Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease

BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.

Two approaches for calculating female fetal DNA fraction in noninvasive prenatal testing based on size analysis of maternal DNA fragments

The concentration of cell-free fetal DNA fragments should be detected before noninvasive prenatal testing(NIPT).The fetal DNA molecules have significant clinical potential in determining the overall performance of NIPT and clinical interpretation.It is important to measure fetal DNA fraction before NIPT.However,there is still little research on how to calculate the concentration of female fetuses.Two estimation approaches were proposed to calculate fetal DNA fraction,including the fragments size-based approach,aneuploid-based approach,which are all approaches based on chromosome segments.Based on high-throughput sequencing data,two approaches to calculate the DNA fraction of male fetuses were tested and obtained the experiment values,which were close to the actual values.The correlation coefficient of fragments size-based approach was 0.9243(P<0.0001)and the aneuploid-based approach reached 0.9339(P<0.0001).We calculated the concentration of female fetuses and obtained remarkable experimental results.We came up with two approaches for calculating the fetal DNA fraction of female fetuses.It provides an important theoretical basis for the detection of female fetal concentration in future clinical diagnosis.

Colorectal cancer screening:The value of early detection and modern challenges

The screening of colorectal cancer(CRC)is pivotal for both the prevention and treatment of this disease,significantly improving early-stage tumor detection rates.This advancement not only boosts survival rates and quality of life for patients but also reduces the costs associated with treatment.However,the adoption of CRC screening methods faces numerous challenges,including the technical limitations of both noninvasive and invasive methods in terms of sensitivity and specificity.Moreover,socioeconomic factors such as regional disparities,economic conditions,and varying levels of awareness affect screening uptake.The coronavirus disease 2019 pandemic further intensified these challenges,leading to reduced screening participation and increased waiting periods.Additionally,the growing prevalence of early-onset CRC necessitates innovative screening approaches.In response,research into new methodologies,including artificial intelligence-based systems,aims to improve the precision and accessibility of screening.Proactive measures by governments and health organizations to enhance CRC screening efforts are underway,including increased advocacy,improved service delivery,and international cooperation.The role of technological innovation and global health collaboration in advancing CRC screening is undeniable.Technologies such as artificial intelligence and gene sequencing are set to revolutionize CRC screening,making a significant impact on the fight against this disease.Given the rise in early-onset CRC,it is crucial for screening strategies to continually evolve,ensuring their effectiveness and applicability.

Multiparametric ultrasound as a new concept of assessment of liver tissue damage

Liver disease accounts for approximately 2 million deaths per year worldwide.All chronic liver diseases(CLDs),whether of toxic,genetic,autoimmune,or infectious origin,undergo typical histological changes in the structure of the tissue.These changes may include the accumulation of extracellular matrix material,fats,triglycerides,or tissue scarring.Noninvasive methods for diagnosing CLD,such as conventional B-mode ultrasound(US),play a significant role in diagnosis.Doppler US,when coupled with B-mode US,can be helpful in evaluating the hemodynamics of hepatic vessels and detecting US findings associated with hepatic decompensation.US elastography can assess liver stiffness,serving as a surrogate marker for liver fibrosis.It is important to note that interpreting these values should not rely solely on a histological classification.Contrast-enhanced US(CEUS)provides valuable information on tissue perfusion and enables excellent differentiation between benign and malignant focal liver lesions.Clinical evaluation,the etiology of liver disease,and the patient current comorbidities all influence the interpretation of liver stiffness measurements.These measurements are most clinically relevant when interpreted as a probability of compensated advanced CLD.B-mode US offers a subjective estimation of fatty infiltration and has limited sensitivity for mild steatosis.The controlled attenuation parameter requires a dedicated device,and cutoff values are not clearly defined.Quan-titative US parameters for liver fat estimation include the attenuation coefficient,backscatter coefficient,and speed of sound.These parameters offer the advantage of providing fat quantification alongside B-mode evaluation and other US parameters.Multiparametric US(MPUS)of the liver introduces a new concept for complete noninvasive diagnosis.It encourages examiners to utilize the latest features of an US machine,including conventional B-mode,liver stiffness evaluation,fat quantification,dispersion imaging,Doppler US,and CEUS for focal liver lesion characterization.This comprehensive approach allows for diagnosis in a single examination,providing clinicians worldwide with a broader perspective and becoming a cornerstone in their diagnostic arsenal.MPUS,in the hands of skilled clinicians,becomes an invaluable predictive tool for diagnosing,staging,and monitoring CLD.

Noninvasive Prenatal Testing for Fetal XXY Aneuploidies Among Pregnancies in Beijing of China

Objective:To evaluate the screening performance of noninvasive prenatal testing(NIPT)based on high-throughput massively parallel sequencing technology for the fetal XXY aneuploidies among pregnancies in Beijing of China.Methods:The study enrolled 26913 consecutive pregnancies,20-50 years old,who attended the Peking Union Medical College Hospital,Beijing,China,for prenatal screening from January 1,2016 to December 31,2019.Cell-free DNA was extracted from maternal peripheral blood to have a high-throughput massively parallel sequencing procedure.Cases with high-risk of fetal XXY were suggested to take invasive prenatal diagnosis(IPD)for confirmation.Maternal DNA sequencing was performed,if necessary,to find other potential factors that may lead to high-risk results of XXY by NIPT.Results:Among a cohort of 26913 pregnant women,34 were high-risk for fetal XXY,among which 30 accepted IPD while 4 declined.In those who accepted IPD,19 cases were confirmed fetal XXY by chromosome karyotyping analysis while 11 were verified as false positive.Among the 19 confirmed fetal XXY cases,14 elected pregnancy termination.For all the 34 high-risk cases,two were verified maternal sex chromosome aneuploidy.The calculated detection rate,positive predictive value,and false-positive rate of NIPT for fetal XXY in this cohort was 100.00%(19/19),63.33%(19/30),and 0.04%(11/26890),respectively.And the percentage of pregnancy termination was 73.68%(14/19).Conclusion:NIPT could be used as a potential method for fetal XXY screening,although the accuracy needs to be improved.As NIPT is not diagnostic,IPD is strongly recommended for those with high-risk results.For cases with discordance between NIPT and fetal karyotyping,maternal DNA sequencing would help to identify the cause of false-positive/false-negative results.

Prenatal Testing or Screening?

Over the past 50 years,the scope and extent of prenatal diagnosis and screening for genetic disorders have improved geometrically.There has been a pendulum like swing from testing to screening back and forth as new technologies emerge.The concurrent developments of cell free fetal DNA analysis of maternal blood has dramatically changed patient’s choices towards screening.However,with the use of array comparative genomic hybridization of fetal DNA that requires diagnostic procedures(Chorionic villus sampling and amniocentesis),much more extensive diagnosis can be obtained.Until noninvasive methods can replicate what can be done with diagnostic procedures there still will be a"price to be paid"for opting for the non-invasive methods.

A Cross-sectional Real-life Study of the Prevalence,Severity,and Determinants of Metabolic Dysfunction-associated Fatty Liver Disease in Type 2 Diabetes Patients

Background and Aims:Most data on liver assessment in type 2 diabetes mellitus(T2DM)patients are from retrospective cohorts with selection bias.We aimed at appraising the feasibility,results,and benefits of an outpatient systematic noninvasive screening for metabolic dysfunction-associated fatty liver disease(MAFLD)severity and determinants in T2DM patients.Methods:We conducted a 50-week crosssectional study enrolling adult T2DM outpatients from a diabetes clinic.An algorithm based on guidelines was applied using simple bioclinical scores and,if applicable,ultrasound and/or elastometry.Results:Two hundred and thirteen patients were included.Mean age and body mass index were 62 years and 31 kg/m^(2) and 29% of patients had abnormal transaminase levels.The acceptance rate of additional liver examinations was 92%.The prevalence of MAFLD,advanced fibrosis and cirrhosis was 87%,11%,and 4%,respectively.More than half of the cases of advanced fibrosis had not been suspected and were detected by this screening.MAFLD was associated with poor glycemic control,elevated transaminases,low HDL-C and the absence of peripheral arterial disease.Advanced fibrosis was linked to high waist circumference and excessive alcohol consumption,which should be interpreted with caution owing to the small number of patients reporting excessive consumption.Conclusions:Simple bioclinical tools allowed routine triage of T2DM patients for MAFLD severity,with high adherence of high-risk patients to subsequent noninvasive exams.