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2.
Ann Clin Biochem ; : 45632211014244, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33874737

RESUMO

BackgroundThere is limited information regarding the role of biomarker levels at predicting mortality in patients with the novel coronavirus pandemic (Covid-19). The purpose of this study is to determine the differences in serum biomarker levels in adults with Covid-19 who survived hospitalization from those who did not.MethodsA comprehensive search was completed on PubMed, EMBASE, and Cochrane libraries to identify studies of interest. Endpoints of interest were blood counts, hepatic function test, acute phase reactants, cytokines and cardiac biomarkers.ResultsA total of 10 studies with 1,584 patients were included in the pooled analyses. Biomarkers that were noted to be significantly higher in those who died from Covid-19 (coronavirus disease 2019) included: white blood cell count, neutrophil count, C-reactive protein, high sensitivity C-reactive protein, procalcitonin, ferritin, D-dimer, interleukins 6, lactate dehydrogenase, creatine kinase, prothrombin time, aspartate aminotransferase, alanine aminotransferase, total bilirubin, and creatinine. Lymphocyte count, platelet count, and albumin were significantly lower in patients who died. ConclusionThis pooled analysis of 10 studies including 1,584 patients identified significant differences in biomarkers on admission in patients who survived from those who did not. Further research is needed to develop risk stratification models to help with judicious use of limited healthcare resources.

3.
Gut ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883248

RESUMO

OBJECTIVE: Emerging data suggest that a 30% relative decline in liver fat, as assessed by MRI-proton density fat fraction (MRI-PDFF), may be associated with Non-Alcoholic Fatty Liver Disease Activity Score improvement, but the association between decline in MRI-PDFF and fibrosis regression is not known. Therefore, we aimed to examine the association between ≥30% relative decline in MRI-PDFF and fibrosis regression in non-alcoholic fatty liver disease (NAFLD). DESIGN: This prospective study included 100 well-characterised patients with biopsy-proven NAFLD with paired contemporaneous MRI-PDFF assessment at two time points. MRI-PDFF response was defined as ≥30% relative decline in MRI-PDFF. The primary outcome was ≥1 stage histological fibrosis regression. RESULTS: The median (IQR) age was 54 (43-62) years and body mass index was 31.9 (29-36) kg/m2. In multivariable-adjusted logistic regression analysis (adjusted for age, gender, diabetes status, race/ethnicity, interval between biopsies, gamma-glutamyl transferase, liver stiffness by magnetic resonance elastography and change in platelet counts), MRI-PDFF response was an independent predictor of fibrosis regression with an adjusted OR of 6.46 (95% CI 1.1 to 37.0, p=0.04). The proportion of patients with MRI-PDFF response with fibrosis regression, no change in fibrosis and fibrosis progression was 40.0%, 24.6% and 13.0%, respectively, and the proportion of patients with MRI-PDFF response increased with fibrosis regression (p=0.03). CONCLUSION: ≥30% reduction in MRI-PDFF in early phase trials can provide a useful estimate of odds of ≥1 stage improvement in fibrosis. These data may be helpful in sample size estimation in non-alcoholic steatohepatitis trials.

4.
J Extra Corpor Technol ; 53(1): 50-56, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33814606

RESUMO

Modified ultrafiltration (MUF) is still used after pediatric cardiopulmonary bypass (CPB) in some pediatric cardiac surgery centers to decrease transfusion requirements. Other potential benefits of MUF include clearance of inflammatory markers and improvement in myocardial function. Our hypothesis is that MUF will hemoconcentrate coagulation factors and improve thromboelastography (TEG) parameters after pediatric CPB. Patients younger than 6 months were prospectively enrolled over a year. TEG was carried out before MUF, after MUF, and after protamine administration. Paired t tests were conducted to compare values pre-MUF and post-MUF as well as post-MUF and post-protamine administration. Thirty patients were enrolled in the study, with 20 (67%) neonates in the cohort. Seven arterial switch operations and nine Norwood procedures were found to be performed among the cohort. Reaction time (R), angle (α), and maximum amplitude (MA) were significantly worse post-MUF compared with pre-MUF (p < .001). They improved significantly after protamine administration compared with post-MUF (p < .001). The amount of fluid removal was significantly associated with a worse post-MUF R, angle, and MA and worse post-protamine administration, angle, and MA but with no effect on post-protamine R. MUF caused worsening of TEG parameters that is reversed by protamine administration.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Tromboelastografia , Ponte Cardiopulmonar , Criança , Humanos , Recém-Nascido , Estudos Prospectivos , Ultrafiltração
5.
Eur Radiol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33899143

RESUMO

OBJECTIVES: To investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis. METHODS: This was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed. RESULTS: In univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20). CONCLUSIONS: 2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease. KEY POINTS: • Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

6.
Curr Diab Rep ; 21(5): 15, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742318

RESUMO

PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are strongly associated. Both also associate with an increased risk of cardiovascular disease (CVD). RECENT FINDINGS: Several studies have provided evidence that NAFLD could be an independent CVD risk factor. Given the strong association between NAFLD and T2DM, assessing the independent CV effect of these two conditions remains challenging. However, patients with T2DM and NAFLD exhibit higher risk of CVD compared with T2DM without NAFLD suggesting a potential synergistic increase of CV risk in patients with both T2DM and NAFLD supported by several shared pathophysiological pathways. Several anti-diabetic therapies have shown beneficial effect on both NAFLD and CVD. Patients with T2DM and NAFLD should be considered at high risk of CVD and could benefit from more intensive CV prevention. Additional long-term follow-up is needed to demonstrate that the treatment of NAFLD effectively reduces the risk of CVD.

7.
Contemp Clin Trials ; 104: 106335, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33657443

RESUMO

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD); no approved therapies for NASH currently exist. Pegbelfermin (PGBF), a human fibroblast growth factor 21 analog, has metabolic effects that may provide benefit for patients with NASH. DESIGN: The FALCON 1 and 2 studies are phase 2b, multicenter, double-blind, placebo-controlled, randomized trials to assess safety and efficacy of PGBF treatment in patients who have histologically-confirmed NASH with stage 3 liver fibrosis (FALCON 1; NCT03486899) or compensated cirrhosis (FALCON 2; NCT03486912). In both studies, randomized patients receive once weekly subcutaneous injections of PGBF (10, 20, or 40 mg) or placebo during a 48-week treatment period and are then followed for an additional 4 weeks. ENDPOINTS: The primary efficacy endpoint for FALCON 1 is the proportion of patients who achieve ≥1 stage improvement in fibrosis (by NASH CRN fibrosis score) without NASH worsening or NASH improvement (≥2 point decrease in NAFLD Activity Score) without fibrosis worsening at Week 24. For FALCON 2, the primary efficacy endpoint is ≥1 stage improvement in fibrosis without NASH worsening at Week 48. Key safety endpoints for both studies include incidence and frequency of adverse events, bone mineral density and immunogenicity. SUMMARY: Previous clinical trial data show that PGBF can reduce hepatic fat and improve metabolic factors and biomarkers of hepatic injury and fibrosis. The FALCON studies aim to evaluate PGBF treatment specifically in patients with NASH and advanced fibrosis, who are at greatest risk of poor clinical outcomes over time.

8.
Gut Microbes ; 13(1): 1-22, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33651661

RESUMO

Fatty liver disease is the most common liver disease in the world. Its connection with the gut microbiome has been known for at least 80 y, but this association remains mostly unstudied in the general population because of underdiagnosis and small sample sizes. To address this knowledge gap, we studied the link between the Fatty Liver Index (FLI), a well-established proxy for fatty liver disease, and gut microbiome composition in a representative, ethnically homogeneous population sample of 6,269 Finnish participants. We based our models on biometric covariates and gut microbiome compositions from shallow metagenome sequencing. Our classification models could discriminate between individuals with a high FLI (≥60, indicates likely liver steatosis) and low FLI (<60) in internal cross-region validation, consisting of 30% of the data not used in model training, with an average AUC of 0.75 and AUPRC of 0.56 (baseline at 0.30). In addition to age and sex, our models included differences in 11 microbial groups from class Clostridia, mostly belonging to orders Lachnospirales and Oscillospirales. Our models were also predictive of the high FLI group in a different Finnish cohort, consisting of 258 participants, with an average AUC of 0.77 and AUPRC of 0.51 (baseline at 0.21). Pathway analysis of representative genomes of the positively FLI-associated taxa in (NCBI) Clostridium subclusters IV and XIVa indicated the presence of, e.g., ethanol fermentation pathways. These results support several findings from smaller case-control studies, such as the role of endogenous ethanol producers in the development of the fatty liver.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33775894

RESUMO

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events.1 Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis,2 and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma.3,4 Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity.5 This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort.

10.
Cardiol Young ; 31(4): 532-540, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33731242

RESUMO

Isomerism, also referred to as "heterotaxy" is a complex set of anatomic and functional perturbations. One of the most obvious manifestations of isomerism is the disturbance of organ arrangement, such that the thoracic organs are no longer asymmetric on the left and right. We report the case of a 14-year-old female in whom exercise-induced dyspnea led to a late diagnosis of left isomerism complicated by Abernethy malformation and portopulmonary hypertension. A comprehensive evaluation revealed two anatomic left lungs and hyparterial bronchi, bilateral left atria, an interrupted inferior caval vein with azygos continuation, multiple spleens, sinus node dysfunction, hepatic hypertrophy with focal nodular hyperplasia, and absence of the portal vein. Pulmonary vasodilator therapy was initiated resulting in clinical improvement. This case exhibits unique features including a late diagnosis of isomerism with Abernethy malformation and portopulmonary hypertension. The patient's presentation, medical workup, and future treatment emphasise the importance of multidisciplinary care in children with complex multisystem disease. We review the multiple cardiac and extracardiac manifestations of isomerism.

11.
Hepatology ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772833

RESUMO

BACKGROUND & AIMS: Chronic liver diseases (CLD) affect ~2% of the US population and are associated with substantial burden of hospitalization and costs. We estimated the national burden and consequences of financial hardship from medical bills in individuals with CLD. APPROACH & RESULTS: Using the National Health Interview Survey from 2014-18, we identified individuals with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of financial hardship from medical bills and other financial toxicity measures (cost-related medication non-adherence, personal and/or healthcare related financial distress, food insecurity). We evaluated the association of financial hardship from medical bills with unplanned healthcare utilization and work productivity, accounting for differences in age, sex, race/ethnicity, insurance, income, education and comorbidities. Of 3,666 (representing 5.3 million) US adults with CLD, 1,377 (representing 2.0 million; [37%, 95% CI: 35-39%]) reported financial hardship from medical bills, including 549 (representing 740,000; [14%, 95% CI: 13-16%]) who were unable to pay medical bills at all. Adults who were unable to pay medical bills had 8.4 times higher odds of cost-related medication non-adherence (aOR, 8.39 [95% CI, 5.72-12.32]), 6.3-times higher odds of financial distress (aOR, 6.33 [4.44-9.03]) and 5.6-times higher odds of food insecurity (aOR, 5.59 [3.74-8.37]), as compared to patients without financial hardship from medical bills. Patients unable to pay medical bills had 1.9-times higher odds of emergency department visits (aOR, 1.85 [1.33-2.57]), and 1.8-times higher odds of missing work due to disease (aOR, 1.83 [1.26-2.67]). CONCLUSIONS: One in 3 adults with CLD experience financial hardship from medical bills, and frequently experience financial toxicity and unplanned healthcare utilization. These financial determinates of health have important implications in the context of value-based care.

12.
Cell Metab ; 33(3): 457, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33657386

RESUMO

Oh et al. address concerns about the influence of proton pump inhibitor (PPI) use on a gut microbiome signature for cirrhosis. By removing PPI using subjects from the training cohort and retraining a 19-species Random Forest model, they demonstrate the impact of PPI usage on the signature's diagnostic accuracy is minimal.

13.
Aliment Pharmacol Ther ; 53(9): 1030-1037, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33764550

RESUMO

BACKGROUND: Magnetic resonance elastography (MRE) is a reliable non-invasive alternative to liver biopsy for assessing liver fibrosis. There are limited data regarding an association between liver fibrosis by MRE and risk of cardiovascular disease (CVD). AIM: To investigate the association of high-risk CVD phenotype determined by coronary artery calcification (CAC) with liver fibrosis by MRE in patients with non-alcoholic fatty liver disease (NAFLD). METHOD: This was a cross-sectional analysis of well-characterised, prospective cohorts including 105 patients with NAFLD (MR imaging-derived proton density fat fraction ≥ 5%) with contemporaneous cardiac computed tomography (CT) and MRE. Patients were assessed using MRE for liver stiffness, and cardiac CT for the presence of CAC (defined as coronary artery calcium score > 0). Odds of presence of CAC were analysed using logistic regression analysis. RESULTS: The average age and body mass index were 54.9 years and 32.9 kg/m2 respectively. In this cohort, 49.5% of patients had CAC and 35.2% had significant liver fibrosis (defined as MRE ≥2.97 kPa). Compared to patients without CAC, those with CAC were older (50.0 [39.0-59.0] vs 63.0 [55.5-67.5], P < 0.001) and had higher Framingham risk score (FRS, 1.0 [0.5-3.5] vs 6.0 [2.0-12.0], P < 0.001). In multivariable-adjusted analysis, liver stiffness as a continuous trait on MRE was independently associated with the presence of CAC in a sex and age-adjusted model (adjusted odd ratios [aOR] = 2.23, 95% confidence interval [CI] = 1.31-4.34, P = 0.007) as well as in a FRS-adjusted model (aOR = 2.16, 95% CI = 1.29-4.09, P = 0.008). When analysed as a dichotomous trait, significant fibrosis (MRE-stiffness ≥2.97 kPa) remained independently associated with the presence of CAC in both FRS-adjusted model and sex and age-adjusted model (aOR = 3.21-3.53, P = 0.013-0.017). In addition, CAC was more prevalent in patients with significant fibrosis than those without as determined by MRE (67.6% vs 39.7%, P = 0.012). CONCLUSION: Liver stiffness determined by MRE is an independent predictor for the presence of CAC in patients with NAFLD. Patients with NAFLD and significant fibrosis by MRE should be considered for further cardiovascular risk assessment, regardless of their FRS.


Assuntos
Doenças Cardiovasculares , Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos Transversais , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/epidemiologia , Imagem por Ressonância Magnética , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Estudos Prospectivos
15.
J Ultrasound Med ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33749862

RESUMO

OBJECTIVES: To develop and evaluate deep learning models devised for liver fat assessment based on ultrasound (US) images acquired from four different liver views: transverse plane (hepatic veins at the confluence with the inferior vena cava, right portal vein, right posterior portal vein) and sagittal plane (liver/kidney). METHODS: US images (four separate views) were acquired from 135 participants with known or suspected nonalcoholic fatty liver disease. Proton density fat fraction (PDFF) values derived from chemical shift-encoded magnetic resonance imaging served as ground truth. Transfer learning with a deep convolutional neural network (CNN) was applied to develop models for diagnosis of fatty liver (PDFF ≥ 5%), diagnosis of advanced steatosis (PDFF ≥ 10%), and PDFF quantification for each liver view separately. In addition, an ensemble model based on all four liver view models was investigated. Diagnostic performance was assessed using the area under the receiver operating characteristics curve (AUC), and quantification was assessed using the Spearman correlation coefficient (SCC). RESULTS: The most accurate single view was the right posterior portal vein, with an SCC of 0.78 for quantifying PDFF and AUC values of 0.90 (PDFF ≥ 5%) and 0.79 (PDFF ≥ 10%). The ensemble of models achieved an SCC of 0.81 and AUCs of 0.91 (PDFF ≥ 5%) and 0.86 (PDFF ≥ 10%). CONCLUSION: Deep learning-based analysis of US images from different liver views can help assess liver fat.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33711479

RESUMO

Nonalcoholic steatohepatitis (NASH) has emerged as one of the important causes of cirrhosis and hepatocellular carcinoma, and over 50 therapeutic agents are in various Phases of clinical development. Recently, obeticholic acid has achieved the interim histological endpoint of fibrosis improvement with no worsening of NASH in the phase 3 REGENERATE study, and now patients are being followed for long-term clinical outcomes. Several drugs are in Phase 3 trials with a goal to achieve conditional registration under the subpart H pathway by the United States Food and Drug Administration (FDA). It is thus timely to consider the current situation and the way ahead in the management of NASH. In this article, we review the natural history of nonalcoholic fatty liver disease, upcoming treatments for NASH and various assessments. Based on the current knowledge, we discuss what should be the target treatment population and whether non-invasive tests are ready to guide NASH treatments, both for patient selection and evaluation of treatment response.

18.
Cardiol Young ; : 1-5, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33622441

RESUMO

BACKGROUND: Manuscripts pertaining to paediatric cardiology and CHD have been published in a variety of different journals. Some of these journals are journals dedicated to paediatric cardiology, while others are focused on adult cardiology. Historically, it has been considered that manuscripts published in journals devoted to adult cardiology have greater citation potential. Our objective was to compare citation performance between manuscripts related to paediatric cardiology and CHD published in paediatric as opposed to adult cardiology journals. METHODS: We identified manuscripts related to paediatric cardiology and CHD published in five journals of interest during 2014. Of these journals, two were primarily concerned with adult cardiology, while the other three focused on paediatric cardiology. The number of citations for these identified manuscripts was gathered from Google Scholar. We compared the number of citations (median, mean, and 25th, 75th, 90th, and 95th percentiles), the potential for citation, and the h-index for the identified manuscripts. RESULTS: We identified a total of 828 manuscripts related to paediatric cardiology and congenital heart as published in the 5 journals during 2014. Of these, 783 (95%) were published in journals focused on paediatric cardiology, and the remaining 45 (5%) were published in journals focused on adult cardiology. The median number of citations was 41 in the manuscripts published in the journals focused on adult cardiology, as opposed to 7 in journals focused on paediatric cardiology (p < 0.001). The h-index, however, was greater for the journals dedicated to paediatric cardiology (36 versus 27). CONCLUSION: Approximately one-twentieth of the work relating to paediatric cardiology and CHD is published in journals that focus predominantly on adult cardiology. The median number of citations is greater when manuscripts concerning paediatric cardiology and CHD are published in these journals focused on adult cardiology. The h-index, however, is higher when the manuscripts are published in journals dedicated to paediatric cardiology. While such publications in journals that focus on adult cardiology tend to generate a greater number of citations than those achieved for works published in specialised paediatric cardiology journals, the potential for citation is no different between the journals. Due to the drastically lower number of manuscripts published in journals dedicated to adult cardiology, however, median performance is different.

20.
Abdom Radiol (NY) ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609166

RESUMO

PURPOSE: To evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF. METHODS: This was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests. RESULTS: The 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC < 1%, 50 (83%) achieved inter-exam RC < 1%, and all (100%) achieved MAE < 1%. Balanced sampling strategies had higher ICCs and lower RCs, and lower MAEs than unbalanced strategies in aggregate (p < 0.001 for comparisons between balanced vs. unbalanced strategies). CONCLUSION: Repeatability improves and error diminishes with more ROIs. Balanced 4-ROI strategies provide high repeatability and low error.

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