Publications by authors named "Cumhur F Oner"

5 Publications

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BMP-2 gene delivery in cell-loaded and cell-free constructs for bone regeneration.

PLoS One 2019 31;14(7):e0220028. Epub 2019 Jul 31.

Dept. Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.

To induce osteogenicity in bone graft substitutes, plasmid-based expression of BMP-2 (pBMP-2) has been successfully applied in gene activated matrices based on alginate polymer constructs. Here, we investigated whether cell seeding is necessary for non-viral BMP-2 gene expression in vivo. Furthermore, to gain insight in the role of BMP-producing cells, we compared inclusion of bone progenitor cells with non-osteogenic target cells in gene delivery constructs. Plasmid DNA encoding GFP (pGFP) was used to trace transfection of host tissue cells and seeded cells in a rat model. Transgene expression was followed in both cell-free alginate-ceramic constructs as well as constructs seeded with syngeneic fibroblasts or multipotent mesenchymal stromal cells (MSCs). Titration of pGFP revealed that the highest pGFP dose resulted in frequent presence of positive host cells in the constructs. Both cell-loaded groups were associated with transgene expression, most effectively in the MSC-loaded constructs. Subsequently, we investigated effectiveness of cell-free and cell-loaded alginate-ceramic constructs with pBMP-2 to induce bone formation. Local BMP-2 production was found in all groups containing BMP-2 plasmid DNA, and was most pronounced in the groups with MSCs transfected with high concentration pBMP-2. Bone formation was only apparent in the recombinant protein BMP-2 group. In conclusion, we show that non-viral gene delivery of BMP-2 is a potentially effective way to induce transgene expression in vivo, both in cell-seeded as well as cell-free conditions. However, alginate-based gene delivery of BMP-2 to host cells or seeded cells did not result in protein levels adequate for bone formation in this setting, calling for more reliable scaffold compatible transfection methods.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220028PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668905PMC
March 2020

Injuries related to bicycle accidents: an epidemiological study in The Netherlands.

Eur J Trauma Emerg Surg 2020 Apr 15;46(2):413-418. Epub 2018 Oct 15.

Departement of Orthopaedics, Diakonessenhuis Utrecht/Zeist, Utrecht/Zeist, The Netherlands.

Background: This study aims to analyze the incidence and outcomes of bicycle-related injuries in hospitalized patients in The Netherlands.

Methods: Bicycle accidents resulting in hospitalization in a level-I trauma center in The Netherlands between 2007 and 2017 were retrospectively identified. We subcategorized data of patients involved in a regular bicycle, race bike, off-road bike or e-bike accident. The primary outcomes were mortality rate and incidence of multitrauma. Secondary outcomes were differences between bicycle subcategories. Independent risk factors were identified using multivariable logistic regression. All variables with a p value < 0.20 in univariable analysis were entered in multivariable analysis.

Results: We identified 1986 patients. The mortality rate after emergency room admission was 5.7%, and 41.0% were multitraumas. A higher age, multitrauma and cerebral haemorrhages were independent risk factors for in hospital mortality. Independent risk factors found for multitrauma were a higher age, two-sided trauma, e-bike accidents and cerebral haemorrhage.

Conclusion: Bicycle accidents resulting in hospitalization have a high mortality rate. Furthermore, a high incidence of multitrauma, fractures and cerebral haemorrhages were found. Considering the increasing incidence of bicycle accident victims needing hospital admission, new and more efficient prevention strategies are essential.
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http://dx.doi.org/10.1007/s00068-018-1033-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113215PMC
April 2020

Fixation of flail chest or multiple rib fractures: current evidence and how to proceed. A systematic review and meta-analysis.

Eur J Trauma Emerg Surg 2019 Aug 1;45(4):631-644. Epub 2018 Oct 1.

Department of Surgery, University Medical Center Utrecht, PO Box 85500, 3508 GA, Utrecht, The Netherlands.

Purpose: The aim of this systematic review and meta-analysis was to present current evidence on rib fixation and to compare effect estimates obtained from randomized controlled trials (RCTs) and observational studies.

Methods: MEDLINE, Embase, CENTRAL, and CINAHL were searched on June 16th 2017 for both RCTs and observational studies comparing rib fixation versus nonoperative treatment. The MINORS criteria were used to assess study quality. Where possible, data were pooled using random effects meta-analysis. The primary outcome measure was mortality. Secondary outcome measures were hospital length of stay (HLOS), intensive care unit length of stay (ILOS), duration of mechanical ventilation (DMV), pneumonia, and tracheostomy.

Results: Thirty-three studies were included resulting in 5874 patients with flail chest or multiple rib fractures: 1255 received rib fixation and 4619 nonoperative treatment. Rib fixation for flail chest reduced mortality compared to nonoperative treatment with a risk ratio of 0.41 (95% CI 0.27, 0.61, p < 0.001, I = 0%). Furthermore, rib fixation resulted in a shorter ILOS, DMV, lower pneumonia rate, and need for tracheostomy. Results from recent studies showed lower mortality and shorter DMV after rib fixation, but there were no significant differences for the other outcome measures. There was insufficient data to perform meta-analyses on rib fixation for multiple rib fractures. Pooled results from RCTs and observational studies were similar for all outcome measures, although results from RCTs showed a larger treatment effect for HLOS, ILOS, and DMV compared to observational studies.

Conclusions: Rib fixation for flail chest improves short-term outcome, although the indication and patient subgroup who would benefit most remain unclear. There is insufficient data regarding treatment for multiple rib fractures. Observational studies show similar results compared with RCTs.
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http://dx.doi.org/10.1007/s00068-018-1020-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689030PMC
August 2019

The evidence on surgical interventions for low back disorders, an overview of systematic reviews.

Eur Spine J 2013 Sep 17;22(9):1936-49. Epub 2013 May 17.

Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, The Netherlands,

Purpose: Many systematic reviews have been published on surgical interventions for low back disorders. The objective of this overview was to evaluate the available evidence from systematic reviews on the effectiveness of surgical interventions for disc herniation, spondylolisthesis, stenosis, and degenerative disc disease (DDD). An earlier version of this review was published in 2006 and since then, many new, better quality reviews have been published.

Methods: A comprehensive search was performed in the Cochrane database of systematic reviews (CDSR), database of reviews of effectiveness (DARE) and Pubmed. Two reviewers independently performed the selection of studies, risk of bias assessment, and data extraction. Included are Cochrane reviews and non-Cochrane systematic reviews published in peer-reviewed journals. The following conditions were included: disc herniation, spondylolisthesis, and DDD with or without spinal stenosis. The following comparisons were evaluated: (1) surgery vs. conservative care, and (2) different surgical techniques compared to one another. The methodological quality of the systematic reviews was evaluated using AMSTAR. We report (pooled) analyses from the individual reviews.

Results: Thirteen systematic reviews on surgical interventions for low back disorders were included for disc herniation (n = 6), spondylolisthesis (n = 2), spinal stenosis (n = 4), and DDD (n = 4). Nine (69 %) were of high quality. Five reviews provided a meta-analysis of which two showed a significant difference. For the treatment of spinal stenosis, intervertebral process devices showed more favorable results compared to conservative treatment on the Zurich Claudication Questionnaire [mean difference (MD) 23.2 95 % CI 18.5-27.8]. For degenerative spondylolisthesis, fusion showed more favorable results compared to decompression for a mixed aggregation of clinical outcome measures (RR 1.40 95 % CI 1.04-1.89) and fusion rate favored instrumented fusion over non-instrumented fusion (RR 1.37 95 % CI 1.07-1.75).

Conclusions: For most of the comparisons, the included reviews were not significant and/or clinically relevant differences between interventions were identified. Although the quality of the reviews was quite acceptable, the quality of the included studies was poor. Future studies are likely to influence our assessment of these interventions.
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http://dx.doi.org/10.1007/s00586-013-2823-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777049PMC
September 2013

The effect of cell-based bone tissue engineering in a goat transverse process model.

Biomaterials 2006 Oct 19;27(29):5099-106. Epub 2006 Jun 19.

Department of Orthopaedics, G05.228, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.

A disadvantage of traditional posterolateral spinal fusion models is that they are highly inefficient for screening multiple conditions. We developed a multiple-condition model that concentrates on the initial process of bone formation from the transverse process and not on a functional fusion. The effect of bone marrow stromal cells (BMSCs) in four different porous ceramic scaffolds was investigated in this setting. Polyacetal cassettes were designed to fit on the goat transverse process and house four different ceramic blocks, i.e: hydroxyapatite (HA) sintered at 1,150 degrees and 1,250 degrees; biphasic calcium phosphate (BCP) and tricalcium phosphate (TCP). Goat BMSCs (n=10) were cultured and per-operatively seeded autologeously on one of two cassettes implanted per animal. The cassettes were bilaterally mounted on the dorsum of decorticated L2-processes for 9 weeks. To asses the dynamics of bone formation, fluorochrome labels were administered and histomorphometry focused on the distribution of bone in the scaffolds. A clear difference in the extent of bone ingrowth was determined for the different scaffold types. An obvious effect of BMSC seeding was observed in three of four scaffold types, especially in scaffold regions adjacent to the overlying muscle. Generally, the BCP and TCP scaffolds showed better osteoconduction and an increased response to BMSCs administration. In conclusion the model provides a reliable and highly efficient method to study bone formation in cell-based tissue engineering. An effect of cell administration was obvious in three of the four scaffold materials.
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http://dx.doi.org/10.1016/j.biomaterials.2006.05.048DOI Listing
October 2006