-88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.

Noninvasive Assessment of Schistosoma-Related Periportal Fibrosis.

Schistosomiasis affects nearly 250 million individuals in the world. Hepatosplenic schistosomiasis (HSS) results in periportal fibrosis (PPF) and portal hypertension (pHTN). Ultrasound has been extensively used for the diagnosis of Schistosoma-related PPF and a number of staging methods have been validated for this purpose such as Strickland classification and Niamey protocol. Nevertheless, the application of noninvasive techniques, particularly elastography modalities, has not been well explored. In this review, we describe the various noninvasive diagnostic tools for assessment of Schistosoma-related PPF including US parameters, serum biomarkers, and US-based elastography techniques. While elastography techniques have demonstrated value in the evaluation of HSS, the evidence remains limited with most studies recruiting a small number of patients. Longitudinal studies with larger sample size are required in order to devise robust criteria to accurately assess the performance of noninvasive techniques in the prediction of both regression and progression of the degree of PPF and identify their cost-effectiveness in community screening.

Noninvasive evaluation of diabetic patients with high fasting blood glucose using DWI and BOLD MRI.

PURPOSE: To investigate the renal microstructure changes and hypoxia changes in type 2 diabetic patients and the relationship between them and glucose using both diffusion-weighted imaging (DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). METHODS: After measuring morning fasting blood glucose, DWI and BOLD MRI were performed in 57 patients with type 2 diabetes mellitus (DM group) and 14 healthy volunteers (NC group). According to the fasting blood glucose levels, diabetic patients were divided into a normoglycemic diabetes group (group A), a less hyperglycemic diabetes group (group B) and a more hyperglycemic diabetes group (group C). The renal parenchymal apparent diffusion coefficient (ADC), renal cortical R2* (CR2*), and medullary R2* (MR2*) were measured, and the R2* ratio between the medulla and cortex (MCR) was calculated. To test for differences in ADC, R2*, and MCR among the four groups, the data were analyzed by separate one-way ANOVAs. The correlations between ADC, R2*, and MCR and the clinical index of renal function were analyzed. RESULTS: Groups B and C had significantly lower ADC values in the renal parenchyma (P = 0.048, 0.002) and significantly higher MR2* and MCR values (P < 0.000, P = 0.001, 0.001, and 0.005, respectively) than the NC group. ADC was negatively correlated with glucose, and MR2*, MCR and glucose showed a weak positive correlation. CONCLUSION: DWI and BOLD may indirectly and qualitatively reflect the kidney microstructure status and hypoxia level of diabetic patients at different blood glucose levels to a certain extent, and possibly guide the clinical treatment of diabetic patients with different blood glucose levels.

Non-invasive imaging of mouse embryo metabolism in response to induced hypoxia.

PURPOSE: This study used noninvasive, fluorescence lifetime imaging microscopy (FLIM)-based imaging of NADH and FAD to characterize the metabolic response of mouse embryos to short-term oxygen deprivation. We investigated the response to hypoxia at various preimplantation stages. METHODS: Mouse oocytes and embryos were exposed to transient hypoxia by dropping the oxygen concentration in media from 5-0% over the course of ~1.5 h, then 5% O2 was restored. During this time, FLIM-based metabolic imaging measurements of oocyte/embryo cohorts were taken every 3 minutes. Experiments were performed in triplicate for oocytes and embryos at the 1- to 8-cell, morula, and blastocyst stages. Maximum hypoxia response for each of eight measured quantitative FLIM parameters was taken from the time points immediately before oxygen restoration. RESULTS: Metabolic profiles showed significant changes in response to hypoxia for all stages of embryo development. The response of the eight measured FLIM parameters to hypoxia was highly stage-dependent. Of the eight FLIM parameters measured, NADH and FAD intensity showed the most dramatic metabolic responses in early developmental stages. At later stages, however, other parameters, such as NADH fraction engaged and FAD lifetimes, showed greater changes. Metabolic parameter values generally returned to baseline with the restoration of 5% oxygen. CONCLUSIONS: Quantitative FLIM-based metabolic imaging was highly sensitive to metabolic changes induced by hypoxia. Metabolic response profiles to oxygen deprivation were distinct at different stages, reflecting differences in metabolic plasticity as preimplantation embryos develop.

Simultaneous Determination of Eight Urinary Metabolites by HPLC-MS/MS for Noninvasive Assessment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health concern for which sensitive and objective diagnostic methods remain lacking. While advances in neuroimaging have improved diagnostic capabilities, the complementary use of molecular biomarkers can provide clinicians with additional insight into the nature and severity of TBI. In this study, a panel of eight metabolites involved in distinct pathophysiological processes related to concussion was quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Specifically, the newly developed method can simultaneously determine urinary concentrations of glutamic acid, homovanillic acid, 5-hydroxyindoleacetic acid, methionine sulfoxide, lactic acid, pyruvic acid, N-acetylaspartic acid, and F2α-isoprostane without intensive sample preparation or preconcentration. The method was systematically validated to assess sensitivity (method detection limits: 1-20 µg/L), accuracy (81-124% spike recoveries in urine), and reproducibility (relative standard deviation: 4-12%). The method was ultimately applied to a small cohort of urine specimens obtained from healthy college student volunteers. The method presented here provides a new technique to facilitate future work aiming to assess the clinical efficacy of these putative biomarkers for noninvasive assessment of TBI.

Quantitative ultrasound approaches for diagnosis and monitoring hepatic steatosis in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a major global health concern with increasing prevalence, associated with obesity and metabolic syndrome. Recently, quantitative ultrasound-based imaging techniques have dramatically improved the ability of ultrasound to detect and quantify hepatic steatosis. These newer ultrasound techniques possess many inherent advantages similar to conventional ultrasound such as universal availability, real-time capability, and relatively low cost along with quantitative rather than a qualitative assessment of liver fat. In addition, quantitative ultrasound-based imaging techniques are less operator dependent than traditional ultrasound. Here we review several different emerging quantitative ultrasound-based approaches used for detection and quantification of hepatic steatosis in patients at risk for nonalcoholic fatty liver disease. We also briefly summarize other clinically available imaging modalities for evaluating hepatic steatosis such as MRI, CT, and serum analysis.

Diagnostic Accuracy of Noninvasive Tests to Detect Advanced Hepatic Fibrosis in Patients With Hepatitis C and End-Stage Renal Disease.

BACKGROUND & AIMS: For patients with liver disease from hepatitis C virus (HCV) infection complicated by end-stage renal disease (ESRD), it is important to assess liver fibrosis before kidney transplantation. We evaluated the accuracy of non-invasive tests to identify advanced hepatic fibrosis in patients with HCV and ESRD. METHODS: In a retrospective study, we collected data on ratio of aspartate aminotransferase:alanine aminotransferase (AST:ALT), AST platelet ratio index (APRI), FIB-4 score, fibrosis index score, and King's score from 139 patients with ESRD and HCV infection (mean age, 52.8 y; 76.3% male; 86.4% African American; 45.3% with increased level of ALT). Results were compared with findings from histologic analyses of biopsies (reference standard). The primary outcome was detection of advanced fibrosis, defined as either bridging fibrosis or cirrhosis. Area under the receiver operating characteristic (AUROC) curves were constructed and optimal cutoff values were determined for each test. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated. We repeated the analysis with stratification for normal levels of ALT (≤ 35 U/L for men and ≤ 25 u/L for women) and increased levels of ALT. RESULTS: FIB-4 scores identified patients with advanced fibrosis with an AUROC of 0.71 (95% CI, 0.61-0.80), the King's score with an AUROC of 0.69 (95% CI, 0.58-0.80), and the APRI with and AUROC of 0.68 (95% CI, 0.59-0.79). The accuracy of these tests increased when they were used to analyze patients with increased levels of ALT. All tests produced inaccurate results when they were used to assess patients with normal levels of AST and ALT. CONCLUSIONS: In patients with ESRD and HCV infection, FIB-4 scores, King's scores, and the APRI identify those with advanced fibrosis with AUROC values ranging from 0.68-0.71. Accuracy increased modestly when patients with increased levels of ALT were tested, but the tests produced inaccurate results for patients with a normal level of ALT.

The role of exercise hemodynamics in assessing patients with chronic heart failure and left ventricular assist devices.

Introduction: Chronic heart failure is characterized by reduced exercise capacity. Invasive exercise hemodynamics are not routinely performed unless patients undergo transplant or left ventricular assist devices (LVAD) assessment, though now with readily available noninvasive devices, exercise hemodynamics are easily obtained. Our contention is that this is a valuable opportunity to acquire a more accurate measure of cardiac status in heart failure. Exercise hemodynamic measures such as cardiac power output can be carried out cheaply and effectively. Recent studies have highlighted the added value of exercise hemodynamics in prognostication of heart failure, and their role in assessing myocardial recovery in LVADs. Areas covered: In this review, we explore the literature available on Medline until 2019 focusing on resting and exercise hemodynamics alongside the methods of assessment (invasive and noninvasive) in heart failure with reduced ejection fraction and patients with implanted LVADs. Expert opinion: Hemodynamics measured both at rest and exercise are expected to play a significant role in the work up of transplant and LVAD patients. Furthermore, there is the potential to utilize noninvasive assessment in a complimentary fashion to support patient selection and improve the monitoring of response to treatment across the full cohort of heart failure patients.