Impact of cannula size on recurrent twin-twin transfusion syndrome and twin anemia-polycythemia sequence after fetoscopic laser surgery.

OBJECTIVE: The optimal outcome after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) depends on the successful ablation of all placental anastomoses. The objective of this study was to determine the incidence of and risk factors for recurrent TTTS (rTTTS) or twin anemia-polycythemia sequence (TAPS) after FLS, focusing on the impact of cannula diameter. METHODS: This was a secondary analysis of data collected prospectively at two centers from 666 consecutive patients undergoing FLS for TTTS. The main outcomes were rTTTS and TAPS following FLS. Variables assessed included gestational age at intervention, stage of disease, recipient maximum vertical pocket, anterior placenta, number of anastomoses ablated, cannula diameter/operative scopes and use of the Solomon technique. Cannula diameter and corresponding scopes used were as follows: 8 Fr and 1.3 mm/0°; 9 Fr and 2.7 mm/0°; 10 Fr and 3 mm/0°; or 12 Fr and 3.3-3.7 mm/30-70°. Cannula diameter was used as a surrogate for scopes during analysis. Multivariate logistic regression analysis was performed to identify risk factors associated with rTTTS or TAPS after FLS; 'center' was considered an independent variable to account for variations in practice. In a nested cohort of pregnancies in which both fetuses survived, placental dye injection was performed in 315 placentae. Multivariate logistic regression analysis was performed to evaluate variables associated with the presence of residual anastomoses. RESULTS: rTTTS or TAPS occurred in 61 (9%) cases following FLS (rTTTS in eight (1%) and TAPS in 53 (8%)). Factors associated significantly with the risk of rTTTS/TAPS on multivariate analysis were cannula diameter (when an 8-Fr, 9-Fr, 10-Fr or 12-Fr cannula was used, there was rTTTS/TAPS in 24%, 13%, 2% or 0.8% of cases, respectively (P < 0.001)) and use of the Solomon technique (rTTTS/TAPS occurred in 4.2% of those in which it was used vs 18.1% in those in which it was not (P < 0.001)). Only use of the Solomon technique was associated significantly with no residual anastomoses found after delivery. CONCLUSIONS: Following FLS for TTTS, a lower incidence of rTTTS/TAPS was seen when the Solomon technique was used, as well as when a 10-Fr or 12-Fr cannula was used. A lower complication rate may be due to the use of a scope with better optics during placental mapping. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Operator competence in fetoscopic laser surgery for twin-twin transfusion syndrome: validation of a procedure-specific evaluation tool.

OBJECTIVES: Fetoscopic laser surgery for twin-twin transfusion syndrome is a procedure for which no objective tools exist to assess technical skills. To ensure that future fetal surgeons reach competence prior to performing the procedure unsupervised, we developed a performance assessment tool. The aim of this study was to validate this assessment tool for reliability and construct validity. METHODS: We made use of a procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure, which was previously created using Delphi methodology. Eleven experts and 13 novices from three fetal medicine centers performed the procedure on the same simulator. Two independent observers assessed each surgery using the instrument (maximum score: 52). Interobserver reliability was assessed using Spearman correlation. We compared the performance of novices and experts to assess construct validity. RESULTS: The interobserver reliability was high (Rs = 0.974, P < 0.001). Checklist scores for experts and novices were significantly different; the median score for novices was 28/52 (54%), whereas that for experts was 47.5/52 (91%) (P < 0.001). The procedure time and fetoscopy time were significantly shorter (P < 0.001) for experts. Residual anastomoses were found in 1/11 (9%) procedures performed by experts and in 9/13 (69%) procedures performed by novices (P = 0.005). Multivariable analysis showed that the checklist score, independent of age and gender, predicted competence. CONCLUSIONS: The procedure-specific assessment tool for fetoscopic laser surgery shows good interobserver reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Simulator training in fetoscopic laser surgery for twin-twin transfusion syndrome: a pilot randomized controlled trial.

OBJECTIVE: To evaluate the effect of a newly developed training curriculum on the performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. METHODS: Ten novices were randomized to receive verbal instructions and either skills training using the simulator (study group; n = 5) or no training (control group; n = 5). Both groups were evaluated with a pre-training and post-training test on the simulator. Performance was assessed by two independent observers and comprised a 52-item checklist for surgical performance (SP) score, measurement of procedure time and number of anastomoses missed. Eleven experts set the benchmark level of performance. Face validity and educational value of the simulator were assessed using a questionnaire. RESULTS: Both groups showed an improvement in SP score at the post-training test compared with the pre-training test. The simulator-trained group significantly outperformed the control group, with a median SP score of 28 (54%) in the pre-test and 46 (88%) in the post-test vs 25 (48%) and 36 (69%), respectively (P = 0.008). Procedure time decreased by 11 min (from 44 to 33 min) in the study group vs 1 min (from 39 to 38 min) in the control group (P = 0.69). There was no significant difference in the number of missed anastomoses at the post-training test between the two groups (1 vs 0). Subsequent feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. CONCLUSIONS: Proficiency-based simulator training improves performance, indicated by SP score, for fetoscopic laser therapy. Despite the small sample size of this study, practice on a simulator is recommended before trainees carry out laser therapy for TTTS in pregnant women.

Intrauterine transfusion combined with partial exchange transfusion for twin anemia polycythemia sequence: modeling a novel technique.

INTRODUCTION: Twin anemia-polycythemia sequence (TAPS) is a newly described disease in monochorionic twin pregnancies, characterized by large inter-twin hemoglobin differences. Optimal management for TAPS is not clear. One of the possible treatment modalities is intrauterine blood transfusion (IUT) in the donor with or without combination of partial exchange transfusion (PET) in the recipient. METHODS: We applied a computational model simulation to illustrate the mechanism of IUT with and without PET in TAPS occurring after laser surgery for twin-twin transfusion syndrome (TTTS). Model simulations were performed with the representative anastomotic pattern as observed during laser intervention, and after placental dye injection. RESULTS: The model was tested against different cases where IUT was combined with PET for the treatment of post-laser TAPS. Model simulations using the observed anastomotic pattern showed a significant reduction of hyperviscosity in the recipient after IUT/PET compared to IUT without PET. DISCUSSION: In this model simulation we show that the addition of PET to IUT reduces the severity of polycythemia in the recipient. PET may thus be important to prevent complications of hyperviscosity. CONCLUSION: This model simulation shows the beneficial effect of PET for the recipient in TAPS cases treated with IUT.

A worldwide survey of laser surgery for twin-twin transfusion syndrome.

OBJECTIVES: To evaluate differences between international fetal centers in their treatment of twin-twin transfusion syndrome (TTTS) by fetoscopic placental laser coagulation. METHODS: Fetal therapy centers worldwide were sent a web-based questionnaire. Participants were identified through networks and through scientific presentations and papers. Questions included physician and center demographics, treatment criteria, operative technique and instrumentation. Laser treatment was compared between low-volume (< 20 procedures/year) and high-volume (≥ 20 procedures/year) centers. Data were analyzed using descriptive statistics. RESULTS: Of 106 fetal therapy specialists approached, 76 (72%) from 64 centers in 25 countries responded. Of these, 48% (31/64) of centers and 63% (48/76) of operators performed fewer than 20 laser procedures annually. Comparison of low- and high-volume centers showed differences in technique, gestational age limits for treatment and geography. High-volume centers more often used the Solomon technique and applied wider gestational age limits for treatment. Europe and Asia had more high-volume centers, whereas South America, the Middle East and Australia had mainly low-volume centers. CONCLUSION: This survey revealed significant differences between fetal centers in several aspects of fetoscopic placental laser therapy for TTTS. Increasing awareness of TTTS, and of laser coagulation as its preferred treatment, will lead to an increase in centers offering this modality, especially in Asia, Africa, South America and the Middle East. Considering the rarity of TTTS and the relative complexity of the procedure, developing international guidelines for techniques, instrumentation and suggested minimum volumes per center may aid in optimizing perinatal outcome.

Identification of essential steps in laser procedure for twin-twin transfusion syndrome using the Delphi methodology: SILICONE study.

OBJECTIVE: To determine, by expert consensus, the essential substeps of fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) that could be used to create an authority-based curriculum for training in this procedure among fetal medicine specialists. METHODS: A Delphi survey was conducted among an international panel of experts (n = 98) in FLS. Experts rated the substeps of FLS on a five-point Likert-type scale to indicate whether they considered them to be essential, and were able to comment on each substep, using a dedicated online platform accessed by the invited tertiary care facilities that specialize in fetal therapy. Responses were returned to the panel until consensus was reached (Cronbach's α ≥ 0.80). All substeps that were rated ≥ 4 by 80% of the experts were included in the evaluation instrument. RESULTS: After the first iteration of the Delphi procedure, a response rate of 74% (73/98) was reached, and in the second and third iterations response rates of 90% (66/73) and 81% (59/73) were reached, respectively. Among a total of 81 substeps rated in the first round, 21 substeps had to be re-rated in the second round. Finally, from the initial list of substeps, 55 were agreed by experts to be essential. In the third round, the 18 categorized substeps were ranked in order of importance, with 'coagulation of all anastomoses that cross the equator' and 'determination of fetoscope insertion site' as the most important. CONCLUSIONS: A total of 55 substeps of FLS for TTTS were defined by a panel of experts to be essential in the procedure. This list is the first authority-based evidence to be used in the development of a final training model for future fetal surgeons.

Continuous non-invasive blood pressure monitoring, a validation study of Nexfin in a pregnant population.

OBJECTIVE: To assess the accuracy of a non-invasive beat-to-beat continuous blood pressure monitoring device (Nexfin) in pregnancy according to the International Protocol of the European Society of Hypertension. METHODS: The validation was performed according to the International Protocol of the European Society of Hypertension. The test device (Nexfin, BMEYE, Amsterdam, the Netherlands) calculates beat to beat blood pressure from finger pulse wave analysis. Measurements of systolic and diastolic BP in 33 volunteers were obtained using the mercury sphygmomanometer and the Nexfin alternatingly. RESULTS: The device passed phase 1 as 30 systolic and 32 diastolic readings fell within 5 mmHg (25 required). In addition, the device also passed phase 2.1 as 68 systolic and 67 diastolic readings fell within 5 mmHg (65 required). Finally, it failed to pass phase 2.2 as 24 subjects for systolic and 23 for diastolic had at least 2/3 of their comparisons falling within 5 mmHg (22 required) but 6 subjects for systolic and 8 for diastolic had all three comparisons more than 5 mmHg different from the mercury readings (three allowed). The mean differences were 2.3 mmHg (SD 6.8) for SBP and 0.8 mmHg (SD 6.3) for DBP. CONCLUSION: The Nexfin device passed phase 1 and phase 2.1 but failed to pass phase 2.2. However, adaptation of the data to the more permissive AAMI (mean difference <5 +/- 8 mmHg) and BHS (systolic grade B, diastolic grade A) protocols indicated adequate accuracy for application in research settings or for longitudinal within-patient tracking of blood pressure, given the possibility for continuous monitoring.

[Review of the activities from the former State Institute for Serum Production]. / Een terugblik op de activiteiten van de voormalige rijksseruminrichting.

This article describes the foundation and development of the State Institute for Serum Production (Rijksseruminrichting) in Rotterdam, the Netherlands, during the period 1904-1959. It describes the work of Dr J. Poels, the founder of the Institute, and the production of antisera in terms of the selection of animals, immunization protocols, blood sampling and collection, and the preservation and use of antisera in practice. Attention is also paid to the production of vaccines and diagnostic tests and to research on animal diseases. Envisaged research goals were not achieved because of a lack of adequate financial support and staffing, and poor laboratory facilities.

Lipolytic and nutritive blood flow response to beta-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men.

OBJECTIVE: beta-Adrenoceptor-mediated whole-body lipolysis is impaired in obesity. This study investigated whether local adipocyte beta-adrenergic sensitivity and changes in nutritive blood flow in subcutaneous abdominal adipose tissue contribute to this impaired response. METHODS: Three microdialysis probes were placed in the subcutaneous abdominal adipose tissue of eight obese and nine lean men. Each probe was perfused with either 0.1, 1 and 10 microM isoprenaline; 1, 10 and 100 microM dobutamine or 1, 10 and 100 microM salbutamol, each dose for 45 min. RESULTS: At baseline, interstitial glycerol concentrations and ethanol out/in ratios were comparable between groups. During nonselective beta-, beta(1)- and beta(2)-adrenergic stimulation, interstitial glycerol concentrations increased and ethanol out/in ratios decreased similarly in obese and lean men. CONCLUSION: The lipolytic and nutritive blood flow response to beta(1)- beta(2)- and nonselective beta-adrenergic stimulation in situ is comparable in lean and obese male subjects. The present data suggest that a blunted beta-adrenergic sensitivity of the fat cell and an impaired local nutritive blood flow response do not contribute to the previously reported diminished whole-body beta-adrenoceptor-mediated lipolytic response in obese males.