Noninvasive Test Results Research Articles

Feasibility of Tailored Unilateral Disconnection vs Callosotomy for Refractory Epilepsy in Patients with Bilateral Parieto-Occipital Gliosis Following Perinatal Insult.

Patients with perinatal hypoxia (PH) and drug-refractory epilepsy (DRE) often have bilateral parieto-occipital gliosis. Surgical management of such patients is a dilemma. To identify preoperative determinants for unilateral disconnection vs callosotomy, and analyze the surgical outcome in such patients. This was a retrospective analysis of patients with DRE and history of PH, with MRI abnormalities restricted to bilateral posterior quadrants. Preoperative semiology, epilepsy duration and seizure frequency were recorded. Based on the concordance between the results of non-invasive tests, patients underwent either posterior quadrant disconnection (PQD) or corpus callosotomy (CC). Preoperative variables were analyzed and corelated to the postoperative seizure freedom. Fourteen patients were identified, 6 underwent PQD and 8 underwent CC. At follow up of 39.17 ± 23.75 months, 66.66% of patients (4/6) in the PQD subgroup had an ILAE Class I outcome. While none in the CC group attained seizure freedom, 87.5% (7/8) had more than 50% reduction in seizure frequency (follow up: 42 ± 27.31 months). Patients with a poor outcome had significantly greater seizure frequency (P = 0.05) and history of drop attacks (P = 0.04) in both the groups. Magnetoencephalography (MEG) accurately localized the epileptogenic zone in all of the patients with good outcome (P = 0.015). Concordance with single photon emission tomography (SPECT) was also a predictor of favorable outcome (P = 0.041). A history of drop attacks with high seizure frequency is associated with poor postoperative seizure outcome. Unilateral PQD is feasible and leads to superior seizure-free outcomes, even in cases with widespread and bilateral imaging and electrical abnormalities, provided the other preoperative investigations are concordant in localizing the epileptogenic zone.

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

Noninvasive prenatal testing (NIPT) for fetal aneuploidy screening using cell-free DNA derived from maternal plasma can incidentally raise suspicion for cancer. Diagnostic routing after malignancy suspicious-NIPT faces many challenges. Here, we detail malignancy suspicious-NIPT cases, and describe the clinical characteristics, chromosomal aberrations, and diagnostic routing of the patients with a confirmed malignancy. Clinical lessons can be learned from our experience. Patients with NIPT results indicative of a malignancy referred for tumor screening between April 2017 and April 2020 were retrospectively included from a Dutch nationwide NIPT implementation study, TRIDENT-2. NIPT profiles from patients with confirmed malignancies were reviewed, and the pattern of chromosomal aberrations related to tumor type was analyzed. We evaluated the diagnostic contribution of clinical and genetic examinations. Malignancy suspicious-NIPT results were reported in 0.03% after genome-wide NIPT, and malignancies confirmed in 16 patients (16/48, 33.3%). Multiple chromosomal aberrations were seen in 23 of 48 patients with genome-wide NIPT, and a malignancy was confirmed in 16 patients (16/23, 69.6%). After targeted NIPT, 0.005% malignancy suspicious-NIPT results were reported, in 2/3 patients a malignancy was confirmed. Different tumor types and stages were diagnosed, predominantly hematologic malignancies (12/18). NIPT data showed recurrent gains and losses in primary mediastinal B-cell lymphomas and classic Hodgkin lymphomas. Magnetic resonance imaging and computed tomography were most informative in diagnosing the malignancy. In 231,896 pregnant women, a low percentage (0.02%) of NIPT results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high. Referral for extensive oncologic examination is recommended, and may be guided by tumor-specific hallmarks in the NIPT profile.

Presenting Symptoms in Patients Undergoing Coronary Artery Disease Evaluation: Association With Noninvasive Test Results and Clinical Outcomes in the PROMISE Trial.

Patients evaluated for coronary artery disease have a range of symptoms and underlying risk. The relationships between patient-described symptoms, clinician conclusions, and subsequent clinical management and outcomes remain incompletely described. In this secondary analysis, we examined the association between 4 types of presenting symptoms (substernal/left-sided chest pain, other chest/neck/arm pain, dyspnea, and other symptoms) and patient risk, noninvasive test results, clinical management, and outcomes for stable outpatients randomized in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Multivariable regression models were used to evaluate differences in noninvasive test result, all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/myocardial infarction by symptom type. Among 9996 patients, most presented with chest pain (47.2% substernal, 29.2% other), followed by dyspnea (14.9%), and other symptoms (8.7%). Patients with dyspnea were older (median age 63 versus 60, P≤0.02) with higher baseline risk (78.2% with atherosclerotic cardiovascular disease >7.5% versus 67.6%, P≤0.02). Using patients with substernal chest pain as a reference, there was no difference in noninvasive test positivity across symptom groups (all P>0.05), but test-positive patients with dyspnea (adjusted odds ratio, 0.66 [95% CI, 0.51-0.85]) or other symptoms (adjusted odds ratio, 0.65 [95% CI, 0.47-0.90]) were less likely to be referred for cardiac catheterization. While symptom type alone was not associated with outcomes, symptom presentation with chest pain or dyspnea did modify the association between a positive noninvasive test and clinical outcome (interaction P=0.025 for both all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/MI). Among low-risk outpatients evaluated for coronary artery disease, typicality of symptoms was not closely associated with higher baseline risk but was related to differences in processes of care and the prognostic value of a positive test. Adverse events were not associated with clinician risk estimates or symptoms alone. These unexpected findings highlight the limitation of relying solely on symptom presentation or clinician risk estimation to evaluate patients for suspected coronary artery disease. URL: https://www. gov; Unique identifier: NCT01174550.

Noninvasive prenatal testing of Duchenne muscular dystrophy in a twin gestation.

Haplotype-based assay has been proved efficient in noninvasive prenatal testing for various monogenic disorders in singleton pregnancies. However, its application in twin pregnancies is still blank. Here we provide a novel algorithmic approach to noninvasively assess fetal genotypes in a dizygotic twin pregnancy at risk for Duchenne muscular dystrophy (DMD). One pregnant woman carrying a dizygotic twin gestation was recruited as she was a heterozygote of DMD gene duplication and has delivered an affected son. Construction of parental haplotypes was achieved by target sequencing of DNA samples from the parent and the proband. Single nucleotide polymorphisms within target regions were classified into six categories according to parental haplotypes. Individual fetal fractions were calculated using paternal heterozygous. Maternal-inherited haplotype was deduced using relative haplotype dosage through a two-step Bayesian model. One male fetus with a lower fetal fraction of 4.6% and one female fetus with a higher fetal fraction of 10.1% were observed. The male fetus was predicted to be a DMD pathogenic variant carrier, while the female fetus was predicted to be homozygous normal. Noninvasive prenatal testing (NIPT) results were concordant with the findings of invasive prenatal diagnosis. This study is the first report of the use of NIPT for the assessment of DMD in a twin pregnancy. The algorithm provided could expand the use of NIPT to monogenic disorders in dizygotic twin pregnancies.

Retrospective analysis of the risk factors associated with failure in obtaining effective noninvasive prenatal test results and pregnancy outcomes: a case-control study

ABSTRACT Objective To explore the pregnancy outcomes of women who couldn't obtain effective results from noninvasive prenatal testing (NIPT) and examine the factors leading to test failure. Methods From April 2017 to December 2019, 120,041 pregnant women enrolled for voluntary NIPT. The case group comprised of 274 (274/120,041) women who failed to obtain effective NIPT results, and the control group (n = 540) was from the same population who obtained effective NIPT results and matched by age at a 1:2 ratio. Abnormal pregnancy rates between the two groups were analyzed using Chi-square analysis. NIPT failure risk factors were analyzed using logistic regression analysis. Results Logistic regression analysis showed that increased maternal age (OR = 0.988; 95% CI = 0.982–0.994), increased pregnancy age (OR = 0.989; 95%CI = 0.988–0.991), and decreased cell-free fetal DNA concentration (OR = 1.050; 95%CI = 1.043–1.058) were independent risk factors for NIPT failure. Fifteen cases showed fetus loss in cases of NIPT failure. There was a significant difference in abnormal pregnancy rate between the NIPT success and failure groups (χ2 = 50.943, P < 0.05). Expert commentary The specific interventions, guidance, and precautions are needed for pregnant women who have no effective NIPT results.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

A multivariate modeling method for the prediction of low fetal fraction before noninvasive prenatal testing.

To investigate factors associated with fetal fraction and to develop a new predictive method for low fetal fraction before noninvasive prenatal testing. The study was a retrospective cohort analysis based on the results of noninvasive prenatal testing, complete blood count, thyroxin test, and Down's syndrome screening during the first or second trimester in 14,043 pregnant women. Random forests algorithm was applied to predict the low fetal fraction status (fetal fraction < 4%) through individual information and laboratory records. The performance of the model was evaluated and compared to predictions using maternal weight. Of 14,043 cases, maternal weight, red blood cell, hemoglobin, and free T3 were significantly negatively correlated with fetal fraction while gestation age, free T4, pregnancy-associated plasma protein-A, alpha-fetoprotein, unconjugated estriol, and β-human chorionic gonadotropin were significantly positively correlated with fetal fraction. Compared to predictions using maternal weight as an isolated parameter, the model had a higher area under the curve of receiver operating characteristic and overall accuracy. The comprehensive predictive method based on combined multiple factors was more effective than a single-factor model in low fetal fraction status prediction. This method can provide more pretest quality control for noninvasive prenatal testing.

Approximation of the Ankle-Brachial Index in the Setting of Medial Arterial Calcific Sclerosis

The presence of medial arterial calcific sclerosis is known to cause inaccuracy in the interpretation of noninvasive vascular testing. This substantially limits the utility of an important baseline diagnostic test for peripheral arterial disease. Therefore, the objective of this investigation was to derive a method to effectively factor out calcification in the interpretation of the ankle and digital brachial indices. The noninvasive vascular testing results of 160 subjects were stratified into the absence of calcification, mild calcification, moderate calcification, and severe calcification based on plain film radiographic findings of the infrageniculate vessels. Measurements were then performed of the pulse volume recording (PVR) waveforms at brachial, ankle and digital anatomic levels to include PVR wavelength and PVR upstroke length, with a calculation of the ratio of PVR upstroke length to PVR wavelength. These measurements were compared between groups and then correlated to the ankle and digital brachial indices. A significant difference was observed in the PVR upstroke ratio between the 3 anatomic levels (0.1818 vs 0.2622 vs 0.3191; p < .001), but not between the 4 calcification groups (0.2457 vs 0.2363 vs 0.2694 vs 0.2631; p = .242). A significant negative correlation was observed between the PVR upstroke ratio and the ankle brachial index (ABI) (Pearson -0.454; p = .002) with linear regression indicating the relationship is defined by the formula: Effective ankle brachial index = 1.17 – (1.33 × PVR upstroke ratio at ankle level). A significant negative correlation was also observed between the PVR upstroke ratio and the digital brachial index (Pearson -0.553; p < .001) with linear regression indicating the relationship is defined by the formula: Effective toe brachial index = 1.04 – (1.61 × PVR upstroke ratio at digital level). The results of this investigation demonstrate the feasibility of, and provide equations to approximate, the effective ankle brachial and toe brachial indices in the setting of medial arterial calcification.

Results of non-invasive prenatal testing for 2473 women with twin pregnancy

To assess the value of non-invasive prenatal testing (NIPT) for the detection of fetal chromosomal aneuploidies in women with twin pregnancy. A total of 2473 women with twin pregnancy underwent the NIPT test to assess the risk for fetal chromosomal aneuploidies from January 2016 to September 2019. Those with a high risk by NIPT were confirmed by amniocentesis or chorionic villus sampling. All cases were followed up to evaluate the positive prediction value of NIPT for twin pregnancies. Among the 2473 women, the NIPT test has identified 31 cases (1.25%) with a high risk for fetal chromosomal aneuploidies, which included 5 cases of trisomy 21, 1 case of chromosome 21 deletion, 4 cases of trisomy 18, 7 cases of sex chromosome abnormality and 14 cases of microdeletion and microduplication. By invasive prenatal diagnosis or chromosomal karyotyping analysis of neonates, 5 cases of trisomy 21, 3 cases of trisomy 18, 1 case of sex chromosome abnormality, and 2 cases of microdeletion and microduplication were confirmed, which yielded a positive predictive value of 100%, 75%, 25% and 25%, respectively. NIPT can be used for the screening of fetal chromosomal aneuploidies in women with twin pregnancy with high accuracy. The method is non-invasive, safe and effective for the screening of fetal chromosomal aneuploidies, in particular trisomy 21.

Prevalence of microvascular angina among patients with stable symptoms in the absence of obstructive coronary artery disease: a systematic review.

Our purpose was to perform a systematic review to assess the prevalence of microvascular angina (MVA) among patients with stable symptoms in the absence of obstructive coronary artery disease (CAD). We performed a systematic review of the literature to group the prevalence of MVA, based on diagnostic pathways and modalities. We defined MVA using three definitions: (i) suspected MVA using non-invasive ischaemia tests; proportion of patients with non-obstructive CAD among patients with symptoms and a positive non-invasive ischaemia test result, (ii) suspected MVA using specific modalities for MVA; proportion of patients with evidence of impaired microvascular function among patients with symptoms and non-obstructive CAD, and (iii) definitive MVA; proportion of patients with positive ischaemia test results among patients with an objectified impaired microvascular dysfunction. We further examined the ratio of women-to-men for the different groups. Of the 4547 abstracts, 20 studies reported data on MVA prevalence. The median prevalence was 43% for suspected MVA using non-invasive ischaemia test, 28% for suspected MVA using specific modalities for MVA, and 30% for definitive MVA. Overall, more women were included in the studies reporting sex-specific data. The women-to-men ratio for included participants was 1.29. However, the average women-to-men ratio for the MVA cases was 2.50. In patients with stable symptoms of ischaemia in the absence of CAD, the prevalences of suspected and definitive MVA are substantial. The results of this study should warrant cardiologists to support, promote and facilitate the comprehensive evaluation of the coronary microcirculation for all patients with symptoms and non-obstructive CAD.

Stratification of Hepatocellular Carcinoma Risk Following HCV Eradication or HBV Control.

Hepatocellular carcinoma (HCC) incidence has dramatically decreased in patients infected with HCV and HBV due to the widespread use of highly effective antiviral agents. Nevertheless, a substantial proportion of patients with advanced fibrosis or cirrhosis following HCV clearance of in case of HBV control whatever the stage of fibrosis remains at risk of liver cancer development. Cancer predictors in these virus-free patients include routine parameters estimating coexisting comorbidities, persisting liver inflammation or function impairment, and results of non-invasive tests which can be easily combined into HCC risk scoring systems. The latter enables stratification according to various liver cancer incidences and allocation of patients into low, intermediate or high HCC risk probability groups. All international guidelines endorse lifelong surveillance of these patients using semi-annual ultrasound, with known sensibility issues. Refining HCC prediction in this growing population ultimately will trigger personalized management using more effective surveillance tools such as contrast-enhanced imaging techniques or circulating biomarkers while taking into account cost-effectiveness parameters.

Coronary Angiography: Indications, Results and Cost-Effectiveness in the Diagnosis of Stable Angina Pectoris in Two Hospitals in Senegal

Background: The current gold standard for the diagnosis of stable coronary artery disease (CAD) is invasive coronary angiography. But a large proportion of patients undergoing coronary angiography don’t have obstructive coronary artery disease. Objective: The aim of the present study was to evaluate the diagnostic performance of invasive coronary angiography for patients without known coronary artery disease presenting with stable chest pain syndrome at two hospitals structures in Senegal. Method: We conducted a prospective, descriptive, and analytical study from March 1, 2019, to December 31, 2020 in the Cardiology Departments of General Hospital Idrissa Pouye (HOGIP) and Aristide Le Dantec Hospital (HALD). During the study period a cohort of patients referred to angiography coronary for diagnostic CAD because of suspected stable angina were enrolled. Demographic characteristics, risk factors, symptoms, and noninvasive test results were correlated with the presence of obstructive coronary artery disease. Results: A total of 143 patients were included in our study with a median age of 60.91 ± 10.58 years; men were 96 (67.13%) and women 47 (32.87%). The prevalence of hypertension was 60.84%; diabetes was 34.27%; dyslipidemia was 32.17% and sedentary was 26.57% in our study population. Typical and atypical angina symptoms were present in 37.76% (n = 54) and 49.65% (n = 71) respectively, while 10.49% had dyspnea. Coronary angiography revealed 59 (41.26%) patients with no CAD as well as 27 (18.88%) with one-vessel; 28 (19.58%) with two-vessel, and 29 (20.28%) with three-vessel disease. Independent predictive factors for stable angina with the presence of obstructive lesion were: patient age (OR, 2.36; 95% CI, 1.05 - 5.29; p = 0.036); male gender (OR, 1.6; 95% CI, 0.72 - 3.57; p = 0.24); diabetes (OR, 2.14; 95% CI, 0.96 - 4.75; p = 0.06) and necrosis Q waves (4.75; CI, 0.98 - 23.09; p = 0.05). Conclusion: In our study, more than half of the patients (58.74%) referred for coronary angiography had a confirmed diagnosis. A better clinical and non-invasive assessment is needed to improve the efficiency of patient selection for coronary angiography.

Echocardiography and Nuclear Scintigraphy in the Diagnosis of Transthyretin Cardiac Amyloidosis.

A 94-year-old man presented with worsening dyspnea and orthopnea of 4 days' duration. Physical examination revealed jugular venous distention, diminished breath sounds, and pitting edema of the lower extremities. An electrocardiogram (Fig. 1) revealed conduction abnormalities, low QRS voltage, and an old myocardial infarction; a chest radiograph (Fig. 2) revealed cardiomegaly. These findings prompted us to obtain speckle-tracking echocardiograms (Figs. 3A–B), which revealed speckling of thickened myocardium, normal left ventricular (LV) size, biatrial enlargement, and a plethoric inferior vena cava. A strain imaging map (Fig. 3C) revealed relative apical sparing of LV function. Together, these findings raised suspicion of a restrictive cardiomyopathy, specifically amyloidosis. To confirm this diagnosis, we performed technetium-99m pyrophosphate (PYP) nuclear scintigraphy and serum immunoassays. The PYP nuclear scintigram was strongly positive for cardiac uptake of the radiotracer (Fig. 4), thus establishing the diagnosis of transthyretin cardiac amyloidosis. Serum protein electrophoresis (SPEP) revealed no monoclonal protein, and the serum free light chain (SFLC) ratio was normal.Identifying a specific cause of heart failure is important for both prognosis and treatment.1 An astute clinician recognizes the clinical, electrocardiographic, and echocardiographic signs of amyloidosis and performs other tests to confirm the diagnosis. Echocardiographic findings suggestive of amyloidosis include an LV wall thickness greater than 1.5 cm (also seen in hypertrophic cardiomyopathy but otherwise unusual, even in the presence of hypertension and aortic stenosis) and a characteristic “cherry on top” strain pattern (readily confirmed with current technology and more diagnostically sensitive and specific than wall thickness and speckling).2 Advanced testing can include cardiac magnetic resonance (CMR) imaging, nuclear scintigraphy, serum immunoassays, and endomyocardial biopsy. Although CMR is both sensitive and specific for cardiac amyloidosis, it cannot reliably distinguish between the light-chain and transthyretin subtypes.3 On the other hand, the combination of PYP nuclear scintigraphy,4 SPEP, and SFLC5 testing can distinguish between them, which is especially important in guiding treatment. Endomyocardial biopsy is reserved for cases in which noninvasive test results are inconclusive.

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Design of the Japanese Comprehensive Health-Economic Assessment for Appropriate Cardiac Imaging Strategy Including Outcome and Cost-Effectiveness in Stable Coronary Artery Disease Study (J-CONCIOUS).

Background: The evaluation of stable coronary artery disease (SCAD) has evolved, and contemporary clinical practice guidelines emphasize the importance of in-depth consideration of procedure indications, risk stratification, and results of non-invasive imaging tests. However, little is known about the appropriate selection of imaging modalities for ischemia evaluation and the comparative cost-effectiveness in real-world clinical practice.Methods and Results: The Japanese Comprehensive Health-Economic Assessment for Appropriate Cardiac Imaging Strategy including Outcome and cost-effectiveness in Stable Coronary Artery Disease Study (J-CONCIOUS), a multicenter observational study, was designed to prospectively enroll 2,500 patients with suspected or known SCAD, register clinical information and administrative records, and follow patients for 3 years. Any diagnostic or cardiac imaging modality (including stress tests using electrocardiography, echocardiography, or myocardial perfusion imaging; coronary computed tomographic angiography; and/or invasive coronary angiography with or without fractional flow reserve assessment) is acceptable. Clinical endpoints, such as all-cause mortality, cardiac death, and non-fatal myocardial infarction, will be obtained, along with quality of life assessment using the Seattle Angina Questionnaire. The cost-effectiveness of individual assessment patterns will be quantified by analysis of Diagnosis Procedure Combination (DPC) data, and quality-adjusted life years and the incremental cost-effectiveness ratio will be calculated.Conclusions: J-CONCIOUS is expected to establish a risk-based and cost-effective imaging strategy for the detection and evaluation of functional myocardial ischemia and/or anatomical coronary imaging in Japan.

Next-generation sequencing: a follow-up of 36,913 singleton pregnancies with noninvasive prenatal testing in central China

PurposeTo evaluate the noninvasive prenatal testing (NIPT) results of 36,913 cases in Jiangxi province of central China and explore its application value in prenatal screening and diagnosis.MethodsThis retrospective analysis included 36,913 singleton pregnant women who underwent NIPT because of moderate-/high-risk pregnancy or voluntary requirements between January 2017 and December 2019 in our hospital. Chromosomal abnormalities such as trisomies 21, 18, and 13 (T21, T18, T13) and sex chromosome aneuploidies (SCAs) were judged by standard Z-score analysis. Positive NIPT results were confirmed by amniocentesis and karyotyping. Pregnancy outcomes were followed up via telephone interview.ResultsA total of 1.01% (371/36,913) positive cases were detected by NIPT, comprising 137, 46, 31, and 157 cases of T21, T18, T13, and SCAs, respectively. A total of 116 of T21, 27 of T18, 13 of T13, and 51 of SCAs were confirmed to be true positive; all normal cases that had been followed up were verified to be true negative. The NIPT sensitivity in T21, T18, T13, and SCAs was 100.00% individually, whereas the specificity was 99.94% (36,488/36,509), 99.95% (36,579/36,598), 99.95% (36,594/36,612), and 99.72% (36,472/36,574), respectively. Furthermore, the negative predictive values of T21, T18, T13, and SCAs were all 100%, while the positive predictive values were 84.67%, 58.70%, 41.94%, and 33.33%, respectively.ConclusionNIPT is highly sensitive and has a low false positive rate in testing clinically significant fetal aneuploidies of general reproductive women. However, this technique cannot substitute for amniocentesis and karyotyping, and detailed genetic counseling is also essential for the high-risk group of NIPT.

Retrospective analysis of 44 578 pregnancies undergoing non-invasive prenatal testing in Weifang

To review the results of non-invasive prenatal testing (NIPT) for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), numerical aberration of sex and other autosomes and copy number variations with a size of >5 Mb. NIPT was carried out for 44 578 pregnant women. For those with a high-risk by NIPT, amniotic fluid or cord blood samples were collected for G-banding karyotype analysis, and the pregnancy outcome was followed up. Among the 44 578 pregnant women, 466 (1.05%) were diagnosed as high risk of T21 (n = 1359), T18 (n = 178) or T13 (n = 129). Among these, 301, 53 and 20 were subjected to prenatal diagnosis by amniocyte or umbilical blood karyotyping analysis, among which 289 were diagnosed as T21, 40 (75.47%) as T18, and 4 (20.00%) as T13. Among the high-risk pregnant women, 2 cases were diagnosed as Down syndrome after birth, while no trisomy 18 and trisomy 13 were recorded. The sensitivity and specificity of NIPT were T21 (99.31%, 99.97%), T18 (100%, 99.97%), T13 (100%, 99.96%), respectively. The positive predictive values for T21, T18 and T13 by NIPT were 96.01%, 75.47% and 20.00%, respectively. Compared with conventional serological screening and invasive prenatal diagnosis, NIPT has a high sensitivity and specificity for T21, T18 and T13, and has provided an ideal method to screen fetal chromosomal abnormalities.

Interpretation of noninvasive prenatal testing results following in vitro fertilization and preimplantation genetic testing for aneuploidy

The positive predictive value of noninvasive prenatal testing is approximately 69% in the general population. However, positive predictive value is dependent on the prevalence of the disease in the population being tested. Patients who undergo invitro fertilization with preimplantation genetic testing for aneuploidy and transfer a euploid embryo are presumably a lower risk population than the general population. In this study, we explored the positive predictive value of noninvasive prenatal testing in women undergoing invitro fertilization with preimplantation genetic testing for aneuploidy and subsequent transfer of a euploid embryo. This study was a retrospective cohort study. All patients who underwent invitro fertilization with preimplantation genetic testing for aneuploidy followed by transfer of a single euploid embryo between 2014 and 2019 at a university-affiliated fertility center were contacted. Noninvasive prenatal testing results were reviewed and those with positive noninvasive prenatal testing were identified. Results of any subsequent prenatal or postnatal diagnostic testing were used to classify each positive noninvasive prenatal testing as a true positive or a false positive. The prevalence and positive predictive value of positive noninvasive prenatal testing was calculated. A total of 1139 patients that underwent noninvasive prenatal testing after transfer of a euploid embryo were identified, 8 of which had positive noninvasive prenatal testing screens. Although 6 of these patients had subsequent definitive prenatal diagnostic testing that revealed a euploid karyotype concordant with their preimplantation genetic testing for aneuploidy results, 1 patient opted out of diagnostic testing and later delivered a normal baby. Of note, 1 patient who had noninvasive prenatal testing positive for Turner syndrome underwent amniocentesis, which confirmed Turner mosaicism (45,X karyotype in 80% of cells). Therefore, the positive predictive value of noninvasive prenatal testing in this patient cohort was 12.5%. Clinicians and patients should recognize that patients undergoing transfer of a euploid embryo are at a relatively lower risk for fetal aneuploidy than the general population, and the positive predictive value of noninvasive prenatal testing is lower in this setting.

Uveal Melanoma Biopsy. A Review

In intraocular tumors, diagnosis is usually based on clinical examination and imaging without the need for invasive surgery or tissue sampling. The diagnosis can be confirmed by biopsy, however, in the case of intraocular malignancy, the biopsy is considered controversial. Due to the development of uveal melanoma cytogenetic prognostics and the progression in generalised uveal melanoma treatment, intraocular melanoma biopsy is becoming increasingly important. Diagnostic biopsy of intraocular tumors is indicated in cases of diagnostic uncertainty for findings with conflicting non-invasive test results and for small melanocyte lesions. Tumor prognostic biopsy is performed to obtain a tissue sample for tumor cytogenetic testing, which can help to determine the prognosis and specific metastatic risk of the patient. For anterior segment tumors, anterior chamber fluid sampling, thin-needle iris biopsy, punch biopsy, surgical biopsy or biopsy using vitrectomy may be used. For posterior segment tumors, procedures include transscleral or transretinal thin-needle biopsy, vitrectomy-assisted biopsy, punch biopsy, endoresection or transscleral exoresection. Complications of intraocular melanoma biopsy include too small or non-valuable sample collection, intra-tumoral heterogeneity, intra-ocular trauma and induction of intraocular or extraocular tumor dissemination.

Outcome of the fetuses with severely increased nuchal translucency thickness in the first trimester.

To study the outcome of pregnancies with severely increased nuchal translucency (NT) thickness at the 11-13-week scan. This study included 162 singleton pregnancies whose fetuses had increased NT thickness ≥ 5.5 mm between September 2013 and August 2018. The cases were divided into two groups: NT ≥ 6.5 mm (n = 112) (group A); and 6.5 mm > NT ≥ 5.5 mm (n = 50) (group B). Fetal (amniotic fluid) or placental (chorionic villous) chromosome analyses were conducted. Subsequent ultrasound findings, pregnancy outcome and structural defects in the neonates were recorded and analyzed. Abnormal karyotype was found in 71% (60/84) (group A) and 57% (21/37) (group B) of the cases respectively. In group A, 15 cases out of 24 with normal karyotype were born. Among these 15 cases, one case died soon after birth and 5 cases had associated abnormalities. In group B, 13 cases out of 18 with normal karyotype or negative noninvasive prenatal testing results and 1 case out of 2 cases with 47,XXY were born. All of them survived with no major anomaly. Incidence of chromosomal aberrations was high in the cases with severely increased NT thickness. But favorable outcome could be expected if the fetus had no chromosomal abnormality and no abnormal findings were found in second trimester ultrasound scan especially in a fetus with increased NT < 6.5 mm.