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2. Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease: An evaluation in the COPDGene cohort

Author

Oudkerk, Sytse F, Mohamed Hoesein, Firdaus AA, PThM Mali, Willem, Öner, F Cumhur, Verlaan, Jorrit-Jan, de Jong, Pim A, Kinney, Gregory L, Hokanson, John, Lynch, David, Silverman, Edwin K, Budoff, Matthew J, and Regan, Elizabeth A

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Heart Disease - Coronary Heart Disease, Prevention, Clinical Research, Cardiovascular, Atherosclerosis, Heart Disease, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Aged, Aged, 80 and over, Coronary Artery Disease, Female, Follow-Up Studies, Humans, Hyperostosis, Incidence, Male, Middle Aged, Multidetector Computed Tomography, Retrospective Studies, Risk Assessment, Risk Factors, United States, Vascular Calcification, Calciumscore, CT, DISH, Coronary artery disease, Agatson score, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background and aimsDiffuse idiopathic skeletal hyperostosis (DISH) is a common incidental finding on medical imaging and often thought to be benign. Our objective was to investigate whether DISH is associated with coronary artery disease as measured with the coronary artery calcification (CAC) score in a large cohort of current and former smokers.MethodsIn a subset of subjects from the COPDGene study, DISH was scored by a minimum of two independent readers if there were four adjacent levels of flowing osteophytes and a third reader adjudicated discrepancies. CAC was calculated using a modified Agatston method. Associations of DISH with the presence and extent of CAC were analyzed with and without adjustment for COPD and known atherosclerotic risk factors, including age, sex, race, diabetes, hypertension, high cholesterol, body mass index and smoking.ResultsDISH was present in 361 subjects (13.2%) from a total group of 2728. Median (interquartile range) Agatston was 81 (0-329) in DISH subjects compared to 0 (0-94 in subjects without DISH (p

Published
2019

3. Surgical versus conservative treatment for odontoid fractures in older people: an international prospective comparative study

Author

MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Neurochirurgen, Huybregts, Jeroen G.J., Polak, Samuel B., Jacobs, Wilco C., Arts, Mark P., Meyer, Bernhard, Wostrack, Maria, Butenschön, Vicki M., Osti, Michael, Öner, F. Cumhur, Slooff, Willem Bart M., Feller, Ricardo E., Bouma, Gert Joan, Harhangi, Biswadjiet S., Depreitere, Bart, Nygaard, Øystein P., Weber, Clemens, Müller, Kay, Timothy, Jake, Pellisé, Ferran, Rasmussen, Mikkel M., van Zwet, Erik W., Steyerberg, Ewout W., Peul, Wilco C., Vleggeert-Lankamp, Carmen L.A., MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Neurochirurgen, Huybregts, Jeroen G.J., Polak, Samuel B., Jacobs, Wilco C., Arts, Mark P., Meyer, Bernhard, Wostrack, Maria, Butenschön, Vicki M., Osti, Michael, Öner, F. Cumhur, Slooff, Willem Bart M., Feller, Ricardo E., Bouma, Gert Joan, Harhangi, Biswadjiet S., Depreitere, Bart, Nygaard, Øystein P., Weber, Clemens, Müller, Kay, Timothy, Jake, Pellisé, Ferran, Rasmussen, Mikkel M., van Zwet, Erik W., Steyerberg, Ewout W., Peul, Wilco C., and Vleggeert-Lankamp, Carmen L.A.

Published
2024

4. Surgical versus conservative treatment for odontoid fractures in older people:an international prospective comparative study

Author

Huybregts, Jeroen G.J., Polak, Samuel B., Jacobs, Wilco C., Arts, Mark P., Meyer, Bernhard, Wostrack, Maria, Butenschön, Vicki M., Osti, Michael, Öner, F. Cumhur, Slooff, Willem Bart M., Feller, Ricardo E., Bouma, Gert Joan, Harhangi, Biswadjiet S., Depreitere, Bart, Nygaard, Øystein P., Weber, Clemens, Müller, Kay, Timothy, Jake, Pellisé, Ferran, Rasmussen, Mikkel M., van Zwet, Erik W., Steyerberg, Ewout W., Peul, Wilco C., Vleggeert-Lankamp, Carmen L.A., Huybregts, Jeroen G.J., Polak, Samuel B., Jacobs, Wilco C., Arts, Mark P., Meyer, Bernhard, Wostrack, Maria, Butenschön, Vicki M., Osti, Michael, Öner, F. Cumhur, Slooff, Willem Bart M., Feller, Ricardo E., Bouma, Gert Joan, Harhangi, Biswadjiet S., Depreitere, Bart, Nygaard, Øystein P., Weber, Clemens, Müller, Kay, Timothy, Jake, Pellisé, Ferran, Rasmussen, Mikkel M., van Zwet, Erik W., Steyerberg, Ewout W., Peul, Wilco C., and Vleggeert-Lankamp, Carmen L.A.

Abstract

Background: The optimal treatment for odontoid fractures in older people remains debated. Odontoid fractures are increasingly relevant to clinical practice due to ageing of the population.Methods: An international prospective comparative study was conducted in fifteen European centres, involving patients aged ≥55 years with type II/III odontoid fractures. The surgeon and patient jointly decided on the applied treatment. Surgical and conservative treatments were compared. Primary outcomes were Neck Disability Index (NDI) improvement, fracture union and stability at 52 weeks. Secondary outcomes were Visual Analogue Scale neck pain, Likert patient-perceived recovery and EuroQol-5D-3L at 52 weeks. Subgroup analyses considered age, type II and displaced fractures. Multivariable regression analyses adjusted for age, gender and fracture characteristics. Results: The study included 276 patients, of which 144 (52%) were treated surgically and 132 (48%) conservatively (mean (SD) age 77.3 (9.1) vs. 76.6 (9.7), P = 0.56). NDI improvement was largely similar between surgical and conservative treatments (mean (SE) −11 (2.4) vs. −14 (1.8), P = 0.08), as were union (86% vs. 78%, aOR 2.3, 95% CI 0.97–5.7) and stability (99% vs. 98%, aOR NA). NDI improvement did not differ between patients with union and persistent non-union (mean (SE) −13 (2.0) vs. −12 (2.8), P = 0.78). There was no difference for any of the secondary outcomes or subgroups. Conclusions: Clinical outcome and fracture healing at 52 weeks were similar between treatments. Clinical outcome and fracture union were not associated. Treatments should prioritize favourable clinical over radiological outcomes.

Published
2024

5. Low-Threshold-For-Surgery Versus Primarily-Conservative Treatment for Odontoid Fractures in the Elderly: Evaluating Practice Variation in The Netherlands

Author

Huybregts, Jeroen G. J., primary, Polak, Samuel B., additional, Jacobs, Wilco C. H., additional, Krekels-Huijbregts, Ilse A., additional, Smeets, Anouk Y. J. M., additional, Arts, Mark P., additional, Slooff, Willem-Bart M., additional, Öner, F. Cumhur, additional, Peul, Wilco C., additional, van Santbrink, Henk, additional, and Vleggeert-Lankamp, Carmen L. A., additional

Published
2023
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6. Research Practices and Needs Among Spine Surgeons Worldwide

Author

MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Germscheid, Niccole, Cheung, Jason P.Y., Neva, Marko H., Öner, F. Cumhur, Kwon, Brian K., Valacco, Marcelo, Awwad, Waleed, Sciubba, Daniel M., Lewis, Stephen J., Rhines, Laurence D., Yoon, S. Tim, Alini, Mauro, Grad, Sibylle, Fisher, Charles G., Samartzis, Dino, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Germscheid, Niccole, Cheung, Jason P.Y., Neva, Marko H., Öner, F. Cumhur, Kwon, Brian K., Valacco, Marcelo, Awwad, Waleed, Sciubba, Daniel M., Lewis, Stephen J., Rhines, Laurence D., Yoon, S. Tim, Alini, Mauro, Grad, Sibylle, Fisher, Charles G., and Samartzis, Dino

Published
2023

7. Time to Surgical Treatment for Metastatic Spinal Disease: Identification of Delay Intervals

Author

Zorgeenheid Orthopaedie Medisch, Cancer, Trialbureau Beeld, Other research (not in main researchprogram), JC onderzoeksprogramma Kanker, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, van Tol, Floris R, Versteeg, Anne L, Verkooijen, Helena M, Öner, F Cumhur, Verlaan, Jorrit-J, Zorgeenheid Orthopaedie Medisch, Cancer, Trialbureau Beeld, Other research (not in main researchprogram), JC onderzoeksprogramma Kanker, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, van Tol, Floris R, Versteeg, Anne L, Verkooijen, Helena M, Öner, F Cumhur, and Verlaan, Jorrit-J

Published
2023

8. Research Practices and Needs Among Spine Surgeons Worldwide.

Author

Germscheid, Niccole, Cheung, Jason P. Y., Neva, Marko H., Öner, F. Cumhur, Kwon, Brian K., Valacco, Marcelo, Awwad, Waleed, Sciubba, Daniel M., Lewis, Stephen J., Rhines, Laurence D., Yoon, S. Tim, Alini, Mauro, Grad, Sibylle, Fisher, Charles G., and Samartzis, Dino

Subjects
SPINE, SURGEONS, REGIONAL differences, RESOURCE allocation, UNIVERSITY hospitals
Abstract

Objective: Resource allocation to research activities is challenging and there is limited evidence to justify decisions. Members of AO Spine were surveyed to understand the research practices and needs of spine surgeons worldwide. Methods: An 84-item survey was distributed to the AO Spine community in September of 2020. Respondent demographics and insights regarding research registries, training and education, mentorship, grants and financial support, and future directions were collected. Responses were anonymous and compared among regions. Results: A total of 333 spine surgeons representing all geographic regions responded; 52.3% were affiliated with an academic/university hospital, 91.0% conducted clinical research, and 60.9% had 5+ years of research experience. There was heterogeneity among research practices and needs across regions. North American respondents had more research experience (P =.023), began conducting research early on (P <.001), had an undergraduate science degree (P <.001), and were more likely to have access to a research coordinator or support staff (P =.042) compared to other regions. While all regions expressed having the same challenges in conducting research, Latin America, and Middle East/Northern Africa respondents were less encouraged to do research (P <.001). Despite regional differences, there was global support for research registries and research training and education. Conclusion: To advance spine care worldwide, spine societies should establish guidelines, conduct studies on pain management, and support predictive analytic modeling. Tailoring local/regional programs according to regional needs is advised. These results can assist spine societies in developing long-term research strategies and provide justified rationale to governments and funding agencies. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Diffuse idiopathic skeletal hyperostosis of the cervical spine causing dysphagia and airway obstruction: an updated systematic review

Author

Orthopaedie Opleiding, Other research (not in main researchprogram), MS Radiologie, Researchgr. Systems Radiology, Circulatory Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, MS Orthopaedie Algemeen, Harlianto, Netanja I., Kuperus, Jonneke S., Mohamed Hoesein, Firdaus A.A., de Jong, Pim A., de Ru, Jacob A., Öner, F. Cumhur, Verlaan, Jorrit Jan, Orthopaedie Opleiding, Other research (not in main researchprogram), MS Radiologie, Researchgr. Systems Radiology, Circulatory Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, MS Orthopaedie Algemeen, Harlianto, Netanja I., Kuperus, Jonneke S., Mohamed Hoesein, Firdaus A.A., de Jong, Pim A., de Ru, Jacob A., Öner, F. Cumhur, and Verlaan, Jorrit Jan

Published
2022

10. Influence of severity and level of injury on the occurrence of complications during the subacute and chronic stage of traumatic spinal cord injury: a systematic review

Author

Revalidatie Medisch Volwassenen, Revalidatiegeneeskunde Onderzoek, Brain, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Adegeest, Charlotte Y, van Gent, Jort A N, Stolwijk-Swüste, Janneke M, Post, Marcel W M, Vandertop, William P, Öner, F Cumhur, Peul, Wilco C, Wengel, Paula V Ter, Revalidatie Medisch Volwassenen, Revalidatiegeneeskunde Onderzoek, Brain, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Adegeest, Charlotte Y, van Gent, Jort A N, Stolwijk-Swüste, Janneke M, Post, Marcel W M, Vandertop, William P, Öner, F Cumhur, Peul, Wilco C, and Wengel, Paula V Ter

Published
2022

11. Costs Associated With Timely and Delayed Surgical Treatment of Spinal Metastases

Author

Zorgeenheid Orthopaedie Medisch, Cancer, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Trialbureau Beeld, JC onderzoeksprogramma Kanker, Orthopaedie Opleiding, van Tol, Floris R, Massier, Julie R A, Frederix, Geert W J, Öner, F Cumhur, Verkooijen, Helena M, Verlaan, Jorrit-Jan, Zorgeenheid Orthopaedie Medisch, Cancer, HEE, Child Health, JC onderzoeksprogramma Methodologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Trialbureau Beeld, JC onderzoeksprogramma Kanker, Orthopaedie Opleiding, van Tol, Floris R, Massier, Julie R A, Frederix, Geert W J, Öner, F Cumhur, Verkooijen, Helena M, and Verlaan, Jorrit-Jan

Published
2022

13. Time to Surgical Treatment for Metastatic Spinal Disease: Identification of Delay Intervals.

Author

van Tol, Floris R., Versteeg, Anne L., Verkooijen, Helena M., Öner, F. Cumhur, and Verlaan, Jorrit-J

Subjects
OPERATIVE surgery, PATHOLOGY, HEALTH outcome assessment, MEDICAL consultation, TUMOR prognosis
Abstract

Study Design: Retrospective cohort study Objectives: Minimizing delays in referral, diagnosis and treatment of patients with symptomatic spinal metastases is important for optimal treatment outcomes. The primary objective of this study was to investigate several forms of delay from the onset of symptoms until surgical treatment of spinal metastases for patients with and without a known preexisting known malignancy. Methods: All patients receiving surgical treatment for spinal metastases in a single tertiary spine center were identified. Referral patterns were reconstructed and the total delay was divided into 4 categories: patient delay (onset of symptoms until medical consultation), diagnostic delay (medical consultation until diagnosis), referral delay (diagnosis until referral to spine surgeon) and treatment delay (referral spine to surgeon until treatment). These intervals were compared between patients with and without a known preexisting malignancy. Results: The median total delay was 99 days, patient delay 19 days, diagnostic delay 21,5 days, referral delay 7 days, treatment delay 8 days and diagnosis and treatment delay combined 18,5 days. No difference in total delay was observed between patients with and without a known preexisting malignancy. Total delay was not significantly associated with patient age, sex, oncological history, tumor prognosis and spinal level of the tumor. Conclusions: Patients with symptomatic spinal metastases experience considerable delays, even after metastatic spinal disease has been diagnosed, regardless of a preexisting malignancy. By identifying and eliminating the causes of these delays, diagnosis, referral and treatment may be expedited leading to improved patient outcome. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Research Practices and Needs Among Spine Surgeons Worldwide

Author

Germscheid, Niccole, primary, Cheung, Jason P. Y., additional, Neva, Marko H., additional, Öner, F. Cumhur, additional, Kwon, Brian K., additional, Valacco, Marcelo, additional, Awwad, Waleed, additional, Sciubba, Daniel M., additional, Lewis, Stephen J., additional, Rhines, Laurence D., additional, Yoon, S. Tim, additional, Alini, Mauro, additional, Grad, Sibylle, additional, Fisher, Charles G., additional, and Samartzis, Dino, additional

Published
2021
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16. Letter to the editor regarding “Two-year results of a double-blind multicenter randomized controlled non-inferiority trial of polyetheretherketone (PEEK) versus silicon nitride spinal fusion cages in patients with symptomatic degenerative lumbar disc disorders”

Author

Kersten, Roel F. M. R., primary, Öner, F. Cumhur, additional, Arts, Mark P., additional, Mitroiu, Marian, additional, Roes, Kit C. B., additional, de Gast, Arthur, additional, and van Gaalen, Steven M., additional

Published
2021
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17. Costs Associated With Timely and Delayed Surgical Treatment of Spinal Metastases.

Author

van Tol, Floris R., Massier, Julie R. A., Frederix, Geert W. J., Öner, F. Cumhur, Verkooijen, Helena M., and Verlaan, Jorrit-Jan

Subjects
SPINAL injury treatment, RETROSPECTIVE studies, NEUROLOGICAL disorders, MEDICAL care costs, TREATMENT effectiveness
Abstract

Study Design: Retrospective cohort study. Objectives: Symptoms caused by spinal metastases are often difficult to distinguish from symptoms caused by non-malignant spinal disease, complicating timely diagnosis, referral and treatment. The ensuing delays may promote the risk of neurological deficits or severe mechanical instability and consequent emergency surgery, leading to poorer prognosis. Presumably, treatment delay may subsequently lead to more health-care consumption and therefore increased average costs of treatment. Methods: All patients surgically treated for spinal metastases were included in the current study. Based on the presence of alarming symptoms and urgency of the required intervention, patients were categorized as having received timely or delayed treatment. Pre-surgical, in-hospital, aftercare and total costs were analyzed and compared between the 2 groups. Results: In total, 299 patients were included, of which 205 underwent timely and 94 delayed treatment. There was no significant difference in pre-surigcal costs (€3.229,13 in the timely treated group vs. €2.528,70 in the delayed treatment group, p = 0.849). The in-hospital costs (€16.738,49 vs. €13.108,81, p < 0.001) and the aftercare costs (€13.950,37 vs. 3.981,93, p < 0.001) were significantly higher for delayed treatment vs. timely treatment, respectively. The total costs were €33.741,71 for delayed treatment and €20.318,52 for timely treatment (p < 0.001). Conclusions: The total costs for timely treated patients with spinal metastases are significantly lower compared with patients receiving delayed treatment. Investing in the optimization of referral patterns may therefore reduce the overall pretreatment delay and subsequently increase patient outcome, leading to better clinical outcomes at lower costs. [ABSTRACT FROM AUTHOR]

Published
2022
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18. Use of therapeutic pathogen recognition receptor ligands for osteo-immunomodulation

Author

Khokhani, Paree (author), Rahmani, Nada R. (author), Kok, Anne (author), Öner, F. Cumhur (author), Alblas, Jacqueline (author), Weinans, H.H. (author), Kruyt, Moyo C. (author), Croes, Michiel (author), Khokhani, Paree (author), Rahmani, Nada R. (author), Kok, Anne (author), Öner, F. Cumhur (author), Alblas, Jacqueline (author), Weinans, H.H. (author), Kruyt, Moyo C. (author), and Croes, Michiel (author)

Abstract

Therapeutic pathogen recognition receptor (PRR) ligands are reaching clinical practice following their ability to skew the immune response in a specific direction. We investigated the effects of various therapeutic PRR ligands on bone cell differentiation and inflammation. Following stimu-lation, alkaline phosphatase (ALP) activity (Day 10), osteocalcin, osteonectin expression (Day 14), and calcium deposition (Day 21) were quantified in bone marrow-derived human mesenchymal stem cells (hMSCs). The osteoclastogenic response was determined by measuring tartrate-resistant acid phosphate (TRAP) activity in human monocytes. TNF-α, IL-6, IL-8, and IL-10 expressions were measured by enzyme-linked immunosorbent assay as an indicator of the ligands’ inflammatory properties. We found that nucleic acid-based ligands Poly(I:C) and CpG ODN C increased early ALP activity in hMSCs by 4-fold without affecting osteoclast formation. These ligands did not enhance expression of the other, late osteogenic markers. MPLA, Curdlan, and Pam3CSK4 did not affect osteogenic differentiation, but inhibited TRAP activity in monocytes, which was associated with increased expression of all measured cytokines. Nucleic acid-based ligands are identified as the most promising osteo-immunomodulators, as they favor early osteogenic differentiation without inducing an exaggerated immune-cell mediated response or interfering in osteoclastogenesis and thus can be potentially harnessed for multifunctional coatings for bone biomaterials., Biomaterials & Tissue Biomechanics

Published
2021
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19. The influence of surgeon experience and subspeciality on the reliability of the AO spine sacral classification system

Author

Eurospine (2021 : Wien), Karamian, Brian, Schroeder, Gregory, Canseco, Jose, Benneker, Lorin, Kandziora, Frank, Rajasekaran, Shanmuganathan, Öner, F. Cumhur, Schnake, Klaus J., Kepler, Christopher, Vaccaro, Alexander R., Eurospine (2021 : Wien), Karamian, Brian, Schroeder, Gregory, Canseco, Jose, Benneker, Lorin, Kandziora, Frank, Rajasekaran, Shanmuganathan, Öner, F. Cumhur, Schnake, Klaus J., Kepler, Christopher, and Vaccaro, Alexander R.

Abstract

Study Design: Cross-sectional survey Objective: To determine the influence of surgeons’ level of experience and subspeciality training on the reliability, reproducibility, and accuracy of sacral fracture classification using the AO Spine Sacral Injury Classification System. Summary of Background Data: An ideal classification system is easily comprehensible and reliable amongst the diverse group of surgeons. A surgeons’ level of experience may have a significant effect on the reliability and accuracy of a classification system. Moreover, surgeons of different subspecialities may have various levels of comfort with imaging assessment of sacral injuries required for accurate diagnosis and classification. Methods: High-resolution computerized tomography (CT) images from 26 cases were assessed by 172 investigators from a diverse array of surgical subspecialities (general orthopaedics, neurosurgery, orthopaedic spine, orthopaedic trauma) and experience (<5, 5-10, 11-20, >20 years). Validation assessments were performed via web conference using high-resolution images, as well as axial/sagittal/coronal CT scan sequences. Two assessments were performed by each investigator independently three weeks apart in randomized order. Reliability and reproducibility were calculated with cohen’s kappa coefficient (k) and gold standard classification agreement was determined for each fracture morphology and subtype and stratified by experience and subspeciality. Results: Respondents achieved an overall k = 0.87 for morphology and k = 0.77 for subtype classification, representing excellent and substantial intraobserver reproducibility, respectively. Respondents from all four practice experience groups demonstrated excellent interobserver reliability when classifying overall morphology (k=0.842/0.850, Assessment 1/Assessment 2) and substantial interobserver reliability in overall subtype (k=0.719/0.751) in both assessments. General orthopaedists, neurosurgeons, and orthopaedic spine surge

Published
2021

20. Letter to the editor regarding 'Two-year results of a double-blind multicenter randomized controlled non-inferiority trial of polyetheretherketone (PEEK) versus silicon nitride spinal fusion cages in patients with symptomatic degenerative lumbar disc disorders'

Author

Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, MS Orthopaedie Algemeen, CTM & Statistical consultation, Kersten, Roel F M R, Öner, F Cumhur, Arts, Mark P, Mitroiu, Marian, Roes, Kit C B, de Gast, Arthur, van Gaalen, Steven M, Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, MS Orthopaedie Algemeen, CTM & Statistical consultation, Kersten, Roel F M R, Öner, F Cumhur, Arts, Mark P, Mitroiu, Marian, Roes, Kit C B, de Gast, Arthur, and van Gaalen, Steven M

Published
2021

21. Validation of the AO Spine Sacral Classification System: Reliability Among Surgeons Worldwide

Author

MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Schroeder, Gregory D., Karamian, Brian A., Canseco, Jose A., Vialle, Luiz R., Kandziora, Frank, Benneker, Lorin M., Rajasekaran, Shanmuganathan, Holstein, Jörg H., Schnake, Klaus J., Kurd, Mark F., Dvorak, Marcel F., Vialle, Emiliano N., Joaquim, Andrei F., Kanna, Rishi M., Fehlings, Michael, Wilson, Jefferson R., Chapman, Jens R., Krieg, James C., Kleweno, Conor P., Firoozabadi, Reza, Öner, F. Cumhur, Kepler, Christopher K., Vaccaro, Alexander R., MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Schroeder, Gregory D., Karamian, Brian A., Canseco, Jose A., Vialle, Luiz R., Kandziora, Frank, Benneker, Lorin M., Rajasekaran, Shanmuganathan, Holstein, Jörg H., Schnake, Klaus J., Kurd, Mark F., Dvorak, Marcel F., Vialle, Emiliano N., Joaquim, Andrei F., Kanna, Rishi M., Fehlings, Michael, Wilson, Jefferson R., Chapman, Jens R., Krieg, James C., Kleweno, Conor P., Firoozabadi, Reza, Öner, F. Cumhur, Kepler, Christopher K., and Vaccaro, Alexander R.

Published
2021

22. Study methodology in trauma care: towards question-based study designs

Author

Zorgeenheid Traumatologie, Other research (not in main researchprogram), Biostatistiek Onderzoek, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Houwert, Roderick M., Beks, Reinier B., Dijkgraaf, Marcel G.W., Roes, Kit C.B., Öner, F. Cumhur, Hietbrink, Falco, Leenen, Luke P.H., Groenwold, Rolf H.H., Zorgeenheid Traumatologie, Other research (not in main researchprogram), Biostatistiek Onderzoek, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Houwert, Roderick M., Beks, Reinier B., Dijkgraaf, Marcel G.W., Roes, Kit C.B., Öner, F. Cumhur, Hietbrink, Falco, Leenen, Luke P.H., and Groenwold, Rolf H.H.

Published
2021

23. Use of therapeutic pathogen recognition receptor ligands for osteo-immunomodulation

Author

ORT Research, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Khokhani, Paree, Rahmani, Nada R., Kok, Anne, Öner, F. Cumhur, Alblas, Jacqueline, Weinans, Harrie, Kruyt, Moyo C., Croes, Michiel, ORT Research, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Khokhani, Paree, Rahmani, Nada R., Kok, Anne, Öner, F. Cumhur, Alblas, Jacqueline, Weinans, Harrie, Kruyt, Moyo C., and Croes, Michiel

Published
2021

24. Current treatment and outcomes of traumatic sternovertebral fractures: a systematic review

Author

Zorgeenheid Traumatologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Klei, Dorine S., Öner, F. Cumhur, Leenen, Luke P.H., van Wessem, Karlijn J.P., Zorgeenheid Traumatologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Klei, Dorine S., Öner, F. Cumhur, Leenen, Luke P.H., and van Wessem, Karlijn J.P.

Published
2021

25. No Need for Sternal Fixation in Traumatic Sternovertebral Fractures: Outcomes of a 10-Year Retrospective Cohort Study

Author

Zorgeenheid Traumatologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Klei, Dorine S., Öner, F. Cumhur, Leenen, Luke P.H., van Wessem, Karlijn J.P., Zorgeenheid Traumatologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Infection & Immunity, Klei, Dorine S., Öner, F. Cumhur, Leenen, Luke P.H., and van Wessem, Karlijn J.P.

Published
2021

33. Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Author

Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, Creemers, Laura B, Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, and Creemers, Laura B

Abstract

Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.

Published
2020

34. Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Author

Faculteit Diergeneeskunde, Chirurgie, dCSCA RMSC-1, Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, Creemers, Laura B, Faculteit Diergeneeskunde, Chirurgie, dCSCA RMSC-1, Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, and Creemers, Laura B

Published
2020

35. Diffuse Idiopathic Skeletal Hyperostosis in Smokers and Restrictive Spirometry Pattern: An Analysis of the COPDGene Cohort

Author

Arts-assistenten Radiologie, MS Radiologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Researchgr. Systems Radiology, Circulatory Health, Infection & Immunity, Cancer, Other research (not in main researchprogram), Oudkerk, Sytse F., Hoesein, Firdaus A.A.Mohamed, Öner, F. Cumhur, Verlaan, Jorrit Jan, Jong, Pim A.De, Kuperus, Jonneke S., Cho, Michael, McDonald, Merry Lynn, Lynch, David A., Silverman, Edwin K., Crapo, James D., Make, Barry J., Lowe, Katherine E., Regan, Elizabeth A., Arts-assistenten Radiologie, MS Radiologie, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Researchgr. Systems Radiology, Circulatory Health, Infection & Immunity, Cancer, Other research (not in main researchprogram), Oudkerk, Sytse F., Hoesein, Firdaus A.A.Mohamed, Öner, F. Cumhur, Verlaan, Jorrit Jan, Jong, Pim A.De, Kuperus, Jonneke S., Cho, Michael, McDonald, Merry Lynn, Lynch, David A., Silverman, Edwin K., Crapo, James D., Make, Barry J., Lowe, Katherine E., and Regan, Elizabeth A.

Published
2020

36. Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Author

ORT Research, Orthopaedie Onderzoek, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, Creemers, Laura B, ORT Research, Orthopaedie Onderzoek, MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Krouwels, Anita, Iljas, Juvita D, Kragten, Angela H M, Dhert, Wouter J A, Öner, F Cumhur, Tryfonidou, Marianna A, and Creemers, Laura B

Published
2020

37. Design of COSMIC: a randomized, multi-centre controlled trial comparing conservative or early surgical management of incomplete cervical cord syndrome without spinal instability

Author

Bartels Ronald HMA, Hosman Allard JF, van de Meent Henk, Hofmeijer Jeannette, Vos Pieter E, Slooff Willem Bart, Öner F Cumhur, Coppes Maarten H, Peul Wilco C, and Verbeek André LM

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Incomplete cervical cord syndrome without spinal instability is a very devastating event for the patient and the family. It is estimated that up to 25% of all traumatic spinal cord lesions belong to this category. The treatment for this type of spinal cord lesion is still subject of discussion. From a biological point of view early surgery could prevent secondary damage due to ongoing compression of the already damaged spinal cord. Historically, however, conservative treatment was propagated with good clinical results. Proponents for early surgery as well those favoring conservative treatment are still in debate. The proposed trial will contribute to the discussion and hopefully also to a decrease in the variability of clinical practice. Methods/Design A randomized controlled trial is designed to compare the clinical outcome of early surgical strategy versus a conservative approach. The primary outcome is clinical outcome according to mJOA. This also measured by ASIA score, DASH score and SCIM III score. Other endpoints are duration of the stay at a high care department (medium care, intensive care), duration of the stay at the hospital, complication rate, mortality rate, sort of rehabilitation, and quality of life. A sample size of 36 patients per group was calculated to reach a power of 95%. The data will be analyzed as intention-to-treat at regular intervals, but the end evaluation will take place at two years post-injury. Discussion At the end of the study, clinical outcomes between treatments attitudes can be compared. Efficacy, but also efficiency can be determined. A goal of the study is to determine which treatment will result in the best quality of life for the patients. This study will certainly contribute to more uniformity of treatment offered to patients with a special sort of spinal cord injury. Trial Registration Gov: NCT01367405

Published
2013
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39. Liposomal drug delivery in an in vitro 3D bone marrow model for multiple myeloma

Author

Braham, Maaike Vj, Deshantri, Anil K, Minnema, Monique C, Öner, F Cumhur, Schiffelers, Raymond M, Fens, Marcel Ham, Alblas, Jacqueline, Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics

Subjects
0301 basic medicine, Pharmaceutical Science, 0302 clinical medicine, Drug Delivery Systems, International Journal of Nanomedicine, Antibiotics, Antineoplastic/administration & dosage, Models, immune system diseases, Bone Marrow, hemic and lymphatic diseases, Drug Discovery, Tumor Cells, Cultured, Multiple myeloma, Original Research, Liposome, Cultured, Antibiotics, Antineoplastic, Bortezomib, targeted delivery, Bone Marrow/drug effects, General Medicine, Tumor Cells, 3. Good health, multiple myeloma, medicine.anatomical_structure, Antibiotics, Antineoplastic/administration & dosage, 030220 oncology & carcinogenesis, Drug delivery, Liposomes/administration & dosage, medicine.drug, liposomes, Biophysics, Multiple Myeloma/drug therapy, Bioengineering, In Vitro Techniques, drug sensitivity and resistance testing, Models, Biological, Biomaterials, 03 medical and health sciences, Therapeutic index, Journal Article, medicine, Humans, tumor microenvironment, Doxorubicin, Progenitor cell, Cell Proliferation, business.industry, Organic Chemistry, Doxorubicin/administration & dosage, Biological, medicine.disease, 030104 developmental biology, Cancer research, Bone marrow, business
Abstract

Maaike VJ Braham,1 Anil K Deshantri,2,3 Monique C Minnema,4 F Cumhur Öner,1 Raymond M Schiffelers,2 Marcel HAM Fens,2,5 Jacqueline Alblas1 1Department of Orthopaedics, University Medical Center Utrecht, Utrecht, the Netherlands; 2Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Pharmacology, Sun Pharma Advanced Research Company Limited, Vadodara, Gujarat, India; 4Department of Hematology, University Medical Center Utrecht Cancer Center, Utrecht, the Netherlands; 5Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands Purpose: Liposomal drug delivery can improve the therapeutic index of treatments for multiple myeloma. However, an appropriate 3D model for the in vitro evaluation of liposomal drug delivery is lacking. In this study, we applied a previously developed 3D bone marrow (BM) myeloma model to examine liposomal drug therapy. Material and methods: Liposomes of different sizes (~75–200 nm) were tested in a 3D BM myeloma model, based on multipotent mesenchymal stromal cells, endothelial progenitor cells, and myeloma cells cocultured in hydrogel. The behavior and efficacy of liposomal drug therapy was investigated, evaluating the feasibility of testing liposomal drug delivery in 3D in vitro. Intracellular uptake of untargeted and integrin α4β1 (very late antigen-4) targeted liposomes was compared in myeloma and supporting cells, as well as the effectivity of free and liposome-encapsulated chemotherapy (bortezomib, doxorubicin). Either cocultured myeloma cell lines or primary CD138+ myeloma cells received the treatments. Results: Liposomes (~75–110 nm) passively diffused throughout the heterogeneously porous (~80–850 nm) 3D hydrogel model after insertion. Cellular uptake of liposomes was observed and was increased by targeting very late antigen-4. Liposomal bortezomib and doxorubicin showed increased cytotoxic effects toward myeloma cells compared with the free drugs, using either a cell line or primary myeloma cells. Cytotoxicity toward supporting BM cells was reduced using liposomes. Conclusion: The 3D model allows the study of liposome-encapsulated molecules on multiple myeloma and supporting BM cells, looking at cellular targeting, and general efficacy of the given therapy. The advantages of liposomal drug delivery were demonstrated in a primary myeloma model, enabling the study of patient-to-patient responses to potential drugs and treatment regimes. Keywords: liposomes, targeted delivery, tumor microenvironment, drug sensitivity and resistance testing, multiple myeloma

Published
2018

40. AOSpine Knowledge Forums: Research in Motion

Author

Samartzis, Dino, primary, Germscheid, Niccole M., additional, Fehlings, Michael G., additional, Fisher, Charles G., additional, de Kleuver, Marinus, additional, Öner, F. Cumhur, additional, Yoon, S. Tim, additional, and Vialle, Luiz R., additional

Published
2019
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42. Answer to the Letter to the Editor of F. M. Kovacs et al. entitled “Overviews should meet the methodological standards of systematic reviews” concerning “The evidence on surgical interventions for low back disorders, an overview of systematic reviews” by Wilco C.H. Jacobs et al.; Eur Spine J, doi:10.1007/s00586-013-2823-4

Author

Jacobs, Wilco C. H., Rubinstein, Sidney M., Willems, Paul C., Moojen, Wouter A., Pellisé, Ferran, Öner, F. Cumhur, Peul, Wilco C., and van Tulder, Maurits W.

Published
2014
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45. Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease : An evaluation in the COPDGene cohort

Author

Oudkerk, Sytse F., Mohamed Hoesein, Firdaus A.A., PThM Mali, Willem, Öner, F. Cumhur, Verlaan, Jorrit Jan, de Jong, Pim A., Kinney, Gregory L., Hokanson, John, Lynch, David, Silverman, Edwin K., Budoff, Matthew J., Regan, Elizabeth A., Oudkerk, Sytse F., Mohamed Hoesein, Firdaus A.A., PThM Mali, Willem, Öner, F. Cumhur, Verlaan, Jorrit Jan, de Jong, Pim A., Kinney, Gregory L., Hokanson, John, Lynch, David, Silverman, Edwin K., Budoff, Matthew J., and Regan, Elizabeth A.

Published
2019

48. A Human Hematopoietic Niche Model Supporting Hematopoietic Stem and Progenitor Cells In Vitro

Author

Braham, Maaike V J, Li Yim, Amélie S P, Garcia Mateos, Jara, Minnema, Monique C, Dhert, Wouter J A, Öner, F Cumhur, Robin, Catherine, Alblas, Jacqueline, Braham, Maaike V J, Li Yim, Amélie S P, Garcia Mateos, Jara, Minnema, Monique C, Dhert, Wouter J A, Öner, F Cumhur, Robin, Catherine, and Alblas, Jacqueline

Abstract

Niches in the bone marrow regulate hematopoietic stem and progenitor cell (HSPC) fate and behavior through cell-cell interactions and soluble factor secretion. The niche-HSPC crosstalk is a very complex process not completely elucidated yet. To aid further investigation of this crosstalk, a functional in vitro 3D model that closely represents the main supportive compartments of the bone marrow is developed. Different combinations of human stromal cells and hydrogels are tested for their potential to maintain CD34+ HSPCs. Cell viability, clonogenic hematopoietic potential, and surface marker expression are assessed over time. Optimal HSPC support is obtained in presence of adipogenic and osteogenic cells, together with progenitor derived endothelial cells. When cultured in a bioactive hydrogel, the supportive cells self-assemble into a hypoxic stromal network, stimulating CD34+ CD38+ cell formation, while maintaining the pool of CD34+ 38- HSPCs. HSPC clusters colocalize with the stromal networks, in close proximity to sinusoidal clusters of CD31+ endothelial cells. Importantly, the primary in vitro niche model supports HSPCs with no cytokine addition. Overall, the engineered primary 3D bone marrow environment provides an easy and reliable model to further investigate interactions between HSPCs and their endosteal and perivascular niches, in the context of normal hematopoiesis or blood-related diseases.

Published
2019

49. Comparison of polyetheretherketone versus silicon nitride intervertebral spinal spacers in a caprine model

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, MS Orthopaedie Spine, Kersten, Roel F.M.R., Wu, Gang, Pouran, Behdad, van der Veen, Albert J., Weinans, Harrie H., de Gast, Arthur, Öner, F. Cumhur, van Gaalen, Steven M., Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, MS Orthopaedie Spine, Kersten, Roel F.M.R., Wu, Gang, Pouran, Behdad, van der Veen, Albert J., Weinans, Harrie H., de Gast, Arthur, Öner, F. Cumhur, and van Gaalen, Steven M.

Published
2019

50. Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease: An evaluation in the COPDGene cohort

Author

MS Radiologie, Cancer, Circulatory Health, Brain, MS Orthopaedie Spine, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Researchgr. Systems Radiology, Infection & Immunity, Oudkerk, Sytse F., Mohamed Hoesein, Firdaus A.A., PThM Mali, Willem, Öner, F. Cumhur, Verlaan, Jorrit Jan, de Jong, Pim A., Kinney, Gregory L., Hokanson, John, Lynch, David, Silverman, Edwin K., Budoff, Matthew J., Regan, Elizabeth A., MS Radiologie, Cancer, Circulatory Health, Brain, MS Orthopaedie Spine, Regenerative Medicine and Stem Cells, Orthopaedie Opleiding, Researchgr. Systems Radiology, Infection & Immunity, Oudkerk, Sytse F., Mohamed Hoesein, Firdaus A.A., PThM Mali, Willem, Öner, F. Cumhur, Verlaan, Jorrit Jan, de Jong, Pim A., Kinney, Gregory L., Hokanson, John, Lynch, David, Silverman, Edwin K., Budoff, Matthew J., and Regan, Elizabeth A.

Published
2019

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