Chromosome microarray analysis should be offered to all invasive prenatal diagnostic testing following a normal rapid aneuploidy test result.

Chromosomal microarray analysis (CMA) has now replaced karyotyping in the analysis of prenatal cases with a fetal structural anomaly, whereas in those pregnancies undergoing invasive prenatal diagnosis with a normal fetal ultrasound, conventional karyotyping is still performed. The aims of this study were to establish the diagnostic yield of CMA in prenatal diagnosis, and to provide new data that might contribute to reconsider current practices. We reviewed 2905 prenatal samples with a normal rapid aneuploidy detection test referred for evaluation by CMA testing. Our study revealed pathogenic and reported susceptibility copy number variants associated with syndromic disorders in 4.8% (n = 138/2905) of cases, being 2.8% (n = 81/2905) the estimated added diagnostic value of CMA over karyotyping. Clinically significant CMA abnormality was detected in 5.4% (107/1975) of the fetuses with ultrasound anomalies and in 1.4% (5/345) of those considered as low-risk pregnancies. Our series shows that in prenatal samples, CMA increases 2-fold the diagnostic yield achieved by conventional karyotyping.

Unmasking the hidden tuberculosis mortality burden in a large post mortem study in Maputo Central Hospital, Mozambique.

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.TB was identified as the cause of death in 31 patients: three out of 54 (6%) children, five out of 57 (9%)maternal deaths and 23 out of 112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI 7.5-37.5) and the specificity was 97.4% (94.0-99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, Mycobacterium tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 (27.8%) cases had TB disease at death and 80 (35.9%) had TB findings.The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.

Multi-site performance evaluation and Sigma metrics of 20 assays on the Atellica chemistry and immunoassay analyzers.

Background The Atellica Solution comprises chemistry (CH) and immunoassay (IM) analyzers. Recently, six early adopter clinical laboratories across Europe evaluated the analytical performance of 20 CH and IM assays. To measure analytical performance quality, Sigma metrics were calculated for individual-site and pooled-site results. Methods Precision, detection capability, linearity, and method comparison studies were performed according to Clinical Laboratory Standards Institute protocols. Global Sigma metrics across sites were calculated from pooled data at the medical decision level using total allowable error (TEa) goals from CLIA for CH assays, and TEa goals from RiliBÄK for IM assays; and, the equation: Sigma metrics=%TEa-%bias/%CV. A pooled %CV was calculated by combining the imprecision obtained from individual sites. Bias calculations were performed against the ADVIA Chemistry system or ADVIA Centaur system using Deming regression analysis (Passing-Bablok regression for electrolytes) on the pooled-site data. The 103 individual-site Sigma metric calculations used individual-site imprecision and pooled-bias. Results The limits of blank and detection results agreed with the manufacturer's claims. Most assays were linear across the assay range tested. Pooled Sigma metrics were good or better (>4 Sigma) for 18 of 20 assays; and, acceptable for urea nitrogen (3.1) and sodium (3.9), the latter values attributable to higher imprecision at one of five sites. Conclusions Sigma metrics for data generated across multiple real-world sites evaluating the Atellica Solution demonstrated good or better performance of greater than 4 Sigma for 18 of 20 assays tested. Overall, results verified the manufacturer's claims that methods were fit for use in clinical laboratories.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl4-treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-ß1 (TGF-ß1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P < 0.05). The decrease of EndMT in cirrhotic livers correlated with a significant decrease in liver fibrosis (P < 0.05) and an improvement in the vascular disorganization rate (P < 0.05). We demonstrated the acquisition of the EndMT phenotype by a subpopulation of endothelial cells from cirrhotic livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization.NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-ß1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization.

Validation of Whole-Slide Imaging for Histolopathogical Diagnosis: Current State.

Rapid advances in informatics and technological improvements have led to the development of high-throughput whole-slide imaging (WSI) scanners able to produce high-quality digital images, which allow achieving a correct diagnosis of the biopsies using virtual viewers. This technology is currently prepared to be introduced in the departments of pathology for routine diagnosis. The aim of this review is to analyze the current evidence regarding the use of WSI in primary or routine diagnosis in the different subspecialties of pathology. An increasing number of studies have shown almost perfect inter- and intraobserver agreement between the diagnoses obtained with WSI and the classical diagnoses based on conventional light microscopy. The only exception seems to be cytology, which still requires some technological development. Although validation studies are needed in some areas of pathology, growing evidence indicates that WSI is a reliable tool for routine diagnosis. Pathologists have a positive perception of the ergonomics of the workstations, the low magnification of WSI and the possibility of making annotations and measurements. WSI can be used from any device and anywhere, thereby providing great opportunities for teleconsultation. New technologies such as the recognition of histopathology patterns using image analysis may facilitate diagnosis and improve the reproducibility among pathologists in the future.

Forms of Circulating Luteinizing Hormone Human Chorionic Gonadotropin Receptor for the Prediction of Early and Late Preeclampsia in the First Trimester of Pregnancy.

OBJECTIVE: To explore the value of circulating luteinizing human chorionic gonadotropin receptor (LHCGR) forms for the prediction of preeclampsia (PE) in the first trimester of pregnancy. METHODS: Case-control study, based on a cohort of 5,759 pregnancies, including 20 early PE, 20 late PE, and 300 controls. We recorded/measured maternal characteristics, mean arterial pressure (MAP), uterine artery (UtA) Doppler, placental growth factor (PlGF), soluble Fms-like tyrosine kinase-1 (sFtl-1), and LHCGR forms (hCG-LHCGR and soluble LHCGR), and their independent predictive values were analyzed by logistic regression. RESULTS: For early PE, the model included black ethnicity, chronic hypertension, previous PE, MAP, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, achieving detection rates (DR) of 83% at 10% of false-positive rates (FPR) [AUC: 0.961 (95% CI: 0.921-1)]. For late PE, the model included body mass index, previous PE, UtA Doppler, PlGF, sFlt-1, and LHCGR forms, with DR of 75% at 10% of FPR [AUC: 0.923 (95% CI: 0.871-0.976)]. In both early and late PE, LHCGR forms improved DR by 6-15%. CONCLUSIONS: LHCGR forms improved the prediction for early and late PE. These results should be confirmed in larger prospective studies.

The utility of circulating LHCGR as a predictor of Down's syndrome in early pregnancy.

BACKGROUND: Previous studies showed that soluble LHCGR/hCG-sLHCGR concentrations in serum or plasma combined with PAPP-A and free ßhCG significantly increased the sensitivity of Down's syndrome screen at early pregnancy without altering the false positive rate. The goal of the present study was to further examine the role of sLHCGR forms as combinatorial markers and to investigate whether sLHCGR could serve as an independent biomarker for Down's syndrome in first trimester pregnancy screens. METHODS: The PAPP-A, free ßhCG, and hCG-sLHCGR concentrations together with nuchal translucency (NT) were measured in 40 Down's and 300 control pregnancies. The sLHCGR concentration was analysed in 40 Down's and 206 control pregnancies. RESULTS: The hCG-LHCGR in combination with PAPP-A and free ßhCG increased the detection rate (DR) by 35% without altering the false positive rate (FPR). The sLHCGR: hCG-sLHCGR ratio alone detected 80% of Down's pregnancies in first trimester screening, with a false positive rate of 0.5%. CONCLUSIONS: While measurement of sLHCGR forms in combination with PAPP-A and free ßhCG significantly increases the detection rate of Down's syndrome at first trimester, the ratio of sLHCGR: hCG-sLHCGR acts as an independent marker with a detection rate that is significantly higher than the existing biochemical markers individually for prenatal first trimester screening of Down's syndrome.

Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.

Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5'fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

Introduction: The Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe. Materials and methods: Precision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer's cut-offs. Sample turnaround time (TAT) was examined. Results: Imprecision repeatability CVs were 1.1-4.7% and within-lab imprecision were 1.8-7.6% (10.0-25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer's values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV). Conclusions: Real-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer.

BACKGROUND: Both clinical and genomic data independently predict survival and treatment response in early-stage HER2-positive breast cancer. Here we present the development and validation of a new HER2DX risk score, and a new HER2DX pathological complete response (pCR) score, both based on a 27-gene expression plus clinical feature-based classifier. METHODS: HER2DX is a supervised learning algorithm incorporating tumour size, nodal staging, and 4 gene expression signatures tracking immune infiltration, tumour cell proliferation, luminal differentiation, and the expression of the HER2 amplicon, into a single score. 434 HER2-positive tumours from the Short-HER trial were used to train a prognostic risk model; 268 cases from an independent cohort were used to verify the accuracy of the HER2DX risk score. In addition, 116 cases treated with neoadjuvant anti-HER2-based chemotherapy were used to train a predictive model of pathological complete response (pCR); two independent cohorts of 91 and 67 cases were used to verify the accuracy of the HER2DX pCR likelihood score. Five publicly available independent datasets with >1,000 patients with early-stage HER2-positive disease were also analysed. FINDINGS: In Short-HER, HER2DX variables were associated with good risk outcomes (i.e., immune, and luminal) and poor risk outcomes (i.e., proliferation, and tumour and nodal staging). In an independent cohort, continuous HER2DX risk score was significantly associated with disease-free survival (DFS) (p=0·002); the 5-year DFS in the low-risk group was 97·4% (94·4-100·0%). For the neoadjuvant pCR predictor training cohort, HER2DX variables were associated with pCR (i.e., immune, proliferation and HER2 amplicon) and non-pCR (i.e., luminal, and tumour and nodal staging). In both independent test set cohorts, continuous HER2DX pCR likelihood score was significantly associated with pCR (p<0·0001). A weak negative correlation was found between the HER2DX risk score versus the pCR score (correlation coefficient -0·19). INTERPRETATION: The two HER2DX tests provide accurate estimates of the risk of recurrence, and the likelihood to achieve a pCR, in early-stage HER2-positive breast cancer. FUNDING: This study received funding from Reveal Genomics, IDIBAPS and the University of Padova.

Improved diagnosis of gastrointestinal infections using a semi-automated multiplex real-time PCR for detection of enteropathogens.

Introduction. The identification of enteropathogens is critical for the clinical management of patients with suspected gastrointestinal infection. The FLOW multiplex PCR system (FMPS) is a semi-automated platform (FLOW System, Roche) for multiplex real-time PCR analysis.Hypothesis/Gap Statement. FMPS has greater sensitivity for the detection of enteric pathogens than standard methods such as culture, biochemical identification, immunochromatography or microscopic examination.Aim.The diagnostic performance of the FMPS was evaluated and compared to that of traditional microbiological procedures.Methodology. A total of 10 659 samples were collected and analysed over a period of 7 years. From 2013 to 2018 (every July to September), samples were processed using standard microbiological culture methods. In 2019, the FMPS was implemented using real-time PCR to detect the following enteropathogens: Shigella spp., Salmonella spp., Campylobacter spp., Giardia intestinalis, Entamoeba histolytica, Blastocystis hominis, Cryptosporidum spp., Dientamoeba fragilis, adenovirus, norovirus and rotavirus. Standard microbiological culture methods (2013-2018) included stool culture, microscopy and immunochromatography.Results. A total of 1078 stool samples were analysed prospectively using the FMPS from July to September (2019): bacterial, parasitic and viral pathogens were identified in 15.3, 9.71 and 5.29 % of cases, respectively. During the same period of 6 years (2013-2018), the proportion of positive identifications using standard microbiological methods from 2013 to 2018 was significantly lower. A major significant recovery improvement was observed for all bacteria species tested: Shigella spp./enteroinvasive Escherichia coli (EIEC) (P <0.05), Salmonella spp. (P <0.05) and Campylobacter spp. (P <0.05). Marked differences were also observed for the parasites G. intestinalis, Cryptosporidium spp. and D. fragilis.Conclusion. These results support the value of multiplex real-time PCR analysis for the detection of enteric pathogens in laboratory diagnosis with outstanding performance in identifying labile micro-organisms. The identification of unsuspected micro-organisms for less specific clinical presentations may also impact on clinical practice and help optimize patient management.

Analytical performance assessment and improvement by means of the Failure mode and effect analysis (FMEA).

INTRODUCTION: Laboratories minimize risks through quality control but analytical errors still occur. Risk management can improve the quality of processes and increase patient safety. This study aims to use the failure mode and effect analysis (FMEA) to assess the analytical performance and measure the effectiveness of the risk mitigation actions implemented. MATERIALS AND METHODS: The measurands to be included in the study were selected based on the measurement errors obtained by participating in an External Quality Assessment (EQA) Scheme. These EQA results were used to perform an FMEA of the year 2017, providing a risk priority number that was converted into a Sigma value (σFMEA). A root-cause analysis was done when σFMEA was lower than 3. Once the causes were determined, corrective measures were implemented. An FMEA of 2018 was carried out to verify the effectiveness of the actions taken. RESULTS: The FMEA of 2017 showed that alkaline phosphatase (ALP) and sodium (Na) presented a σFMEA of less than 3. The FMEA of 2018 revealed that none of the measurands presented a σFMEA below 3 and that σFMEA for ALP and Na had increased. CONCLUSIONS: Failure mode and effect analysis is a useful tool to assess the analytical performance, solve problems and evaluate the effectiveness of the actions taken. Moreover, the proposed methodology allows to standardize the scoring of the scales, as well as the evaluation and prioritization of risks.

Optimisation of cardiac resynchronisation therapy device selection guided by cardiac magnetic resonance imaging: Cost-effectiveness analysis.

BACKGROUND: A recent study showed that the presence and characteristics of myocardial scar could independently predict appropriate implantable cardioverter-defibrillator therapies and the risk of sudden cardiac death in patients receiving a de novo cardiac resynchronisation device. DESIGN: The aim was to evaluate the cost-effectiveness of cardiac magnetic resonance imaging-based algorithms versus clinical practice in the decision-making process for the implantation of a cardiac resynchronisation device pacemaker versus cardiac resynchronisation device implantable cardioverter-defibrillator device in heart failure patients with indication for cardiac resynchronisation therapy. METHODS: An incidental Markov model was developed to simulate the lifetime progression of a heart failure patient cohort. Key health variables included in the model were New York Heart Association functional class, hospitalisations, sudden cardiac death and total mortality. The analysis was done from the healthcare system perspective. Costs (€2017), survival and quality-adjusted life years were assessed. RESULTS: At 5-year follow-up, algorithm I reduced mortality by 39% in patients with a cardiac resynchronisation device pacemaker who were underprotected due to misclassification by clinical protocol. This approach had the highest quality-adjusted life years (algorithm I 3.257 quality-adjusted life years; algorithm II 3.196 quality-adjusted life years; clinical protocol 3.167 quality-adjusted life years) and the lowest lifetime costs per patient (€20,960, €22,319 and €28,447, respectively). Algorithm I would improve results for three subgroups: non-ischaemic, New York Heart Association class III-IV and ≥65 years old. Furthermore, implementing this approach could generate an estimated €702 million in health system savings annually in European Society of Cardiology countries. CONCLUSION: The application of cardiac magnetic resonance imaging-based algorithms could improve survival and quality-adjusted life years at a lower cost than current clinical practice (dominant strategy) used for assigning cardiac resynchronisation device pacemakers and cardiac resynchronisation device implantable cardioverter-defibrillators to heart failure patients.

Monocyte Subsets Are Differently Associated with Infarct Size, Left Ventricular Function, and the Formation of a Potentially Arrhythmogenic Scar in Patients with Acute Myocardial Infarction.

To investigate the role of classical (CLM, CD14++CD16-), intermediate (INTM, CD14++CD16+), and non-classical (Non-CLM, CD14+CD16++) monocytes in scar formation after ST-elevation myocardial infarction (STEMI), evaluated with cardiac magnetic resonance (CMR). One hundred two patients with a first STEMI had serial blood analyses after 1, 3, and 7 days. A CMR was performed at 7 days and 6 months, depicting scar core (CO), border zone (BZ), and the presence of BZ channels. CLM and INTM levels progressively decreased, correlated with the scar mass, CO, and BZ at 7 days and 6 months (p < 0.05), and inversely with left ventricular ejection fraction (LVEF, p < 0.01). Non-CLM levels gradually increased, correlated with BZ mass and the presence of BZ channels at 7 days and 6 months (p < 0.001).CLM and INTM are associated with infarct size and inversely with LVEF, whereas Non-CLM are associated with BZ mass and the presence of potentially arrhythmogenic substrate.

A balanced scorecard for assessing a strategic plan in a clinical laboratory.

The Balanced Scorecard (BSC) is a tool for strategic management that is used in many companies and organizations worldwide, both in the public and private sector. With this purpose it has also been used in healthcare organizations and institutions but there are not many studies on the implementation of BSC methodology in the day-to-day clinical laboratory. This review shows the strategy for the development of a BSC, which includes theoretical perspective objectives, as well as some indicators and goals with which the monitoring and quantitative measurement of the achievements of a strategic plan in a clinical laboratory can be done. Moreover, the results of the indicators allow the prioritization of the initiatives to be implemented each year. The methodology for the development of the proposed BSC includes the following steps: definition of theoretical objectives of each of the perspectives most used in the management of a clinical laboratory (customers, financial, internal processes and learning) taking into account the vision and the organizational model of the laboratory; creation of a strategic map of perspective objectives; definition of the relevant indicators to follow up on the objectives in a quantitative manner and establishment of the goals. Whether or not the laboratory is a reference laboratory, in which specific and infrequent analysis and health population programs are performed, is another fact to take into account. In this review a BSC for a reference clinical laboratory of the Spanish public sector is shown.

Cost-effectiveness of enhanced liver fibrosis test to assess liver fibrosis in chronic hepatitis C virus and alcoholic liver disease patients.

AIM: To assess liver fibrosis (LF) in hepatitis C virus (HCV) and alcoholic liver disease (ALD), estimate health outcomes and costs of new noninvasive testing strategies. METHODS: A Markov model was developed to simulate LF progression in HCV and ALD for a cohort of 40-year-old men with abnormal levels of transaminases. Three different testing alternatives were studied: a single liver biopsy; annual Enhanced liver fibrosis (ELF™) followed by liver stiffness measurement (LSM) imaging as a confirmation test if the ELF test is positive; and annual ELF test without LSM. The analysis was performed from the perspective of a university hospital in Spain. Clinical data were obtained from published literature. Costs were sourced from administrative databases of the hospital. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In HCV patients, annual sequential ELF test/LSM and annual ELF test alone prevented respectively 12.9 and 13.3 liver fibrosis-related deaths per 100 persons tested, compared to biopsy. The incremental cost-effectiveness ratios (ICERs) were respectively €13400 and €11500 per quality-adjusted life year (QALY). In ALD, fibrosis-related deaths decreased by 11.7 and 22.1 per 100 persons tested respectively with sequential ELF test/LSM and annual ELF test alone. ICERs were €280 and €190 per QALY, respectively. CONCLUSION: The use of the ELF test with or without a confirmation LSM are cost-effective options compared to a single liver biopsy for testing liver fibrosis in HCV and ALD patients in Spain.

Identification of the potentially arrhythmogenic substrate in the acute phase of ST-segment elevation myocardial infarction.

BACKGROUND: Predicting sudden cardiac death risk in the first months after ST-segment elevation myocardial infarction (STEMI) remains challenging. OBJECTIVE: The purpose of this study was to investigate the ability of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) to identify the potentially arrhythmogenic substrate and its temporal evolution after STEMI. METHODS: One hundred consecutive patients with a first STEMI were included. Three-dimensional high-resolution LGE-CMR was obtained at 3 T on days 7 and 180. Left ventricular wall was segmented and characterized by pixel signal intensity algorithm in 5 layers from endocardium to epicardium. A 3-dimensional color-coded shell map was obtained for each layer, depicting scar core and border zone (BZ) distribution. Presence and characteristics of BZ channels were registered for each layer. RESULTS: At 180 days, left ventricular ejection fraction had improved significantly (from 46.7% ± 10% to 51.5% ± 10%; P <.001) and scar mass was reduced (from 22.6 ± 20 g to 13.8 ± 12 g; P <.001). Most BZ channels (89%) were identified in the same myocardial layer and American Heart Association (AHA) segment, with the same orientation and morphology in both studies. Early LGE-CMR had 96% sensitivity and 90% specificity for predicting presence of BZ channels at 180 days. Greater presence was observed in patients with no-reflow phenomenon at baseline (P = .01). CONCLUSION: Most BZ channels can be identified by LGE-CMR at day 7 post-STEMI and, despite scar mass reduction, remain unaltered at 6 months, suggesting that the potentially arrhythmogenic substrate is established within the first week post-STEMI.

Economic Impact of a New Rapid PCR Assay for Detecting Influenza Virus in an Emergency Department and Hospitalized Patients.

Seasonal influenza causes significant morbidity and mortality and has a substantial economic impact on the healthcare system. The main objective of this study was to compare the cost per patient for a rapid commercial PCR assay (Xpert® Flu) with an in-house real-time PCR test for detecting influenza virus. Community patients with influenza like-illness attending the Emergency Department (ED) as well as hospitalized patients in the Hospital Clínic of Barcelona were included. Costs were evaluated from the perspective of the hospital considering the use of resources directly related to influenza testing and treatment. For the purpose of this study, 366 and 691 patients were tested in 2013 and 2014, respectively. The Xpert® Flu test reduced the mean waiting time for patients in the ED by 9.1 hours and decreased the mean isolation time of hospitalized patients by 23.7 hours. This was associated with a 103€ (or about $113) reduction in the cost per patient tested in the ED and 64€ ($70) per hospitalized patient. Sensitivity analyses showed that Xpert® Flu is likely to be cost-saving in hospitals with different contexts and prices.

Utility of galectin-3 in predicting post-infarct remodeling after acute myocardial infarction based on extracellular volume fraction mapping.

AIMS: ST-segment elevation myocardial infarction (STEMI) triggers remote extracellular matrix expansion. Myocardial extracellular volume fraction (ECV), determined by cardiovascular magnetic resonance, permits quantification of interstitial space expansion. Our aim was to determine the relationship between early serum fibrosis biomarkers and 180-day post-infarct remote myocardium remodeling using ECV. METHODS AND RESULTS: In 26 patients with STEMI, functional imaging, T1-mapping, and late-gadolinium-enhancement were performed on a 3-T CMR scanner at baseline (days 3 to 5) and 180days. Biomarkers were measured at days 1, 3, and 7 after STEMI. The mean initial and follow-up left ventricular ejection fraction (LVEF) were 48.3±18.1% and 52.6±12.3%, respectively. Initial infarct size was 11.6±16.8% of LV mass. ECV in the remote myocardium at 180days correlated with indexed end-systolic volume (r=0.4, p=0.045). A significant correlation was observed between galectin-3 at day 7 and ECV at 6months (r=0.428, p=0.037). A trend towards a direct correlation was found for BNP (r=0.380, p=0.059). Multivariate analysis revealed that BNP and galectin-3 were independent predictors of long-term changes in ECV and explained nearly 30% of the variance in this parameter (r2=0.34; p=0.01). A galectin-3 cutoff value of 10.15ng/mL was the most powerful predictor of high ECV values (≥28.5%) at follow-up. Galectin-3 at day 7 was an independent predictor of high ECV values at follow-up (OR=22.51; CI 95%: 2.1-240.72; p=0.01) with 0.76 AUC (CI: 0.574-0.964; p=0.03). CONCLUSIONS: Galectin-3 measured acutely after STEMI is an independent predictor of increased ECV at 6-month follow-up that might be useful for long-term risk stratification.

Rapid Diagnosis of Staphylococcal Catheter-Related Bacteraemia in Direct Blood Samples by Real-Time PCR.

Catheter-related bacteremia (CRB) is an important cause of morbidity and mortality among hospitalized patients, being staphylococci the main etiologic agents. The objective of this study was to assess the use of a PCR-based assay for detection of staphylococci directly from blood obtained through the catheter to diagnose CRB caused by these microorganisms and to perform a cost-effectiveness analysis. A total of 92 patients with suspected CRB were included in the study. Samples were obtained through the catheter. Paired blood cultures were processed by standard culture methods and 4 ml blood samples were processed by GeneXpert-MRSA assay for the detection of methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci (MR-CoNS). Sixteen CRB caused by staphylococci were diagnosed among 92 suspected patients. GeneXpert detected 14 out of 16 cases (87.5%), including 4 MSSA and 10 MR-CoNS in approximately 1 hour after specimen receipt. The sensitivity and specificity of GeneXpert were 87.5% (CI 95%: 60.4-97.8) and 92.1% (CI 95%: 83-96.7), respectively, compared with standard culture methods. The sensitivity of GeneXpert for S. aureus was 100%. Regarding a cost-effectiveness analysis, the incremental cost of using GeneXpert was of 31.1€ per patient while the incremental cost-effectiveness ratio of GeneXpert compared with blood culture alones was about 180€ per life year gained. In conclusion, GeneXpert can be used directly with blood samples obtained through infected catheters to detect S. aureus and MR-CoNS in approximately 1h after sampling. In addition, it is cost-effective especially in areas with high prevalence of staphylococcal CRB.