First-trimester combined screening for trisomy 21 with different combinations of placental growth factor, free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A.

OBJECTIVE: To examine placental growth factor (PlGF) in euploid and trisomy 21 pregnancies at 11-13 weeks' gestation and to model the impact on first-trimester combined screening. METHODS: PlGF was measured in 509 (409 euploid and 100 trisomic) fetal serum samples derived from prospective first-trimester combined screening for trisomy 21 at 11-13 weeks' gestation. The serum samples were stored at -80°C, following the measurement of free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein-A (PAPP-A) levels, for median time spans of 0.9 and 4.1 years in the euploid and trisomy 21 pregnancies, respectively. The effect of additional PlGF measurement at the time of combined screening was investigated by simulating fetal nuchal translucency (NT) measurements and multiples of the median (MoM) values for PAPP-A, free ß-hCG and PlGF for 20,000 euploid and 20,000 trisomy 21 pregnancies. Patient-specific combined risks were calculated based on maternal age and fetal NT in addition to free ß-hCG, PAPP-A and PlGF, PAPP-A and PlGF or free ß-hCG and PlGF, and detection and false-positive rates were calculated. RESULTS: Median PlGF-MoM was 1.0 (95% confidence interval (CI), 0.96-1.04) in euploid fetuses and significantly lower, at 0.73 (95% CI, 0.70-0.76), in trisomy-21 fetuses (P < 0.0001). There was no significant dependency between PlGF-MoM and either gestational age at the time of blood sampling (r = 0.087, P = 0.392) or sample storage time (r = 0.028, P = 0.785). Modeled detection and false-positive rates for first-trimester combined screening (based on maternal and gestational age, fetal NT and maternal serum biochemistry) without PlGF were 85% and 2.7% for a fixed risk cut-off of 1:100. The addition of PlGF increased the detection rate to 87% and reduced the false-positive rate to 2.6%. Screening by maternal age and fetal NT in combination with PlGF and PAPP-A or in combination with PlGF and free ß-hCG provided detection rates of 82% and 79%, with false-positive rates of 2.7% and 3.0%, respectively. CONCLUSION: In pregnancies with trisomy 21 PlGF is reduced. The impact on the overall screening performance for trisomy 21 is low and does not justify the measurement of PlGF solely for trisomy 21 screening. However, as PlGF is measured with the aim of assessing the risk for pre-eclampsia, further improvement in screening for trisomy 21 can be considered as an added benefit.

[First-trimester screening for trisomies 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13]. / Screening auf Trisomie 18 und Trisomie 13 durch das kombinierte Anwenden der Risiko-Algorithmen für Trisomie 21, 18 und 13.

PURPOSE: Assessment of first-trimester combined screening for trisomy 18 and 13 with the combined use of the risk algorithms for trisomy 21, 18 and 13. MATERIALS AND METHODS: First-trimester combined screening based on maternal and gestational age, fetal NT, PAPP-A and free ß-hCG was assessed in 39 ,004 pregnancies. Patient-specific risks for trisomy 21, 18, 13 were computed based on the current FMF London algorithm. RESULTS: The study population consisted of 38 ,751 singleton pregnancies including 39 cases with trisomy 18 or 13. In the aneuploid group, median delta NT was 0.72 mm, PAPP-A was 0.21 MoM and free ß-hCG was 0.33 MoM. Although only 41 % of the NT measurements of fetuses with trisomy 18 or 13 were above the 95th percentile, the detection rates for trisomy 18 or 13 were 82 % with the trisomy 18/13 algorithm and 56.4 % with the trisomy 21 algorithm. The respective false-positive rates were 0.7 % and 4.7 %. The combination of the trisomy 18/13 and the trisomy 21 algorithm with the same cut-offs led to a detection rate of 94.9 % at an overall false-positive rate of 5.0 %. CONCLUSION: Despite a substantial underestimation of the fetal NT, the combined use of the trisomy 18/13 and the trisomy 21 algorithm of the FMF London leads to a detection rate for trisomy 18/13 of about 95 % for a false-positive rate of 5.0 %.

[Cross-validation of the first trimester screening algorithm of the FMF London on 38,700 pregnancies in Germany]. / Cross-Validierung des Screening-Algorithmus der FMF London an 38,700 Ersttrimester-Untersuchungen in Deutschland.

PURPOSE: Validation of the performance of the new algorithm of the FMF London for screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT) and maternal serum free ß-hCG and PAPP-A. MATERIALS AND METHODS: Between 2002 and 2007, NT was measured prospectively in 39,004 pregnancies in the context of routinely performed first trimester screening in Germany. Individual trisomy 21 risks were calculated by a combination of NT, maternal age, free ß-hCG, and PAPP-A using the FMF algorithm in force at the time of investigation. In this study we recalculated the trisomy 21 risks applying the new algorithm of the FMF UK that includes the new mixture model for the NT measurement. RESULTS: 38,751 singleton pregnancies could be included in the study of which 109 (0.3 %) had a trisomy 21. Only 35 % of the NT measurements of euploids were above the median and 25 % of the NT measurements were below the 5th percentile of the FMF UK. For sonographers that were qualified according to level II or III of the German DEGUM system, the median NT of fetuses with trisomy 21 was 0.9 mm above the median of the FMF UK and only 0.5 mm above the median for all other sonographers. Despite the limited performance of the NT measurement, the overall detection rate for a trisomy 21 was 90.8 % when combining the NT with maternal age, PAPP-A and free ß-hCG. The overall false-positive rate for a trisomy 21 was 6.5 % at a cut-off value of 1:300. CONCLUSION: In this study we were able to show that the use of the new risk algorithm of the FMF UK leads to a trisomy 21 detection rate of about 90 % at a 5 % false-positive rate in a German collective despite a significant underestimation of the NT.

Validation of the first automated chemiluminescence protein-binding assay for the detection of 25-hydroxycalciferol.

BACKGROUND: Measurement of 25-hydroxyvitamin D, 25(OH)D is the ideal parameter to indicate the access of the organism to vitamin D. Numerous studies have shown that serum levels of 25(OH)D are the best markers of vitamin D deficiency, normal vitamin D supply or vitamin D intoxication. The aim of the study was to validate a beta-site version of the first fully automated chemiluminescence protein-binding assay (CLPBA) for the detection of 25-hydroxycalciferol. METHODS: The newly developed CLPBA run on the Nichols Advantage Specialty Systems was compared to an inhouse radioimmunoassay (RIA), focussing on the major assay features such as imprecision, functional sensitivity, linearity, method comparison and suitability of serum or EDTA-plasma as well as establishing a preliminary reference range. RESULTS: Within-run imprecision is approximately 4.5% and total imprecision approximately 6% respectively (NCCLS protocol), functional sensitivity 6.8 microg/l. With mean recovery values of 96.9% and 98.7% for two diluted serum samples linearity is given over the measuring range. Due to different calibrations used for RIA and CLPBA the CLPBA reads approximately 70% lower (CLPBA = 0.321xRIA + 0.571, n = 469) but correlates well with the RIA (r = 0.9045). Method comparison with HPLC reveals a regression line of CLPBA = 0.8921xHPLC + 0.1358 (n = 54, r = 0.9117). Serum or EDTA-plasma is not equally suitable. Plasma samples read on average 5 microg/l higher than serum samples. The preliminary reference range is 11 microg/l to 84 microg/l (95% of all values). CONCLUSION: The validated 25(OH)D CLPBA is a very promising alternative to established commercially available 25(OH)D measurements and will, with its use on a fully automated platform, simplify the reliable quantification of 25-hydroxycalciferol significantly.

[The time requirement for endoscopic diagnosis and therapy: results of a multicenter study]. / Zeitbedarf für endoskopische Diagnostik und Therapie: Ergebnisse einer Multicenterstudie.

For evaluation of the time requirements for endoscopic diagnostic and therapeutic procedures data of 13,321 patients gathered from 155 endoscopic units were collected. Time requirements were calculated for preparation of the procedure, examination and after-care of patients and instruments. The data indicate, that time requirement is significantly influenced by the special procedure. Therefore, calculation of the time requirement of an individual unit needs exact consideration of the frequency of different procedures. Only cleaning of instruments by washing machines could be shown to reduce time requirement. Education of endoscopists was demonstrated to be time intensive. Age (exemption children) sex of patients and video-endoscopy did not effect duration of procedures.

[Therapy of choledocholithiasis using extracorporeal shock wave lithotripsy and adjuvant surgical endoscopy]. / Therapie der Choledocholithiasis durch extrakorporale Stosswellenlithotripsie und adjuvante operative Endoskopie.

Extracorporeal shock wave lithotripsy of extra- and intrahepatic bile duct stones is indicated after failure of conventional operative endoscopic procedures including mechanical lithotripsy. An overview of the current literature (12 centers, 568 patients) indicates that this novel procedure has attracted international acceptance. It was applied in elderly patients (means = 65 years) with solitary (37.5%) or multiple (62.5%) concrements. Clearance of the bile ducts was achieved in 71.6% after 1.3 to 3.0 lithotripsy sessions (1900-4000 shocks) if additional endoscopic sphincterotomy was performed. Without sphincterotomy 61% of patients were treated successfully. The most frequent side effects were macrohematuria (6.9%), hemobilia (6.2%) cholangitis (4.5%) and pancreatitis (1.3%). A lethality of 0-3.6% (means = 0.6%) was reported. The current results demonstrate that therapy of extra- and intrahepatic bile duct stones with extracorporeal shock wave lithotripsy is effective, safe and provides high therapeutic comfort.