First-Trimester Crown-Rump Length and Embryonic Volume of Fetuses with Structural Congenital Abnormalities Measured in Virtual Reality

Background With the introduction of three-dimensional (3D) ultrasound it has become possible to measure volumes. The relative increase in embryonic volume (EV) is much larger than that of the crown-rump length (CRL) over the same time period. We examined whether EV is a better parameter to determine growth restriction in fetuses with structural congenital abnormalities. Study Design, Subjects, and Outcome Measures CRL and EV were measured using a Virtual Reality (VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses diagnosed with structural congenital abnormalities in the first trimester of pregnancy (gestational age 7+5 to 14+5 weeks). Measured CRL and EV were converted to z-scores and to percentages of the expected mean using previously published reference curves of euploid fetuses. The one-sample t-test was performed to test significance. Results The EV was smaller than expected for GA in fetuses with structural congenital abnormalities (-35% p<0.001, z-score -1.44 p<0.001), whereas CRL was not (-6.43% p=0.118, z-score -0.43 p=0.605). Conclusions CRL is a less reliable parameter to determine growth restriction in fetuses with structural congenital abnormalities as compared with EV. By measuring EV, growth restriction in first-trimester fetuses with structural congenital abnormalities becomes more evident and enables an earlier detection of these cases

Dynamic 3D echocardiography in virtual reality

BACKGROUND: This pilot study was performed to evaluate whether virtual reality is applicable for three-dimensional echocardiography and if three-dimensional echocardiographic 'holograms' have the potential to become a clinically useful tool. METHODS: Three-dimensional echocardiographic data sets from 2 normal subjects and from 4 patients with a mitral valve pathological condition were included in the study. The three-dimensional data sets were acquired with the Philips Sonos 7500 echo-system and transferred to the BARCO (Barco N.V., Kortrijk, Belgium) I-space. Ten independent observers assessed the 6 three-dimensional data sets with and without mitral valve pathology. After 10 minutes' instruction in the I-Space, all of the observers could use the virtual pointer that is necessary to create cut planes in the hologram. RESULTS: The 10 independent observers correctly assessed the normal and pathological mitral valve in the holograms (analysis time approximately 10 minutes). CONCLUSION: this report shows that dynamic holographic imaging of three-dimensional echocardiographic data is feasible. However, the applicability and use-fullness of this technology in clinical practice is still limited

Evaluation of First-Trimester Physiological Midgut Herniation Using Three-Dimensional Ultrasound

Introduction: The aim of this study was to investigate the development of midgut herniation in vivo using three-dimensional (3D) ultrasonographic volume and distance measurements and to create reference data for physiological midgut herniation in ongoing pregnancies in a tertiary hospital population. Materials and Methods: The transvaginal 3D ultrasound volumes of 112 women, seen weekly during the first trimester of pregnancy, were obtained and subsequently analysed in a virtual reality environment. The width of the umbilical cord insertion, the maximum diameter of the umbilical cord, and the volume of midgut herniation were measured from 6 until 13 weeks gestational age (GA). Results: All parameters had a positive relation with GA, crown-rump length, and abdominal circumference. In approximately 1 of 10 volumes no midgut herniation could be observed at 9 and 10 weeks GA. In 5.0% of the fetuses the presence of midgut herniation could still be visualised at 12 weeks GA. Conclusion: Reference charts for several dimensions of physiological midgut herniation were created. In the future, our data might be used as a reference in the first trimester for comparison in case of a suspected pathological omphalocele

Rapid Low-Cost Microarray-Based Genotyping for Genetic Screening in Primary Immunodeficiency

Background: Genetic tests for primary immunodeficiency disorders (PIDs) are expensive, time-consuming, and not easily accessible in developing countries. Therefore, we studied the feasibility of a customized single nucleotide variant (SNV) microarray that we developed to detect disease-causing variants and copy number variation (CNV) in patients with PIDs for only 40 Euros. Methods: Probes were custom-designed to genotype 9,415 variants of 277 PID-related genes, and were added to the genome-wide Illumina Global Screening Array (GSA). Data analysis of GSA was performed using Illumina GenomeStudio 2.0, Biodiscovery Nexus 10.0, and R-3.4.4 software. Validation of genotype calling was performed by comparing the GSA with whole-genome sequencing (WGS) data of 56 non-PID controls. DNA samples of 95 clinically diagnosed PID patients, of which 60 patients (63%) had a genetically established diagnosis (by Next-Generation Sequencing (NGS) PID panels or Sanger sequencing), w

Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor α

Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TRα), which is the predominant TR in these cells, has not been studied to date. Studies in TRα0/0 mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TRα affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TRα (RTHα) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHα patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTHα patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTHα. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTHαD211G patient. RTHα macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T3 found in patients with RTHα

Increased circulating interleukin-8 in patients with resistance to thyroid hormone receptor alpha

Innate immune cells have recently been identified as novel thyroid hormone (TH) target cells in which intracellular TH levels appear to play an important functional role. The possible involvement of TH receptor alpha (TR alpha), which is the predominant TR in these cells, has not been studied to date. Studies in TR alpha(0/0) mice suggest a role for this receptor in innate immune function. The aim of this study was to determine whether TR alpha affects the human innate immune response. We assessed circulating interleukin-8 concentrations in a cohort of 8 patients with resistance to TH due to a mutation of TR alpha (RTH alpha) and compared these results to healthy controls. In addition, we measured neutrophil and macrophage function in one of these RTHa patients (mutation D211G). Circulating interleukin-8 levels were elevated in 7 out of 8 RTH alpha patients compared to controls. These patients harbor different mutations, suggesting that this is a general feature of the syndrome of RTH alpha. Neutrophil spontaneous apoptosis, bacterial killing, NAPDH oxidase activity and chemotaxis were unaltered in cells derived from the RTH alpha D211G patient. RTH alpha macrophage phagocytosis and cytokine induction after LPS treatment were similar to results from control cells. The D211G mutation did not result in clinically relevant impairment of neutrophil or pro-inflammatory macrophage function. As elevated circulating IL-8 is also observed in hyperthyroidism, this observation could be due to the high-normal to high levels of circulating T-3 found in patients with RTH alph