Noninvasive Test Results Research Articles

Is intermediate risk really intermediate? Comparison of karyotype and non-invasive prenatal testing results of pregnancies at intermediate risk of trisomy 21 on maternal serum screening.

The purpose of this study was to assess the additional contribution of karyotyping compared with genome-wide non-invasive prenatal testing (NIPT) for pregnancies at intermediate risk for trisomy 21 (T21), calculated using the maternal serum screening without major structural anomalies detected through sonography. Karyotype results of all pregnancies undergoing invasive prenatal diagnostic testing between January 2013 and March 2022 were obtained from a large hospital-based laboratory. Pregnancies with no major structural anomalies on ultrasound (including soft markers) and an intermediate risk for T21 on maternal serum screening were included in this study. The additional contribution of karyotyping for abnormal karyotype results was calculated after excluding results that could theoretically be identified with genome-wide NIPT. Among the 511 pregnancies analyzed, 13 (2.54%) were found to have abnormal karyotype results, 9 (1.76%) of which could theoretically have been detected with genome-wide NIPT. Within the cohort, 6/263 (2.28%) of women aged 35 years and older, and 3/248 (1.20%) of women younger than 35 years had results that could have been detected with genome-wide NIPT. After excluding results detectable using genome-wide NIPT, the additional contribution of karyotyping was found as 4/502 (0.79%) for the entire cohort, 2/257 (0.77%) for women aged 35 years and older, 2/245 (0.81%) for women younger than 35 years. Of the 511 examined pregnancies at intermediate risk for T21 by maternal serum screening, genome-wide NIPT would have failed to detect 4 of 13 abnormal karyotype results. The findings hold importance in guiding couples' informed decision-making processes regarding their choice of genetic screening and diagnostic testing in case of intermediate risk for T21.

Hierarchical Classification of Factors Associated With Noninvasive Prenatal Testing Failures and Its Impact on Pregnancy Outcomes

Abstract Objective To conduct a hierarchical classification analysis of the nonreportable results of noninvasive prenatal testing in an attempt to reduce failure rates and provide pregnant women with accurate information to alleviate their anxiety. Methods In this study, 30,039 singleton pregnancies who underwent noninvasive prenatal testing in a single center from May 2019 to April 2022 were collected, and 811 samples with initial noninvasive prenatal testing failure were retrospectively analyzed. Grouping was based on the reasons for initial test failure; tracking the noninvasive prenatal testing results and prenatal diagnosis results (if any) of the “z-scores in the gray area” group and analyzing the possible influencing factors of the “low fetal fraction” group in the pre-experimental and experimental period by using one-way analysis of variance, Mann-Whitney U test, and χ2 test; and tracking the pregnancy outcomes of the test failures samples to analyze the risk of perinatal complications and adverse pregnancy outcomes of the different types of test failures. Results None of the samples' initial inconclusive results because of z-scores in the gray area were found to have chromosomal aneuploidy. However, pregnancy complications (P = 0.018) and a high likelihood of adverse pregnancy outcomes (P = 0.048) may still occur. Maternal gestational age (P < 0.001), body mass index (P < 0.001), library concentration (P < 0.001), and fetal gender (P < 0.001) were considered to be the associated factors for the initial low fetal fraction results. This may be associated with pregnancy complications (P < 0.001) and a high likelihood of adverse pregnancy outcomes (P = 0.034). The body mass index (P = 0.015) and time between draws (P = 0.001) were associated with the second test’s success. The incidence of low fetal fraction samples was more frequent with blood collection tubes of the G type than with the K type (P < 0.001). Conclusion Initial inconclusive results because of z-scores in the gray area did not imply an increased risk of aneuploidy, but vigilance is needed for an increased risk of pregnancy complications and adverse pregnancy outcomes. Because of the low fetal fraction, the initial absence of results may be related to the assay method, as well as the effect of blood collection tubes and the need to be alert to the risk of pregnancy complications and adverse pregnancy outcomes.

Importance of Kidney Biopsy in Interstitial Nephritis Caused by Mycobacterium Tuberculosis: A Case with Negative Noninvasive Test Results

Importance of Kidney Biopsy in Interstitial Nephritis Caused by Mycobacterium Tuberculosis: A Case with Negative Noninvasive Test Results

Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study

The author describes the results and implications of a study on noninvasive prenatal test results that indicate maternal malignancies.

Use of non-invasive diagnostic tools for metabolic dysfunction-associated steatohepatitis: A qualitative exploration of challenges and barriers.

Non-invasive tests (NITs) are underutilized for diagnosis and risk stratification in metabolic dysfunction-associated steatotic liver disease (MASLD), despite good accuracy. This study aimed to identify challenges and barriers to the use of NITs in clinical practice. We conducted a qualitative exploratory study in Germany, Italy, United Kingdom and United States. Phase 1 participants (primary care physicians, hepatologists, diabetologists, researchers, healthcare administrators, payers and patient advocates; n = 29) were interviewed. Phase 2 participants (experts in MASLD; n = 8) took part in a group discussion to validate and expand on Phase 1 findings. Finally, we triangulated perspectives in a hybrid deductive/inductive thematic analysis. Four themes hindering the use of NITs emerged: (1) limited knowledge and awareness; (2) unclear referral pathways for patients affected by liver conditions; (3) uncertainty over the value of NITs in monitoring and managing liver diseases; and (4) challenges justifying system-level reimbursement. Through these themes, participants perceived a stigma associated with liver diseases, and primary care physicians generally lacked awareness, adequate knowledge and skills to use recommended NITs. We identified uncertainties over the results of NITs, specifically to guide lifestyle intervention or to identify patients that should be referred to a specialist. Participants indicated an ongoing need for research and development to improve the prognostic value of NITs and communicating their cost-effectiveness to payers. This qualitative study suggests that use of NITs for MASLD is limited due to several individual and system-level barriers. Multi-level interventions are likely required to address these barriers.

CACS, CCTA and mCAD-LT score in the pre-transplant assessment of coronary artery disease and the prediction of post-transplant cardiovascular events.

The optimal cardiovascular assessment of liver transplant (LT) candidates is unclear. We aimed to evaluate the performance of CT-based coronary tests (coronary artery calcium score [CACS] and coronary CT angiography [CCTA]) and a modification of the CAD-LT score (mCAD-LT, excluding family history of CAD) to diagnose significant coronary artery disease (CAD) before LT and predict the incidence of post-LT cardiovascular events (CVE). We retrospectively analysed a single-centre cohort of LT candidates who underwent non-invasive tests; invasive coronary angiography (ICA) was performed depending on the results of non-invasive tests. mCAD-LT was calculated in all patients. Six-hundred-and-thirty-four LT candidates were assessed and 351 of them underwent LT. CACS, CCTA and ICA were performed in 245, 123 and 120 LT candidates, respectively. Significant CAD was found in 30% of patients undergoing ICA. The AUROCs of mCAD-LT (.722) and CCTA (.654) were significantly higher than that of CACS (.502) to predict the presence of significant CAD. Specificity of the tests ranged between 31% for CCTA and 53% for CACS. Among patients who underwent LT, CACS ≥ 400 and mCAD-LT were independently associated with the incidence of CVE; in patients who underwent CCTA before LT, significant CAD at CCTA also predicted post-LT CVE. In this cohort, mCAD-LT score and CT-based tests detect the presence of significant CAD in LT candidates, although they tend to overestimate it. Both mCAD-LT score and CT-based tests classify LT recipients according to their risk of post-LT CVE and can be used to improve post-LT risk mitigation.

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting

Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

Limited additional value of karyotyping cultured amniotic fluid cell colonies in addition to microarray on uncultured cells for confirmation of abnormal non-invasive prenatal testing results.

Non-invasive prenatal testing (NIPT) allows the detection of placental chromosome aberrations. To verify whether the fetus also has the chromosome aberration, diagnostic follow-up testing is required. The aim of this retrospective study was to assess the added value of analyzing amniotic fluid (AF) cell cultures in addition to uncultured AF cells for the detection of fetal mosaicism. NIPT was performed as part of the Dutch TRIDENT study. Cytogenetic studies in uncultured AF were performed using single nucleotide polymorphism (SNP)-array. Cultured AF cell colonies (in situ method) were investigated with fluorescent in situ hybridization and/or karyotyping. Clinical outcome data were collected in cases with discordant results. Between April 2014 and December 2021, 368 amniocenteses were performed after a chromosomal aberration was detected with NIPT. Excluding 134 cases of common aneuploidies (confirmed by quantitative fluorescence polymerase chain reaction), 29 cases with investigation of uncultured cells only and 1 case without informed consent, 204 cases were eligible for this study. In 196 (96%) cases, the results in uncultured and cultured cells were concordant normal, abnormal or mosaic. Five cases (2%) showed mosaicism in cultured AF cells, whereas uncultured AF cells were normal. Two (1%) of these, one mosaic trisomy 13 and one mosaic trisomy 16, were considered true fetal mosaics. The added value of investigating AF cell cultures in addition to uncultured cells is limited to two of 204 (1%) cases in which true fetal mosaicsm would otherwise be missed. The clinical relevance of one (trisomy 13) remained unknown and the other case also showed ultrasound anomalies, which determined pregnancy management. This seems to justify limiting prenatal cytogenetic confirmatory testing to SNP arrays on uncultured AF cells, considerably shortening the reporting time.

A Machine Learning Web App to Predict Diabetic Blood Glucose Based on a Basic Noninvasive Health Checkup, Sociodemographic Characteristics, and Dietary Information: Case Study.

Over the past few decades, diabetes has become a serious public health concern worldwide, particularly in Bangladesh. The advancement of artificial intelligence can be reaped in the prediction of blood glucose levels for better health management. However, the practical validity of machine learning (ML) techniques for predicting health parameters using data from low- and middle-income countries, such as Bangladesh, is very low. Specifically, Bangladesh lacks research using ML techniques to predict blood glucose levels based on basic noninvasive clinical measurements and dietary and sociodemographic information. To formulate strategies for public health planning and the control of diabetes, this study aimed to develop a personalized ML model that predicts the blood glucose level of urban corporate workers in Bangladesh. Based on the basic noninvasive health checkup test results, dietary information, and sociodemographic characteristics of 271 employees of the Bangladeshi Grameen Bank complex, 5 well-known ML models, namely, linear regression, boosted decision tree regression, neural network, decision forest regression, and Bayesian linear regression, were used to predict blood glucose levels. Continuous blood glucose data were used in this study to train the model, which then used the trained data to predict new blood glucose values. Boosted decision tree regression demonstrated the greatest predictive performance of all evaluated models (root mean squared error=2.30). This means that, on average, our model's predicted blood glucose level deviated from the actual blood glucose level by around 2.30 mg/dL. The mean blood glucose value of the population studied was 128.02 mg/dL (SD 56.92), indicating a borderline result for the majority of the samples (normal value: 140 mg/dL). This suggests that the individuals should be monitoring their blood glucose levels regularly. This ML-enabled web application for blood glucose prediction helps individuals to self-monitor their health condition. The application was developed with communities in remote areas of low- and middle-income countries, such as Bangladesh, in mind. These areas typically lack health facilities and have an insufficient number of qualified doctors and nurses. The web-based application is a simple, practical, and effective solution that can be adopted by the community. Use of the web application can save money on medical expenses, time, and health management expenses. The created system also aids in achieving the Sustainable Development Goals, particularly in ensuring that everyone in the community enjoys good health and well-being and lowering total morbidity and mortality.

Analysis of the results of non-invasive prenatal testing (NIPT) in 545 pregnant women in advanced maternal age.

This research aimed to explore the value of non-invasive prenatal testing (NIPT) as a prenatal screening method for common aneuploidy in pregnant women in advanced maternal age. A retrospective analysis was conducted on a cohort of 545 mothers with singleton pregnancy who were of advanced age and underwent NIPT testing voluntarily at the Second Affiliated Hospital of Guangxi Medical University between November 2020 and February 2023. In cases where NIPT testing suggested chromosomal abnormalities, amniocentesis was conducted, karyotype analysis or gene copy number variation (CNV) testing was performed, and the pregnancy outcome was tracked. Among 545 pregnant women in advanced maternal age, 11 cases had high risk of NIPT, and the detection rate was 2.02%. Among 11 pregnant women deemed to be at high risk for NIPT, 10 cases underwent amniotic fluid puncture, and one case refused amniocentesis despite a suggestive chromosomal abnormality in NIPT. The overall rate of amniocentesis was 1.83%. Among 11 pregnant women deemed to be at high risk for NIPT, the results suggested that 5 of them had trisomy 21, 1 had trisomy 18, 2 had sex chromosome abnormalities (specifically, 47, XYY), and 3 had other autosomal abnormalities. The positive predictive values of NIPT were 100.00% for the cases of trisomy 21 and trisomy 18, while the values were 0.00% for the cases of sex chromosome abnormalities and other autosomal abnormalities, respectively. After the follow-up, each of the 6 cases that were diagnosed with definite chromosomal abnormalities during prenatal screening opted to induce labor and terminate the pregnancy, including 5 cases that exhibited a high risk of trisomy 21 (47, XN,+21) and 1 case that showed a high risk of trisomy 18 (47, XN,+18). One instance of NIPT indicated a potential abnormality in the sex chromosomes, the individual declined to undergo amniocentesis. Another instance of NIPT suggested a sex chromosome abnormality, amniocentesis revealed a deletion of 0.72 Mb in the 4q22.1 region. They all had normal pregnancies and normal newborns. The remaining three cases had normal prenatal diagnoses (46, XN) and experienced normal pregnancies with healthy neonatal outcomes. NIPT has demonstrated its efficacy as a screening tool in the face of increasing maternal age. As a result, it can substantially decrease the requirement for invasive prenatal diagnosis. Nonetheless, there are instances of erroneous positive outcomes in NIPT testing, and therefore, interventional prenatal diagnosis remains necessary for individuals with high-risk screening outcomes to prevent false positives or unwarranted labor induction.

P-732 High degree of concordance between the genetic results of Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) and those obtained with analysis of the whole embryo

Abstract Study question What is the degree of concordance between Noninvasive Preimplantation Genetic Testing for Aneuploidies (NIPGT-A) versus genetic analysis of the whole embryo? Summary answer Cell free DNA ploidy evaluated by NIPGT-A presents very good concordance that of the DNA from whole embryo cells (Cohen's Kappa concordance coefficient: 0.84). What is known already After many years of using PGT-A, there are still many concerns, such as risks of invasive action and difficulties in the correct interpretation of mosaicism, which may lead to errors in the interpretation of false-positive and false-negative results. Recently, a new technology (NIPGT-A) has arisen using cell-free DNA present in the spent culture media of human blastocysts. However, there are still few genetic analyses of concordance between NIPGT-A and the whole embryo (gold standard). Study design, size, duration This cohort study included a total of 56 blastocysts vitrified on Day-5 that were previously biopsied for PGT-A. All embryos had a diagnosis of aneuploidy and were donated under informed consent by patients following the Human Medical Authority regulations. Blastocysts were thawed and cultured in 15µl drops of culture medium under oil. After their expansion(4-8 hours), the blastocysts and their corresponding spent media were transferred to PCR tubes and stored at -80 °C until analysis. Participants/materials, setting, methods DNA in all samples(spent culture medium and whole embryo) was amplified by MALBAC® technology(Yikon Genomics). The DNA concentration of the amplified product was measured using a Qubit 3.0Fluorometer(Thermo Fisher Scientific). The samples were subjected to next-generation sequencing (NGS) using the Illumina MiSeq® system. The ploidy status results obtained from ChromGoTM software(Yikon Genomics) for spent culture medium and the whole embryo were compared to determine the accuracy of NIPGT-A for screening chromosomal abnormalities in each embryo. Main results and the role of chance DNA from all 56 spent medium samples and whole embryos were successfully amplified. Comparing the results of NIPGT-A and whole-embryo sequencing (Table 1), the positive predictive value (PPV) was 93.5%, and the false-positive rate (FPR) was 6.5%. Agreement analysis showed very good coefficient concordance (Cohen's Kappa coefficient: 0.84).

The value of detailed first-trimester ultrasound in the era of noninvasive prenatal testing

In 2020, the American College of Obstetricians and Gynecologists recommended noninvasive prenatal testing be offered to all patients. However, current societal guidelines in the United States do not universally recommend a detailed first-trimester ultrasound. This study aimed to determine the additional findings identified through first-trimester ultrasound that would have otherwise been missed if noninvasive prenatal testing was used alone as a first-trimester screening method. This was a retrospective cohort study involving 2158 pregnant patients and 2216 fetuses that were seen at a single medical center between January 1, 2020, and December 31, 2022. All those included underwent both noninvasive prenatal testing and detailed first-trimester ultrasound between 11.0 and 13.6 weeks of gestation. Noninvasive prenatal testing results were categorized as low risk or high risk, and first-trimester ultrasound results were categorized as normal or abnormal. Abnormal first-trimester ultrasounds were further classified as first-trimester screening markers (increased nuchal translucency, absent nasal bone, tricuspid regurgitation, and ductus venosus reverse a-wave) or structural defects (the cranium, neck, heart, thorax, abdominal wall, stomach, kidneys, bladder, spine, and extremities). Descriptive statistics were used to report our findings. Of 2216 fetuses, 65 (3.0%) had a high-risk noninvasive prenatal testing result, whereas 2151 (97.0%) had a low-risk noninvasive prenatal testing result. Of those with a low-risk noninvasive prenatal testing result, 2035 (94.6%) had a normal first-trimester ultrasound, whereas 116 (5.4%) had at least 1 abnormal finding on first-trimester ultrasound. The most common screening marker detected within the low-risk noninvasive prenatal testing group was absent nasal bone (52/2151 [2.4%]), followed by reversed a-wave of the ductus venosus (30/2151 [1.4%]). The most common structural defect in this group was cardiac abnormality (15/2151 [0.7%]). Overall, 181 fetuses were identified as having "abnormal screening" through either a high-risk noninvasive prenatal testing result (n=65) or through a low-risk noninvasive prenatal testing result but abnormal first-trimester ultrasound (n=116). In summary, the incorporation of first-trimester ultrasound screening identified 116 additional fetuses (5.4%) that required further follow-up and surveillance than noninvasive prenatal testing alone would have identified. Detailed first-trimester ultrasound identified more fetuses with a potential abnormality than noninvasive prenatal testing alone. Therefore, first-trimester ultrasound remains a valuable screening method that should be used in combination with noninvasive prenatal testing.

Eosinophilic granulomatosis with polyangiitis - Advances in pathogenesis, diagnosis, and treatment.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by eosinophil-rich granulomatous inflammation and necrotizing vasculitis, pre-dominantly affecting small-to-medium-sized vessels. It is categorized as a primary antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) but also shares features of hypereosinophilic syndrome (HES); therefore, both vessel inflammation and eosinophilic infiltration are suggested to cause organ damage. This dual nature of the disease causes variable clinical presentation. As a result, careful differentiation from mimicking conditions is needed, especially from HES, given the overlapping clinical, radiologic, and histologic features, and biomarker profile. EGPA also remains a diagnostic challenge, in part because of asthma, which may pre-dominate for years, and often requires chronic corticosteroids (CS), which can mask other disease features. The pathogenesis is still not fully understood, however, the interaction between eosinophils and lymphocytes B and T seems to play an important role. Furthermore, the role of ANCA is not clear, and only up to 40% of patients are ANCA-positive. Moreover, two ANCA-dependent clinically and genetically distinct subgroups have been identified. However, a gold standard test for establishing a diagnosis is not available. In practice, the disease is mainly diagnosed based on the clinical symptoms and results of non-invasive tests. The unmet needs include uniform diagnostic criteria and biomarkers to help distinguish EGPA from HESs. Despite its rarity, notable progress has been made in understanding the disease and in its management. A better understanding of the pathophysiology has provided new insights into the pathogenesis and therapeutic targets, which are reflected in novel biological agents. However, there remains an ongoing reliance on corticosteroid therapy. Therefore, there is a significant need for more effective and better-tolerated steroid-sparing treatment schemes.

Application value of CNV-seq for the prenatal diagnosis of women with high-risk pregnancies

To assess the application value of copy number variation sequencing (CNV-seq) for women with a high risk for fetal anomalies. Based on the results of non-invasive prenatal testing (NIPT), 271 high-risk pregnant women were divided into NIPT positive group (n = 83) and other anomaly group (advanced age, high risk by serological screening, repeated NIPT failure, adverse pregnancy history, abnormal ultrasound finding, and abnormal phenotype) (n = 188). CNV-seq was carried out to detect copy number variations (CNVs) in amniocytic DNA from the two groups of pregnant women, and karyotyping analysis of the amniotic cells was carried out for verification and comparison. The amniocytes from 271 pregnant women were detected. The detection rate was 20.66% (56/271) for pathogenic CNVs by CNV-seq and 19.19% (52/271) for pathogenic karyotypes by karyotyping analysis. The difference was statistically significant (P < 0.05). CNV-seq had shown that, compared with NIPT positive group, the detection rates for likely pathogenic CNVs and variants of unknown significance (VUS) in other abnormality group were significantly higher [2.41%(2/83) vs. 5.32%(10/188)](P < 0.05). CNV-seq can well suit the first-tier diagnosis for pregnant women suspected for fetal abnormality. In prenatal diagnosis settings, CNV-seq can identify additional and clinically significant cytogenetic abnormalities. In those with other abnormalities, the detection rates for likely pathogenic CNVs and VUS are higher than with the NIPT positive cases.

QUALITY OF LIFE IN PATIENTS WITH CORONARY HEART DISEASE AND BRONCHIAL ASTHMA

The purpose of the paper is to estimate the quality of life in patients with coronary heart disease (CHD) and bronchial asthma, taking gender into account.&#x0D; Materials and methods. An open prospective clinical study included 60 patients with stable angina (Grade I-III) and bronchial asthma. The patients were divided into two groups according to their gender: group I consisted of 32 men, group II included 28 women. CHD was detected by diagnostic search algorithms (recommendations of the Russian Society of Cardiology for stable coronary heart disease, 2020). The results of non-invasive and invasive tests and the clinical features of a disease were also taken into account. Patients’ quality of life was estimated by SF-36 questionnaire. The authors used statistical analysis to process the obtained data.&#x0D; Results. Psychological and mental components of health were calculated by SF-36 questionnaire. Psychological distress was observed in both study groups equifrequently. Women’s physical activity was almost two times lower than that in men. Thus, health problems limited women’s daily activities more often.&#x0D; Conclusion. Physical health in patients with stable angina and bronchial asthma, assessed by SF-36 questionnaire, is significantly lower in women compared to men. At the same time, psychological distress, manifested by anxiety or depression, is observed in men and women equifrequently.

Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province

Objective: To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects. Methods: Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed. Results: (1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively. Conclusions: NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

S1345 Weight Loss Outcomes With and Without Diabetes in Patients With NAFLD in a Specialty Fatty Liver Disease Program

Introduction: Nonalcoholic fatty liver disease (NAFLD) is strongly linked to insulin resistance. As a result, type 2 diabetes mellitus (T2DM) is commonly comorbid in NAFLD and can increase morbidity and reduce weight loss treatment efficacy. We studied weight loss in adult NAFLD patients without and with T2DM (NAFLD-DM) receiving care in the Yale Fatty Liver Disease Program (YFLDP), which focuses on the integration of medical weight management treatments and hepatology care. Methods: We analyzed retrospective data for adult patients with diagnostic codes for NAFLD and T2DM with complete data on body weight and at least one clinic visit between 5/23/2018 and 5/02/2022. Patients were categorized as NAFLD or NAFLD-DM. Total body weight loss (WL) was quantified using 0%, 5%, and 10% thresholds. Between NAFLD and NAFLD-DM groups, we compared total body weight loss (WL) and across WL threshold groups, we also compared initial weights, follow-up time, medical interventions received, and results of non-invasive liver fibrosis tests. Results: There were 933 patients with NAFLD, of whom 463 (49.6%) had NAFLD-DM. After a median follow-up of 7.7 months, 632 (67.7%) of all patients achieved any weight loss. Significantly more patients with NAFLD-DM lost weight compared to NAFLD alone (73.9 vs 61.7%, p< 0.0001). Weight loss between NAFLD and NAFLD-DM groups varied, respectively: 0-5% WL: 34.7% vs. 34.8% (p=0.98); 5-10% WL: 13.2% vs. 19.2% (p=0.01), >10% WL: 13.8% vs. 19.9% (p=0.01). Compared to those not losing weight, NAFLD and NAFLD-DM patients with >10% WL had significantly greater proportion of participation in a complete meal replacement program (Optifast®) or treatment with GLP-1 agonist semaglutide. For NAFLD and NAFLD-DM groups, there was no significant difference between initial Fibroscan stiffness or FIB-4 index and subsequent WL percentages (Table). Conclusion: The majority of NAFLD and NAFLD-DM patients receiving care in a specialty clinic incorporating medical weight management with liver care successfully achieved weight loss in a relatively short period. Patients with NAFLD-DM did not have significantly worse outcomes with weight loss, and NAFLD-T2DM patients lost more weight than NAFLD patients. These findings suggest that an integrative care liver clinic with concurrent weight management care can help patients improve metabolic diseases associated with NAFLD, particularly T2DM, and in turn improve liver-related outcomes.Figure 1.: Comparison of Clinic Interventions between No Weight Loss (WL) versus >10% WL patients with NAFLD (top panel, a) and NAFLD-DM (bottom panel, b). *Statistically significant p-values using chi-square analysis, which can be found in Table Table 1. - Characteristics of and Clinical Interventions for NAFLD and NAFLD-DM Patients in the Yale Fatty Liver Disease Program (YFLDP). There was a significantly lower proportion of patients with NAFLD compared to NAFLD-DM who were able to achieve > 10% Weight Loss (13.8 vs. 19.9, p=0.014), and significantly more NAFLD patients compared to NAFLD-DM who did not achieve any weight loss (38.3 vs. 26.1, p<0.001) NAFLD (n=470 patients) NAFLD-DM (n=463 patients) Patient Categories n (%) No WL180 (38.3) >10% WL65 (13.8) p No WL121 (26.1) >10% WL92 (19.9) p Clinic Interventions n (%) Nutrition Consultation 80 (44.4) 31 (47.7) 0.652 58 (47.9) 40 (43.5) 0.518 OPTIFAST® Program 4 (2.2) 5 (7.7) 0.045 2 (1.7) 8 (8.7) 0.016 Naltrexone/Buproprion 6 (3.3) 5 (7.7) 0.146 16 (13.2) 6 (6.5) 0.111 Semaglutide 15 (8.3) 17 (26.2) < 0.001 30 (24.8) 37 (40.2) 0.016 Liraglutide 11 (6.1) 7 (10.8) 0.217 21 (17.4) 7 (7.6) 0.037 Phentermine 9 (5.0) 10 (15.4) 0.007 15 (12.4) 17 (18.5) 0.219 Bariatric Surgery Referral 13 (7.2) 5 (7.7) 0.901 21 (17.4) 31 (33.7) 0.006 Health Outcomes mean (SD) Follow-Up Time, days 256 (276.5) 422 (296.8) < 0.001 271 (280.2) 403 (297.3) 0.001 Initial FibroScan® Stiffness, kPa 8.63 (6.72) 13.18 (14.01) 0.663 13.18 (14.01) 12.48 (12.49) 0.701 Initial FIB-4 Score 1.32 (1.13) 1.70 (1.98) 0.068 1.70 (1.98) 1.83 (2.11) 0.648 Initial Weight, kg 93.82 (25.45) 102.20 (24.90) 0.015 102.20 (24.90) 109.61 (25.07) 0.056 *Denotes statistical significance p<0.05. WL = Weight Loss.

Cases of tetrasomy 9p and trisomy 9p in prenatal diagnosis-Analysis of noninvasive and invasive test results.

Objective: Tetrasomy 9p and trisomy 9p are rare chromosomal aberrations. The phenotypes of tetrasomy 9p and trisomy 9p are variable. Most cases are diagnosed in the postnatal period. The study aims to analyze the prenatal phenotype of tetrasomy 9p and trisomy 9p in terms of ultrasound and screening tests. Methods: A set of 1573 prenatal tests performed from 2016 to 2021 was reviewed to identify all cases with trisomy 9p and tetrasomy 9p. In four cases with 9p gain, non-invasive and invasive test results were analyzed. Results: Four cases with the 9p gain were diagnosed in the prenatal period: two cases with tetrasomy 9p and two cases with trisomy 9p. Nasal bone hypoplasia and ventriculomegaly are common features of 9p gain. In two out of four cases with the 9p gain, an increased risk of trisomy 21 was found in the combined first-trimester screening test. Conclusion: Trisomy 9p and tetrasomy 9p are characterized by a variable phenotype in the prenatal period, manifesting in genetically abnormal fetuses. The tetrasomy 9p and trisomy 9p may suggest trisomy 21 in the first trimester.

Ischemia With Nonobstructive Coronary Arteries: Insights From the ISCHEMIA Trial

BackgroundIschemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. ObjectivesThe authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. MethodsCore laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. ResultsAmong 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). ConclusionsAmong participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)

Combined Liver Stiffness and Α-fetoprotein Further beyond the Sustained Virologic Response Visit as Predictors of Long-Term Liver-Related Events in Patients with Chronic Hepatitis C.

Aims Long-term risk stratification using combined liver stiffness (LS) and clinically relevant blood tests acquired at the baseline further beyond the sustained virologic response (SVR) visit for chronic hepatitis C (CHC) has not been thoroughly investigated. This study retrospectively investigated the prognostics of liver-related events (LREs) further beyond the SVR visit. Methods Cox regression and random forest models identified the key factors, including longitudinal LS and noninvasive test results, that could predict LREs, including hepatocellular carcinoma, during prespecified follow-ups from 2010 to 2021. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results Of the entire eligible cohort (n = 520) of CHC patients with SVR to antiviral therapy, 28 (5.4%) patients developed post-SVR LREs over a median follow-up period of 6.1 years (interquartile range = 3.5–8.7). The multivariate Cox regression analysis identified two significant predictors of LREs after the year 3 post-SVR (Y3PSVR) baseline (LRE, n = 15 of 28, 53.6%, median follow-up = 4.1 [1.6–6.4] years after Y3PSVR): LS at Y3PSVR (adjusted hazard ratio [aHR] = 3.980, 95% confidence interval [CI] = 2.085–7.597, P < 0.001), and α-fetoprotein (AFP) at Y3PSVR (aHR = 1.017, 95% CI = 1.001–1.034, P=0.034). LS ≥1.45 m/s and AFP ≥3.00 ng/mL for Y3PSVR yielded positive likelihood ratios of 4.24 and 2.62, respectively. Kaplan–Meier analysis revealed that among the stratified subgroups, the subgroup with concurrent LS ≥1.45 m/s and AFP ≥3.00 ng/mL at Y3PSVR exhibited the highest risk of LREs after Y3PSVR (log-rank P < 0.001). Conclusion We recommend the combined use of concurrent LS and AFP in future prediction models for LREs in CHC. Patients with concurrently high LS and AFP values further beyond the SVR visit may require a recall policy involving intense surveillance.