Publications by authors named "Moyo C Kruyt"

80 Publications

What a stranded whale with scoliosis can teach us about human idiopathic scoliosis.

Sci Rep 2021 Mar 30;11(1):7218. Epub 2021 Mar 30.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Scoliosis is a deformation of the spine that may have several known causes, but humans are the only mammal known to develop scoliosis without any obvious underlying cause. This is called 'idiopathic' scoliosis and is the most common type. Recent observations showed that human scoliosis, regardless of its cause, has a relatively uniform three-dimensional anatomy. We hypothesize that scoliosis is a universal compensatory mechanism of the spine, independent of cause and/or species. We had the opportunity to study the rare occurrence of scoliosis in a whale (Balaenoptera acutorostrata) that stranded in July 2019 in the Netherlands. A multidisciplinary team of biologists, pathologists, veterinarians, taxidermists, radiologists and orthopaedic surgeons conducted necropsy and imaging analysis. Blunt traumatic injury to two vertebrae caused an acute lateral deviation of the spine, which had initiated the development of compensatory curves in regions of the spine without anatomical abnormalities. Three-dimensional analysis of these compensatory curves showed strong resemblance with different types of human scoliosis, amongst which idiopathic. This suggests that any decompensation of spinal equilibrium can lead to a rather uniform response. The unique biomechanics of the upright human spine, with significantly decreased rotational stability, may explain why only in humans this mechanism can be induced relatively easily, without an obvious cause, and is therefore still called 'idiopathic'.
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http://dx.doi.org/10.1038/s41598-021-86709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009909PMC
March 2021

Induction of a representative idiopathic-like scoliosis in a porcine model using a multi directional dynamic spring-based system.

Spine J 2021 Mar 20. Epub 2021 Mar 20.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Heidelberglaan 100, NL-3584CX Utrecht, The Netherlands. Electronic address:

Background Context: Scoliosis is a 3D deformity of the spine in which vertebral rotation plays an important role. However, no treatment strategy currently exists that primarily applies a continuous rotational moment over a long period of time to the spine, while preserving its mobility. We developed a dynamic, torsional device that can be inserted with standard posterior instrumentation. The feasibility of this implant to rotate the spine and preserve motion was tested in growing mini-pigs.

Purpose: To test the quality and feasibility of the torsional device to induce the typical axial rotation of scoliosis while maintaining growth and mobility of the spine.

Study Design: Preclinical animal study with 14 male, 7 month old Gottingen mini-pigs. Comparison of two scoliosis induction methods, with and without the torsional device, with respect to 3D deformity and maintenance of the scoliosis after removal of the implants.

Methods: Fourteen mini-pigs received either a unilateral tether-only (n=6) or a tether combined with a contralateral torsional device (n=8). X-rays and CT-scans were made post-operative, at 8 weeks and at 12 weeks. Flexibility of the spine was assessed at 12 weeks. In 3 mini-pigs per condition, the implants were removed and the animals were followed until no further correction was expected.

Results: At 12 weeks the tether-only group yielded a coronal Cobb angle of 16.8±3.3°For the tether combined with the torsional device this was 22.0±4.0°. The most prominent difference at 12 weeks was the axial rotation with 3.6±2.8° for the tether-only group compared to 18.1±4.6° for the tether-torsion group. Spinal growth and flexibility remained normal and comparable for both groups. After removal of the devices, the induced scoliosis reduced by 41% in both groups. There were no adverse tissue reactions, implant complications or infections.

Conclusion: The present study indicates the ability of the torsional device combined with a tether to induce a flexible idiopathic-like scoliosis in mini-pigs. The torsional device was necessary to induce the typical axial rotation found in human scoliosis.

Clinical Significance: The investigated torsional device could induce apical rotation in a flexible and growing spine. Whether this may be used to reduce a scoliotic deformity remains to be investigated.
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http://dx.doi.org/10.1016/j.spinee.2021.03.015DOI Listing
March 2021

Use of Therapeutic Pathogen Recognition Receptor Ligands for Osteo-Immunomodulation.

Materials (Basel) 2021 Feb 27;14(5). Epub 2021 Feb 27.

Department of Orthopedics, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

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 stimulation, 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.
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http://dx.doi.org/10.3390/ma14051119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957819PMC
February 2021

Letter to the editor regarding "Is rod diameter associated with the rate of rod fracture in patients treated with magnetically controlled growing rods?"

Spine Deform 2021 Feb 26. Epub 2021 Feb 26.

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

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http://dx.doi.org/10.1007/s43390-021-00306-6DOI Listing
February 2021

Letter to the editor regarding "Growth‑preserving instrumentation in early‑onset scoliosis patients with multi‑level congenital anomalies".

Spine Deform 2020 Nov 23. Epub 2020 Nov 23.

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

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http://dx.doi.org/10.1007/s43390-020-00249-4DOI Listing
November 2020

Comparison of annulus fibrosus cell collagen remodeling rates in a microtissue system.

J Orthop Res 2020 Nov 22. Epub 2020 Nov 22.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

It has been suggested that curvature progression in adolescent idiopathic scoliosis occurs through irreversible changes in the intervertebral discs. Strains of mice have been identified who differ in their disc wedging response upon extended asymmetrical compression. Annulus fibrosus (AF) tissue remodeling could contribute to the faster disc wedging progression previously observed in these mice. Differences in collagen remodeling capacity of AF cells between these in-bred mice strains were compared using an in vitro microtissue system. AF cells of 8-10-week-old LG/J ("fast-healing") and C57BL/6J ("normal healing") mice were embedded in a microtissue platform and cultured for 48 h. Hereafter, tissues were partially released and cultured for another 96 h. Microtissue surface area and waistcoat contraction, collagen orientation, and collagen content were measured. After 96 h postrelease, microtissues with AF cells of LG/J mice showed more surface area contraction (p < .001) and waistcoat contraction (p = .002) than C57BL/6J microtissues. Collagen orientation did not differ at 24 h after partial release. However, at 96 h, collagen in the microtissues from LG/J AF cells was aligned more than in those from C57BL/6J mice (p < .001). Collagen content did not differ between microtissues at 96 h. AF cells of inbred LG/J mice were better able to remodel and realign their collagen fibers than those from C57BL/6J mice. The remodeling of AF tissue could be contributing to the faster disc wedging progression observed in LG/J mice.
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http://dx.doi.org/10.1002/jor.24921DOI Listing
November 2020

Spring distraction system for dynamic growth guidance of early onset scoliosis: two-year prospective follow-up of 24 patients.

Spine J 2021 Apr 20;21(4):671-681. Epub 2020 Nov 20.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.

Background: Current surgical treatment options for early onset scoliosis (EOS), with distraction- or growth-guidance implants, show limited growth and high complication rates during follow-up. We developed a novel implant concept, which uses compressed helical springs positioned around the rods of a growth-guidance construct. This spring distraction system (SDS) provides continuous corrective force to stimulate spinal growth, can be easily contoured, and can be used with all standard spinal instrumentation systems.

Purpose: To assess curve correction and -maintenance, spinal growth, complication rate, and health-related quality of life following SDS treatment.

Study Design: Prospective cohort study.

Patient Sample: All skeletally immature EOS patients with an indication for growth-friendly surgery and without bone- or soft tissue weakness were eligible to receive SDS. For this study, all included patients with at least 2-year follow-up were analyzed.

Outcome Measures: Coronal Cobb angle, sagittal parameters, T1-T12, T1-S1, and instrumented (ie, bridged segment) spinal height and freehand length, complications and re-operations, and the 24-Item Early Onset Scoliosis Questionnaires (EOSQ-24) score.

Methods: All primary- and conversion patients (conversion from failed other systems) with SDS and ≥2 years follow-up were included. Radiographic parameters were compared preoperatively, postoperatively and at latest follow-up. Spinal length increase was expressed as mm/year.

Results: Twenty-four skeletally immature EOS patients (18 primary and 6 conversion cases) were included. There were five idiopathic, seven congenital, three syndromic, and nine neuromuscular EOS patients. Mean age at implantation was 9.1 years (primary: 8.4; conversion: 11.2). Major curve improved from 60.3° to 35.3°, and was maintained at 40.6° at latest follow-up. Mean spring length increase during follow-up was 10.4 mm/year. T1-S1 height increased 9.9mm/year and the instrumented segment height showed a mean increase of 0.7 mm/segment/year. EOSQ-24 scores dropped after surgery from 75.6 to 67.4 but recovered to 75.0 at latest follow-up. In total, 17 reoperations were performed. Ten reoperations were performed to treat 9 implant-related complications. In addition, 7 patients showed spinal growth that exceeded expected growth velocity; their springs were retensioned during a small reoperation.

Conclusion: The 2-year follow-up results from this prospective cohort study indicate that the concept of spring distraction may be feasible as an alternative to current growing spine solutions. Curve correction and growth could be maintained satisfactory without the need for repetitive lengthening procedures. However, as in all growth-friendly implants, complications and reoperations could not be prevented, which emphasizes the need for further improvement.
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http://dx.doi.org/10.1016/j.spinee.2020.11.007DOI Listing
April 2021

Variations in the sagittal spinal profile precede the development of scoliosis: a pilot study of a new approach.

Spine J 2021 Apr 28;21(4):638-641. Epub 2020 Oct 28.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.spinee.2020.10.025DOI Listing
April 2021

The potential of spring distraction to dynamically correct complex spinal deformities in the growing child.

Eur Spine J 2021 Mar 6;30(3):714-723. Epub 2020 Oct 6.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

Purpose: Current treatment of progressive early onset scoliosis involves growth-friendly instrumentation if conservative treatment fails. These implants guide growth by passive sliding or repeated lengthenings. None of these techniques provide dynamic correction after implantation. We developed the spring distraction system (SDS), by using one or multiple compressed springs positioned around a standard sliding rod, to provide active continuous distraction of the spine to stimulate growth and further correction. The purpose of this study was to determine feasibility and proof of concept of the SDS.

Methods: We developed a versatile, dynamic spring distraction system for patients who would benefit from active continuous distraction. This prospective case series evaluates four patients with exceptional and progressive congenital spine deformities.

Results: Four patients had a mean age of 6.8 years at surgery with a mean follow-up of 36 months (range 25-45). The mean progressive thoracic lordosis, which was the reason for initiating surgical treatment in two patients, changed from 32° lordosis preoperatively to 1° kyphosis post-operatively. During follow-up, this further improved to 32° thoracic kyphosis. In the two other patients, with cervicothorcacic scoliosis, the main coronal curve improved from 79° pre-operatively to 56° post-operatively and further improved to 42°. The mean T1-S1 spine growth during follow-up for all patients was 1.3 cm/year. There was one reoperation because of skin problems and no device-failures.

Conclusion: These early results show the feasibility and the proof of concept of spring-based distraction as a dynamic growth-enhancing system with the potential of further correction of the deformity after implantation.
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http://dx.doi.org/10.1007/s00586-020-06612-3DOI Listing
March 2021

Cutibacterium acnes and autoinflammatory bone disease: Case series of three patients.

Clin Immunol 2020 Oct 16;219:108540. Epub 2020 Jul 16.

Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, the Netherlands.

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http://dx.doi.org/10.1016/j.clim.2020.108540DOI Listing
October 2020

Spinal Growth in Patients With Juvenile Idiopathic Scoliosis Treated With Boston Brace: A Retrospective Study.

Spine (Phila Pa 1976) 2020 Jul;45(14):976-982

Department of Orthopaedic Surgery, OLVG, Amsterdam, The Netherlands.

Study Design: Retrospective comparative cohort.

Objective: The aim of this study was to determine whether spinal growth is restricted by brace treatment in patients with juvenile idiopathic scoliosis (JIS).

Summary Of Background Data: Spinal fusion can negatively affect spinal growth if performed before the growth spurt. Brace treatment is often given in this young population to control the spinal deformity while allowing spinal growth. It is unknown whether the applied pressure of brace treatment on spine results in growth restriction. The aim of the study is to evaluate spinal growth in braced JIS patients.

Methods: A total of 49 JIS patients treated with Boston brace were retrospectively selected from a scoliosis database. T1-T12/T1-S1 perpendicular and freehand (height following the curvature of the spine) height were measured on radiographs of patients that had reached skeletal maturity and were matched with 49 controls without scoliosis. Spinal growth was calculated from brace initiation until cessation and was compared with normal spinal growth values as reported by Dimeglio.

Results: The mean age of diagnosis was 7.4 years. The age of the braced scoliosis patients at skeletal maturity was 17.5 years. The average T1-T12 and T1-S1 freehand height measured by following the curvature of the scoliosis was 29.3 cm (±2.4) and 47.2cm (±4.0), respectively, and was not significant different from the control group. Brace treatment was initiated at a mean age of 11.2 and the mean age of cessation was 14.8. Spinal growth (freehand) during brace treatment was 1.10 cm/year for the thoracic spine and 1.78 cm/year for the full spine and was not significant different from normal values.

Conclusion: No significant influence of bracing on spinal growth could be detected in this cohort of JIS patients. The spinal height measurements at skeletal maturity were similar to matched controls. In addition, spinal growth did not significantly differ from Dimeglio normal growth data, indicating that the effect of bracing on spinal growth is absent or minimal.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003435DOI Listing
July 2020

Increasing Fusion Rate Between 1 and 2 Years After Instrumented Posterolateral Spinal Fusion and the Role of Bone Grafting.

Spine (Phila Pa 1976) 2020 Oct;45(20):1403-1410

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Study Design: Two-year clinical and radiographic follow-up of a double-blind, multicenter, randomized, intra-patient controlled, non-inferiority trial comparing a bone graft substitute (AttraX Putty) with autograft in instrumented posterolateral fusion (PLF) surgery.

Objectives: The aim of this study was to compare PLF rates between 1 and 2 years of follow-up and between graft types, and to explore the role of bone grafting based on the location of the PLF mass.

Summary Of Background Data: There are indications that bony fusion proceeds over time, but it is unknown to what extent this can be related to bone grafting.

Methods: A total of 100 adult patients underwent a primary, single- or multilevel, thoracolumbar PLF. After instrumentation and preparation for grafting, the randomized allocation side of AttraX Putty was disclosed. The contralateral posterolateral gutters were grafted with autograft. At 1-year follow-up, and in case of no fusion at 2 years, the fusion status of both sides of each segment was blindly assessed on CT scans. Intertransverse and facet fusion were scored separately. Difference in fusion rates after 1 and 2 years and between grafts were analyzed with a Generalized Estimating Equations (GEE) model (P < 0.05).

Results: The 2-year PLF rate (66 patients) was 70% at the AttraX Putty and 68% at the autograft side, compared to 55% and 52% after 1 year (87 patients). GEE analysis demonstrated a significant increase for both conditions (odds ratio 2.0, 95% confidence interval 1.5-2.7, P < 0.001), but no difference between the grafts (P = 0.595). Ongoing bone formation was only observed between the facet joints.

Conclusion: This intra-patient controlled trial demonstrated a significant increase in PLF rate between 1 and 2 years after instrumented thoracolumbar fusion, but no difference between AttraX Putty and autograft. Based on the location of the PLF mass, this increase is most likely the result of immobilization instead of grafting.

Level Of Evidence: 1.
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http://dx.doi.org/10.1097/BRS.0000000000003558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515483PMC
October 2020

A multifaceted biomimetic interface to improve the longevity of orthopedic implants.

Acta Biomater 2020 07 25;110:266-279. Epub 2020 Apr 25.

Department of Orthopedics, University Medical Center Utrecht, Utrecht 3508GA, the Netherlands.

The rise of additive manufacturing has provided a paradigm shift in the fabrication of precise, patient-specific implants that replicate the physical properties of native bone. However, eliciting an optimal biological response from such materials for rapid bone integration remains a challenge. Here we propose for the first time a one-step ion-assisted plasma polymerization process to create bio-functional 3D printed titanium (Ti) implants that offer rapid bone integration. Using selective laser melting, porous Ti implants with enhanced bone-mimicking mechanical properties were fabricated. The implants were functionalized uniformly with a highly reactive, radical-rich polymeric coating generated using a unique combination of plasma polymerization and plasma immersion ion implantation. We demonstrated the performance of such activated Ti implants with a focus on the coating's homogeneity, stability, and biological functionality. It was shown that the optimized coating was highly robust and possessed superb physico-chemical stability in a corrosive physiological solution. The plasma activated coating was cytocompatible and non-immunogenic; and through its high reactivity, it allowed for easy, one-step covalent immobilization of functional biomolecules in the absence of solvents or chemicals. The activated Ti implants bio-functionalized with bone morphogenetic protein 2 (BMP-2) showed a reduced protein desorption and a more sustained osteoblast response both in vitro and in vivo compared to implants modified through conventional physisorption of BMP-2. The versatile new approach presented here will enable the development of bio-functionalized additively manufactured implants that are patient-specific and offer improved integration with host tissue. STATEMENT OF SIGNIFICANCE: Additive manufacturing has revolutionized the fabrication of patient-specific orthopedic implants. Although such 3D printed implants can show desirable mechanical and mass transport properties, they often require surface bio-functionalities to enable control over the biological response. Surface covalent immobilization of bioactive molecules is a viable approach to achieve this. Here we report the development of additively manufactured titanium implants that precisely replicate the physical properties of native bone and are bio-functionalized in a simple, reagent-free step. Our results show that covalent attachment of bone-related growth factors through ion-assisted plasma polymerized interlayers circumvents their desorption in physiological solution and significantly improves the bone induction by the implants both in vitro and in vivo.
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http://dx.doi.org/10.1016/j.actbio.2020.04.020DOI Listing
July 2020

3-Year follow-up of a single magnetically controlled growing rod with contralateral gliding system and apical control for early onset scoliosis.

Spine Deform 2020 08 30;8(4):751-761. Epub 2020 Mar 30.

Department of Orthopaedic Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus, Denmark.

Study Design: Two-center retrospective cohort study.

Objective: The aim of this study is to investigate the clinical effectiveness and safety of the MCGR hybrid in terms of spinal growth, 3D correction, balance, and complications. The magnetic-controlled growing-rod (MCGR) growth instrumentation method has gained popularity for early onset scoliosis (EOS) treatment in the past years due to the non-invasiveness of the subsequent interval elongation procedures. To improve 3D correction and reduce the costs, we combined a single concave MCGR with a sliding rod on the convex side to control the apex.

Methods: A retrospective cohort study of 18 EOS children with an average 3-year follow-up (range 2.0-3.7) from two European spine centers treated with the single MCGR hybrid concept; 14 primary and 4 conversion cases. The primary and conversion cases were both evaluated preoperatively, postoperatively, 1 year, 2 years, and last follow-up.

Results: Mean age was 9.9 (SD ± 2.9 years). The average frontal Cobb angle was reduced from mean 65° to 30° postoperatively, and had increased to 37° at latest follow-up. Rotation of the apical vertebra improved from mean 27° to 20° postoperatively which was partially lost to 23°. Kyphosis and lordosis both increased by an average of 5° during the time of follow-up. Spinal balance was improved. The post-implantation T1-S1 spine growth rate averaged 10 mm/year at last follow-up. There were 13 implant-related complications in 6 out of 18 patients. No screw pull-outs and nor surgical site infections were registered.

Conclusions: This is the first medium-term results of a single MCGR hybrid construct. Maintenance of correction and growth are reasonable, and the complication rate is relatively low as compared to bilateral MCGR application.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s43390-020-00098-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366570PMC
August 2020

Anterior lengthening in scoliosis occurs only in the disc and is similar in different types of scoliosis.

Spine J 2020 10 14;20(10):1653-1658. Epub 2020 Mar 14.

Department of Orthopedic Surgery, University Medical Center Utrecht, P.O. Box 85500, Utrecht 3508, the Netherlands. Electronic address:

Background Context: Relative anterior spinal overgrowth was proposed as a generalized growth disturbance and a potential initiator of adolescent idiopathic scoliosis (AIS). However, anterior lengthening has also been observed in neuromuscular (NM) scoliosis and was shown to be restricted to the apical areas and located in the intervertebral discs, not in the bone. This suggests that relative anterior spinal overgrowth does not rightfully describe anterior lengthening in scoliosis, as it seems not a generalized active growth phenomenon, nor specific to AIS.

Purpose: To determine if compensatory curves in congenital scoliosis exhibit a mechanism of anterior lengthening without changes in the vertebral body, similar to curves in AIS and NM scoliosis.

Study Design/setting: Cross-sectional.

Patient Sample: CT-scans were included of patients in whom a short segment congenital malformation had led to a long thoracic compensatory curve without bony abnormality. Based on data of other scoliosis types, the calculated required sample size was n=12 to detect equivalence of vertebral bodies as compared with nonscoliotic controls. Out of 143 congenital scoliosis patients, 18 fit the criteria and compared with 30 nonscoliotic controls, 30 AIS and 30 NM scoliosis patients.

Outcome Measures: The anterior-posterior length discrepancy (AP%) of the total curve and for vertebral bodies and intervertebral discs separately.

Methods: Of each vertebral body and intervertebral disc in the compensatory curve, the anterior and posterior length was measured on CT-scans in the exact mid-sagittal plane, corrected for deformity in all three planes. The AP% was calculated for the total compensatory curve (Cobb-to-Cobb) and for the vertebral bodies and the intervertebral discs separately. Positive AP% indicated that the anterior side was longer than the posterior side.

Results: The total AP% of the compensatory curve in congenital scoliosis showed lordosis (+1.8%) that differed from the kyphosis in nonscoliotic controls (-3.0%; p<.001) and was comparable to the major curve in AIS (+1.2%) and NM scoliosis (+0.5%). This anterior lengthening was not located in the bone; the vertebral body AP% showed kyphosis (-3.2%), similar to nonscoliotic controls (-3.4%) as well as AIS (-2.5%) and NM scoliosis (-4.5%; p=1.000). However, the disc AP% showed lordosis (+24.3%), which sharply contrasts to the kyphotic discs of controls (-1.5%; p<.001), but was similar to AIS (+17.5%) and NM scoliosis (+20.5%).

Conclusions: The current study on compensatory curves in congenital scoliosis confirms that anterior lengthening is part of the three-dimensional deformity in different types of scoliosis and is exclusively located in the intervertebral discs. The bony vertebral bodies maintain their kyphotic shape, which indicates that there is no active anterior bony overgrowth. Anterior lengthening appears to be a passive result of any scoliotic deformity, rather than being related to the specific cause of AIS.
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http://dx.doi.org/10.1016/j.spinee.2020.03.005DOI Listing
October 2020

Efficacy of a Standalone Microporous Ceramic Versus Autograft in Instrumented Posterolateral Spinal Fusion: A Multicenter, Randomized, Intrapatient Controlled, Noninferiority Trial.

Spine (Phila Pa 1976) 2020 Jul;45(14):944-951

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Study Design: in the rest of the article written as patient- and observer-blinded, multicenter, randomized, intrapatient controlled, noninferiority trial.

Objective: The aim of this study was to determine noninferiority of a biphasic calcium-phosphate (AttraX® Putty) as a bone graft substitute for autograft in instrumented posterolateral fusion (PLF).

Summary Of Background Data: Spinal fusion with autologous bone graft is a frequently performed surgical treatment. Several drawbacks of autografting have driven the development of numerous alternatives including synthetic ceramics. However, clinical evidence for the standalone use of these materials is limited.

Methods: This study included 100 nontraumatic adults who underwent a primary, single- or multilevel, thoracolumbar, instrumented PLF. After instrumentation and preparation for grafting, the randomized allocation side of AttraX® Putty was disclosed. Autograft was applied to the contralateral side of the fusion trajectory, so each patient served as his/her own control. For the primary efficacy outcome, PLF was assessed at 1-year follow-up on computed tomography scans. Each segment and side was scored as fused, doubtful fusion, or nonunion. After correction for multilevel fusions, resulting in a single score per side, the fusion performance of AttraX Putty was tested with a noninferiority margin of 15% using a 90% confidence interval (CI).

Results: There were 49 males and 51 females with a mean age of 55.4 ± 12.0 (range 27-79) years. Two-third of the patients underwent a single-level fusion and 62% an additional interbody fusion procedure. The primary analysis was based on 87 patients, including 146 instrumented segments. The fusion rate of AttraX Putty was 55% versus 52% at the autograft side, with an overall fusion rate of 71%. The 90% CI around the difference in fusion performance excluded the noninferiority margin (difference = 2.3%, 90% CI = -9.1% to +13.7%).

Conclusion: The results of this noninferiority trial support the use of AttraX Putty as a standalone bone graft substitute for autograft in instrumented thoracolumbar PLF.

Level Of Evidence: 1.
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http://dx.doi.org/10.1097/BRS.0000000000003440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337108PMC
July 2020

The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis.

Spine J 2020 06 18;20(6):956-963. Epub 2020 Jan 18.

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, ON, Canada M5G 2N2; The Dalglish Family 22q Clinic for Adults, University Health Network, 200 Elizabeth St, Toronto, ON, Canada; Toronto Congenital Cardiac Centre for Adults, Peter Munk Cardiac Centre, 585 University Ave, Toronto, ON, Canada M5G 2N2; Division of Cardiology, Department of Medicine, University Health Network, Toronto, ON, Canada; Toronto General Research Institute and Campbell Family Mental Health Research Institute, Toronto, ON, Canada. Electronic address:

Background Context: For over four decades, clinicians and researchers have suggested a relationship between congenital heart disease (CHD) and scoliosis, attributed to either the disease itself or to the long-term effects of cardiac surgery on the immature thoracic cage. However, no study has yet accounted for 22q11.2 deletion syndrome (22q11.2DS), the second most common cause of CHD after Down syndrome. 22q11.2DS has a scoliosis risk of 50%, but within 22q11.2DS a previous report found no significant association between scoliosis and CHD. We, therefore, hypothesized that scoliosis within a CHD cohort would be related to an underlying 22q11.2 deletion.

Purpose: To determine the prevalence of scoliosis in CHD patients with and without 22q11.2DS.

Study Design/setting: Cross-sectional.

Patient Sample: A well-characterized existing database of 315 adults with CHD (primarily tetralogy of Fallot), with (n=86) and without (n=229) 22q11.2DS, matched by sex and CHD severity, and excluding other known syndromic diagnoses. We compared the scoliosis prevalence of patients with 22q11.2DS and CHD patients to the prevalence of scoliosis in a cohort of adults with 22q11.2DS without CHD based on medical records.

Outcome Measures: Presence of scoliosis (Cobb angle ≥10°).

Methods: We systematically determined the presence of scoliosis in all included patients using chest radiographs, blind to genetic diagnosis. Besides 22q11.2DS, we analyzed other suspected risk factors for scoliosis using a regression model: thoracotomy before the age of 12 years, severe CHD type and sex.

Results: The prevalence of scoliosis in adults with CHD and 22q11.2DS (n=46, 53.5%) was significantly greater than in those without 22q11.2DS (n=18, 7.9%, p<.0001). The presence of a 22q11.2 deletion (odds ratio [OR] 25.4, 95% confidence interval [95% CI] 11.2-57.4, p<.0001), a history of thoracotomy before the age of 12 years (OR 3.5, 95% CI 1.6-8.1, p=.0027) and most complex CHD class (OR 2.3, 95% CI 1.1-4.7, p=.0196), but not sex, were significant independent predictors of scoliosis. In the 22q11.2DS group, a right-sided aortic arch was associated with a left thoracic scoliotic curve (p=.036).

Conclusions: The prevalence of scoliosis in those with CHD but without a 22q11.2 deletion approximates that of the general population. However, in the CHD population with a 22q11.2 deletion, the prevalence of scoliosis approximates that of others with 22q11.2DS. The pediatric surgical approach and severity of CHD were weaker independent contributors as compared to the 22q11.2 deletion. The results support the importance of a genetic diagnosis of 22q11.2DS to the risk of developing scoliosis in individuals with CHD. The 22q11.2 deletion may represent a common etiopathogenetic pathway for both CHD and scoliosis, possibly involving early laterality mechanisms.
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http://dx.doi.org/10.1016/j.spinee.2020.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246162PMC
June 2020

Effect of unfocused extracorporeal shockwave therapy on bone mineral content of twelve distal forearms of postmenopausal women: a clinical pilot study.

Arch Osteoporos 2019 11 26;14(1):113. Epub 2019 Nov 26.

Department of Orthopaedics, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.

Extracorporeal shockwave therapy showed a pronounced effect on bone mass in previous animal studies. We showed in this pilot study that a single treatment with unfocused shockwave therapy in unselected patients does not show side effects. Although our study did not show any effect of shockwave on BMD, the limited sample size does not definitively exclude this and a study with 174 subjects per group would be needed to show an effect size of 0.3 with a power of 80%.

Purpose: Unfocused extracorporeal shockwave therapy might stimulate bone formation to reduce the fracture risk. In this study, we assessed the safety of unfocused extracorporeal shockwave therapy and its effects on bone mass.

Methods: A clinical pilot study with twelve female patients free of bone disease undergoing elective surgery of the lower extremity or elective spinal surgery under general anesthesia received 3.000 electrohydraulic-generated unfocused extracorporeal shockwaves (energy flux density 0.3 mJ/mm) to one distal forearm. The contralateral forearm served as a control. We examined the effect on bone mass with the use of repeated dual energy X-ray absorptiometry measurements and we measured patient discomfort around the therapy.

Results: No difference in bone mineral content and density was measured 6 and 12 weeks after therapy. shockwave therapy occasionally caused transient erythema or mild hematoma, but no discomfort in daily life or (late) adverse events.

Conclusions: Unfocused extracorporeal shockwave therapy is a safe treatment, but no increase in bone mass on the forearm was found at 0.3 mJ/mm energy flux density. In this study, we were not able to demonstrate that a single treatment with unfocused shockwave therapy in unselected patients had any effect in terms of bone mineral density (BMD) or bone mineral content (BMC). A power analysis indicated that 174 patients per group are required to show an effect size of 0.3 with a power of 80%.
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http://dx.doi.org/10.1007/s11657-019-0650-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877705PMC
November 2019

Reliability and Validity of the Adapted Dutch Version of the Early-Onset Scoliosis-24-Item Questionnaire (EOSQ-24).

Spine (Phila Pa 1976) 2019 Aug;44(16):E965-E973

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.

Study Design: Translation and validation of the Early Onset Scoliosis-24 Questionnaire (EOSQ-24).

Objective: To cross-culturally adapt the English version of the EOSQ-24 to the Dutch language and to assess the questionnaire's reliability and validity.

Summary Of Background Data: Early-onset scoliosis (EOS) has a profound impact on health-related quality of life. The EOSQ-24 is health-related quality of life questionnaire filled in by parents of children with EOS. The EOSQ-24 was already translated into multiple languages and its application was confirmed in clinical studies. However, the EOSQ-24 is not yet translated and validated for the Dutch population.

Methods: The adaption of the EOSQ-24 for the Dutch population was done in three steps: 1) translation to the Dutch language, 2) cross-cultural adaptation, and 3) cross-cultural validation. To ensure that the Adapted Dutch EOSQ-24 is applicable for clinical use, the measurement properties were tested in four steps: 1) floor and ceiling effects, 2) validation, 3) reliability, and 4) discriminative ability. One hundred three parents completed the Adapted Dutch EOSQ-24, the Child Health Questionnaire (CHQ-28 PF), and the Scoliosis Research Society Questionnaire (SRS-22r). A second EOSQ-24 was completed for test-retest reproducibility.

Results: The EOSQ-24 was successfully translated, adapted, and validated for the Dutch language. Almost all response items showed a normal distribution. The EOSQ-24 showed excellent reliability (Cronbach α of 0.950). The EOSQ-24 was successfully validated against the CHQ-28-PF and the SRS-22r. Test-retest was excellent (ICC ≥ 0.8). Finally, The EOSQ-24 was found capable to discriminate patients with different curve severities (P = 0.003), diagnosis (P = 0.006), and ambulatory status (P < 0.001).

Conclusion: The current Dutch EOSQ-24 proved to be a valid and reliable quality of life assessment tool for patients with EOS. Currently, long follow-up studies using the EOSQ-24, including the Dutch EOSQ-24, are lacking and are needed to fully validate the EOSQ-24 for use in a clinical setting.

Level Of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003017DOI Listing
August 2019

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

Challenges in the design and regulatory approval of 3D-printed surgical implants: a two-case series.

Lancet Digit Health 2019 08 23;1(4):e163-e171. Epub 2019 Jul 23.

Department of Orthopaedics, University Medical Centre Utrecht, Utrecht, Netherlands.

Background: Additive manufacturing or three-dimensional (3D) printing of metal implants can provide novel solutions for difficult-to-treat conditions, yet legislation concerning patient-specific implants complicates the implementation of these techniques in daily practice. In this Article, we share our acquired knowledge of the logistical and legal challenges associated with the use of patient-specific 3D-printed implants to treat spinal instabilities.

Methods: Two patients with semiurgent cases of spinal instability presented to our hospital in the Netherlands. In case 1, severe kyphotic deformity of the thoracic spine due to neurofibromatosis type 1 had led to incomplete paralysis, and a strong metallic strut extending from C6 to T11 was deemed necessary to provide long-term anterior support. In case 2, the patient presented with progressive paralysis caused by cervicothoracic dissociation due to vanishing bone disease. As the C5-T1 vertebral bodies had mostly vanished, an implant spanning the anterior spine from C4 to T2 was required. Because of the complex and challenging nature of both cases, conventional approaches were deemed inadequate; instead, patient-specific implants were designed with use of CT scans and computer-aided design software, and 3D printed in titanium with direct metal printing. For each implant, to ensure patient safety, a comprehensive technical file (describing the clinical substantiation, technical and design considerations, risk analysis, manufacturing process, and labelling) was produced in collaboration with a university department certified for the development and manufacturing of medical devices. Because the implants were categorised as custom-made or personalised devices under the EU Medical Device Regulation, the usual procedures for review and approval of medical devices by a notified body were not required. Finite-element analyses, compression strength tests, and cadaveric experiments were also done to ensure the devices were safe to use.

Findings: The planning, design, production, and insertion of the 3D-printed personalised implant took around 6 months in the first patient, but, given the experience from the first case, only took around 6 weeks in the second patient. In both patients, the surgeries went as planned and good positioning of each implant was confirmed. Both patients were discharged home within 1 week after the surgery. In the first patient, a fatigue fracture occured in one of the conventional posterior fusion rods after 10 months, which we repaired, without any deformation of the spine or signs of failure of the personalised implant observed. No other adverse events occurred up to 25 months of follow-up in case 1 and 6 months of follow-up in case 2.

Interpretation: Patient-specific treatment approaches incorporating 3D-printed implants can be helpful in carefully selected cases when conventional methods are not an option. Comprehensive and efficient interactions between medical engineers and physicians are essential to establish well designed frameworks to navigate the logistical and regulatory aspects of technology development to ensure the safety and legal validity of patient-specific treatments. The framework described here could encourage physicians to treat (once untreatable) patients with novel personalised techniques.

Funding: Interreg VA Flanders-The Netherlands programme, Applied and Engineering Sciences research programme, the Netherlands Organisation for Scientific Research, and the Dutch Arthritis Foundation VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/S2589-7500(19)30067-6DOI Listing
August 2019

[Applications of 3D printing in medicine; 5 years later].

Ned Tijdschr Geneeskd 2019 05 22;163. Epub 2019 May 22.

UMC Utrecht, afd. Orthopedie, Utrecht.

5 years ago, we described the emergence of 3D printing in medicine. It was about 3D printing of anatomical structures, patient-specific drilling guides, cutting templates and implants and printing of living cells, growth factors and biomaterials ('bioprinting'). Surgeons are increasingly making use of 3D printing possibilities in preparation of surgeries on patients with complicated anatomies. Using tangible 3D models, it is easier for surgeons to prepare for surgeries and discussions with patients. They can also use 3D models as a tool to help with the training of young surgeons. Permanent titanium implants are increasingly being printed. Bioprinting is still in its infancy and there are no direct clinical applications yet. As we already predicted 5 years ago, many hurdles still have to be taken before broad clinical application of bioprinted products will become a reality.
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May 2019

The efficacy of intrawound vancomycin powder and povidone-iodine irrigation to prevent surgical site infections in complex instrumented spine surgery.

Spine J 2019 10 31;19(10):1648-1656. Epub 2019 May 31.

Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.

Background Context: Surgical site infections (SSIs) are notorious complications in spinal surgery and cause substantial patient morbidity. Intraoperative decontamination of the wound with povidone-iodine irrigation or vancomycin powder has gained attention lately, but the efficacy of either intervention is unclear.

Purpose: To determine the efficacy of intrawound povidone-iodine or vancomycin in reducing the incidence of deep- and superficial SSIs in instrumented spinal surgery.

Study Design/setting: Retrospective cohort study.

Patient Sample: A retrospective chart review was performed including all consecutive adult patients undergoing open, posterior, instrumented spinal surgery at any level between January 2012 and August 2017.

Outcome Measures: The presence of SSI was evaluated according to the criteria published by the Centers for Disease Control and Prevention. The SSIs were divided into deep SSIs (below the muscular fascia) and superficial SSIs (above the muscular fascia).

Methods: A retrospective cohort without intrawound treatment was compared with two separate, consecutive intervention groups. One intrawound group received 1.3g/L povidone-iodine irrigation and the other received 1-2 grams of intrawound vancomycin powder at the end of surgery. Incidence of SSIs, as well as demographic, surgical and patient-related variables were registered and compared between groups. In patients with SSI, additional microbiological data were collected.

Results: In total, 853 patients were included. In the control group (N=257), 25 (9.7%) patients developed a deep and 13 (5.1%) developed a superficial SSI. In the povidone-iodine group (N=217), 21 (9.7%) patients developed a deep and two (0.9%) developed a superficial SSI. Compared with the control group, there was no significant difference in the incidence of deep SSIs (risk ratio [RR]: 1.00, 95% CI 0.57-1.73), although the number of superficial SSIs was reduced significantly (RR 0.18, 95% CI 0.04-0.80). In the vancomycin group (N=379), 19 (5.0%) patients developed a deep and six (1.6%) developed a superficial SSI. Both deep (RR: 0.52, 95% CI 0.29-0.92) and superficial SSIs (RR: 0.31, 95% CI 0.12-0.81) were significantly reduced in the vancomycin group compared with the control group, even when correcting for several risk factors associated with SSIs in a multivariable logistic regression analysis. There were no significant differences in complications between the 3 groups. No gram-negative selection or vancomycin-resistance was seen in the vancomycin group.

Conclusions: Intrawound application of vancomycin was associated with a significant reduction in both deep and superficial SSIs in instrumented spinal surgery. A 1.3g/L intrawound povidone-iodine solution did not show a reduction in deep SSIs, although a reduction of superficial SSIs was observed.
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http://dx.doi.org/10.1016/j.spinee.2019.05.592DOI Listing
October 2019

[Teenagers with torticollis].

Ned Tijdschr Geneeskd 2019 05 3;163. Epub 2019 May 3.

UMC Utrecht, afd. Orthopedie, Utrecht.

Teenagers with torticollis In this article we describe three cases of children with torticollis. A 17-year-old patient who appears to have Klippel-Feil syndrome and is treated conservatively. An 11-year-old-patient with torticollis, present since a fall two days earlier and attributed to a subluxation of C1-C2. Ultimately, she had to be treated surgically with an atlantoaxial spondylodesis and has made a good recovery. Finally, a 15-year-old who presents with torticollis which has been present from early childhood. The diagnosis neglected congenital muscular torticollis is made. Because of increasing discomfort she is treated surgically with release of the sternocleidomastoideus. Postoperative, the patient has fewer symptoms. Physicians should be aware of different causes when there is persistent torticollis. Furthermore, children presenting with posttraumatic torticollis require a strict follow-up because atlanto-axial subluxation can lead to permanent deformity.
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May 2019

Changes in the Position of the Junctional Vertebrae After Posterior Spinal Fusion in Adolescent Idiopathic Scoliosis: Implication in Risk Assessment of Proximal Junctional Kyphosis Development.

J Pediatr Orthop 2020 Feb;40(2):e84-e90

Division of Orthopaedic Surgery, The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA.

Background: The development of proximal junctional kyphosis (PJK) after posterior spinal fusion in adolescent idiopathic scoliosis is a major problem. Changes in the global sagittal parameters as they relate to PJK have been reported after surgery, however, the relationships between the changes in the upper-instrumented vertebra (UIV) during and after surgery as they relate to development of PJK have not been quantified. We hypothesize that the compensatory changes in the unfused segments of the spine over time are correlated with the surgically induced changes in the UIV position.

Methods: Sixty adolescent idiopathic scoliosis patients (with at least 1-year follow-up) who underwent posterior spinal surgery were included retrospectively. Global spinal parameters were calculated using 3-dimensional models of the spine, additional parameters [proximal junctional kyphosis angle (PJKA), cervical lordosis angle] were measured manually before surgery and at 3 postoperative follow-ups. The 3-dimensional position of the vertebral body centroids was calculated for T1, UIV, and lower-instrumented vertebra at all timepoints. The sagittal position of T1, UIV, and lower-instrumented vertebra were correlated to the cervical lordosis, PJKA, lumbar lordosis, and pelvic tilt.

Results: The position of T1 and UIV were significantly more anterior at first erect for patients who developed PJK. The posterior shift of UIV at the most recent follow-up as compared with the preoperative position was significant in both the PJK and non-PJK cohort. A larger anterior shift in UIV at first erect correlated with a larger T1 and UIV posterior shift at the most recent follow-up. At the most recent follow-up, a more posterior position of the UIV correlated with a larger angle of PJKA (P<0.05).

Conclusion: Both a larger anterior shift of UIV between preoperative and first erect and a more posterior position of UIV at the most recent follow-up was correlated with a higher PJKA. A larger anterior shift in the position of the UIV after surgery was associated with a higher posterior shift of UIV at the last follow-up. The surgically induced changes in the UIV are an important parameter associated with the development of PJK.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1097/BPO.0000000000001400DOI Listing
February 2020

The 22q11.2 deletion syndrome as a model for idiopathic scoliosis - A hypothesis.

Med Hypotheses 2019 Jun 27;127:57-62. Epub 2019 Mar 27.

Department of Orthopaedic Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address:

Adolescent idiopathic scoliosis (AIS), defined as a lateral deviation of the spine of at least ten degrees, is a classic enigma in orthopaedics and affects 1-4% of the general population. Despite (over) a century of intensive research, the etiology is still largely unknown. One of the major problems in all existing AIS research is the fact that most patients come to medical attention after onset of the curve. Therefore, it is impossible to know whether current investigated parameters are causative, or an effect of the scoliosis. Moreover, up until now there is no known animal model that captures the core features of AIS. In order to identify causal pathways leading to AIS we propose another approach, which has been of great value in other medical disciplines: To use a subset of the population, with a higher risk for a certain disease as a "model" for the general population. Such a "model" may allow the identification of causative mechanisms that might be applicable to the general population. The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome and occurs in ∼1:3000-6000 children and 1:1000 pregnancies. Nearly half of the population of patients with 22q11.2DS develop a scoliosis that in most cases resembles AIS as far as age at onset and curve pattern. We postulate that within 22q11.2DS certain causal pathways leading to scoliosis can be identified and that these are applicable to the general population.
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http://dx.doi.org/10.1016/j.mehy.2019.03.024DOI Listing
June 2019

Spinal Balance/Alignment - Clinical Relevance and Biomechanics.

J Biomech Eng 2019 May 2. Epub 2019 May 2.

Engineering Center for Orthopaedic Research Excellence (E-CORE), Departments of Bioengineering and Orthopaedic Surgery, Colleges of Engineering and Medicine, University of Toledo, Toledo, OH.

In the normal spine due to its curvature in various regions, C7 plumb line (C7PL) passes through the sacrum so that the head is centered over the pelvis-ball and socket hip joints and ankle joints. This configuration leads to the least muscular activities to maintain the spinal balance. For any reason like deformity, scoliosis, kyphosis, trauma, and/or surgery this optimal configuration gets disturbed requiring higher muscular activity to maintain the posture and balance. Several parameters like the thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), Hip- and leg position influence the sagittal balance and thus the optimal configuration of spinal alignment. Global sagittal imbalance is energy consuming and often painful compensatory mechanisms are developed, that in turn negatively influence the quality of life. This review looks at the clinical aspects of spinal imbalance, and the biomechanics of spinal balance as dictated by the deformities- ankylosing spondylitis, scoliosis and kyphosis; surgical corrections- pedicle subtraction osteotomies and long segment stabilizations and consequent postural complications like the proximal and distal junctional kyphosis. This review suggests several potential research topics as well.
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http://dx.doi.org/10.1115/1.4043650DOI Listing
May 2019

Intrawound Treatment for Prevention of Surgical Site Infections in Instrumented Spinal Surgery: A Systematic Comparative Effectiveness Review and Meta-Analysis.

Global Spine J 2019 Apr 26;9(2):219-230. Epub 2018 Jul 26.

Department of Orthopaedics, University Medical Center Utrecht, Utrecht, Netherlands.

Study Design: Systematic review and meta-analysis.

Objectives: To determine the efficacy of intrawound treatments in reducing deep surgical site infections (SSIs) in instrumented spinal surgery.

Methods: The electronic databases MEDLINE, EMBASE, and Cochrane were systematically searched for intrawound treatments for the prevention of SSIs in clean instrumented spine surgery. Both randomized controlled trials and comparative cohort studies were included. The results of included studies were pooled for meta-analysis.

Results: After full text- and reference screening, 20 articles were included. There were 2 randomized controlled trials and 18 observational studies. Sixteen studies investigated the use of intrawound antibiotics, and 4 studies investigated the use of intrawound antiseptics. The relative risk of deep SSI for any treatment was 0.26 (95% confidence interval [CI] 0.16-0.44, < .0001), a significant reduction compared with controls receiving no treatment. For patients treated with local antibiotics the relative risk was 0.29 (95% CI 0.17-0.51, < .0001), and patients treated with local antiseptics had a relative risk of 0.14 (95% CI 0.05-0.44, = .0006).

Conclusions: Both the use of antibiotic and antiseptic intrawound prophylactics was associated with a significant 3 to 7 times reduction of deep SSIs in instrumented spine surgery. No adverse events were reported in the included studies.
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http://dx.doi.org/10.1177/2192568218786252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448203PMC
April 2019

The diagnostic accuracy of F-FDG PET/CT in diagnosing fracture-related infections.

Eur J Nucl Med Mol Imaging 2019 Apr 7;46(4):999-1008. Epub 2018 Dec 7.

Department of Trauma Surgery, Utrecht University, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.

Purpose: F-Fluorodeoxyglucose positron emission tomography (F-FDG PET/CT) is frequently used to diagnose fracture-related infections (FRIs), but its diagnostic performance in this field is still unknown. The aims of this study were: (1) to assess the diagnostic performance of qualitative assessment of F-FDG PET/CT scans in diagnosing FRI, (2) to establish the diagnostic performance of standardized uptake values (SUVs) extracted from F-FDG PET/CT scans and to determine their associated optimal cut-off values, and (3) to identify variables that predict a false-positive (FP) or false-negative (FN) F-FDG PET/CT result.

Methods: This retrospective cohort study included all patients with suspected FRI undergoing F-FDG PET/CT between 2011 and 2017 in two level-1 trauma centres. Two nuclear medicine physicians independently reassessed all F-FDG PET/CT scans. The reference standard consisted of the result of at least two deep, representative microbiological cultures or the presence/absence of clinical confirmatory signs of FRI (AO/EBJIS consensus definition) during a follow-up of at least 6 months. Diagnostic performance in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was calculated. Additionally, SUVs were measured on F-FDG PET/CT scans. Volumes of interest were drawn around the suspected and corresponding contralateral areas to obtain absolute values and ratios between suspected and contralateral areas. A multivariable logistic regression analysis was also performed to identify the most important predictor(s) of FP or FN F-FDG PET/CT results.

Results: The study included 156 F-FDG PET/CT scans in 135 patients. Qualitative assessment of F-FDG PET/CT scans showed a sensitivity of 0.89, specificity of 0.80, PPV of 0.74, NPV of 0.91 and diagnostic accuracy of 0.83. SUVs on their own resulted in lower diagnostic performance, but combining them with qualitative assessments yielded an AUC of 0.89 compared to an AUC of 0.84 when considering only the qualitative assessment results (p = 0.007). F-FDG PET/CT performed <1 month after surgery was found to be the independent variable with the highest predictive value for a false test result, with an absolute risk of 46% (95% CI 27-66%), compared with 7% (95% CI 4-12%) in patients with F-FDG PET/CT performed 1-6 months after surgery.

Conclusion: Qualitative assessment of F-FDG PET/CT scans had a diagnostic accuracy of 0.83 and an excellent NPV of 0.91 in diagnosing FRI. Adding SUV measurements to qualitative assessment provided additional accuracy in comparison to qualitative assessment alone. An interval between surgery and F-FDG PET/CT of <1 month was associated with a sharp increase in false test results.
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http://dx.doi.org/10.1007/s00259-018-4218-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450834PMC
April 2019