Detection Rate Of Abnormalities Research Articles

Real-world genome profiling in Japanese patients with pancreatic ductal adenocarcinoma focusing on HRD implications.

Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges due to its high mortality, making it a critical area of research. This retrospective observational study aimed to analyze real-world data from comprehensive genome profiling (CGP) of Japanese patients with PDAC, mainly focusing on differences in gene detection rates among panels and the implications for homologous recombination deficiency (HRD) status. This study enrolled 2568 patients with PDAC who had undergone CGP between June 2019 and December 2021 using data from the nationwide Center for Cancer Genomics and Advanced Therapeutics database. Two types of CGP assays (tissue and liquid biopsies) were compared and a higher detection rate of genetic abnormalities in tissue specimens was revealed. HRD-related gene alterations were detected in 23% of patients, with BRCA1/2 mutations accounting for 0.9% and 2.9% of patients, respectively. Treatment outcome analysis indicated that patients with BRCA1/2 mutations had a longer time to treatment discontinuation with FOLFIRINOX than gemcitabine plus nab-paclitaxel as first-line therapy (9.3 vs. 5.6 months, p = 0.028). However, no significant differences were observed in the treatment response among the other HRD-related genes. Logistic regression analysis identified younger age and family history of breast, prostate, and ovarian cancers as predictive factors for HRD-related gene alterations. Despite the lack of progression-free survival data and the inability to discriminate between germline and somatic mutations, this study provides valuable insights into the clinical implications of CGP in Japanese patients with PDAC. Further research is warranted to optimize panel selection and elucidate the efficacy of platinum-based therapies depending on the HRD status.

ETDRS grading with CLARUS ultra-widefield images shows agreement with 7-fields colour fundus photography

BackgroundTo analyse and compare the grading of diabetic retinopathy (DR) severity level using standard 35° ETDRS 7-fields photography and CLARUS™ 500 ultra-widefield imaging system.MethodsA cross-sectional analysis of retinal images of patients with type 2 diabetes (n = 160 eyes) was performed for this study. All patients underwent 7-fields colour fundus photography (CFP) at 35° on a standard Topcon TRC-50DX® camera, and ultra-widefield (UWF) imaging at 200° on a CLARUS™ 500 (ZEISS, Dublin, CA, USA) by an automatic montage of two 133° images (nasal and temporal). 35° 7-fields photographs were graded by two graders, according to the Early Treatment Diabetic Retinopathy Study (ETDRS). For CLARUS UWF images, a prototype 7-fields grid was applied using the CLARUS review software, and the same ETDRS grading procedures were performed inside that area only. Grading of DR severity level was compared between these two methods to evaluate the agreement between both imaging techniques.ResultsImages of 160 eyes from 83 diabetic patients were considered for analysis. According to the 35° ETDRS 7-fields images, 22 eyes were evaluated as DR severity level 10–20, 64 eyes were evaluated as DR level 35, 41 eyes level 43, 21 eyes level 47, 7 eyes level 53, and 5 eyes level 61. The same DR severity level was achieved with CLARUS 500 UWF images in 92 eyes (57%), showing a perfect agreement (k > 0.80) with the 7-fields 35° technique. Fifty-seven eyes (36%) showed a higher DR level with CLARUS UWF images, mostly due to a better visualization of haemorrhages and a higher detection rate of intraretinal microvascular abnormalities (IRMA). Only 11 eyes (7%) showed a lower severity level with the CLARUS UWF system, due to the presence of artifacts or media opacities that precluded the correct evaluation of DR lesions.ConclusionsUWF CLARUS 500 device showed nearly perfect agreement with standard 35° 7-fields images in all ETDRS severity levels. Moreover, CLARUS images showed an increased ability to detect haemorrhages and IRMA helping with finer evaluation of lesions, thus demonstrating that a UWF photograph can be used to grade ETDRS severity level with a better visualization than the standard 7-fields images.Trial registrationApproved by the AIBILI - Association for Innovation and Biomedical Research on Light and Image Ethics Committee for Health with number CEC/009/17- EYEMARKER.

Genomic insights into prenatal diagnosis of congenital heart defects: value of CNV-seq and WES in clinical practice.

This study aimed to assess the efficiency of CNV-seq and WES in detecting genetic cause of congenital heart disease (CHDs) in prenatal diagnoses and to compare CNV detection rate between isolated and non-isolated CHD cases. We conducted a retrospective study of 118 Chinese fetuses diagnosed with CHD by prenatal ultrasound. Participants underwent CNV-seq and, if necessary, WES to detect chromosomal and single nucleotide variations. The overall detection rate for pathogenic or likely pathogenic chromosomal abnormalities was 16.9%, including 7.6% aneuploidies and 9.3% pathogenic/likely pathogenic copy number variations (CNVs), predominantly 22q11.2 deletion syndrome (54.4%). The sensitivity and specificity of CNV-Seq for detecting P/Lp CNVs were 95% and 100%, respectively. CNV-Seq offered a 6.7% improvement in detecting chromosomal abnormalities over karyotyping. WES further identified significant single nucleotide and small indel variations contributing to CHD in genes such as TMEM67, PLD1, ANKRD11, and PNKP, enhancing diagnostic yield by 14.8% in cases negative for CNVs. Non-isolated CHD cases exhibited higher rates of detectable chromosomal abnormalities compared to isolated cases (32.4% vs. 9.9%, p = 0.005), underlining the genetic complexity of these conditions. The combined use of CNV-seq and WES provides a comprehensive approach to prenatal genetic testing for CHDs, unveiling significant genetic cause that could impact clinical management and parental decision-making. This study supports the integration of these advanced genomic technologies in routine prenatal diagnostics to increase detection diagnostic yields of causal genetic variants associated with CHDs.

Whole exome sequencing analysis of 37 fetuses with cardiac abnormalities

To explore the genetic etiology of fetuses with congenital heart disease (CHD) through whole exome sequencing (WES). Thirty seven fetuses identified with CHD by prenatal ultrasonography but with negative results by chromosomal microarray analysis (CMA) at Jinhua Maternal and Child Health Care Hospital from January 2020 to June 2022 were selected as the study subjects, for whom WES was carried out. WES and Sanger sequencing had detected 6 pathogenic or likely pathogenic variants, and 6 variants with unknown clinical significance. The variants had involved 15 loci within 11 genes, in addition with one copy number variation. WES can increase the detection rate for genetic abnormalities among fetuses with CHD, which can facilitate the prenatal diagnosis, evaluation of prognosis and genetic counseling for the couples.

The Impact of Different Regions and Dietary Structures on Blood Glucose and Lipid Levels

<i>Objective: </i>To explore the effects of different regions and dietary structures on the blood glucose and lipid levels of residents. <i>Method: </i>1220 examinees from Fenyang City, Shanxi Province were selected as the research subjects and included in the study group. In addition, 1225 examinees from Xinjiang Communist Youth League Farm were selected as the control group 1, and 1200 examinees from Wujiaqu City, Xinjiang Uygur Autonomous Region (limited to regular physical labor and light diet) were selected as the control group 2. Collect general information such as the regional situation and dietary structure of personnel in each group, and use a fully automated biochemical analyzer to detect blood glucose (GLU) and lipid indicators (including total cholesterol (TC) and triglycerides (TG)). Compare the levels of the above indicators and the differences in the abnormal detection rates of each indicator in each group. <i>The results: </i>The levels of GLU, TC, and TG in the study group were significantly higher than those in control group 1 and control group 2 [GLU (mmol/L): 5.30±1.45 compared to 5.03±1.50, 4.18±0.39; TC (mmol/L): 1.67± 1.20 compared to 1.58±1.01, 0.69±0.36; TG (mmol/L): 5.02±1.71 compared to 4.72±1.17, 3.19±0.89], and the differences were statistically significant (all P<0.01). The abnormal detection rates of GLU, TC, and TG in the study group were significantly higher than those in the control group 1 and control group 2 (GLU: 18.43% compared to 13.64% and 2.00%, TC: 35.43% compared to 28.42% and 0.00%, TG: 14.05% compared to 5.63% and 0.00%), and the differences were statistically significant (all P<0.01). <i>Conclusion: </i>Regional differences and dietary structures are important factors affecting the blood sugar and lipid levels of residents. Balanced diet is beneficial for the stability of blood indicators and physical health of residents.

Umbilical Vein Flows and Cardiac Size, Shape, and Ventricular Contractility in Fetuses With Estimated Weight Less-Than 10th Centile.

In a cohort of patients with estimated fetal weights (EFWs) <10th centile, we aimed 1) to compare the prevalence of abnormalities of fetal 4-chamber view (4CV) cardiac size, shape, and ventricular contractility in fetal growth restricted (FGR) and small-for-gestational-age (SGA) fetuses and 2) to compare umbilical vein flow (UVF) measurements to standard Doppler surveillance in predicting abnormalities of cardiac function. Prospective observational cohort study of fetuses with EFW <10th percentile. Measurements of size and shape used were 4CV transverse width, 4CV cardiac area, 4CV global sphericity index, and right-to-left ventricular mid-chamber width ratio. Variables of contractility used were fractional shortening change at the mid-ventricle chamber, global longitudinal strain, fractional area change, and left ventricular cardiac output. The UVF and standard Doppler surveillance including umbilical artery (UA), middle cerebral artery, and cerebroplacental ratio (CPR) were collected. Control data were from previously published studies. A total of 95 fetuses with EFWs <10th centile were included in the study. The rates of abnormalities of cardiac size and shape and ventricular contractility were all significantly elevated compared with normally grown control fetuses but similar between FGR and SGA fetuses. In a subset of 76 patients with UVF data, evaluation UVF identified more patients with any abnormality of contractility compared with UA (37.9 vs 17.2%, P = .02). The addition of UVF doubled the detection rate of ventricular contractility abnormalities. The addition of UVF should be considered in the surveillance of FGR and SGA fetuses to further stratify the severity of hypoxemia and to identify those at greater risk for future cardiovascular dysfunction.

The influence of night shift work and associated factors on serum uric acid in aircraft maintenance workers

Background and objectiveThe prevalence of 12-hour shift work is increasing in various occupations. Shift work has been linked to circadian rhythm disruption, which may lead to hormonal changes and metabolic disorders, including alterations in glucose, lipid, and purine metabolism. Despite this, there is limited research on the potential connection between work shifts and abnormal serum uric acid (SUA) levels. Furthermore, the factors that contribute to abnormal SUA levels in shift workers are not well-understood. Therefore, this study aimed to analyze the SUA levels of shift workers employed in an aircraft maintenance company, investigate the potential association between shift work and SUA levels, and explore the factors that may influence abnormal SUA levels in shift workers.MethodsA total of 2263 male workers from an aircraft maintenance company were included in this study using the cluster sampling method. The workers were divided into two groups based on their working shifts: night shift (N = 1047, 46.27%) and day working (N = 1216, 53.73%). A survey was conducted between April 1st and June 30th, 2022 to gather information on work, lifestyle, physical examination results, and other relevant factors. The survey included a self-designed demographic information questionnaire to collect data on workers’ characteristics, medical history, years of employment, smoking and drinking habits, and main lifestyle behaviors. The workers’ SUA levels were measured using uricase colorimetry. One-way ANOVA was used to compare the difference in the abnormal detection rate of SUA between the two groups, and multi-factor logistic regression analysis was used to identify the factors that influence abnormal SUA levels.ResultsThe study indicated that 48.9% of night shift workers and 43.8% in the regular day workers had abnormal SUA levels, with a significant difference between the two groups (χ2 = 6.125, P = 0.013). Factors such as circadian rhythm type, shift work, age, the taste of diet, type of diet, smoking, overweight or obesity based on body mass index (BMI), concentration of urine creatinine (CREA), total cholesterol, triglyceride, and low-density lipoprotein cholesterol were found to be correlated with SUA abnormalities (P < 0.05). The risk of developing SUA abnormalities was found to be higher in individuals with an intermittent (OR = 1.34, 95% CI: 0.83–2.12, P < 0.05) or evening circadian rhythm type (OR = 1.45, 95% CI: 0.86–2.43, P > 0.05) compared to those with a morning type. Additionally, factors such as night shift work, a high-sodium diet, smoking, a diet high in meat and low in vegetables, being overweight or obese, and higher levels of CREA were also found to increase the risk of developing SUA abnormalities. The study also revealed a significant dose-response relationship between BMI and abnormal uric acid levels. After controlling for other factors, the risk of developing SUA abnormalities was found to be 1.18 times higher in the night shift work group than in the day work group (OR = 1.18, 95% CI:1.02–1.34, P = 0.01).ConclusionShift work has been linked to a higher risk of developing SUA abnormalities, and there are several factors that may contribute to this risk. To prevent diseases, it is recommended that enterprises implement better health monitoring and management practices for shift workers.

Analysis of the relationship between solar greenhouse operation and occupational high incidence diseases

Objective: To understand the health status of solar greenhouse workers, to provide scientific basis for the development of occupational high incidence diseases prevention and control strategies. Methods: In July 2019, a random cluster sampling method was used to select 245 workers engaged in solar greenhouse vegetable cultivation in Daba Village, Jingyuan County, Baiyin City, Gansu Province as the solar greenhouse operation group. Matched by gender, age, marital status, body mass index (BMI), 282 people from adjacent Shaliang Village who did not engage in solar greenhouse operation were selected as the control group. Field investigation and health examination were carried out among the study subjects. The general situation, facial features examination results, ophthalmic examination results, bone and joint examination results and skin examination results were compared between the two groups. And the multiple logistic regression analysis was used to analyze the influencing factors of abnormal bone and joint examination (upper limbs, lower limbs, hands and spine bone joints) in study subjects. Results: There were statistically significant differences in smoking age and alcohol consumption between the two groups (P<0.001). Compared with the control group, the abnormal detection rates of nose examination, throat examination, slit lamp examination, conjunctival examination, lower limb bone joint examination, hand bone joint examination, spine examination, head and neck skin examination, trunk skin examination, upper limb skin examination, and lower limb skin examination in the solar greenhouse operation group were higher, and the differences were statistically significant (χ(2)=11.53, 7.94, 9.92, 27.93, 79.32, 81.42, 9.43, 6.79, 9.76, 4.34, 8.29, P<0.05). Multivariate logistic regression analysis showed that after adjusting for gender, age, marital status, education level, BMI, compared with the control group, solar greenhouse operation was a risk factor for abnormal bone and joint examination (OR=1.178, 95%CI: 1.151-2.143, P=0.001) . Conclusion: Solar greenhouse operation has a certain harmful effect on health of workers, and solar greenhouse workers have an increased risk of abnormal diseases of upper limbs, lower limbs, hands and spine bone joints.

Chromosomal abnormalities detected by chromosomal microarray analysis and pregnancy outcomes of 4211 fetuses with high-risk prenatal indications

With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Cytoplasmic light-chain immunofluorescence combined with FISH in bone marrow smears to detect cytogenetic abnormalities in multiple myeloma

Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

First-trimester 3D fetal neurosonography: five standardised views

Background There are several international guidelines for foetal anomalies scanning at 11–14 weeks’ gestation. The aim of this study is to present our first-trimester specialist neurosonography protocol with examples of pathology in order to develop a systematic approach to evaluating the first-trimester foetal brain. Methods Women undergoing a first-trimester foetal medicine ultrasound scan between 2010 and 2020 for multiple indications underwent neurosonography according to a set protocol. 3D transvaginal brain examination was performed in all cases (2000 pregnancies scanned). We retrospectively reviewed all imaging to develop this protocol. Results We propose that the following five axial-plane parallel views should be obtained when performing neurosonography in the first trimester, moving from cranial to caudal: 1. Lateral ventricles; 2. Third ventricle; 3. Thalamus and mesencephalon; 4. Cerebellum; 5. Fourth ventricle. Examples of these images and abnormalities that can be seen in each plane are given. Conclusions We have presented a specialist protocol for systematically assessing the foetal brain in the first trimester and given examples of pathology which may be seen in each plane. Further work is needed to prospectively assess detection rates of major abnormalities using this protocol and assess the reproducibility and learning curve of this technique.

Evaluation the Application of Karyotype Analysis and Chromosome Microarray in Prenatal Diagnosis

Background: We aimed to compare the difference of the chromosomal abnormalities using karyotype analysis and chromosomal microarray (CMA) as well as to evaluate their application in different prenatal diagnosis indications. Methods: Overall, 3007 pregnant women with prenatal diagnosis indications from Medical Genetics Department of Linyi Women and Children’s Health Care Hospital, who underwent standard G-banded karyotype analysis and CMA, were enrolled from 2018-2022. G-banded karyotype analysis and CMA were undergone simultaneously. All fetuses with genetic variants were enrolled for further analyzing. The frequency and differences of chromosomal abnormalities of the two methods were compared in different prenatal diagnosis indications groups. Results: CMA improved 4.09% (123/3007) of genetic changes compared karyotype analysis. CMA is on par with karyotyping for detection of aneuploidies and gross unbalanced rearrangements. Serological screening and ultrasound abnormalities were the main indications of prenatal diagnosis. The detection rate of chromosomal abnormalities was highest in non-invasive prenatal testing (NIPT) abnormal group. In the ultrasound abnormality group, the detection rate of genetic variants in nuchal translucency (NT) increased group was higher than other subgroups and there was statistically significant difference in the detection rate of pCNVs. CMA can detect 5.57% (40/718) more genetic abnormalities in ultrasound abnormality group on the normal karyotype. CMA improved 0.67% (20/3007) of genetic changes with clinically significant compared karyotype, brought 3.42% (103/3007) of variants with uncertain significance (VOUS). Conclusion: CMA identified additional, clinically significant genetic variants on the basis of normal karyotype analysis, brought a proportion of unclear significant variants. All the pregnant women accepted amniocentesis should be informed about their characteristics of karyotype analysis and CMA by genetic counselors.

The genetics and clinical outcomes in 151 cases of fetal growth restriction: A Chinese single-center study

ObjectiveTo determine the detection rate of chromosomal abnormalities and pregnancy outcomes in fetuses with intrauterine growth restriction.Study designA total of 151 fetal samples with intrauterine growth restriction were divided into the isolated fetal growth restriction (FGR) group, FGR group with structural malformation, and FGR group with non-structural malformation, according to ultrasound abnormalities. The enrolled patients were divided into an early onset FGR group (<32 weeks) and a late-onset FGR group (≥32 weeks). Chromosomal karyotype and microarray analyses were performed and pregnancy outcomes were monitored.ResultsThe karyotypes of 122 patients were analyzed. Four patients exhibited abnormal chromosome numbers or structures. Variations in copy number were detected in 151 cases; 19 cases were found to have chromosomal abnormalities, with a positivity rate of 12.6 %. There was one trisomy in 18 cases, one trisomy in 21 cases, eight pathogenic copy number variations (CNVs), and nine CNVs of unknown clinical significance. The detection rate of FGR combined with structural malformation was significantly higher than that of isolated FGR group. The detection rate of FGR with structural malformations was significantly higher than that with non-structural malformations. The positive detection rate in the FGR group was similar to that in the FGR group with non-structural malformations, with no statistical significance. Chromosomal abnormalities were detected in 17 patients with early onset FGR, with a positivity rate of 13.8 %. Two cases of chromosomal abnormalities were detected in the late-onset FGR group, with a positive rate of 7.1 %, with no statistical significance. A total of 151 fetuses with FGR were followed up for pregnancy outcomes, resulting in 36 cases of pregnancy termination and 13 cases of loss to follow-up. Among the 102 delivered fetuses, six exhibited delayed growth and development, one presented with hypospadias, and another failed the hearing screening. The remaining 94 fetuses demonstrated normal growth and development.ConclusionsThis study confirms the value of CNV detection in fetuses and dynamic ultrasound monitoring for fetuses with intrauterine growth restriction.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly.

Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Prenatal ultrasound diagnosis and quality control of fetal nuchal translucency.

In clinical ultrasound examinations, it is challenging to perform quality control on the images of each fetal nuchal translucency (NT) and crown-rump length (CRL). However, small measurement differences can increase the probability of false-positive or false-negative diagnosis. Therefore, it is necessary to establish a quality control system for fetal NT examination. This study aims to control the quality of fetal NT and CRL measurements, evaluate the accuracy of ultrasound physicians in early pregnancy NT measurements, and analyze the impact of increased fetal structure screening on the detection rate of chromosomal abnormalities. Data were collected from cases before and after 12 months of NT examination quality control, with 2 214 before quality control and 2 538 cases after quality control. Three quality control data metrics were analyzed: NT multiple of median (NT-MoM), standard deviation (SD) of log10MoM [(SD) log10MoM], and the slope of NT on CRL (SNC). The performance of NT measurements was monitored through the individual CRL NT-MoM within the 0.9-1.1 MoM range of the normal median curve, while grouped based on different years of experience (<3 years, 3-6 years, >6 years), and NT-MoM values among these groups were compared. Data on NT thickening, structural anomalies, and chromosomal abnormalities were retrospectively analyzed during the quality control period. According to the curve equation of the American NTQR project group, the NT-MoM value before quality control was 0.921 7 MoM, the (SD) log10MoM value was 0.091 92, and the SNC value was 12.20%. After quality control, the NT-MoM value was 0.948 3 MoM, the (SD) log10MoM value was 0.094 81, and the SNC value was 11.43%. The comparison of NT-MoM values before and after quality control showed a statistically significant difference (P<0.000 1). The comparison of NT-MoM values measured by ultrasound physicians with different years of experience before and after quality control also showed statistically significant differences (P<0.000 1). The NT-MoM values for the 3-6 years and >6 years groups were higher after quality control (P<0.05), while the <3 years group showed no significant difference before and after quality control (P>0.05). After quality control, cases of NT thickening without significant structural abnormalities accounted for 19.05%, NT thickening with structural abnormalities accounted for 47.62%, and NT normal with structural abnormalities accounted for 33.33%. There were 36 cases of fetal heart abnormalities, accounting for 20.34% of the total abnormality rate, with a positive rate of 36% in chromosome tests. After quality control, ultrasound physicians measure NT more accurately, but differences among measurements remain. Measurements by experienced ultrasound physicians are closer to expected values, usually lower than expected. Monitoring fetal NT and CRL measurements helps improve measurement accuracy. Increasing structural screening during NT examinations, especially for the fetal heart, enhances the detection rate of chromosomal abnormalities.

The status and influencing factors of abnormal fetal pregnancy outcomes in 265 cases in China: a retrospective study.

With the advancement of prenatal diagnosis technology, the detection rate of fetal abnormalities continues to increase, imposing a significant burden on both society and families. A retrospective analysis of essential information about pregnant women, such as their pregnancy history and delivery details, is crucial for understanding the primary factors that influence pregnancy outcomes in women with fetal abnormalities. This analysis is of great significance for improving the level of pregnancy management and outcomes in pregnant women with fetal abnormalities. To retrospectively analyze the pregnancy outcomes of women with fetal abnormalities and explore the factors that influence these outcomes. Pregnant women's pregnancy outcomes were collected from the medical information system and through telephone follow-ups. The chi-square test and logistic regression were used to analyze the factors influencing pregnancy outcomes. Among 265 pregnant women diagnosed with fetal abnormalities, 190 chose to continue the pregnancy, while 75 chose to terminate it. Pregnant women with multiple fetal abnormalities (OR = 3.774, 95% CI [1.640-8.683]) were more likely to choose termination of pregnancy (TOP), and pregnant women who were advised to terminate their pregnancy or make a careful choice were more likely to terminate the pregnancy (OR = 41.113, 95% CI [11.028-153.267]). The number of organs involved in fetal abnormalities and treatment recommendations were identified as the primary factors influencing pregnancy outcomes. Improving awareness of maternal health care during pregnancy, early pregnancy screening technology, and a multidisciplinary diagnosis and treatment approach are of great significance in assisting pregnant women in making informed decisions and improving fetal prognosis.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35.

Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

Prevalence of High-Risk HPV Detection and HPV Vaccination in Cervical Cancer Screening During the HPV Vaccination Era at Siriraj Hospital - Thailand's Largest National Tertiary Referral Center.

To investigate the prevalence of high-risk (HR) human papillomavirus (HPV) detection and HPV vaccination among women undergoing cervical cancer screening during the HPV vaccination era at Siriraj Hospital - Thailand's largest national tertiary referral center. This prospective cross-sectional study was conducted at our center's outpatient gynecology clinic during September-December 2021. Women aged ≥18 years with no previous hysterectomy, no history of preinvasive or invasive cervical cancer, and no current pregnancy who visited for cervical cancer screening were eligible for enrollment. Women with abnormal vaginal discharge/bleeding, and specimens with inadequate cellularity were excluded. We collected sociodemographic data, history of HPV vaccination, cervical cytology results, and high-risk HPV testing results. Reverse transcription polymerase chain reaction was used to determine HPV genotype. A total of 216 women (mean age: 41.7 years (range: 25-65), 75.9% premenopausal) were enrolled. Twenty of 216 (9.3%) women tested positive for HR-HPV, and 15 of 216 (6.9%) women had been previously vaccinated for HPV. The most common HPV genotypes detected were Group B infection (HPV 35/39/51/56/59/66/68) (38.9%), followed by HPV16 (27.78%), Group A infection (HPV 31/33/52/58) (27.8%), and HPV18 (5.56%). No HPV45 infection was detected. The detection rate of cytologic abnormalities was 4.16%. Three-quarters (77.8%) of patients with cytologic abnormalities were HR-HPV positive. Among the 216 women who underwent cervical cancer screening in this study, there was a 9.3% prevalence of HR-HPV infection, and a 6.9% prevalence of HPV vaccination. Among the 15 vaccinated women, 2 tested positive for HPV16 (1 normal cytology, 1 abnormal cytology).

Diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery

Objective: To analyze the diagnosis and surgical treatment of high-risk anomalous aortic origin of coronary artery (AAOCA). Methods: This is a retrospective case series study. From January 2016 to July 2023, 24 cases of high-risk AAOCA underwent surgical treatment in Department of Cardiac Surgery, Guangdong Provincial People's Hospital. There were 18 males and 6 females, operatively aged (M (IQR)) 13 (26) years (range: 0.3 to 57.0 years). They were confirmed by cardiac ultrasound and cardiac CT, all of which had anomalous coronary running between the aorta and the pulmonary artery. There were 15 cases of the right coronary artery from the left aortic sinus of Valsalva, 6 cases of left coronary artery from the right aortic sinus of Valsalva, 3 cases of the sigle coronary artery. Only 3 patients had no obvious related symptoms (2 cases were complicated with a positive exercise stress test and 1 case with other intracardiac malformations), 21 cases had a history of chest tightness, chest pain, or syncope after exercise. Three patients suffered syncope after exercise and underwent cardiopulmonary resuscitation (2 cases were treated with an extracorporeal membrane oxygenerator (ECMO)). The gap from the first symptom to the diagnosis was 4.0 (11.5) months (range: 0.2 to 84.0 months). The detection rate of coronary artery abnormalities suggested by the first cardiac ultrasound was only 37.5% (9/24). Seven patients were complicated with other cardiac diseases (4 cases with congenital heart defects, 2 cases with coronary atherosclerotic heart disease, 1 case with mitral valve disease). Results: All 24 patients underwent surgical treatment (23 cases underwent abnormal coronary artery unroofing, 1 case underwent coronary artery bypass grafting), and 5 patients underwent other intracardiac malformation correction at the same time. There were no death or surgery related complications in the hospital for 30 days after the operation. A patient with preoperative extracorporeal cardiopulmonary resuscitation was continuously assisted by ECMO after emergency AAOCA correction and had complications such as limb ischemia necrosis and renal dysfunction after the operation. During the follow-up of 2.2 (3.3) years (range: 1 month to 7.2 years), one patient who previously underwent percutaneous transluminal coronary angioplasty with a stent implant experienced significant postoperative symptomatic relief, and the other discharged patients had no related symptoms. Conclusions: The accurate rate of initial diagnosis for high-risk AAOCA is still low, but the risk of cardiovascular accidents is high. For sports-related chest pain and other symptoms, more attention should be paid to the detection of AAOCA, especially for adolescents. Exercise stress testing can be helpful in evaluating the cardiovascular risk of asymptomatic AAOCA. Instant surgical treatment can achieve satisfactory curative effects.