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3. Significant association between circumvallate placenta, placental abruption and acute chorioamnionitis in preterm birth:A 23-year retrospective cohort study

Author

Stuijt, D. G., Bos, M., Nikkels, P. G.J., Wolterbeek, R., van der Meeren, L. E., Stuijt, D. G., Bos, M., Nikkels, P. G.J., Wolterbeek, R., and van der Meeren, L. E.

Abstract

Aim:circumvallate placenta, placental abruption and acute chorioamnionitis separately are associated with unfavourable clinical outcomes. We aimed to determine the prevalence and define whether an association exists between the three abnormalities. Methods: 16,042 placenta pathology reports between 1997 and 2020 from a tertiary care centre in the Netherlands were retrospectively analysed. For the statistical analysis, the chi-square test and bootstrapping were used to evaluate an association. Results: In our cohort the prevalence of circumvallate placenta is 2.2 %, placental abruption cases 4.0 % and acute chorioamnionitis 20.6 %. We observed a statistically significant association between all three placental abnormalities: circumvallate placenta, placental abruption and acute chorioamnionitis. In addition, there was also an association between circumvallate placenta and acute chorioamnionitis. Conclusion: Our results show that combined presence of circumvallate placenta, placental abruption and acute chorioamnionitis are associated in preterm birth (p = 0.001). A remarkable finding is that the combination of all three abnormalities (circumvallate placenta, placental abruption and acute chorioamnionitis) was not observed in term pregnancies >37 weeks.

Published
2024

5. Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia

Author

Mann, I., Tseng, C. C. S., Rodrigo, S. F., Koudstaal, S., van Ramshorst, J., Beeres, S. L., Dibbets-Schneider, P., de Geus-Oei, L. F., Lamb, H. J., Wolterbeek, R., Zwaginga, J. J., Fibbe, W. E., Westinga, K., Bax, J. J., Doevendans, P. A., Schalij, M. J., Chamuleau, S. A. J., and Atsma, D. E.

Published
2019
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17. AS PER PDF: AS PER PDF

Author

Hogendoorn, G.K., Bruggink, S.C., Hermans, K.E., Kouwenhoven, S.T.P., Quint, K.D., Wolterbeek, R., Eekhof, J.A.H., de Koning, M.N.C., Rissmann, R., Burggraaf, J., and Bouwes Bavinck, J.N.

Published
2018
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20. Use of Glomerular CD68+ Cells as a Surrogate Marker for Endocapillary Hypercellularity in Lupus Nephritis

Author

Bos, E.M.J., Sangle, S.R., Wilhelmus, S., Wolterbeek, R., Jordan, N., D'Cruz, D., Isenberg, D., Cook, H.T., Bruijn, J.A., and Bajema, I.M.

Subjects
lupus nephritis, Nephrology, activity index, endocapillary hypercellularity, glomerular CD68+ cells
Abstract

Introduction: Lupus nephritis (LN) class III or IV is strongly related to patient mortality and morbidity. The interobserver agreement of endocapillary hypercellularity by routine light microscopy, one of the most important lesions determining whether class III or IV is present, is moderate. In IgA nephropathy (IgAN), the presence of glomerular CD68+ cells was found to be a good surrogate marker for endocapillary hypercellularity. We investigated whether the presence of glomerular CD68+ cells could serve as a surrogate marker for endocapillary hypercellularity as well in LN.Methods: A total of 92 LN biopsies were scored for the number of glomerular CD68+ cells using CD68 staining, including endocapillary hypercellularity and the activity index (AI). A new AI was calculated in which CD68+ cells replaced endocapillary hypercellularity. Clinical parameters were obtained from time of biopsy, 1 year after, and 2 years after.Results: The number of glomerular CD68+ cells significantly correlated with endocapillary hypercellularity. A cutoff value of 7 for the maximum number of CD68+ cells within 1 glomerulus in a biopsy yielded a sensitivity of 88% and a specificity of 67% for the presence of endocapillary hypercellularity. Both endocapillary hypercellularity and CD68+ cells correlated with renal function during follow-up. The current and the new AI correlated equally well with the clinical outcome.Conclusion: In LN, CD68+cells can be used as a surrogate marker for endocapillary hypercellularity.

Published
2022
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21. Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy

Author

Bos, E.M., Rijnink, E.C., Zandbergen, M., Pool, J.D.N. Diaz de, Almekinders, M.M., Berden, J.H., Bijl, M. de, Hagen, E.C., Kolster-Bijdevaate, C., Steup-Beekman, G.M., Wolterbeek, R.., Bloemenkamp, K.W.M., Baelde, H.J., Bruijn, J.A., Bajema, I.M., Wilhelmus, S., Bos, E.M., Rijnink, E.C., Zandbergen, M., Pool, J.D.N. Diaz de, Almekinders, M.M., Berden, J.H., Bijl, M. de, Hagen, E.C., Kolster-Bijdevaate, C., Steup-Beekman, G.M., Wolterbeek, R.., Bloemenkamp, K.W.M., Baelde, H.J., Bruijn, J.A., Bajema, I.M., and Wilhelmus, S.

Abstract

Item does not contain fulltext, OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Published
2022

25. Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy

Author

Bos, E.M., Rijnink, E.C., Zandbergen, M., Pool, J.D.N. Diaz de, Almekinders, M.M., Berden, J.H., Bijl, M. de, Hagen, E.C., Kolster-Bijdevaate, C., Steup-Beekman, G.M., Wolterbeek, R.., Bloemenkamp, K.W.M., Baelde, H.J., Bruijn, J.A., Bajema, I.M., and Wilhelmus, S.

Subjects
Pregnancy Complications, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Rheumatology, Pregnancy, Immunology, Leukocytes, Mononuclear, Immunology and Allergy, Humans, Lupus Erythematosus, Systemic, Female, Real-Time Polymerase Chain Reaction, Chimerism
Abstract

Item does not contain fulltext OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Published
2021

27. Endothelial endothelin receptor a expression is associated with podocyte injury and oxidative stress in patients with focal segmental glomerulosclerosis

Author

Lest, N.A. van de, Bakker, A.E., Dijkstra, K.L., Zandbergen, M., Heemskerk, S.A.C., Wolterbeek, R., Bruijn, J.A., and Scharpfenecker, M.

Subjects
focal segmental glomerulosclerosis, endothelin receptor A, podocytes, glomerular endothelial cells, oxidative stress, crosstalk
Abstract

Introduction: The podocyte is thought to be the mainly affected cell type in focal segmental glomerulosclerosis (FSGS). However, recent studies have also indicated a role for glomerular endothelial cells and podocyte-endothelial crosstalk in FSGS development. An experimental model for podocyte injury showed that increased endothelin-1 (ET-1) signaling between podocytes and endothelial cells induces endothelial oxidative stress and subsequent podocyte loss. In the current study, we investigated endothelial endothelin receptor A (ETAR) expression in patients with FSGS and its association with podocyte injury and glomerular oxidative stress.Methods: We selected 39 biopsy samples of patients with FSGS and 8 healthy control subjects, and stained them for ETAR, nephrin and 8-oxo-guanine, a DNA lesion caused by oxidative damage. Glomeruli with ETAR-positive endothelium and with nephrin loss were scored, and the 8-oxo-guanine-positive glomerular area was measured.Results: The mean percentage of glomeruli with ETAR-positive endothelial cells in patients with FSGS was higher compared to that in healthy control subjects (52% vs. 7%; P < 0.001). The presence of glomerular ETAR-positive endothelium was strongly associated with nephrin loss both on the biopsy level (rho = 0.47; P < 0.01), as on the level of individual glomeruli (odds ratio = 2.0; P < 0.001). Moreover, glomeruli with ETAR-positive endothelium showed more 8-oxo-guanine-positive staining (1.9% vs. 2.4%; P = 0.037). Finally, 8-oxo-guanine positivity in glomeruli was associated with increased levels of proteinuria.Conclusion: Taking together our findings, we show that ETAR is increased in glomerular endothelial cells of patients with FSGS and associated with podocyte damage and glomerular oxidative stress. These findings support the hypothesis that ET-1 signaling in glomerular endothelial cells contributes to disease development in patients with FSGS.

Published
2021

28. Safety and effects of two red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial

Author

de Gast-Bakker, D. H., de Wilde, R. B. P., Hazekamp, M. G., Sojak, V., Zwaginga, J. J., Wolterbeek, R., and de Jonge, E.

Subjects
Analysis, Congenital heart defects -- Analysis, Surgery -- Analysis, Health care costs -- Analysis, Hospital patients -- Analysis, Medical centers -- Analysis, Child health -- Analysis, Medical research -- Analysis, Pediatric cardiology -- Analysis, Cardiac patients -- Analysis, Biological products -- Analysis, Genetic disorders -- Analysis, Coronary artery bypass -- Analysis, Congenital heart disease -- Analysis, Medicine, Experimental -- Analysis, Medical care, Cost of -- Analysis, Children -- Health aspects
Abstract

Author(s): D. H. de Gast-Bakker [sup.1], R. B. P. de Wilde [sup.1] [sup.6], M. G. Hazekamp [sup.2], V. Sojak [sup.2], J. J. Zwaginga [sup.3] [sup.4], R. Wolterbeek [sup.5], E. de [...], Objective To investigate the safety and effects of a restrictive red blood cell (RBC) transfusion strategy in pediatric cardiac surgery patients. Design Randomized controlled trial. Setting Pediatric ICU in an academic tertiary care center, Leiden University Medical Center, Leiden, The Netherlands. Patients One hundred seven patients with non-cyanotic congenital heart defects between 6 weeks and 6 years of age. One hundred three patients underwent corrective surgery on cardiopulmonary bypass. Interventions Prior to surgery patients were randomly assigned to one of two groups with specific RBC transfusion thresholds: Hb 10.8 g/dl (6.8 mmol/l) and Hb 8.0 g/dl (5.0 mmol/l). Measurements Length of stay in hospital (primary outcome), length of stay in PICU, duration of ventilation (secondary outcome), incidence of adverse events and complications related to randomization (intention to treat analysis). Results In the restrictive transfusion group, mean volume of transfused RBC was 186 (±70) ml per patient and in the liberal transfusion group 258 (±87) ml per patient, (95 % CI 40.6-104.6), p < 0.001. Length of hospital stay was shorter in patients with a restrictive RBC transfusion strategy: median 8 (IQR 7-11) vs. 9 (IQR 7-14) days, p = 0.047. All other outcome measures and incidence of adverse effects were equal in both RBC transfusion groups. Cost of blood products for the liberal transfusion group was 438.35 (±203.39) vs. 316.27 (±189.96) euros (95 % CI 46.61-197.51) per patient in the restrictive transfusion group, p = 0.002. Conclusions For patients with a non-cyanotic congenital heart defect undergoing elective cardiac surgery, a restrictive RBC transfusion policy (threshold of Hb 8.0 g/dl) during the entire perioperative period is safe, leads to a shorter hospital stay and is less expensive.

Published
2013
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46. Does mucosal inflammation drive recurrence of primary sclerosing cholangitis in liver transplantion recipients with ulcerative colitis?

Author

Dekkers, N., Westerouen van Meeteren, M.J.A., Wolterbeek, R.., Sarasqueta, A.F., Laleman, W., Inderson, A., Desschans, B., Hoek, B. van, Korkmaz, K.S., Vermeire, S., Maljaars, J., Dekkers, N., Westerouen van Meeteren, M.J.A., Wolterbeek, R.., Sarasqueta, A.F., Laleman, W., Inderson, A., Desschans, B., Hoek, B. van, Korkmaz, K.S., Vermeire, S., and Maljaars, J.

Abstract

Contains fulltext : 220062.pdf (Publisher’s version ) (Closed access), BACKGROUND: Liver transplantation remains the only effective evidence based treatment for advanced primary sclerosing cholangitis. However, recurrence of disease occurs in approximately 18%. AIMS: This study aimed to assess risk factors of recurrence of primary sclerosing cholangitis. METHODS: A retrospective cohort study was performed on patients undergoing transplantation for recurrence of primary sclerosing cholangitis in two academic centers (Leuven, Belgium and Leiden, The Netherlands). Besides other risk factors, the degree of mucosal inflammation was assessed as a potential risk factor using histological Geboes scores. RESULTS: 81 patients were included, of which 62 (76.5%) were diagnosed with ulcerative colitis. Seventeen patients (21.0%) developed rPSC during a median follow-up time of 5.2 years. In a subset of 42 patients no association was found between the degree of mucosal inflammation and recurrence, using both original Geboes scores and multiple cut-off points. In the total cohort, cytomegaloviremia post-transplantation (HR: 4.576, 95%CI 1.688-12.403) and younger receiver age at time of liver transplantation (HR: 0.934, 95%CI 0.881-0.990) were independently associated with an increased risk of recurrence of disease. CONCLUSION: This study found no association between the degree of mucosal inflammation and recurrence of primary sclerosing cholangitis. An association with recurrence was found for cytomegaloviremia post-liver transplantation and younger age at time of liver transplantation.

Published
2020

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