Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities. Methods This is a national study including 1901 pregnancies with NT &gt;= 95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected. Results In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95(th) and 99(th) percentile and 62% for fetuses with NT &gt;= 99(th) percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively. Conclusion Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement.</p

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives: To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities. Methods: This is a national study including 1901 pregnancies with NT≥95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected. Results: In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95th and 99th percentile and 62% for fetuses with NT≥99th percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively. Conclusion: Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement

Age-specific and family-centered information modalities to prepare children at home for day-care surgery

Background: Surgery induced stress and anxiety in children and parents can be reduced by providing preoperative information adapted to their needs. Aim of this study was to evaluate the effects of three different information modalities (coloring page, mobile application and videos) to prepare children and their parents for day-care surgery on preoperative anxiety and postoperative pain experienced by the child, and preoperative anxiety and satisfaction of parents. Methods: Prospective observational study including children and their parents that were offered specifically developed information modalities to prepare for day-care surgery. Results were compared between children and their parents that used none (i.e., control group) versus one or more information modalities (i.e., intervention group). Primary outcomes were preoperative anxiety measured using PROMIS v2.0 Anxiety and postoperative pain in children. Secondary outcomes were preoperative parental anxiety (STAI questionnaire) and family satisfaction with information and communication (modified PedsQL Healthcare Satisfaction questionnaire). Subgroup analyses were performed between preschoolers (0-5 years) and school-aged (≥5) children. Results: 93 patients (male 53%) were included in the intervention (n=56) and control group (n=37). Levels of children's preoperative anxiety and postoperative pain, and parental anxiety did not differ between both groups. Families of prepared children were more satisfied with information and communication about preoperative surgical information (8 vs. 6.6, p=0.004) and satisfaction with how parents (7 vs 8, p=0.019) and children (8 vs 6, p=0.018) were prepared for surgery. Conclusions: Preoperative anxiety did not differ between prepared and unprepared children. The use of specifically developed family-centered and age-appropriate information modalities to prepare children for day-care surgery at home results in superior family satisfaction. Level of Evidence: II

Comparative Analysis of Urine Fractions for Optimal Bladder Cancer Detection Using DNA Methylation Markers

DNA methylation analysis of full void urine and urine pellet seems promising for bladder cancer (BC) detection and surveillance. Urinary cell-free DNA from urine supernatant is now gaining interest for other molecular tests in BC. This study aims to evaluate which urine fraction is preferred for BC diagnosis using methylation markers: full void urine, urine pellet or supernatant. Methylation levels of nine markers were determined in the three urine fractions and correlated with their respective tumor tissues in BC patients and compared to controls. For all markers and marker panel GHSR/MAL, diagnostic performance was determined by calculating the area under the curve (AUC) of the respective receiver operating characteristic curves. For most of the markers, there was a significant correlation between the methylation levels in each of the urine fractions and the matched tumor tissues. Urine pellet was the most representative fraction. Generally, AUCs for BC diagnosis were comparable among the fractions. The highest AUC was obtained for GHSR/MAL in urine pellet: AUC 0.87 (95% confidence interval: 0.73-1.00), corresponding to a sensitivity of 78.6% and a specificity of 91.7%. Our results demonstrate that cellular and cell-free DNA in urine can be used for BC diagnosis by urinary methylation analysis. Based on our comparative analysis and for practical reasons, we recommend the use of urine pellet

A two-gene methylation signature for the diagnosis of bladder cancer in urine

Aim: To analyze the potential of 14 cancer-associated genes, including six miRNAs, for bladder cancer (BC) diagnosis in urine. Patients & methods: DNA methylation levels of 14 genes were analyzed in urine of 72 BC patients and 75 healthy controls using quantitative methylation-specific PCR. Multivariate logistic regression analysis was used to determine an optimal marker panel. Results: Ten genes were significantly hypermethylated in BC patients. The GHSR/MAL combination showed the best diagnostic performance, reaching a sensitivity of 92% (95% CI: 86-99) and a specificity of 85% (95% CI: 76-94). Conclusion: We identified a novel two-gene panel with a high diagnostic accuracy for BC that can be applied in a noninvasive, urine-based test

The diagnostic accuracy of methylation markers in urine for the detection of bladder cancer: a systematic review

AIM: Several urinary hypermethylation-markers (hmDNA) have been described for bladder cancer (BC) detection, but none have been able to replace cystoscopy yet. We systematically reviewed and evaluated current literature on urinary hmDNA markers for BC diagnostics. PATIENTS & METHODS: A systematic search of PubMed, EMBASE.com and The Cochrane Library up to February 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was conducted. RESULTS: A total of 30/42 studies included compared gene panels, with varying sensitivities (52-100%) and specificities (0-100%). Considerable heterogeneity across studies was observed and most was case-control studies. CONCLUSION: Reported diagnostic accuracy of urinary hmDNA for BC detection is highly variable and there is a lack of validation studies. Recent studies indicate that complementary markers are needed to allow for clinical implementation

A two-gene methylation signature for the diagnosis of bladder cancer in urine

AIM: To analyze the potential of 14 cancer-associated genes, including six miRNAs, for bladder cancer (BC) diagnosis in urine. PATIENTS & METHODS: DNA methylation levels of 14 genes were analyzed in urine of 72 BC patients and 75 healthy controls using quantitative methylation-specific PCR. Multivariate logistic regression analysis was used to determine an optimal marker panel. RESULTS: Ten genes were significantly hypermethylated in BC patients. The GHSR/MAL combination showed the best diagnostic performance, reaching a sensitivity of 92% (95% CI: 86-99) and a specificity of 85% (95% CI: 76-94). CONCLUSION: We identified a novel two-gene panel with a high diagnostic accuracy for BC that can be applied in a noninvasive, urine-based test

The association between biomarker angiopoietin-like protein five and obstructive sleep apnea in patients undergoing bariatric surgery

Purpose: Obstructive sleep apnea (OSA) is prevalent in the bariatric population. OSA should be recognized in patients undergoing bariatric surgery preoperatively to prevent peri- and post-operative complications. Lipid metabolism-related biomarkers are associated with OSA. Triglyceride metabolism is, among others, regulated by angiopoietin-like protein five (ANGPTL5). We aimed to evaluate the level of ANGPTL5 in patients with OSA of different severity levels before and after bariatric surgery. Methods: We performed a single-center prospective cohort study including a consecutive series of patients who underwent bariatric surgery. We collected the clinical data, polysomnography (PSG) or polygraphy (PG) parameters, and plasma derived via venipuncture before and 6 to 12 months after surgery. Lipid profile, glucose levels, and ANGPTL5 levels were assessed. ANGPTL5 levels were measured using an enzyme-linked immunosorbent assay (ELISA). Results: The study included 88 patients for analysis. The patients were divided into two subgroups: no or mild OSA (apnea–hypopnea index (AHI) < 15 events/hour, n = 57) and moderate-to-severe OSA (AHI ≥ 15 events/hour, n = 31). The ANGPTL5 level was higher in the moderate-to-severe OSA group (20.5 [15.6, 26.5] ng/mL) compared to the no or mild OSA group (16.3 [12.5, 19.4] ng/mL) (p = 0.008). A significant positive correlation was observed between ANGPTL5 and AHI (ρ = 0.256, p = 0.017), apnea index (AI) (ρ = 0.318, p = 0.003), and triglyceride levels (ρ = 0.240, p = 0.025). ANGPTL5 levels were reduced significantly after bariatric surgery in both moderate-to-severe OSA (15.6 [10.3, 18.7] ng/mL) and no or mild OSA (13.4 [9.2, 15.8] ng/mL) groups, though to a lower level in the group without or mild OSA. Post-surgery, the significant positive correlation between ANGPTL5 and AHI (ρ = 0.210, p = 0.047), AI (ρ = 0.230, p = 0.034), and triglyceride (ρ = 0.397, p < 0.001) remained. Conclusion: The data showed increased levels of ANGPTL5 in patients with moderate-to-severe OSA. Both AHI and ANGPTL5 levels decreased significantly after bariatric surgery. We also report an association between ANGPTL5 levels and OSA severity