Jan Deprest

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

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Publications (722)2246.81 Total impact

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    ABSTRACT: Objectives Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/ R) model and prevent late stage fibrosis. Methods A total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey's test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p <0.05.
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    ABSTRACT: 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. A procedure-specific evaluation instrument containing all essential steps of the fetoscopic laser procedure was 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). Inter-observer reliability was assessed using Spearman correlation. We compared performance of novices and experts to assess construct validity. Inter-observer reliability was high (r=0.974, p<0.001). Checklist scores for experts and novices were significantly different: median score for novices was 28/52 (54%) while for experts 42/52 (81%) (p<0.001). 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 9/14 (64%) performed by novices (p=0.006). Multivariate analysis showed that the checklist score independently from age and gender predicted competence. The procedure-specific assessment tool for fetoscopic laser surgery shows a good inter-observer reliability and discriminates experts from novices. This instrument may therefore be a useful tool in the training curriculum for starting fetal surgeons. Further intervention studies with reassessment before and after training may increase the construct validity of the tool. This article is protected by copyright. All rights reserved.
    Ultrasound in Obstetrics and Gynecology 08/2015; DOI:10.1002/uog.15734 · 3.14 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) increases surfactant protein expression in type 2 pneumocytes. Herein, we determine if transplacental GLP-1 treatment accelerates lung growth in the fetal rabbit model of congenital diaphragmatic hernia (DH). Time-mated does had an induction of DH on day 23 followed by daily GLP-1 or placebo injection until term. At that time, the does were weighed, fetal blood was obtained for GLP-1 assay, and the lungs were dissected. Fetal outcome measures were lung-to-body-weight ratio (LBWR), morphometry, and Ki67 and surfactant protein B (SPB) expression. Maternal weight loss in the GLP-1 group was 7.1%. Fetal survival was lower in GLP-1 fetuses compared to placebo controls (27/85, 32% vs. 35/57, 61%; p < 0.05). Fetal GLP-1 levels were increased 3.6-fold. The LBWR of GLP-1 DH fetuses fell within the range of DH placebo fetuses (1.166 ± 0.207% vs. 1.312 ± 0.418%), being significantly lower than that of placebo-exposed unoperated fetuses (2.280 ± 0.522%; p < 0.001). GLP-1 did not improve airway morphometry. GLP-1 DH lungs had a reduced adventitial and medial thickness within the range of controls, and lesser muscularization of vessels measuring 30-60 µm. There were no differences in Ki67 and SPB expression. GLP-1 at this dosage improves peripheric pulmonary vessel morphology in intra-acinar vessels with no effect on airway morphometry but with significant maternal and fetal side effects. Thus, it is an unlikely medical strategy. © 2015 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 08/2015; DOI:10.1159/000436962 · 2.30 Impact Factor
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    ABSTRACT: Fetal surgery has become a clinical reality, with interventions for twin-to-twin transfusion syndrome (TTTS) and spina bifida demonstrated to improve outcome. Fetal imaging is evolving, with the use of 3D ultrasound and fetal MRI becoming more common in clinical practise. Medical imaging analysis is also changing, with technology being developed to assist surgeons by creating 3D virtual models that improve understanding of complex anatomy, and prove powerful tools in surgical planning and intraoperative guidance. We introduce the concept of computer-assisted surgical planning, and present the results of a systematic review of image reconstruction for fetal surgical planning that identified six articles using such technology. Indications from other specialities suggest a benefit of surgical planning and guidance to improve outcomes. There is therefore an urgent need to develop fetal-specific technology in order to improve fetal surgical outcome. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 07/2015; DOI:10.1002/pd.4660 · 3.27 Impact Factor
  • BJOG An International Journal of Obstetrics & Gynaecology 07/2015; DOI:10.1111/1471-0528.13505 · 3.86 Impact Factor
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    ABSTRACT: Neonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes. 2.0x1.0 cm diaphragmatic defects were created in 6-weeks old New-Zealand white rabbits. We compared reconstruction with a purpose-designed cross-linked ACM (Matricel) to 4-layer non-cross-linked small intestinal submucosa (SIS) and a 1-layer synthetic Dual Mesh (Gore-Tex). Unoperated animals or animals undergoing primary closure (4/0 polyglecaprone) served as age-matched controls. 60 (n = 25) resp. 90 (n = 17) days later, animals underwent chest x-ray and obduction for gross examination of explants, scoring of adhesion and inflammatory response. Also, uniaxial tensiometry was done, comparing explants to contralateral native diaphragmatic tissue. Overall weight nearly doubled from 1,554±242 g at surgery to 2,837±265 g at obduction (+84%). X-rays did show rare elevation of the left diaphragm (SIS = 1, Gore-Tex = 1, unoperated control = 1), but no herniation of abdominal organs. 56% of SIS and 10% of Matricel patches degraded with visceral bulging in four (SIS = 3, Matricel = 1). Adhesion scores were limited: 0.5 (Matricel) to 1 (SIS, Gore-Tex) to the left lung (p = 0.008) and 2.5 (Gore-Tex), 3 (SIS) and 4 (Matricel) to the liver (p<0.0001). Tensiometry revealed a reduced bursting strength but normal compliance for SIS. Compliance was reduced in Matricel and Gore-Tex (p<0.01). Inflammatory response was characterized by a more polymorphonuclear cell (SIS) resp. macrophage (Matricel) type of infiltrate (p<0.05). Fibrosis was similar for all groups, except there was less mature collagen deposited to Gore-Tex implants (p<0.05). Matricel induced a macrophage-dominated inflammatory response, more adhesions, had appropriate strength but a lesser compliance compared to native tissue. The herein investigated ACM is not a viable option for CDH repair.
    PLoS ONE 07/2015; 10(7):e0132021. DOI:10.1371/journal.pone.0132021 · 3.23 Impact Factor
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    ABSTRACT: To assess in vivo changes in lung and liver volume in fetuses with isolated congenital diaphragmatic hernia (CDH), either expectantly managed or treated in utero. This is a secondary analysis of prospectively collected data at 2 fetal therapy centers. We used archived magnetic resonance (MR) images of fetuses taken ≥7 days apart, creating paired observations in 20 expectantly managed cases, 41 with a second MR prior to balloon reversal and 64 after balloon removal. We measured observed to expected total fetal lung volume (O/E TFLV) and liver-to-thoracic volume ratio (LiTR). We calculated changes in volume as compared to the initial measurement and its rate as a function of gestational age (GA) at occlusion. The LiTR did not change in either group. In expectantly managed fetuses, O/E TFLV did not increase with gestation. In fetuses undergoing tracheal occlusion (TO) the measured increase in volume was 2.6-times larger with balloon in place as compared to after its removal. GA at TO was an independent predictor of the O/E TFLV. The net rate seems to initially increase and plateau at a maximum of 1.5%/week by 35-45 days after occlusion. TO induces a net increase in volume, its magnitude essentially dependent on the GA at occlusion. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Prenatal Diagnosis 07/2015; DOI:10.1002/pd.4642 · 3.27 Impact Factor
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    ABSTRACT: To evaluate the effect of a newly developed training curriculum on performance of fetoscopic laser surgery for twin-twin transfusion syndrome (TTTS) using an advanced high-fidelity simulator model. Ten novices were randomized to receive verbal instructions and skills training using the simulator (study group, n = 5) or no training (control group, n = 5). Both groups were evaluated with a pre-training test and post-training test. Assessment was performed by two independent observers and compromised a 52-item checklist for surgical performance (SP score), measurement of procedure time and number of anastomoses missed. Face validity and educational value of the simulator were assessed using a questionnaire. Eleven experts set the benchmark level of performance. Both groups showed an improvement in SP score compared to 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 versus 25 (48%) and 36 (69%) (p = 0.008). Procedure time decreased 11 min in the study group versus 1 min in the control group; to 32 min versus 38 min, respectively (p = 0.69). The number of missed anastomoses was not different between groups (1 versus none). Feedback provided by the participants indicated that training on the simulator was perceived as a useful educational activity. Proficiency-based simulator training improves performance on surgical performance 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. This article is protected by copyright. All rights reserved.
    Ultrasound in Obstetrics and Gynecology 06/2015; DOI:10.1002/uog.14916 · 3.14 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate the prevalence of veno-venous (VV) anastomoses in a large cohort of monochorionic (MC) twin placentas with twin-twin transfusion syndrome (TTTS) compared to a control group of MC placentas without TTTS. All TTTS placentas not treated with fetoscopic laser surgery (TTTS group) and examined at five international fetal therapy centers were included in this study and compared with a control group of MC placentas without TTTS (non-TTTS group). MC placentas were routinely injected with colored dye. We recorded the presence of VV and arterio-arterial (AA) anastomoses. A total of 414 MC placentas were included in this study (TTTS group, n = 106; non-TTTS group, n = 308). The prevalence of VV anastomoses was significantly higher in the TTTS group than in the non-TTTS group, 36% (38/106) and 25% (78/308), respectively (p = .04; odds ratio (OR) 1.65; 95% confidence interval (CI): 1.03-2.64). In the subgroup of MC placentas without AA anastomoses, the prevalence of VV anastomoses in the TTTS group and non-TTTS group was 32% (18/57) and 8% (2/25), respectively (p = .03; OR: 5.31; 95% CI: 1.13-24.98). VV anastomoses are detected more frequently in TTTS placentas than in MC placentas without TTTS and may thus play a role in the development of TTTS. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Placenta 05/2015; DOI:10.1016/j.placenta.2015.05.014 · 3.29 Impact Factor
  • Materials 05/2015; 8(5):2794-2808. DOI:10.3390/ma8052794 · 1.88 Impact Factor
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    ABSTRACT: The properties of meshes used in reconstructive surgery affect the host response and biomechanical characteristics of the grafted tissue. Whereas durable synthetics induce a chronic inflammation, biological grafts are usually considered as more biocompatible. The location of implantation is another determinant of the host response: the vagina is a different environment with specific function and anatomy. Herein, we evaluated a cross-linked acellular collagen matrix (ACM), pretreated by the anti-calcification procedure ADAPT® in a sheep model for vaginal surgery. Ten sheep were implanted with a cross-linked ACM, and six controls were implanted with a polypropylene (PP; 56 g/m2) control. One implant was inserted in the lower rectovaginal septum, and one was used for abdominal wall defect reconstruction. Grafts were removed after 180 days; all graft-related complications were recorded, and explants underwent bi-axial tensiometry and contractility testing. Half of ACM-implanted animals had palpable induration in the vaginal implantation area, two of these also on the abdominal implant. One animal had a vaginal exposure. Vaginal ACMs were 63 % less stiff compared to abdominal ACM explants (p = 0.01) but comparable to vaginal PP explants. Seven anterior vaginal ACM explants showed areas of graft degradation on histology. There was no overall difference in vaginal contractility. Considering histologic degradation in the anterior vaginal implant as representative for the host, posterior ACM explants of animals with degradation had a 60 % reduced contractility as compared to PP (p = 0.048). Three abdominal implants showed histologic degradation; those were more compliant than non-degraded implants. Vaginal implantation with ACM was associated with graft-related complications (GRCs) and biomechanical properties comparable to PP. Partially degraded ACM had a decreased vaginal contractility.
    Gynecological Surgery 05/2015; 12(2). DOI:10.1007/s10397-015-0883-7
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    ABSTRACT: Objective We aimed to systematically review all published pre-clinical research on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Background The neonatal mortality due to isolated CDH remains high. Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to be demonstrated. Therefore more potent preferentially medical therapy would be welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science including all studies from the earliest date (1951) to December 2013. Article quality was assessed using the modified CAMRADES checklist. Inclusion criteria were those animal studies addressing prenatal medical interventions and principal variables were confirmation of a diaphragmatic defect, lung to body weight ratio (LBWR), formal airway morphometry or DNA/protein content. Results In total 983 articles were identified. Following abstract review, 96 articles were assessed by two authors in agreement with a third for eligibility. Of these, 43 were included in the final analysis. The median number of study quality checklist items (maximum 10) scored was 4 (IQ range: 2–5). Thirty (69.8%) of studies were in the nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single studies reported some improvement in lung morphology with alternative therapies. It was impossible to identify a pattern in animal model selection or creation, mode, time point or duration of treatment and readouts. Only one study reported a sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is challenging due to methodological variation. Agreed standardized methods need to be applied in future investigation of new medical therapies. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.
    Pediatric Pulmonology 05/2015; DOI:10.1002/ppul.23206 · 2.30 Impact Factor
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    ABSTRACT: To evaluate the feasibility of tracheo-amniotic shunting in a sheep model for congenital high airway obstruction syndrome. High airway obstruction was induced around day 95 (term = 145 days) in 10 lamb fetuses by tracheal clipping. Five days later, ultrasound-guided tracheoamniotic shunting was done using either the Harrison double-pigtail bladder stent (HS) or a double-basket device (BS). Caesarean section (CS) was done around day 110. At each time point, the cardiothoracic index (CTI) was measured. Lung-to-body weight ratio (LBWR) was calculated at fetal necropsy. The primary endpoint was successful shunting defined as anatomically correct placement and functional airway decompression; the secondary endpoint was survival until CS. Two sheep aborted 3 fetuses after tracheal occlusion. Overall, the median CTI at CS was significantly smaller compared to baseline [0.52 (interquartile range, IQR: 0.52-0.54) vs. 0.58 (IQR: 0.54-0.63); p = 0.01]. In the HS group (n = 4), none of the shunts were correctly positioned. In the BS group (n = 3), there was 1 correct shunt placement; however, this fetus was stillborn. Median LBWR suggested pulmonary overgrowth [0.10 (IQR: 0.08-0.11)]. In our hands, using this model with a long and mobile neck and relative oligohydramnios, tracheoamniotic shunting for airway obstruction has a high failure rate. If further pursued, alternative techniques or different models should be considered. © 2015 S. Karger AG, Basel.
    Fetal Diagnosis and Therapy 04/2015; DOI:10.1159/000381145 · 2.30 Impact Factor
  • European Urology Supplements 04/2015; 14(2):e74. DOI:10.1016/S1569-9056(15)60076-8 · 3.37 Impact Factor
  • European Urology Supplements 04/2015; 14(2):e1005. DOI:10.1016/S1569-9056(15)60993-9 · 3.37 Impact Factor
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    ABSTRACT: Our primary objective was to develop relevant algorithms for quantification of mesh position and 3D shape in magnetic resonance (MR) images. In this proof-of-principle study, one patient with severe anterior vaginal wall prolapse was implanted with an MR-visible mesh. High-resolution MR images of the pelvis were acquired 6 weeks and 8 months postsurgery. 3D models were created using semiautomatic segmentation techniques. Conformational changes were recorded quantitatively using part-comparison analysis. An ellipticity measure is proposed to record longitudinal conformational changes in the mesh arms. The surface that is the effective reinforcement provided by the mesh is calculated using a novel methodology. The area of this surface is the effective support area (ESA). MR-visible mesh was clearly outlined in the images, which allowed us to longitudinally quantify mesh configuration between 6 weeks and 8 months after implantation. No significant changes were found in mesh position, effective support area, conformation of the mesh's main body, and arm length during the period of observation. Ellipticity profiles show longitudinal conformational changes in posterior arms. This paper proposes novel methodologies for a systematic 3D assessment of the position and morphology of MR-visible meshes. A novel semiautomatic tool was developed to calculate the effective area of support provided by the mesh, a potentially clinically important parameter.
    International Urogynecology Journal 03/2015; DOI:10.1007/s00192-015-2681-1 · 2.16 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S103. DOI:10.1016/j.ajog.2014.10.223 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S44-S45. DOI:10.1016/j.ajog.2014.10.109 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S273. DOI:10.1016/j.ajog.2014.10.593 · 3.97 Impact Factor
  • American Journal of Obstetrics and Gynecology 01/2015; 212(1):S171. DOI:10.1016/j.ajog.2014.10.363 · 3.97 Impact Factor

Publication Stats

10k Citations
2,246.81 Total Impact Points

Institutions

  • 1970–2015
    • Universitair Ziekenhuis Leuven
      • Department of Gynaecology and obstetrics
      Louvain, Flanders, Belgium
  • 1995–2014
    • University of Leuven
      • • Department of Development and Regeneration
      • • Faculty of Medicine
      • • Department of Human Genetics
      Louvain, Flemish, Belgium
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2012
    • University of Sarajevo
      • Department of Pharmacology, Toxicology and Clinical Pharmacology
      Bosna-Sarai, Federation of Bosnia and Herzegovina, Bosnia and Herzegovina
  • 2009–2012
    • Catholic University of Louvain
      Лувен-ла-Нев, Walloon, Belgium
  • 2008–2012
    • Universitair Ziekenhuis Ghent
      Gand, Flemish, Belgium
    • St. Michael's Hospital
      Toronto, Ontario, Canada
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2010
    • Cliniques Universitaires Saint-Luc
      • Division of Obstetrics
      Bruxelles, Brussels Capital Region, Belgium
  • 2008–2009
    • Leiden University Medical Centre
      • • Department of Neonatology
      • • Department of Pediatrics
      Leiden, South Holland, Netherlands
  • 2007–2009
    • Hospital Clínic de Barcelona
      • Servicio de Medicina Materno Fetal
      Barcino, Catalonia, Spain
    • King's College Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2006–2007
    • King's College London
      • Division of Asthma, Allergy and Lung Biology
      Londinium, England, United Kingdom
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
    • University of Cincinnati
      Cincinnati, Ohio, United States
    • University of Texas Health Science Center at San Antonio
      • Department of Obstetrics and Gynecology
      San Antonio, Texas, United States
  • 2005
    • University of Zurich
      Zürich, Zurich, Switzerland
    • University Hospital Vall d'Hebron
      Barcino, Catalonia, Spain
  • 2001–2005
    • ՊԵՐԻՆԱՏՈԼՈԳԻԱՅԻ, ՄԱՆԿԱԲԱՐՁՈՒԹՅԱՆ ԵՎ ԳԻՆԵԿՈԼՈԳԻԱՅԻ ԻՆՍՏԻՏՈՒՏ
      Ayrivan, Yerevan, Armenia
  • 2004
    • Wayne State University
      • Department of Obstetrics and Gynecology
      Detroit, Michigan, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
  • 1995–2004
    • Universitair Psychiatrisch Centrum KU Leuven
      Cortenberg, Flanders, Belgium
  • 2003
    • Harbor-UCLA Medical Center
      Torrance, California, United States
    • Fukushima Medical University
      Hukusima, Fukushima, Japan
    • Boston University
      Boston, Massachusetts, United States
  • 2002
    • University of Milan
      Milano, Lombardy, Italy
    • The University of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 2000
    • University of Hamburg
      Hamburg, Hamburg, Germany
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1998
    • McGill University
      • Department of Surgery
      Montréal, Quebec, Canada
  • 1996
    • Rhode Island Hospital
      Providence, Rhode Island, United States