Search

Objective: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. Methods: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. Results: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. Discussion: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

Contains fulltext : 307032.pdf (Publisher’s version ) (Open Access)

01 januari 2023, Item does not contain fulltext, Introduction: Acquiring and retaining minimally invasive surgery (MIS) skills may be aided by using MIS take-home box simulators. This study aims to evaluate the use of a take-home MIS box trainer for training sessions at-home. Methods: Trainees who previously bought the LaparoscopyBoxx (between 2016 and 2020) were asked to complete an online questionnaire. The first part was on their demographic data, and the second part was on their use and opinion on the box trainer (on a 5-point Likert scale). Results: A total of 39 participants (9 surgeons and 30 trainees) completed the questionnaire (response rate 40%). Overall, participants had a positive opinion on the use of the box trainer and would recommend it to others for training (mean 4.2). Basic tasks, such as needle trail and ring transfer, were practiced most often and were regarded most relevant (mean 4.1-4.3). They regarded practicing on the stimulator of added value to practicing in the clinic (mean 4.2), were more confident during clinical procedures (mean 3.9), and felt that their skills had improved (mean 4.1). Of quarter of the participants who bought the MIS box trainer during the COVID-19 pandemic reported an increased use during times of less clinical exposure. Conclusion: Surgeons and trainees have a positive opinion on using a take-home MIS box trainer for at-home training for general as well as for pediatric MIS skills. Especially during periods of less exposure in the clinical setting and less hands-on courses, such as during the COVID-19 pandemic, at-home training may be a valuable addition.

Radboud University, 04 april 2023, Promotor : Blaauw, I. de Co-promotores : Botden, S.M.B.I., Verhoeven, B.H., Contains fulltext : 291331.pdf (Publisher’s version ) (Closed access)

01 januari 2023, Item does not contain fulltext, BACKGROUND: Simulation-based training may be used to acquire MIS skills. While mostly done in a simulation center, it is proposed that this training can be undertaken at-home as well. The aim of this study is to evaluate whether unsupervised at-home training and assessment of MIS skills is feasible and results in increased MIS skills. METHODS: Medical doctors and senior medical students were tested on their innate abilities by performing a pre-test on a take-home simulator. Henceforth, they followed a two-week interval training practicing two advanced MIS skills (an interrupted suture with knot tying task and a precise peg transfer task) and subsequently performed a post-test. Both tests and all training moments were performed at home. Performance was measured using motion analysis software (SurgTrac) and by expert-assessment and self-assessment using a competency assessment tool for MIS suturing (LS-CAT). RESULTS: A total of 38 participants enrolled in the study. Participants improved significantly between the pre-test and the post-test for both tasks. They were faster (632 s vs. 213 s, p < 0.001) and more efficient (distance of instrument tips: 9.8 m vs. 3.4 m, p = 0.001) in the suturing task. Total LS-CAT scores, rated by an expert, improved significantly with a decrease from 36 at the pre-test to 20 at the post-test (p < 0.001) and showed a strong correlation with self-assessment scores (R 0.771, p < 0.001). The precise peg transfer task was completed faster (300 s vs. 163 s, p < 0.001) and more efficient as well (14.8 m vs. 5.7 m, p = 0.005). Additionally, they placed more rings correctly (7 vs. 12, p = 0.010). CONCLUSION: Unsupervised at-home training and assessment of MIS skills is feasible and resulted in an evident increase in skills. Especially in times of less exposure in the clinical setting and less education on training locations this can aid in improving MIS skills.

01 juni 2023, Item does not contain fulltext, INTRODUCTION: Sufficient training is needed to acquire and retain the procedural skills needed for the surgical correction of congenital anatomical malformations. This study aims to assess the opinions of trainees and pediatric surgeons on the use of simulation-based continued at-home training, which can help to acquire these skills. METHODS: This study consisted of two parts. First, an international survey among trainees and pediatric surgeons assessed their opinions on simulation-based at-home training for pediatric surgical procedures (5-point Likert scale). Second, participants of pediatric colorectal courses were instructed to practice the posterior sagittal anorectoplasty procedure at-home on a simulation model and, subsequently, complete a questionnaire regarding their opinions on continuous at-home training (5-point Likert scale). RESULTS: A total of 163 participants (83% pediatric surgeons) completed the international survey (response rate 43%). Overall, participants considered the training useful for both laparoscopic (mean 4.7) and open procedures (mean 4.2) and agreed that it may be used at home after a hands-on course (mean 4.3).Twenty participants completed the questionnaire on continued training (response rate 36%). All agreed that at-home training was of added value (mean 4.5) and that the skills were transferable to the clinical setting (mean 4.3). At-home training was regarded a suitable exercise after a hands-on workshop (mean 4.3), but less so without a workshop (mean 3.7, p=0.017). CONCLUSION: Participating trainees and pediatric surgeons were of the opinion that simulation models and at-home training have added value. This implies that simulation-based training may be used more often in pediatric surgical training.

Item does not contain fulltext, BACKGROUND: Skill deterioration of minimally invasive surgical (MIS) skills may be prevented by continuous training. The aim of this study is to evaluate whether unsupervised continuous at-home training of MIS skills results in better skill retention compared to no training. METHODS: Medical doctors followed a two-week interval training for two MIS tasks (precise peg transfer and interrupted suture with knot tying), ending with a baseline test. They were randomly assigned to the no-practice group or continuous-practice group. The latter practiced unsupervised at home every two weeks during the study period. Skill retention was measured after three and six months on both tasks by the total time needed, distance traveled by instruments and LS-CAT score (8 best possible score and > 40 worst score). RESULTS: A total of 38 participants were included. No significant differences in performance were found at pre-test or baseline. At six months the no-practice group needed more time for the suturing task (309 s vs. 196 s at baseline, p = 0.010) and the LS-CAT score was significantly worse (30 vs. 20 at baseline, p < 0.0001). The continuous-practice group performed the suturing task significantly better than the no-practice group at both three and six months (17 vs. 25, p < 0.001 and 17 vs. 30, p < 0.001) and faster as well (p = 0.034 and p = 0.001). CONCLUSION: This study shows a skill decay after only a few months of non-use and shows better skill retention after continuous unsupervised at-home practice of MIS skills. This indicates an added value of regular at-home practice of surgical skills.

Item does not contain fulltext, INTRODUCTION: The correction of an anorectal malformation (ARM) is complex and relatively infrequent. Simulation training and subsequent assessment may result in better clinical outcomes. Assessment can be done using a competency assessment tool (CAT). This study aims to develop and validate a CAT for the posterior sagittal anorectoplasty (PSARP) on a simulation model. MATERIALS AND METHODS: The CAT-PSARP was developed after consultation with experts in the field. The PSARP was divided into five steps, while tissue and instrument handling were scored separately. Participants of pediatric colorectal hands-on courses in 2019 and 2020 were asked to participate. They performed one PSARP procedure on an ARM simulation model, while being assessed by two objective observers using the CAT-PSARP. RESULTS: A total of 82 participants were enrolled. A fair interobserver agreement was found for general skills (intraclass correlation coefficient [ICC] = 0.524, p < 0.001), a good agreement for specific skills (ICC = 0.646, p < 0.001), and overall performance (ICC = 0.669, p < 0.001). The experienced group scored higher on all steps (p < 0.001), except for "anoplasty (p = 0.540)," compared with an inexperienced group. CONCLUSION: The CAT-PSARP is a suitable objective assessment tool for the overall performance of the included steps of the PSARP for repair of an ARM on a simulation model.

Item does not contain fulltext, INTRODUCTION: This review evaluates the validation and availability of simulation models in the field of pediatric surgery that can be used for training purposes. METHODS: MEDLINE and EMBASE were searched for studies describing a simulation models in pediatric surgery. Articles were included if face, content and/or construct validity was described. Additionally, the costs and availability were assessed. Validation scores for each model were depicted as percentage (0-100), based on the reported data, to compare the outcomes. A score of >70% was considered adequate. RESULTS: Forty-three studies were identified, describing the validation process of 38 simulation models. Face validity was evaluated in 33 articles, content in 36 and construct in 19. Twenty-two models received adequate validation scores (>70%). The majority (27/38, 70%) was strictly inanimate. Five models were available for purchase and eleven models were replicable based on the article. CONCLUSION: The number of validated inanimate simulation models for pediatric surgery procedures is growing, however, few are replicable or available for widespread training purposes. LEVEL OF EVIDENCE: Level II.

Item does not contain fulltext, INTRODUCTION: An anorectal malformation (ARM) is a congenital malformation that requires surgical correction. To acquire the skills needed to perform this complex procedure, an affordable simulation model has previously been developed and validated. The aim of this study is to evaluate the suitability of this ARM model (with perineal fistula) for training in hands-on workshops. MATERIALS AND METHODS: The ARM model consists of a wooden casing with disposable perineal body. Participants in several international pediatric colorectal hands-on workshops in 2019 and 2020 were asked to participate. They were divided in a target group and an experienced group based on experience. All practiced the posterior sagittal anorectoplasty procedure on the model with multimodality guidance. Subsequently, statements on the suitability of the model for use during hands-on workshops were scored on a 5-point Likert scale. RESULTS: A total of 80 participants were included (43 surgical specialists, 13 pediatric surgery fellows, and 25 residents). Nearly, all statements scored at least a mean of >4.0, all scored significantly better than a neutral opinion. The target group (n = 58) scored higher compared with the experienced group (n = 22) on "transferability of the skills to the clinical setting" (means 4.4 vs. 4.0, p = 0.038); however, the "suitability as a replacement for an animal model" scored significantly lower (means 3.6 vs. 3.9, p = 0.049). No other differences were found. CONCLUSION: This affordable ARM model was regarded a suitable model for training during preclinical hands-on workshops and could be used for the specified steps of the procedure.

Contains fulltext : 285306.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, INTRODUCTION: Self-assessment aids "reflection-before-practice," which is expected to result in a better understanding of one's strengths and weaknesses and consequently a better overall performance. This is, however, rarely used in surgical training. This study aims to evaluate the correlation between self-, peer-, and expert assessment on surgical skills of pediatric surgical trainees. MATERIALS AND METHODS: A competency assessment tool for the posterior sagittal anorectoplasty (CAT-PSARP) was previously developed and validated. During international hands-on pediatric colorectal workshops in 2019 and 2020, participants practiced the PSARP on an inanimate anorectal malformation model. They were assisted by a peer and assessed by two independent expert observers, using the CAT-PSARP. After the training session, both self- and peer assessment were completed, using the same CAT-PSARP. RESULTS: A total of 79 participants were included. No correlation was found between the overall CAT-PSARP scores of the expert observers and the self-assessment (r = 0.179, p = 0.116), while a weak correlation was found between experts and peer assessment (r = 0.317, p = 0.006). When comparing the self-assessment scores with peer assessment, a moderate correlation was found for the overall performance score (r = 0.495, p < 0.001). Additionally, the participants who were first to perform the procedure scored significantly better than those who trained second on the overall performance (mean 27.2 vs. 24.4, p�< 0.001). CONCLUSION: Participants, peers, and experts seemed to have a unique view on the performance during training because there was little correlation between outcomes of the trainees and the experts. Self-assessment may be useful for reflection during training; however, expert assessment seems to be essential for assessment of surgical skills.

Item does not contain fulltext, Background: Current training programs for complex pediatric minimal invasive surgery (MIS) are usually bulk training, consisting of 1- or 2-day courses. The aim of this study was to examine the effects of bulk training versus interval training on the preservation of high-complex, low-volume MIS skills. Materials and Methods: Medical students, without prior surgical experience, were randomly assigned to either a bulk or interval training program for complex MIS (congenital diaphragmatic hernia [CDH] and esophageal atresia [EA] repair). Both groups trained for 5 hours; the bulk group twice within 3 days and the interval groups five times in 3 weeks. Skills retention was assessed at 2 weeks, 6 weeks, and 6 months posttraining, using a composite score (0%-100%) based on the objective parameters tracked by SurgTrac. Results: Seventeen students completed the training sessions (bulk n = 9, interval n = 8) and were assessed accordingly. Retention of the skills for EA repair was significantly better for the interval training group than for the bulk group at 6 weeks (P = .004). However, at 6 months, both groups scored significantly worse than after the training sessions for EA repair (bulk 60 versus 67, P = .176; interval 63 versus 74, P = .028) and CDH repair (bulk 32 versus 67, P = .018; interval 47 versus 62, P = .176). Conclusion: This pilot study suggests superior retention of complex pediatric MIS skills after interval training, during a longer period of time, than bulk training. However, after 6 months, both groups scored significantly worse than after their training, indicating the need for continuous training.

Item does not contain fulltext, Background: To increase complex minimally invasive skills (MIS), frequent training outside the clinical setting is of uttermost importance. This study compares two low-cost pediatric MIS simulators, which can easily be used preclinically. Materials and Methods: The LaparoscopyBoxx is a portable simulator without a tracking system, with costs ranging from €90 to €315. The EoSim simulator has a built-in camera and tracking system and costs range from €780 to €1800. During several pediatric surgical conferences and workshops (January 2017-December 2018), participants were asked to use both simulators. Afterward, they completed a questionnaire regarding their opinion on realism and didactic value, scored on a five-point Likert scale. Results: A total of 50 participants (24 experts and 25 target group, one unknown) evaluated one or both simulators. Both simulators scored well on the questionnaire. The LaparoscopyBoxx scored significantly better regarding the "on screen representation of the instrument actions" (mean 4.2 versus 3.5, P = .001), "training tool for pediatric surgery" (mean 4.4 versus 3.9, P = .005), and "appealing take-home simulator" (mean 4.6 versus 4.0, P = .002). Conclusion: The simulators tested in this study were both regarded an appealing take-home simulator. The LaparoscopyBoxx scored significantly better than the EoSim, even though this is a low budget simulator without tracking capabilities.

Contains fulltext : 231631.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 205151.pdf (publisher's version ) (Open Access), PURPOSE: We aimed to assess the biological and clinical significance of the human cysteine protease inhibitor cystatin M/E, encoded by the CTS6 gene, in diseases of human hair and skin. METHODS: Exome and Sanger sequencing was performed to reveal the genetic cause in two related patients with hypotrichosis. Immunohistochemical, biophysical, and biochemical measurements were performed on patient skin and 3D-reconstructed skin from patient-derived keratinocytes. RESULTS: We identified a homozygous variant c.361C>T (p.Gln121*), resulting in a premature stop codon in exon 2 of CST6 associated with hypotrichosis, eczema, blepharitis, photophobia and impaired sweating. Enzyme assays using recombinant mutant cystatin M/E protein, generated by site-directed mutagenesis, revealed that this p.Gln121* variant was unable to inhibit any of its three target proteases (legumain and cathepsins L and V). Three-dimensional protein structure prediction confirmed the disturbance of the protease/inhibitor binding sites of legumain and cathepsins L and V in the p.Gln121* variant. CONCLUSION: The herein characterized autosomal recessive hypotrichosis syndrome indicates an important role of human cystatin M/E in epidermal homeostasis and hair follicle morphogenesis.

Contains fulltext : 215504.pdf (publisher's version ) (Closed access), BACKGROUND: This study evaluates 6 years of prenatal rasopathy testing in the Netherlands, updates on previous data and gives recommendations for prenatal rasopathy testing. METHODS: 424 fetal samples, sent in for prenatal rasopathy testing in 2011-2016, were collected. Cohort 1 included 231 samples that were sequenced for 1-5 rasopathy genes. Cohort 2 included 193 samples that were analysed with a 14-gene next generation sequencing (NGS) panel. For all mutation-positive samples in both cohorts, the referring physician provided detailed ultrasound findings and postnatal follow-up. For 168 mutation-negative samples in cohort 2, solely clinical information on the requisition form was collected. RESULTS: In total, 40 (likely) pathogenic variants were detected (9.4%). All fetuses showed a variable degree of involvement of prenatal findings: increased nuchal translucency (NT)/cystic hygroma, distended jugular lymph sacs (JLS), hydrops fetalis, polyhydramnios, pleural effusion, ascites, cardiac defects and renal anomalies. An increased NT was the most common finding. Eight fetuses showed solely an increased NT/cystic hygroma, which were all larger than 5.5 mm. Ascites and renal anomalies appeared to be poor predictors of pathogenic outcome. CONCLUSION: Fetuses with a rasopathy show in general multiple ultrasound findings. The larger the NT and the longer it persists, the more likely it is to find a pathogenic variant. Rasopathy testing is recommended when the fetus shows an isolated increased NT >/=5.0 mm or when NT of >/=3.5 mm and at least one of the following ultrasound anomalies is present: distended JLS, hydrops fetalis, polyhydramnios, pleural effusion, ascites, cardiac defects and renal anomalies.

Background: Two technological innovations in the last decade significantly influenced the diagnostic yield of prenatal cytogenetic testing: genomic microarray allowing high resolution analysis and noninvasive prenatal testing (NIPT) focusing on aneuploidy. To anticipate future trends in prenatal screening and diagnosis, we evaluated the number of invasive tests in our center and the number of aberrant cases diagnosed in the last decade. Methods: We retrospectively analyzed fetal chromosomal aberrations diagnosed in 2009–2018 in 8,608 pregnancies without ultrasound anomalies. Results: The introduction of NIPT as the first-tier test led to a substantial decrease in the number of invasive tests and a substantially increased diagnostic yield of aneuploidies in the first trimester. However, we have also noted a decreased detection of submicroscopic aberrations, since the number of invasive tests substantially decreased. We have observed that pregnant women were interested in broader scope of prenatal screening and diagnosis than detection of common trisomies. Conclusion: Since the frequency of syndromic disorders caused by microdeletions/ microduplications is substantial and current routine NIPT and ultrasound investigations are not able to detect them, we suggest that a noninvasive test with resolution comparable to microarrays should be developed, which will also meet patient's needs.