Relationship Between Gene-Phenotype and Clinical Manifestations of Chromosomal Copy Number Variations Indicated by Non-Invasive Prenatal Testing

Objective:To analyze the clinical value of non-invasive prenatal testing(NIPT)in detecting chromosomal copy number variations(CNVs)and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations.Methods:3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study.The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13,18,and 21.Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination.Interventional prenatal diagnosis and chromosome microarray analysis(CMA)were performed.The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed.Additionally,a follow-up was conducted by telephone to track fetal development after birth,at six months,and one year post-birth.Results:A total of 53 cases among 3551 cases showed chromosomal copy number variation.Interventional prenatal diagnosis was performed in 36 cases:27 cases were negative and 8 were consistent with the NIPT test results.This indicates that NIPT’s positive predictive value(PPV)in CNVs is 22.22%.Conclusion:NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications.However,further interventional prenatal diagnosis is still needed to identify fetal CNVs.

Effects of Continuous Non-Invasive Blood Pressure Monitoring on Intraoperative Hemodynamics and Postoperative Myocardial Injury in Craniotomy:Comparison Between Groups Based on Self-Control and Propensity Score Matching

Objective:To explore the effect of continuous non-invasive blood pressure monitoring on intraoperative hemodynamics and postoperative myocardial injury in craniotomy.Methods:120 cases of elective craniotomy were divided into the self-control group(continuous non-invasive blood pressure monitoring and intermittent cuff non-invasive blood pressure monitoring,CNAP group)and propensity score matching group(only intermittent cuff non-invasive blood pressure measurement in previous craniotomy,PSM group);Goal-directed hemodynamic management in CNAP group included heart rate(HR),blood pressure(BP),stroke volume(SV),stroke variability(SVV),and systemic vascular resistance index(SVRI).The main index is to compare the troponin level within 72 hours after operation between the CNAP group and the PSM group;The secondary indicators are the comparison of the hemodynamic conditions between the CNAP group and the PSM at 10 specific time points.Results:The incidence of postoperative myocardial injury in the CNAP group was significantly lower than that in the PSM group(12%vs.30%,P=0.01);in the CNAP group hypotensive episodes(6 vs.3,P=0.01),positive balance of fluid therapy(700 vs.500 mL,P<0.001),more use of vasoactive drugs(29 vs.18,P=0.04),more stable hemodynamics medical status(P=0.03)were recorded.Conclusion:The hemodynamic management strategy based on continuous non-invasive blood pressure monitoring can reduce the incidence of myocardial injury after elective craniotomy and maintain a more stable hemodynamic state.

Recent developments in non-invasive methods for assessing metabolic dysfunction-associated fatty liver disease

The prevalence of metabolic dysfunction-associated fatty liver disease(MAFLD)is increasing,affecting over one-third of the global population and contributing to significant morbidity and mortality.Diagnosing MAFLD,especially with advan-ced fibrosis,remains challenging due to the limitations of liver biopsy,the current gold standard.Non-invasive tests are crucial for early detection and management.Among these,the fibrosis-4 index(Fib-4)is widely recommended as a first-line test for screening for liver fibrosis.Advanced imaging techniques,including ultrasound-based elastography and magnetic resonance elastography,offer high accuracy but are limited by cost and availability.Combining biomarkers,such as in the enhanced liver fibrosis score and FibroScan-AST score,enhances diagnostic precision and is recommended to further stratify patients who are considered to be intermediate or high risk from the Fib-4 score.We believe that the future lies in the combined use of biomarkers to improve diagnostic accuracy.

Effects of rh BNP after PCI on non-invasive hemodynamic in acute myocardial infarction patients with left heart failure

Objective: To investigate the effects of exogenous recombinant human brain natriuretic peptide(rh BNP) after primary percutaneous coronary intervention(PCI) on non-invasive hemodynamic in acute myocardial infarction patients with left ventricular failure. Methods: A number of 96 acute myocardial infarction patients accompanied with heart failure after PCI hospitalized in the People's Hospital of Sanya during February 2012 to October 2015 were selected. They were randomly divided into the therapy group(n = 50) and control group(n = 46). On the basis of routine treatment, patients in the therapy group were treated with intravenous rh BNP(1.5 μg/kg was intravenous injection with uniform speed of 3 min, followed by continuous infusion 0.007 5 μg/kg·min for 72 h), while the control group received conventional treatment. Bio Z-2011 non-invasive hemodynamic real-time monitoring system was used to monitor the hemodynamic parameters changes and the leves of plasma pro-BNP, serum creatinine, serum potassium, serum sodium and urine volume of each group before and after treating for 30 min, 1 h, 3 h, 6 h, 12 h, 24 h, 48 h, 72 h. Results: Patients in the therapy group showed no effect on heart rate, while after 30 min of intravenous injection of rh BNP, CO, CI, SV, and SI increased significantly and LVET and TFC reduced at the same time, which had certain effect on blood pressure(SBP/DBP). Compared with the control group, the therapy group showed a faster and more effective improvement on haemodynamics. Conclusions: Acute myocardial infarction patients complicated with left heart failure after primary PCI can significantly improve hemodynamics by treating with rh BNP.

Non-invasive tests for the prediction of primary hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most common malignancies in the world and it is one of the main complications of cirrhosis and portal hypertension.Even in the presence of a well-established follow-up protocol for cirrhotic patients,to date poor data are available on predictive markers for primary HCC occurrence in the setting of compensated advanced chronic liver disease patients(cACLD).The gold standard method to evaluate the prognosis of patients with cACLD,beyond liver fibrosis assessed with histology,is the measurement of the hepatic venous pressure gradient(HVPG).An HVPG≥10 mmHg has been related to an increased risk of HCC in cACLD patients.However,these methods are burdened by additional costs and risks for patients and are mostly available only in referral centers.In the last decade increasing research has focused on the evaluation of several,simple,non-invasive tests(NITs)as predictors of HCC development.We reviewed the currently available literature on biochemical and ultrasound-based scores developed for the noninvasive evaluation of liver fibrosis and portal hypertension in predicting primary HCC.We found that the most reliable methods to assess HCC risk were the liver stiffness measurement,the aspartate aminotransferase to platelet ratio index score and the fibrosis-4 index.Other promising NITs need further investigations and validation for different liver disease aetiologies.

Declining diagnostic accuracy of non-invasive fibrosis tests is associated with elevated alanine aminotransferase in chronic hepatitis B

AIM To explore the effect of alanine aminotransferase(ALT) on the performance of non-invasive fibrosis tests in chronic hepatitis B(CHB) patients. METHODS A total of 599 treatment-naive and biopsy-proven CHB patients were included in the study. The cohort was divided into the following three groups: Normal ALT(ALT ≤ 40), slightly elevated ALT(40 < ALT ≤ 80) and elevated ALT(ALT > 80). The diagnostic performance of five common non-invasive fibrosis tests for liver fibrosis(stages S2-4), including the aspartate aminotransferase(AST)-to-platelet(PLT) ratio index(APRI), fibrosis index based on 4 factors(FIB-4), King's score, Forns index and gamma-glutamyl transpeptidase(GGT)-to-PLT ratio(GPR), were evaluated for each group. RESULTS Higher ALT levels were associated with higher non-invasive fibrosis test scores. Patients with the same fibrosis stage but higher ALT levels showed higher noninvasive test scores. The areas under the receiver operating characteristics curves(AUROCs) of the noninvasive tests for prediction of ≥ S2 were higher for patients with ALT ≤ 40 U/L(range 0.705-0.755) and 40 < ALT ≤ 80 U/L(range 0.726-0.79) than for patients with ALT > 80 U/L(range 0.604-0.701). The AUROCs for predicting ≥ S3 and S4 were higher in patients with ALT ≤ 40 U/L(range 0.736-0.814 for ≥ S3, 0.79-0.833 for S4) than in patients with 40 < ALT ≤ 80 U/L(range 0.732-0.754 for ≥ S3, range 0.626-0.723 for S4) and ALT > 80 U/L(range 0.7-0.784 for ≥ S3, range 0.662-0.719 for S4). The diagnostic accuracy of the non-invasive tests decreased in a stepwise manner with the increase in ALT.CONCLUSION ALT has a significant effect on the diagnostic performance of non-invasive fibrosis tests. The ALT level should be considered before performing these noninvasive tests.

Comparing a non-invasive hemodynamic monitor with minimally invasive monitoring during major open abdominal surgery

As part of the enhanced recovery after surgery （ERAS） protocol, the goal-directed fluid management with hemodynamic monitoring can effectively guide perioperative fluid use and significantly improve the outcomes in highrisk patients undergoing major surgeries. Several minimally invasive and non-invasive monitoring devices are commercially available for clinical use. As part of an internal evaluation, we reported the results from three different hemodynamic monitoring devices used in a patient undergoing a major abdominal surgery.

Evaluation of Non-Invasive Markers of Liver Fibrosis in Chronic Hepatitis B Patients in a Sub-Saharan African Setting: Transient Elastography versus APRI, FIB4, GTT/Platelet Scores

Background: Non-invasive markers which use routine laboratory tests are less expensive and highly needed to assess and stage liver fibrosis in chronic hepatitis B patients in Sub-Saharan Africa. We aimed at evaluating liver fibrosis, using the Aspartate aminotransferase to Platelet Ratio Index (APRI), Fibrosis Index Based on 4 factors (FIB4), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) in chronic hepatitis B patients with transient elastography as the reference so as to choose an alternative to transient elastography. Method: We carried out a cross-sectional study using the records of patients who attended the Douala General Hospital and Marie O Polyclinic Douala from 2012 to 2017. Non-invasive tests were compared with Transient Elastography. The Spearman coefficient was used to determine correlation. The sensitivity, specificity, positive predictive values and negative predictive values were used to get the optimal cut-off values. The diagnostic accuracy was estimated by calculating the area under the Receiver Operating Characteristic Curve (ROC). P Results: Of the 243 patient records studied, the median age or interquartile range (IQR) was 35 (29 - 42) years with a male predominance of 73.7%. More than 60% of the study population had normal transaminases. Significant fibrosis was found in 88 (36.2%) patients and 32 (13.7%) patients had cirrhosis. APRI had the best cut-off values and highest area under the ROC Curve, for significant fibrosis and cirrhosis with 0.55 (0.823 95% CI [0.769 - 0.869], P Conclusion: APRI, had the best diagnostic properties to detect liver fibrosis and cirrhosis in patients with Chronic Hepatitis B in Douala. The cut-off values are 0.55 and 0.65 for significant fibrosis and cirrhosis respectively.

Triple non-invasive diagnostic test for exclusion of common bile ducts stones before laparoscopic cholecystectomy

AIM: To evaluate the impact of a preoperative "triple non-invasive diagnostic test" for diagnosis and/or exclusion of common bile duct stones. METHODS: All patients with symptomatic gallstone disease, operated on by laparoscopic cholecystectomy from March 2004 to March 2006 were studied retrospectively. Two hundred patients were included and reviewed by using a triple diagnostic test including: patient's medical history, routine liver function tests and routine ultrasonography. All patients were followed up 2-24 mo after surgery to evaluate the impact of triple diagnostic test. RESULTS: Twenty-five patients were identified to have common bile duct stones. Lack of history of stones, negative laboratory tests and normal ultrasonography alone was proven to exclude common bile duct stones in some patients. However, a combination of these three components (triple diagnostic), was proven to be the most statistically significant test to exclude common bile duct stones in patients with gallstone disease. CONCLUSION: Using a combination of routinely used diagnostic components as triple diagnostic modality would increase the diagnostic accuracy of common bile duct stones preoperatively. This triple non-invasive test is recommended for excluding common bile duct stones and to identify patients in need for other investigations.

A Retrospective Analysis of Three Non-Invasive Tests for Initial Diagnosis of <i>Helicobacter pylori</i>Infection in Children

Proper diagnosis in the pediatric population is required to eradicate Helicobacter pylori (H. pylori) and prevent gastric cancer. Our aim was to assess the performance of non-invasive tests to diagnose H. pylori infection in pediatric patients. A retrospective analysis was performed on 141 pediatric patients requiring endoscopic evaluation and diagnostic tests for H. pylori infection to define the cause of abdominal symptoms. Non-invasive tests included the 13C-urea breath test (UBT), a monoclonal stool antigen test using enzyme-linked immuno-sorbent assay (mSAT), and a serum immunoglobulin G antibody test using antigens derived from Japanese individuals (S-Ab). This study investigated sensitivity, specificity, likelihood ratios for a positive and a negative test (LR+ and LR-), and accuracy of non-invasive tests, in comparison with invasive tests. Eighty two of 141 patients (58%) were recognized as H. pylori positive by invasive methods. When UBT, mSAT or S-Ab were analyzed, all were found to be effective over 94% accurate. Specificity ranged between 86.7% and 95.8%, and sensitivity ranged between 93.8% and 97.1%. When subjects were stratified into three distinct age groups, the best performance was achieved for 1-6 years old with mSAT at 100% for sensitivity, specificity, and accuracy. S-Ab yielded the best results for children 7-12 years old and the UBT test performed best for 13-18 years old. These results demonstrate the utility of UBT, mSAT, and S-Ab non-invasive tests in diagnosing H. pylori but suggest that certain tests may be optimal for children of distinct ages. Three non-invasive tests, UBT, mSAT and S-Ab showed sufficient sensitivity, specificity and accuracy for the initial diagnosis of H. pylori infection among pediatric patients. Non-invasive tests may contribute to achieving minimum invasive diagnosis with combining with a histological test and a culture test in children.

Non-invasive tests for predicting liver outcomes in chronic hepatitis C patients: A systematic review and meta-analysis

BACKGROUND Liver fibrosis leads to liver-related events in patients with chronic hepatitis C(CHC)infection.Although non-invasive tests(NITs)are critical to early detection of the development of liver fibrosis,the prognostic role of NITs remains unclear due to the limited types of NITs and liver outcomes explored in previous studies.AIM To determine the prognostic value of NITs for risk stratification in CHC patients.METHODS The protocol was registered in PROSPERO(International Prospective Register of Systematic Reviews;no.CRD42019128176).The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Search was performed using MEDLINE and EMBASE databases under a timeframe from the inception of the databases through February 25,2020.We restricted our search to CHC cohort studies reporting an association between liver fibrosis assessed by NITs and the development of hepatocellular carcinoma,decompensation,or mortality.Pooled hazard ratios(HR)and area under the receiver operating characteristic(AUROC)for each NIT were estimated using a random effects model.Subgroup analyses were performed for NITs assessed at pre-treatment or post-treatment with sustained virologic response(SVR),treatment with either pegylated interferon and ribavirin or direct acting antiviral,Eastern or Western countries,and different cutoff points.RESULTS The present meta-analysis included 29 cohort studies,enrolling 69339 CHC patients.Fibrosis-4(FIB-4)index,aspartate aminotransferase to platelet ratio(APRI)score,and liver stiffness measurement(LSM)were found to have hepatocellular carcinoma predictive potential with pooled adjusted HRs of 2.48[95%confidence interval(CI):1.91-3.23,I2=96%],4.24(95%CI:2.15-8.38,I2=20%)and 7.90(95%CI:3.98-15.68,I2=52%)and AUROCs of 0.81(95%CI:0.73-0.89,I2=77%),0.81(95%CI:0.75-0.87,I2=68%),and 0.79(95%CI:0.63-0.96,I2=90%),respectively.Pooled adjusted HR with a pre-treatment FIB-4 cutoff of 3.25 was 3.22(95%CI:2.32-4.47,I2=80%).Pooled adjusted HRs for post-treatment with SVR FIB-4,APRI,and LSM were 3.01(95%CI:0.32-28.61,I2=89%),9.88(95%CI:2.21-44.17,I2=24%),and 6.33(95%CI:2.57-15.59,I2=17%),respectively.Pooled adjusted HRs for LSM in patients with SVR following direct acting antiviral therapy was 5.55(95%CI:1.47-21.02,I2=36%).Pooled AUROCs for post-treatment with SVR FIB-4 and LSM were 0.75(95%CI:0.55-0.95,I2=88%)and 0.84(95%CI:0.66-1.03,I2=88%),respectively.Additionally,FIB-4 and LSM were associated with overall mortality,with pooled adjusted HRs of 2.07(95%CI:1.49-2.88,I2=27%)and 4.04(95%CI:2.40-6.80,I2=63%),respectively.CONCLUSION FIB-4,APRI,and LSM showed potential for risk stratification in CHC patients.Cutoff levels need further validation.

Discrepancy between non-invasive prenatal testing result and fetal karyotype caused by rare confined placental mosaicism: A case report

BACKGROUND Confined placental mosaicism(CPM)is one of the major reasons for discrepancies between the results of non-invasive prenatal testing(NIPT)and fetal karyotype analysis.CASE SUMMARY We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,who obtained a false-positive result on NIPT with a high risk for trisomy 21.Copy-number variation sequencing on amniotic fluid cells,fetal tissue,and placental biopsies showed that the fetal karyotype was 47,XXY,while the placenta was a rare mosaic of 47,XY,+21;47,XXY;and 46,XY.CONCLUSION The patient had a rare CPM consisting of 47,XY,+21;47,XXY;and 46,XY,which caused a discrepancy between the result of NIPT and the actual fetal karyotype.It is important to remember that NIPT is a screening test,not a diagnostic test.Any positive result should be confirmed with invasive testing,and routine ultrasound examination is still necessary after a negative result.

Comparison of next generation sequencing-based and methylated DNA immunoprecipitation-based approaches for fetal aneuploidy non-invasive prenatal testing

Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed.

Invasive and non-invasive diagnosis of cirrhosis and portal hypertension

With advances in the management and treatment of advanced liver disease,including the use of antiviral therapy,a simple,one stage description for advanced fibrotic liver disease has become inadequate.Although refining the diagnosis of cirrhosis to reflect disease heterogeneity is essential,current diagnostic tests have not kept pace with the progression of this new paradigm.Liver biopsy and hepatic venous pressure gradient measurement are the gold standards for the estimation of hepatic fibrosis and portal hypertension(PHT),respectively,and they have diagnostic and prognostic value.However,they are invasive and,as such,cannot be used repeatedly in clinical practice.The ideal noninvasive test should be safe,easy to perform,inexpensive,reproducible as well as to give numerical and accurate results in real time.It should be predictive of long term outcomes related with fibrosis and PHT to allow prognostic stratification.Recently,many types of noninvasive alternative tests have been developed and are under investigation.In particular,imaging and ultrasound based tests,such as transient elastography,have shown promising results.Although most of these noninvasive tests effectively identify severe fibrosis and PHT,the methods available for diagnosing moderate disease status are still insufficient,and further investigation is essential to predict outcomes and individualize therapy in this field.

Biomarkers for detecting colorectal cancer non-invasively: DNA,RNA or proteins?

Colorectal cancer(CRC)is a global problem affecting millions of people worldwide.This disease is unique because of its slow progress that makes it preventable and often curable.CRC symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this cancer.CRC screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are used.However,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic biomarkers.The main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome composition.Numerous tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically studied.While some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening techniques.Such DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening tools.It can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC screening.The combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC screening.However,continuing intense research in the area promises the emergence of new superior non-invasive CRC screening tests that will allow the development of improved disease prevention strategies.

无创血流动力学检测指标对心力衰竭易损期预后的预测价值

目的探讨无创血流动力学检测指标对心力衰竭易损期预后的预测价值。方法随机选取2021年11月至2022年11月于承德市中心医院住院的慢性心力衰竭患者85例,记录患者出院后3个月药物治疗、再就诊、再住院和死亡等情况。采用多因素logistic回归分析,分析影响心力衰竭易损期预后的因素。结果共完成随访85例患者,预后不良26例。预后不良组患者的左心室射血分数(LVEF)、心输出量(CO)、心脏指数(CI)、左心室做功(LCW)均低于预后良好组,差异有统计学意义(P<0.05);预后不良组患者的胸液水平(TFC)、外周阻力(SVR)高于预后良好组,差异有统计学意义(P<0.05)。其中LVEF、LCW、TFC是慢性心力衰竭易损期的预后预测因素(P<0.05)。结论无创血流动力学检测指标中LVEF、LCW、TFC是心力衰竭患者易损期重要的预测因素,对心力衰竭易损期的预后或可具有预测价值,对慢性心力衰竭患者临床治疗具有指导意义。

基于超声的家兔肾脏结构参数和血流动力参数研究

为探究正常家兔肾脏的超声影像学特征和血流动力学参数,筛选购买相同月龄,体重在2.5 kg左右的家兔30只,购进后对家兔进行检查,确保家兔未患有任何有关肾脏的疾病。实验前期对家兔进行为期1周的适应性饲养,每天喂养适量饲料,定期观察家兔的采食和精神状况。结果表明,家兔左右肾横断面肾脏形态参数测量结果无显著差异,健康成年家兔左右肾的三级动脉的各项血流参数无显著差异,健康成年家兔不同性别之间肾脏的三级动脉的各项血流参数无显著差异。结果提示,兔肾脏结构参数和血流动力参数左右肾以及雌雄动物之间进行T-检验分析差异不显著。

Clinical utility of non-invasive tests to predict clinical outcomes in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is the leading cause of chronic liver disease,and the fastest-growing cause of hepatocellular carcinoma(HCC)worldwide(1,2).As the number of people with NAFLD is too great to perform surveillance in all,risk-stratification strategies are increasingly important to identify those at the highest risk of decompensation and HCC(3,4).

Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in patients with chronic hepatitis C

BACKGROUND:The prognosis and clinical management of patients with chronic liver diseases are closely related to the severity of liver fibrosis.Liver biopsy is considered the gold standard for the staging of liver fibrosis.However,it is an invasive test sometimes related to complications.This study aimed to assess the diagnostic value of enhanced liver fibrosis(ELF) test to predict liver fibrosis in patients with chronic hepatitis C.METHODS:This study included 162 patients with liver disease and 67 healthy controls.Hyaluronic acid,tissue inhibitor of matrix metalloproteinase type 1,and amino-terminal propeptide type III procollagen were measured by enzymelinked immunosorbent assay with the ELF test ADVIA Centaur(Siemens Healthcare Diagnostics Inc.).Fibrosis stage was determined using the Metavir scoring system.RESULTS:In our study,for the diagnosis of significant fibrosis(Metavir F≥2) a cut-off value 】7.72 provides a sensitivity of 93.0% and a specificity of 83.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,93.3%,81.0%,93.3%,and 81.0%,respectively(P【0.001).For the diagnosis of cirrhosis(Metavir F=4) a cut-off value 】9.3 provides a sensitivity of 93.0% and a specificity of 86.0%.The areas under the receiver operator characteristic curve,sensitivity,specificity,and positive and negative predictive values were 0.94,79.1%,90.8%,75.6%,and 92.3%,respectively(P【0.001).CONCLUSIONS:The ELF test is a promising non-invasive method for assessing liver fibrosis in patients with chronic hepatitis C.It is effective in the diagnosis of both fibrosis and cirrhosis.

Nutrient drink test: A promising new tool for irritable bowel syndrome diagnosis

BACKGROUND Irritable bowel syndrome(IBS) is a highly prevalent condition. It is diagnosed on the basis of chronic symptoms after the clinical and/or investigative exclusion of organic diseases that can cause similar symptoms. There is no reproducible noninvasive test for the diagnosis of IBS, and this raises diagnostic uncertainty among physicians and hinders acceptance of the diagnosis by patients.Functional gastrointestinal(GI) syndromes often present with overlapping upper and lower GI tract symptoms, now believed to be generated by visceral hypersensitivity. This study examines the possibility that, in IBS, a nutrient drink test(NDT) provokes GI symptoms that allow a positive differentiation of these patients from healthy subjects.AIM To evaluate the NDT for the diagnosis of IBS.METHODS This prospective case-control study compared the effect of two different nutrient drinks on GI symptoms in 10 IBS patients(patients) and 10 healthy controls(controls). The 500 kcal high nutrient drink and the low nutrient 250 kcal drink were given in randomized order on separate days. Symptoms were assessed just before and at several time points after drink ingestion. Global dyspepsia and abdominal scores were derived from individual symptom data recorded by two questionnaires designed by our group, the upper and the general GI symptomquestionnaires, respectively. Psycho-social morbidity and quality of life were also formally assessed. The scores of patients and controls were compared using single factor analysis of variance test.RESULTS At baseline, IBS patients compared to controls had significantly higher levels of GI symptoms such as gastro-esophageal reflux(P = 0.05), abdominal pain(P =0.001), dyspepsia(P = 0.001), diarrhea(P = 0.001), and constipation(P = 0.001) as well as higher psycho-social morbidity and lower quality of life. The very low incidence of GI symptoms reported by control subjects did not differ significantly for the two test drinks. Compared with the low nutrient drink, IBS patients with the high nutrient drink had significantly more dyspeptic symptoms at 30(P =0.014), 45(P = 0.002), 60(P = 0.001), and 120 min(P = 0.011). Dyspeptic symptoms triggered by the high nutrient drink during the first 120 min gave the best differentiation between healthy controls and patients(area under receiver operating curve of 0.915 at 45 min for the dyspepsia score). Continued symptom monitoring for 24 h did not enhance separation of patients from controls.CONCLUSION A high NDT merits further evaluation as a diagnostic tool for IBS.