Publications by authors named "Brian D Snyder"

105 Publications

Raman needle arthroscopy for in vivo molecular assessment of cartilage.

J Orthop Res 2021 Aug 9. Epub 2021 Aug 9.

Department of Mechanical Engineering, Boston University, Boston, Massachusetts, USA.

The development of treatments for osteoarthritis (OA) is burdened by the lack of standardized biomarkers of cartilage health that can be applied in clinical trials. We present a novel arthroscopic Raman probe that can "optically biopsy" cartilage and quantify key extracellular matrix (ECM) biomarkers for determining cartilage composition, structure, and material properties in health and disease. Technological and analytical innovations to optimize Raman analysis include (1) multivariate decomposition of cartilage Raman spectra into ECM-constituent-specific biomarkers (glycosaminoglycan [GAG], collagen [COL], water [H O] scores), and (2) multiplexed polarized Raman spectroscopy to quantify superficial zone (SZ) COL anisotropy via a partial least squares-discriminant analysis-derived Raman collagen alignment factor (RCAF). Raman measurements were performed on a series of ex vivo cartilage models: (1) chemically GAG-depleted bovine cartilage explants (n = 40), (2) mechanically abraded bovine cartilage explants (n = 30), (3) aging human cartilage explants (n = 14), and (4) anatomical-site-varied ovine osteochondral explants (n = 6). Derived Raman GAG score biomarkers predicted 95%, 66%, and 96% of the variation in GAG content of GAG-depleted bovine explants, human explants, and ovine explants, respectively (p < 0.001). RCAF values were significantly different for explants with abrasion-induced SZ COL loss (p < 0.001). The multivariate linear regression of Raman-derived ECM biomarkers (GAG and H O scores) predicted 94% of the variation in elastic modulus of ovine explants (p < 0.001). Finally, we demonstrated the first in vivo Raman arthroscopy assessment of an ovine femoral condyle through intraarticular entry into the synovial capsule. This study advances Raman arthroscopy toward a transformative low-cost, minimally invasive diagnostic platform for objective monitoring of treatment outcomes from emerging OA therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.25155DOI Listing
August 2021

Health-related quality of life and caregiver burden after hip reconstruction and spinal fusion in children with spastic cerebral palsy.

Dev Med Child Neurol 2021 Jul 23. Epub 2021 Jul 23.

Orthopedic Center, Boston Children's Hospital, Boston, MA, USA.

Aim: To evaluate the effect of hip reconstruction or spinal fusion on health-related quality of life (HRQoL) in non-ambulatory children with spastic cerebral palsy (CP) and caregiver burden.

Method: This was a prospective, longitudinal study of changes in HRQoL and caregiver burden over the 5 years after surgical correction of hip instability or scoliosis in children with bilateral spastic CP classified in Gross Motor Function Classification levels IV or V. Serial parent proxy measures of HRQoL and caregiver burden were obtained before and 6 weeks, and 3, 6, 9, 12, 24, and 60 months after surgery using the Caregiver Priorities and Child Health Index of Life with Disabilities and the Assessment of Caregiver Experience with Neuromuscular Disease. Scores 5 years or more after surgery were compared to pre-surgery scores using paired Student's t-tests. Serial outcome trajectories were estimated by linear mixed modeling.

Results: Of 69 participants (40 males, 29 females; mean age 11y 6mo, SD 4y 1mo, range 3y 10mo-20y 7mo), 43 had hip reconstruction and 26 had spinal fusion. Clinically significant improvements in HRQoL were detected (average increase 7.6 points) 5 years or more postoperatively, with hip reconstruction providing greater benefit. Domains improved by surgery included positioning, transferring/mobility, comfort/emotions, and health. Caregiver burden did not change as these children remain maximally dependent.

Interpretation: Surgical treatment of hip and spine deformity improves HRQoL, especially for painful hip instability, but does not change caregiver burden.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dmcn.14994DOI Listing
July 2021

Variability in Antibiotic Treatment of Pediatric Surgical Site Infection After Spinal Fusion at A Single Institution.

J Pediatr Orthop 2021 Jul;41(6):e380-e385

Department of Orthopaedic Surgery, Rainbow Babies and Children's Hospital, Cleveland, OH.

Background: Recent focus on surgical site infections (SSIs) after posterior spine fusion (PSF) has lowered infection rates by standardizing perioperative antibiotic prophylaxis. However, efforts have neglected to detail antibiotic treatment of SSIs. Our aim was to document variability in antibiotic regimens prescribed for acute and latent SSIs following PSF in children with idiopathic, neuromuscular, and syndromic scoliosis.

Methods: This study included patients who developed a SSI after PSF for scoliosis at a pediatric tertiary care hospital between 2004 and 2019. Patients had to be 21 years or younger at surgery. Exclusion criteria included growing rods, staged surgery, and revision or removal before SSI diagnosis. Infection was classified as acute (within 90 d) or latent. Clinical resolution of SSI was measured by return to normal lab values. Each antibiotic was categorized as empiric or tailored.

Results: Eighty subjects were identified. The average age at fusion was 14.7 years and 40% of the cohort was male. Most diagnoses were neuromuscular (53%) or idiopathic (41%).Sixty-three percent of patients had an acute infection and 88% had a deep infection. The majority (54%) of subjects began on tailored antibiotic therapy versus empiric (46%). Patients with a neuromuscular diagnosis had 4.0 times the odds of receiving initial empiric treatment compared with patients with an idiopathic diagnosis, controlling for infection type and time (P=0.01). Ninety-two percent of patients with acute SSI retained implants at the time of infection and 76% retained them as of August 2020. In the latent cohort, 27% retained implants at infection and 17% retained them as of August 2020.

Conclusions: Patients with acute infections were on antibiotics longer than patients with latent infections. Those with retained implants were on antibiotics longer than those who underwent removal. By providing averages of antibiotic duration and lab normalization, we hope to standardize regimens moving forward and develop SSI-reducing pathways encompassing low-risk patients.

Level Of Evidence: Level III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001811DOI Listing
July 2021

Quantitative Evaluation of Equine Articular Cartilage Using Cationic Contrast-Enhanced Computed Tomography.

Cartilage 2021 04 2;12(2):211-221. Epub 2018 Dec 2.

Boston University, Boston, MA, USA.

Objective: To investigate the diffusion trajectory of a cationic contrast medium (CA4+) into equine articular cartilage, and to assess normal and degenerative equine articular cartilage using cationic contrast-enhanced computed tomography (CECT).

Design: In the first experiment (Exp1), equine osteochondral specimens were serially imaged with cationic CECT to establish the diffusion time constant and time to reach equilibrium in healthy articular cartilage. In a separate experiment (Exp2), articular cartilage defects were created on the femoral trochlea (defect joint) in a juvenile horse, while the opposite joint was a sham-operated control. After 7 weeks, osteochondral biopsies were collected throughout the articular surfaces of both joints. Biopsies were analyzed for cationic CECT attenuation, glycosaminoglycan (GAG) content, mechanical stiffness (E), and histology. Imaging, biochemical and mechanical data were compared between defect and control joints.

Results: Exp1: The mean diffusion time constant was longer for medial condyle cartilage (3.05 ± 0.1 hours) than lateral condyle cartilage (1.54 ± 0.3 hours, = 0.04). Exp2: Cationic CECT attenuation was lower in the defect joint than the control joint ( = 0.005) and also varied by anatomic location ( = 0.045). Mean cationic CECT attenuation from the lateral trochlear ridge was lower in the defect joint than in the control joint (2223 ± 329 HU and 2667 ± 540 HU, respectively; = 0.02). Cationic CECT attenuation was strongly correlated with both GAG (ρ = 0.79, < 0.0001) and E (ρ = 0.61, < 0.0001).

Conclusions: The equilibration time of CA4+ into equine articular cartilage is affected by tissue volume. Quantitative cationic CECT imaging reflects the biochemical, biomechanical and histological state of normal and degenerative equine articular cartilage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1947603518812562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970376PMC
April 2021

Scoliosis with Chiari I malformation without associated syringomyelia.

Spine Deform 2021 Jul 20;9(4):1105-1113. Epub 2021 Jan 20.

Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA, USA.

Purpose: Many patients with presumed idiopathic scoliosis are found to have Chiari I malformation (CM-I) on MRI. The objective of this study is to report on scoliosis progression in CM-I with no syringomyelia.

Methods: A retrospective review of patients with scoliosis and CM-I was conducted from 1997 to 2015. Patients with syringomyelia and/or non-idiopathic scoliosis were excluded. Clinical and radiographic characteristics were recorded at presentation and latest follow-up. CM-I was defined as the cerebellar tonsil extending 5 mm or more below the foramen magnum on MRI.

Results: Thirty-two patients (72% female) with a mean age of 11 years (range 1-16) at scoliosis diagnosis were included. The average initial curve was 30.3° ± SD 16.3. The mean initial Chiari size was 9.6 mm SD ± 4.0. Fifteen (46.9%) experienced Chiari-related symptoms, and three (9%) patients underwent Posterior Fossa Decompression (PFD) to treat these symptoms. 10 (31%) patients went on to fusion, progressing on average 13.6° (95% CI 1.6-25.6°). No association was detected between decompression and either curve progression or fusion (p = 0.46, 0.60). For those who did not undergo fusion, curve magnitude progressed on average 1.0° (95% CI - 4.0 to 5.9°). There was no association between age, Chiari size, presence of symptoms, initial curve shape, or bracing treatment and fusion.

Conclusion: Patients with CM-I and scoliosis may not require surgical treatment, including PFD and fusion. Scoliosis curvature stabilized in the non-surgical population at an average progression of 1.0°. These results suggest that CM-I with no syringomyelia has minimal effect on scoliosis progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43390-021-00286-7DOI Listing
July 2021

Part 2. Review and meta-analysis of studies on modulation of longitudinal bone growth and growth plate activity: A micro-scale perspective.

J Orthop Res 2021 05 29;39(5):919-928. Epub 2021 Jan 29.

School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.

Macro-scale changes in longitudinal bone growth resulting from mechanical loading were shown in Part 1 of this review to depend on load magnitude, anatomical location, and species. While no significant effect on longitudinal growth was observed by varying frequency and amplitude of cyclic loading, such variations, in addition to loading duration and species, were shown to affect the morphology, viability, and gene and protein expression within the growth plate. Intermittent compression regimens were shown to preserve or increase growth plate height while stimulating increased chondrocyte presence in the hypertrophic zone relative to persistent and static loading regimens. Gene and protein expressions related to matrix synthesis and degradation, as well as regulation of chondrocyte apoptosis were shown to exhibit magnitude-, frequency-, and duration-dependent responses to loading regimen. Chondrocyte viability was shown to be largely preserved within physiological bounds of magnitude, frequency, amplitude, and duration. Persistent static loading was shown to be associated with overall growth plate height in tension only, reducing it in compression, while affecting growth plate zone heights differently across species and encouraging mineralization relative to intermittent cyclic loading. Lateral loading of the growth plate, as well as microfluidic approaches are relatively understudied, and age, anatomical location, and species effects within these approaches are undefined. Understanding the micro-scale effects of varied loading regimes can assist in the development of growth modulation methods and device designs optimized for growth plate viability preservation or mineralization stimulation based on patient age and anatomical location.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24992DOI Listing
May 2021

Thoracic vertebral morphology in normal and scoliosis deformity in skeletally immature rabbits: A Longitudinal study.

JOR Spine 2020 Dec 17;3(4):e1118. Epub 2020 Sep 17.

School of Biomedical Engineering, Science and Health Systems Drexel University Philadelphia Pennsylvania USA.

Objective: To measure age-related changes in thoracic vertebral body heights (VBH) in skeletally immature normative and scoliotic rabbits to assess how VBH change during growth. To examine the potential link between the moment-arm of the rib tether and vertebral wedging as well as the sum of the curvature angles at the apical level (T7). To assess the correlation between the magnitude of initial spine curve and final spine curve in the scoliotic group.

Methods: Eight healthy, skeletally immature normative New Zealand rabbits and ten skeletally immature scoliotic rabbits which underwent unilateral rib tethering were included retrospectively. Each rabbit was scanned at two to four time points (at 7, 11, 14 and 28 weeks). Three dimensional bone models of thoracic vertebrae (T1-T12) were digitally segmented and reconstructed. VBH were calculated using surface landmark points from each thoracic vertebra. Apical level (T7) ± 2 levels in scoliotic rabbits were compared to their corresponding levels and time points in the normative group. The moment-arms between the centroids of 2D projections of T3-T9 vertebral bodies and the line which connects the centroids of the end levels were calculated.

Results: Bilateral left-right (L-R) symmetry and anterior-posterior (A-P) asymmetry were observed in normative VBH. Bilateral concave-convex (CC-CX) asymmetry and (A-P) asymmetry were observed in scoliotic VBH. No significant differences in growth rates were found between the normative and scoliotic groups. Vertebral wedging as well as curvature magnitude were positively correlated with the moment-arms.

Conclusion: Unilateral rib tether applies compressive forces on both concave and convex sides, whereas compressive forces are lower on the latter. Knowing the amount of vertebral wedging or curve magnitude would enable us to predict the applied force (moment-arms), which is important for planning a corrective surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jsp2.1118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770206PMC
December 2020

Part 1. Review and meta-analysis of studies on modulation of longitudinal bone growth and growth plate activity: A macro-scale perspective.

J Orthop Res 2021 05 13;39(5):907-918. Epub 2021 Jan 13.

School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.

Growth modulation is an emerging method for treatment of angular skeletal deformities such as adolescent idiopathic scoliosis (AIS). The Hueter-Volkmann law, by which growth is stimulated in tension and inhibited in compression, is widely understood, and applied in current growth-modulating interventions such as anterior vertebral body tethering (AVBT) for AIS. However, without quantification of the growth rate effects of tension or compression, the possibility of under- or over- correction exists. A definitive mechanical growth modulation relationship relating to treatment of such skeletal deformities is yet to exist, and the mechanisms by which growth rate is regulated and altered are not fully defined. Review of current literature demonstrates that longitudinal (i.e., lengthwise) growth rate in multiple animal models depend on load magnitude, anatomical location, and species. Additionally, alterations in growth plate morphology and viability vary by loading parameters such as magnitude, frequency, and whether the load was applied persistently or intermittently. The aggregate findings of the reviewed studies will assist in work towards increasingly precise and clinically successful growth modulation methods. Part 1 of this review focuses on the effects of mechanical loading, species, age, and anatomical location on the macro-scale alterations in longitudinal bone growth, as well as factors that affect growth plate material properties. Part 2 considers the effects on micro-scale alterations in growth plate morphology such as zone heights and proportions, chondrocyte viability, and related gene and protein expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24976DOI Listing
May 2021

Cationic contrast-enhanced computed tomography distinguishes between reparative, degenerative, and healthy equine articular cartilage.

J Orthop Res 2021 Aug 2;39(8):1647-1657. Epub 2020 Nov 2.

Orthopaedic Research Center, C. Wayne McIlwraith Translational Medicine Institute, Colorado State University, Fort Collins, Colorado, USA.

Cationic contrast-enhanced computed tomography (CECT) is a quantitative imaging technique that characterizes articular cartilage, though its efficacy in differentiating repair tissue from other disease states is undetermined. We hypothesized that cationic CECT attenuation will distinguish between reparative, degenerative, and healthy equine articular cartilage and will reflect biochemical, mechanical, and histologic properties. Chondral defects were created in vivo on equine femoropatellar joint surfaces. Within defects, calcified cartilage was retained (Repair 1) or removed (Repair 2). At sacrifice, plugs were collected from within defects, and at locations bordering (adjacent site) and remote to defects along with site-matched controls. Articular cartilage was analyzed via CECT using CA4+ to assess glycosaminoglycan (GAG) content, compressive modulus (E ), and International Cartilage Repair Society (ICRS) II histologic score. Comparisons of variables were made between sites using mixed model analysis and between variables with correlations. Cationic CECT attenuation was significantly lower in Repair 1 (1478 ± 333 Hounsfield units [HUs]), Repair 2 (1229 ± 191 HUs), and adjacent (2139 ± 336 HUs) sites when compared with site-matched controls (2587 ± 298, 2505 ± 184, and 2563 ± 538 HUs, respectively; all p < .0001). Cationic CECT attenuation was significantly higher at remote sites (2928 ± 420 HUs) compared with Repair 1, Repair 2, and adjacent sites (all p < .0001). Cationic CECT attenuation correlated with ICRS II score (r = .79), GAG (r = .76), and E (r = .71; all p < .0001). Cationic CECT distinguishes between reparative, degenerative, and healthy articular cartilage and highly correlates with biochemical, mechanical, and histological tissue properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24894DOI Listing
August 2021

Why Irrigate for the Same Contamination Rate: Wound Contamination in Pediatric Spinal Surgery Using Betadine Versus Saline.

J Pediatr Orthop 2020 Nov/Dec;40(10):e994-e998

Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA.

Background: The risk of surgical site infection in pediatric posterior spine fusion (PSF) is up to 4.3% in idiopathic populations and 24% in patients with neuromuscular disease. Twenty-three percent of pediatric PSF tissue cultures are positive before closure, with a higher rate in neuromuscular patients. Our primary aim was to evaluate the feasibility of a complete randomized controlled trial to study the efficacy of surgical site irrigation with povidone-iodine (PVP-I) compared with sterile saline (SS) to reduce the bacterial contamination rate before closure in children undergoing PSF.

Methods: One hundred seventy-five subjects undergoing PSF were enrolled in a multicenter, single-blind, pilot randomized controlled trial. We recruited patients at low-risk (LR) and high-risk (HR) for infection 3:1, respectively. Before closure, a wound culture was collected. Nonviable tissues were debrided and the wound was soaked with 0.35% PVP-I or SS for 3 minutes. The wound was then irrigated with 2 L of saline and a second sample was collected.

Results: One hundred fifty-three subjects completed the protocol. Seventy-seven subjects were allocated to PVP-I (18 HR, 59 LR) and 76 to SS (19 HR, 57 LR). Cultures were positive in 18% (14/77) of PVP-I samples (2 HR, 12 LR) and in 17% (13/76) of SS samples (3 HR, 10 LR) preirrigation and in 16% (12/77) of PVP-I samples (5 HR, 7 LR) and in 18% (14/76) of SS samples (4 HR, 10 LR) postirrigation. Eight percent (3/37) HR subjects (1 PVP-I, 2 SS) experienced infection at 30 days postoperative. No LR subjects experienced infection.

Conclusions: Positive cultures were similar across treatment and risk groups. The bacterial contamination of wounds before closure remains high regardless of irrigation type. A complete randomized controlled trial would be challenging to adequately power given the similarity of tissue positivity across groups.

Level Of Evidence: Level II-pilot randomized controlled trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001620DOI Listing
March 2021

Nanotechnology and Osteoarthritis. Part 2: Opportunities for advanced devices and therapeutics.

J Orthop Res 2021 03 22;39(3):473-484. Epub 2020 Sep 22.

Departments of Biomedical Engineering, Mechanical Engineering, Chemistry, and Medicine Boston University, Boston, Massachusetts, USA.

Osteoarthritis (OA) is a multifactorial disease of the entire joint which afflicts 140 million individuals worldwide regardless of economic or social status. Current clinical treatments for OA primarily center on reducing pain and increasing mobility, and there are limited therapeutic interventions to restore degraded cartilage or slow disease pathogenesis. This second installment of a two-part review on nanotechnology and OA focuses on novel treatment strategies. Specifically, Part 2 first discusses current surgical and nonsurgical treatments for OA and then summarizes recent advancements in nanotechnology-based treatments, while Part 1 (10.1002/jor.24817) described advances in imaging and diagnostics. We review nano delivery systems for small molecule drugs, nucleic acids, and proteins followed by nano-based scaffolds for neocartilage formation and osteochondral regeneration, and lastly nanoparticle lubricants. We conclude by identifying opportunities for nanomedicine advances, and prospects for OA treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24842DOI Listing
March 2021

Nanotechnology and osteoarthritis; part 1: Clinical landscape and opportunities for advanced diagnostics.

J Orthop Res 2021 03 14;39(3):465-472. Epub 2020 Sep 14.

Departments of Biomedical Engineering, Mechanical Engineering, Chemistry, and Medicine Boston University, Boston, Massachusetts.

Osteoarthritis (OA) is a disease of the entire joint, often triggered by cartilage injury, mediated by a cascade of inflammatory pathways involving a complex interplay among metabolic, genetic, and enzymatic factors that alter the biochemical composition, microstructure, and biomechanical performance. Clinically, OA is characterized by degradation of the articular cartilage, thickening of the subchondral bone, inflammation of the synovium, and degeneration of ligaments that in aggregate reduce joint function and diminish quality of life. OA is the most prevalent joint disease, affecting 140 million people worldwide; these numbers are only expected to increase, concomitant with societal and financial burden of care. We present a two-part review encompassing the applications of nanotechnology to the diagnosis and treatment of OA. Herein, part 1 focuses on OA treatment options and advancements in nanotechnology for the diagnosis of OA and imaging of articular cartilage, while part 2 (10.1002/jor.24842) summarizes recent advances in drug delivery, tissue scaffolds, and gene therapy for the treatment of OA. Specifically, part 1 begins with a concise review of the clinical landscape of OA, along with current diagnosis and treatments. We next review nanoparticle contrast agents for minimally invasive detection, diagnosis, and monitoring of OA via magnetic resonace imaging, computed tomography, and photoacoustic imaging techniques as well as for probes for cell tracking. We conclude by identifying opportunities for nanomedicine advances, and future prospects for imaging and diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24817DOI Listing
March 2021

Evaluation of musculoskeletal phenotype of the G608G progeria mouse model with lonafarnib, pravastatin, and zoledronic acid as treatment groups.

Proc Natl Acad Sci U S A 2020 06 13;117(22):12029-12040. Epub 2020 May 13.

Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA 02215;

Hutchinson-Gilford progeria syndrome (HGPS) is a uniformly fatal condition that is especially prevalent in skin, cardiovascular, and musculoskeletal systems. A wide gap exists between our knowledge of the disease and a promising treatment or cure. The aim of this study was to first characterize the musculoskeletal phenotype of the homozygous G608G BAC-transgenic progeria mouse model, and to determine the phenotype changes of HGPS mice after a five-arm preclinical trial of different treatment combinations with lonafarnib, pravastatin, and zoledronic acid. Microcomputed tomography and CT-based rigidity analyses were performed to assess cortical and trabecular bone structure, density, and rigidity. Bones were loaded to failure with three-point bending to assess strength. Contrast-enhanced µCT imaging of mouse femurs was performed to measure glycosaminoglycan content, thickness, and volume of the femoral head articular cartilage. Advanced glycation end products were assessed with a fluorometric assay. The changes demonstrated in the cortical bone structure, rigidity, stiffness, and modulus of the HGPS G608G mouse model may increase the risk for bending and deformation, which could result in the skeletal dysplasia characteristic of HGPS. Cartilage abnormalities seen in this HGPS model resemble changes observed in the age-matched WT controls, including early loss of glycosaminoglycans, and decreased cartilage thickness and volume. Such changes might mimic prevalent degenerative joint diseases in the elderly. Lonafarnib monotherapy did not improve bone or cartilage parameters, but treatment combinations with pravastatin and zoledronic acid significantly improved bone structure and mechanical properties and cartilage structural parameters, which ameliorate the musculoskeletal phenotype of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1906713117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275760PMC
June 2020

Mega macromolecules as single molecule lubricants for hard and soft surfaces.

Nat Commun 2020 05 1;11(1):2139. Epub 2020 May 1.

Centre for Blood Research, Life Sciences Institute, The University of British Columbia, Vancouver, BC, Canada.

A longstanding goal in science and engineering is to mimic the size, structure, and functionality present in biology with synthetic analogs. Today, synthetic globular polymers of several million molecular weight are unknown, and, yet, these structures are expected to exhibit unanticipated properties due to their size, compactness, and low inter-chain interactions. Here we report the gram-scale synthesis of dendritic polymers, mega hyperbranched polyglycerols (mega HPGs), in million daltons. The mega HPGs are highly water soluble, soft, nanometer-scale single polymer particles that exhibit low intrinsic viscosities. Further, the mega HPGs are lubricants acting as interposed single molecule ball bearings to reduce the coefficient of friction between both hard and soft natural surfaces in a size dependent manner. We attribute this result to their globular and single particle nature together with its exceptional hydration. Collectively, these results set the stage for new opportunities in the design, synthesis, and evaluation of mega polymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-15975-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195476PMC
May 2020

Diagnosing and treating native spinal and pelvic osteomyelitis in adolescents.

Spine Deform 2020 10 18;8(5):1001-1008. Epub 2020 Apr 18.

Department of Orthopedic Surgery, Boston Children's Hospital, Hunnewell 2, 300 Longwood Avenue, Boston, MA, 02115, USA.

Study Design: Retrospective case series.

Objectives: To describe how pediatric patients with spinal and pelvic osteomyelitis are diagnosed and treated and assess the diagnostic value of magnetic resonance imaging (MRI), needle aspiration biopsy (NAB), and blood cultures in this population. Spinal and pelvic osteomyelitis de novo are uncommon in children and minimal literature exists on the subject. Research has shown that NAB and blood cultures have variable diagnostic yield in adult native osteomyelitis. At our institution, there is no standard protocol for diagnosing and treating pediatric spinal and pelvic osteomyelitis de novo.

Methods: All diagnoses of spinal and pelvic osteomyelitis at a pediatric tertiary care center from 2003 to 2017 were reviewed. Patients aged 0-21 at diagnosis were included. Patients with osteomyelitis resulting from prior spinal operations, wounds, or infections and those with chronic recurrent multifocal osteomyelitis were eliminated. All eligible patients' diagnoses were confirmed by MRI.

Results: 29 patients (18 men, 11 women) met the inclusion criteria. The median age at diagnosis was 11 years old (range 1-18). More than half of all cases (17/29, 59%) affected the lumbar spine. The most common symptoms were back pain (20/29, 69%), fever (18/29, 62%), hip pain (11/29, 38%), and leg pain (8/29, 28%). The majority of NABs and blood cultures performed were negative, but of the positive tests Staphylococcus aureus was the most prevalent bacteria. 86% (25/29) had an MRI before a diagnosis was made and 72% (13/18) had an NAB performed post-diagnosis.

Conclusions: MRI is a popular and helpful tool in diagnosing spinal osteomyelitis de novo. NAB cultures are often negative but can be useful in determining antibiotic treatment.

Level Of Evidence: Level IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43390-020-00110-8DOI Listing
October 2020

Occipital Plate Fixation in the Pediatric Population.

J Pediatr Orthop 2020 Oct;40(9):462-467

Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, MA.

Background: Occipital plate fixation has been shown to improve outcomes in cervical spine fusion. There is a paucity of literature describing occipital plate fixation, especially in the pediatric population. The authors reviewed a case series of 34 patients at a pediatric hospital who underwent cervical spine fusion with occipital plate fixation between 2003 and 2016. This study describes how occipital plates aid the cervical spine union in a case series of diverse, complex pediatric patients.

Methods: Our orthopaedic database at our institution was queried for patients undergoing an instrumented cervical spine procedure between 2003 and 2016. Medical records were used to collect diagnoses, fusion levels, surgical technique, and length of hospitalization, neurophysiological monitoring, complications, and revision procedures.

Results: Thirty-four patients met the inclusion criteria. The mean age was 10.9 years (range, 3-21 y). Indications for surgery included cervical instability, basilar invagination, and os odontoideum. These indications were often secondary to a variety of diagnoses, including trisomy 21, Klippel-Feil syndrome, and rheumatoid arthritis. The mean length of hospitalization was 10 days (range, 2 to 80 d). There were no cases of intraoperative dural leak, venous sinus bleeding from occipital screw placement, or implant-related complications. Postoperative complications included 2 cases of nonunion. Eight patients (24%) had follow-up surgery, only 3 (9%) of which were instrumentation revisions. Both patients with nonunion had repeat occipitocervical fixation procedures and achieved union with revision.

Conclusions: Occipital plate fixation was successful for pediatric cervical spine fusion in this diverse cohort. The only procedure-related complication demonstrated was delayed union or nonunion and implant loosening (4/34, 12%) and there were no plate-related complications. This novel case series shows that occipital plate fixation is safe and effective for pediatric patients with complex diagnoses.

Level Of Evidence: Level IV-case series.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001564DOI Listing
October 2020

The Use of Tranexamic Acid (TXA) in Neuromuscular Hip Reconstruction: Can We Alter the Need for Blood Transfusion?

J Pediatr Orthop 2020 Sep;40(8):e766-e771

Department of Orthopaedics, Boston Children's Hospital.

Background: Children with neuromuscular complex chronic conditions (NMCCC) frequently undergo hip reconstruction surgery requiring blood transfusion. The purpose of this study is to examine the efficacy of tranexamic acid (TXA) to reduce blood loss and transfusion requirement in NMCCC children undergoing hip reconstruction surgery.

Methods: Children with NMCCC undergoing hip reconstruction surgery between 2013 and 2018 were identified. Two cohorts were identified: those who received TXA and those who did not. Patient and surgical characteristics between cohorts were used for propensity matching. Patients were matched on the basis of comorbid factors, bilateral involvement, pelvic osteotomy, open reduction, and surgeon. Comparative outcomes between cohorts were analyzed for intraoperative and postoperative blood loss and transfusion requirements and length of hospital stay (LOS).

Results: A total of 166 patients underwent hip surgery at an average of 9.6 years (SD, 4.0). Propensity matching utilized 72% of the cohort including 47 TXA and 72 non-TXA subjects. There were no differences in patient or surgical characteristics across matched groups. Fifteen (15/47, 32%) TXA subjects required a postoperative blood transfusion compared with the 47% (34/72) of non-TXA subjects who required a transfusion and intraoperative transfusion rates were similar between the 2 groups. There was no significant difference in complication rate (TXA, 79%; non-TXA, 86%), reported estimated blood loss (median=200 mLfor both) or LOS (median=6 d for both). Hematocrit levels were slightly higher in TXA subjects intraoperatively (P=0.047), at the end of surgery (P=0.04), and for the overall lowest perioperative level (P=0.04). The overall percent loss of estimated blood volume was less for those who were given TXA compared with those who were not (P=0.001).

Conclusions: The use of TXA during hip reconstruction surgery in NMCCC children significantly reduced the percent loss of estimated blood volume and postoperative transfusion rate. Further prospective multicenter studies are needed to verify the positive effects and safety of TXA in the setting of hip reconstruction surgery in NMCCC children.

Level Of Evidence: Level III-retrospective comparative study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BPO.0000000000001534DOI Listing
September 2020

Chiari I malformations with syringomyelia: long-term results of neurosurgical decompression.

Spine Deform 2020 04 13;8(2):233-243. Epub 2020 Jan 13.

Department of Orthopaedic Surgery, University Hospital Cleveland Medical Center, Cleveland, OH, USA.

Study Design: Retrospective case series.

Objectives: The objective was to assess the long-term outcomes on scoliosis following Chiari-I (CM-I) decompression in patients with CM-I and syringomyelia (SM). A secondary objective was to identify risk factors of scoliosis progression.

Background: The association between CM-I with SM and scoliosis is recognized, but it remains unclear if CM-I decompression alters the long-term evolution of scoliosis in patients with associated syringomyelia.

Methods: A retrospective review of children with scoliosis, CM-I, and SM during 1997-2015 was performed. Congenital, syndromic, and neuromuscular scoliosis were excluded. Clinical and radiographic characteristics were recorded at presentation, pre-decompression, after 1-year, and latest follow-up. A scale to measure syringomyelia area on MRI was used to evaluate SM changes post-decompression.

Results: 65 children with CM-I, SM, and scoliosis and a mean age of 8.9 years (range 0.7-15.8) were identified. Mean follow-up was 6.9 years (range 2.0-20.4). Atypical curves were present in 28 (43%) children. Thirty-eight patients (58%) underwent decompression before 10 years. Syringomyelia size reduced a mean of 70% after decompression (p < 0.001). Scoliosis improved in 26 (40%), stabilized in 17 (26%), and progressed in 22 (34%) cases. Early spinal fusion was required in 7 (11%) patients after a mean of 0.5 ± 0.37 years and delayed fusion in 16 (25%) patients after 6.0 ± 3.24 years. The remaining 42 (65%) patients were followed for a median of 6.1 years (range 2.0-12.3) without spine instrumentation or fusion. Fusion patients experienced less improvement in curve magnitude 1-year post-decompression (p < 0.001) and had larger curves at presentation (43° vs. 34°; p = 0.004).

Conclusions: Syringomyelia size decreased by 70% after CM-I decompression and scoliosis stabilized or improved in two-thirds of patients. Greater curve improvement within the first year post-decompression and smaller curves at presentation decreased the risk of spinal fusion. Neurosurgical decompression is recommended in children with CM-I, SM, and scoliosis with the potential to treat all three conditions.

Level Of Evidence: Level IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43390-019-00009-zDOI Listing
April 2020

dGEMRIC and CECT Comparison of Cationic and Anionic Contrast Agents in Cadaveric Human Metacarpal Cartilage.

J Orthop Res 2020 04 14;38(4):719-725. Epub 2019 Nov 14.

Department of Pharmacology, Boston University, Boston, Massachusetts.

Magnetic resonance imaging (MRI) and computed tomography (CT) are widely used to image cartilage and their diagnostic capability is enhanced in the presence of contrast agents. The aim of the study is to directly compare the performance between commercial anionic MRI (Gd(DTPA), Gd2-) and CT (Ioxaglate, Iox1-) contrast agents with novel cationic MRI (Gd(DTPA)Lys , Gd4+) and CT (CA4+) contrast agents for assessment of cartilage mechanical and biochemical properties using the ex vivo human osteoarthritis metacarpal cartilage model. First, indentation testing was conducted to obtain the compressive modulus of the human fifth metacarpals. The samples were then immersed in the anionic and cationic contrast agents prior to delayed gadolinium-enhanced MRI of cartilage and CT scanning, respectively. The cartilage glycosaminoglycan (GAG) content and distribution were determined using the 1,9-dimethylmethylene blue assay and Safranin-O histology. Cationic agents significantly accumulate in cartilage compared with anionic agents. Significant positive correlations (p < 0.05) exist between imaging results of cationic agents and GAG content (Gd4+: R  = 0.43; CA4+: R  = 0.67) and indentation equilibrium modulus (Gd4+: R  = 0.48; CA4+: R  = 0.77). Significant negative correlations are observed between anionic MRI relaxation times, but not contrast-enhanced computed tomography attenuation and cartilage GAG content (Gd2-: R  = 0.56, p < 0.05; Iox1-: R  = 0.31, p > 0.05) and indentation equilibrium modulus (Gd2-: R  = 0.38, p < 0.05; Iox1-: R  = 0.17, p > 0.05). MRI or CT with cationic contrast agents provides greater sensitivity than their anionic analogs at assessing the biochemical and biomechanical properties of ex vivo human metacarpal cartilage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:719-725, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071952PMC
April 2020

A Synthetic Bottle-brush Polyelectrolyte Reduces Friction and Wear of Intact and Previously Worn Cartilage.

ACS Biomater Sci Eng 2019 Jun 17;5(6):3060-3067. Epub 2019 May 17.

Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, 1 Overland Street, Boston, MA.

A poly(7-oxanorbornene-2-carboxylate) polymer containing pendent triethyleneglycol (TEG) chains of 2.8 MDa ("2.8M TEG") was synthesized and evaluated for long-term lubrication and wear reduction of ex vivo bovine cartilage as well as for synovitis in rats and dogs after intra-articular administration. Bovine cartilage surfaces were tested under torsional friction for 10,080 rotations while immersed in either saline, bovine synovial fluid (BSF), or 2.8M TEG. For each solution, coefficient of friction (μ), changes in surface roughness, and lost cartilage glycosaminoglycan were compared. To directly compare 2.8M TEG and BSF, additional samples were tested sequentially in BSF, BSF, 2.8M TEG, and then BSF. Finally, another set of samples were tested twice in saline to induce surface roughness and then tested in BSF, Synvisc, or 2.8M TEG to determine each treatment's effect on worn cartilage. Next, male Lewis rats were injected in one knee with 2.8M TEG or saline and evaluated for effects on gait, and female beagles were injected with either 2.8M TEG or saline in one knee, and their synovial tissues analyzed for inflammation by H&E staining. Treatment with 2.8M TEG lowers μ, lessens surface roughness, and minimizes glycosaminoglycan loss compared to saline. The 2.8M TEG also reduces μ compared to BSF in pairwise testing and on worn cartilage surfaces. Injection of 2.8M TEG in rat or beagle knees gives comparable effects to treatment with saline, and does not cause significant synovitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsbiomaterials.9b00085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788642PMC
June 2019

Protocol development for synchrotron contrast-enhanced CT of human hip cartilage.

Med Eng Phys 2019 11 13;73:1-8. Epub 2019 Sep 13.

Department of Orthopaedics, University of British Columbia, Centre for Hip Health and Mobility, 2635 Laurel St, Vancouver BC V5Z 1M9, Canada. Electronic address:

Understanding hip osteoarthritis requires new investigational tools for quantitative studies of biophysical and biomechanical properties as well as for determination of structure. Three new protocols to study pathological changes in cartilage and to measure cartilage thickness in intact human hips are described using synchrotron contrast enhanced computed tomography (sCECT) with the iodinated contrast agent CA4+. Ten human cadaver hips were prepared and injected with CA4+ using three different methods, all of which included rotation and distraction of the joint. CA4+ diffusion into cartilage was monitored using sCECT. The thickness of acetabular and femoral cartilage was also measured. Diffusion times ranged from 2 h to 75 h, depending on the injection protocol and the cartilage region. Direct single injection of the contrast through the labrum resulted in the fastest diffusion times. The iodine attenuation coefficient, which reflects the contrast agent distribution in the cartilage, ranged from 0.0142/cm to 0.1457/cm. Three injections at the head/neck conjunction area yielded the highest iodine attenuation coefficients in cartilage. The femoral cartilage in the Superior-Medial compartment was significantly thicker than in the other 3 femoral compartments, and femoral cartilage in the Superior-Anterior compartment was significantly thinner than the other 3 femoral compartments. The acetabular cartilage in the Superior compartment was significantly thicker than that in the Superior-Posterior compartment. sCECT with CA4+ allows assessment of hip cartilage thickness with 0.1 mm isotropic voxel size, sufficient for evaluating cartilage pathology and biomechanics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.medengphy.2019.08.003DOI Listing
November 2019

Long-Duration Tracking of Cervical-Spine Kinematics With Ultrasound.

IEEE Trans Ultrason Ferroelectr Freq Control 2019 11 30;66(11):1699-1707. Epub 2019 Aug 30.

Cervical-spine (C-spine) pathoanatomy is commonly evaluated by plane radiographs, computed tomography (CT), or magnetic resonance imaging (MRI); however, these modalities are unable to directly measure the dynamic mechanical properties of the functional spinal units (FSU) comprising the C-spine that account for its functional performance. We have developed an ultrasound-based technique that provides a non-invasive, real-time, quantitative, in vivo assessment of C-spine kinematics and FSU viscoelastic properties. The fidelity of the derived measurements is predicated on accurate tracking of vertebral motion over a prolonged time duration. The purpose of this work was to present a bundle adjustment method that enables accurate tracking of the relative motion of contiguous cervical vertebrae from ultrasound radio-frequency data. The tracking method was validated using both a plastic anatomical model of a cervical vertebra undergoing prescribed displacements and also human cadaveric C-spine specimens subjected to physiologically relevant loading configurations. While the velocity of motion and thickness of the surrounding soft tissue envelope affected accuracy, using the bundle adjustment method, B-mode ultrasound was capable of accurately tracking vertebral motion under clinically relevant physiologic conditions. Therefore, B-mode ultrasound can be used to evaluate in vivo real-time C-spine kinematics and FSU mechanical properties in environments where radiographs, CT, or MRI cannot be used.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TUFFC.2019.2928184DOI Listing
November 2019

Contrast-Enhanced Computed Tomography Scoring System for Distinguishing Early Osteoarthritis Disease States: A Feasibility Study.

J Orthop Res 2019 10 21;37(10):2138-2148. Epub 2019 Jun 21.

Department of Biomedical Engineering, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts, 02215.

Early detection of osteoarthritis (OA) remains a diagnostic challenge owing to insensitive diagnostic techniques currently available. Herein a new semiquantitative scoring system, based upon contrast-enhanced computed tomographic (CECT) imaging, is described for further refinement of early OA disease staging. Trochlear ridge cartilage defects were surgically created in the femoropatellar joint of an adult horse (ACUC approved protocols). Seven weeks post-surgery, CECT imaging was performed on a clinical scanner after intra-articular injection of a cationic iodinated contrast agent, CA4+, into both injured and control femoropatellar joint compartments. The femoral cartilage surface was densely biopsied, and specimens were assessed for visual (Outerbridge score), functional (equilibrium compressive modulus), and biochemical (glycosaminoglycan content) measures of cartilage quality. Cartilage CECT attenuation was compared with cartilage quality measures using receiver operating characteristic curve analysis to establish attenuation thresholds for distinguishing among cartilage quality levels. CECT imaging identifies macroscopically damaged cartilage regions and in morphologically identical tissue provides moderately sensitive and specific semiquantitative segregation of cartilage quality based upon CECT attenuation, reflecting both glycosaminoglycan content and compressive stiffness of cartilage area under the curve (AUC = 0.83 [95% confidence interval [CI]: 0.72-0.93] for distinguishing poor quality and AUC = 0.76 [95% CI: 0.65-0.90] for distinguishing healthy quality cartilage). A semiquantitative 6-point scoring system-the Osteoarthritis Attenuation and Morphological Assessment (OAMA) score-is proposed as a tool for assessing cartilage quality from CECT images. The OAMA scoring system expands the current disease staging capability of early OA by inclusion of morphological, biochemical, and biomechanical assessments. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2138-2148, 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739126PMC
October 2019

Assessment of healthy trapeziometacarpal cartilage properties using indentation testing and contrast-enhanced computed tomography.

Clin Biomech (Bristol, Avon) 2019 01 21;61:181-189. Epub 2018 Dec 21.

Muscles & Movement, Department of Development and Regeneration, Biomedical Sciences Group, KU Leuven Kulak, Kortrijk, Belgium. Electronic address:

Background: The trapeziometacarpal joint is a common site for osteoarthritis development in the hand. When osteoarthritis is present, it results in significant functional disabilities due to the broad range of activities performed by this joint. However, our understanding of osteoarthritis initiation and progression at this joint is limited because of the current lack of knowledge regarding the properties and structure of the corresponding cartilage layers. The objective of this study is to assess the morphological and mechanical properties of trapeziometacarpal cartilage via the combination of indentation testing and contrast-enhanced computed tomography. Such research may lead to the development of medical imaging-based approaches to measure cartilage properties in vivo.

Methods: Intact first metacarpals and trapezia were extracted from 16 fresh-frozen human cadaver hands. For each specimen, load-displacement behavior was measured at 9 testing sites using a standardized indentation testing device to calculate the normal force and Young's modulus of the cartilage sub-regions. The specimens were then immersed in CA4+ contrast agent solution for 48 h and subsequently scanned with a resolution of 41 μm in a HR-pQCT scanner to measure cartilage thickness and attenuation. Finally, correlations between compressive Young's modulus and contrast-enhanced computed tomography attenuation of the cartilage were assessed.

Findings: No significant difference was found in cartilage thickness between the trapezium and first metacarpal, but the comparison between articular regions showed thinner cartilage around the volar aspect of both the first metacarpal and the trapezium. The first metacarpal cartilage was stiffer than the trapezial cartilage. A significant positive correlation was observed between Young's modulus and mean contrast-enhanced CT attenuations in superficial and full-depth cartilage in both the first metacarpal and the trapezium cartilage.

Interpretation: The quantitative measurements of trapeziometacarpal thickness and stiffness as well as a correlation between Young's modulus and contrast-enhanced computed tomography attenuation provides a method for the non-destructive in vivo assessment of cartilage properties, a greater understanding of thumb cartilage behavior, and a dataset for the development of more accurate computer models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiomech.2018.12.015DOI Listing
January 2019

Measuring the Reliability and Construct Validity of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) in Children With Cerebral Palsy.

Arch Phys Med Rehabil 2019 01 18;100(1):45-51. Epub 2018 Aug 18.

Franciscan Children's Hospital, Boston, MA.

Objective: The purpose of this study was to (1) investigate the construct validity and (2) test-retest reliability of the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) in children with cerebral palsy (CP).

Design: A prospective convenience cross-sectional sample.

Setting: Multidisciplinary CP clinic in a tertiary level pediatric children's hospital.

Participants: English- and Spanish-speaking school-aged children (N=101) with a diagnosis of CP, stratified by Gross Motor Function Classification System level, who presented to our multidisciplinary clinic. Participants were excluded if they underwent recent surgery (<6mo) or botulinum neurotoxin A injection (<3mo). A subset of 17 families participated in retest reliability.

Main Outcome Measures: Convergent and divergent validity were evaluated using Spearman correlation coefficient analysis; test-retest reliability was assessed using intraclass correlation coefficients (ICCs).

Results: Mean age was 12±3.7 years. Convergent validity was established between Mobility (PEDI-CAT) and Functional Mobility Scale (FMS) (5 m, r=0.85; 50 m, r=0.84; 500 m, r=0.76; P<.001). In ambulant children, convergent validity was established between Daily Activities (PEDI-CAT vs Pediatric Quality of Life CP [PedsQL-CP] [r=0.85, P<.001]) and between Social/Cognitive (PEDI-CAT) and Speech and Communication (PedsQL-CP) (r=0.42, P<.001). In nonambulant children, convergent validity was established between Daily Activities (PEDI-CAT) and Personal Care (Caregiver Priorities and Child Health Index of Life with Disabilities [CPCHILD]) (r=0.44, P<.001) and between social/cognitive (PEDI-CAT) and Communication (CPCHILD) (r=0.64, P<.001). A lack of correlation between Daily Activities, Social/Cognitive, and Responsibility (PEDI-CAT) and FMS and between the Mobility (PEDI-CAT) and Communication (PedsQL) domains confirmed divergent validity. Test-retest reliability was excellent for all domains of the PEDI-CAT (ICC=0.96-0.99).

Conclusions: The PEDI-CAT is an outcome measure that demonstrates strong construct validity and reliability in children with CP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apmr.2018.07.427DOI Listing
January 2019

A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal tear model.

Biomaterials 2018 11 7;182:13-20. Epub 2018 Aug 7.

Department of Chemistry, Boston University, Boston, MA, USA; Department of Biomedical Engineering, Boston University, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address:

Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis (OA) as a viscosupplement, yet it only provides short-term benefit because HA is cleaved by hyaluronidase and cleared out of the joint after several days. Therefore, we developed a new polymer biolubricant based on poly-oxanorbornane carboxylate to enhance joint lubrication for a prolonged time. Rheological and biotribological studies of the biolubricant reveal viscoelastic properties and coefficient of friction equivalent and superior to that of healthy synovial fluid, respectively. Furthermore, in an ex vivo bovine cartilage plug model, the biolubricant exhibits superior long-term reduction of friction and wear prevention compared to saline and healthy synovial fluid. ISO 10993 biocompatibility tests demonstrate that the biolubricant polymer is non-toxic. In an in vivo rat medial meniscal tear OA model, where the performance of the leading HA viscosupplement (Synvisc-one) is comparable to the saline control, treatment with the biolubricant affords significant chondroprotection compared to the saline control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2018.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287749PMC
November 2018

Active agents, biomaterials, and technologies to improve biolubrication and strengthen soft tissues.

Biomaterials 2018 10 26;181:210-226. Epub 2018 Jul 26.

Department of Chemistry, Boston University, Boston, MA, United States; Department of Biomedical Engineering, Boston University, Boston, MA, United States; Department of Medicine, Boston University, Boston, MA, United States. Electronic address:

Normal functioning of articulating tissues is required for many physiological processes occurring across length scales from the molecular to whole organism. Lubricating biopolymers are present natively on tissue surfaces at various sites of biological articulation, including eyelid, mouth, and synovial joints. The range of operating conditions at these disparate interfaces yields a variety of tribological mechanisms through which compressive and shear forces are dissipated to protect tissues from material wear and fatigue. This review focuses on recent advances in active agents and biomaterials for therapeutic augmentation of friction, lubrication, and wear in disease and injured states. Various small-molecule, biological, and gene delivery therapies are described, as are tribosupplementation with naturally-occurring and synthetic biolubricants and polymer reinforcements. While reintroduction of a diseased tissue's native lubricant received significant attention in the past, recent discoveries and pre-clinical research are capitalizing on concurrent advances in the molecular sciences and bioengineering fields, with an understanding of the underlying tissue structure and physiology, to afford a desired, and potentially patient-specific, tissue mechanical response for restoration of normal function. Small and large molecule drugs targeting recently elucidated pathways as well as synthetic and hybrid natural/synthetic biomaterials for restoring a desired tissue mechanical response are being investigated for treatment of, for example, keratoconjunctivitis sicca, xeroderma, and osteoarthritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2018.07.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766080PMC
October 2018

Expansion Thoracoplasty in Rabbit Model: Effect of Timing on Preserving Pulmonary Growth and Correcting Spine Deformity.

Spine (Phila Pa 1976) 2018 08;43(15):E877-E884

Center for Advanced Orthopaedic Studies, Beth Israel Deaconess Medical Center, Boston, MA.

Study Design: In a treatment-control animal study expansion thoracoplasty (ET) was performed in a juvenile rabbit model of thoracic insufficiency syndrome (TIS) and benefits to thoracic development and respiratory function quantified. Rabbits treated early versus late were compared to age-matched normal and disease control rabbits through to skeletal maturity.

Objective: Evaluate (1) how ET changes the natural TIS disease trajectory and (2) how timing of ET affects changes in spine growth, lung growth, and respiratory mechanics.

Summary Of Background Data: Pulmonary growth potential is thought to diminish with age; thus, early therapeutic intervention may increase pulmonary growth in children with TIS. However, no direct empirical evidence exists to support this treatment paradigm.

Methods: Convex left scoliosis and resultant TIS was induced in 3-week-old rabbits via surgical rib tethering. We compare the efficacy of ET performed at 7 weeks and expanded at 11 weeks (early, n = 7) versus only at 11 weeks of age (late, n = 7) in preserving lung growth and respiratory function relative to normal (n = 8) and disease (n = 10) rabbits. Sequential computed tomography images and pulmonary function testing was performed to quantify spine curvature, lung growth, and respiratory volumes. At 28 weeks of age chest wall elastance was measured in vivo then acinar complexity analyzed histologically via radial alveolar counts.

Results: ET performed early or late altered the predicted trajectory of spine deformity, pulmonary growth inhibition, and respiratory dysfunction seen in disease rabbits. Growth was not significantly different between early and late rabbits and post-treatment gains remained below those of age-matched normal rabbits. Chest wall elastance was impaired by ET and more so in early rabbits, there were no differences in pulmonary elastance.

Conclusion: ET interrupted the natural progression of deformity and pulmonary hypoplasia associated with spine curvature in disease rabbits. However, growth benefits are only seen in cases of the most severe initial deformity and must be balanced against the further impairment to chest wall function associated with repetitive surgery.

Level Of Evidence: N/A.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0000000000002573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042970PMC
August 2018

Contrast-enhanced computed tomography (CECT) attenuation is associated with stiffness of intact knee cartilage.

J Orthop Res 2018 10 13;36(10):2641-2647. Epub 2018 Jul 13.

University of British Columbia, Department of Orthopaedics, Vancouver, BC, Canada.

Contrast-enhanced computed tomography (CECT) using charged contrast-agents enables quantification of cartilage glycosaminoglycan content. Since glycosaminoglycan content is a key determinant of cartilage compressive stiffness, CECT measurements have the potential to non-invasively assess cartilage stiffness. The objective of this study was to determine whether CECT attenuation, using a cationic contrast-agent (CA4+), correlates with the stiffness of intact cartilage. Six fresh femoral and six fresh tibial compartments with intact cartilage were obtained from patients undergoing total knee replacement surgery. The instantaneous stiffness was determined for 25-50 points on the surface of each compartment using an established indentation technique. The samples were then immersed in CA4+ solution for 48 h, scanned in a micro-CT scanner, and the average CECT attenuation at each indentation site was found for the superficial cartilage. A significant (p < 0.01) and positive correlation was observed between stiffness and CECT attenuation for sites from each individual cartilage surface, with correlation coefficients ranging from r = 0.37-0.57 and r = 0.48-0.69 (p < 0.01) for the tibia and femur, respectively. When data for each type of cartilage surface were pooled together, the correlation coefficients were r = 0.73 for femoral condyle data points and r = 0.49 for tibial plateau data points. CECT provided a map of cartilage stiffness across each surface, which allows regions of low stiffness to be identified. These findings support continued evaluation and development of quantitative imaging techniques to assess the functional properties of cartilage. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2641-2647, 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24022DOI Listing
October 2018

The Pursuit of Scholarship: Why We Should Care About Resident Research.

J Bone Joint Surg Am 2017 Nov;99(22):e119

1Departments of Orthopaedic Surgery (J.E.B., B.R.W., and D.W.P.) and Biomedical Engineering (J.E.B.), University of Minnesota, Minneapolis, Minnesota 2Department of Orthopaedics (S.L.W., A.J.P., and J.A.B.), University of Iowa, Iowa City, Iowa 3Upstate Medical University, East Syracuse, New York 4Dell Medical School, University of Texas at Austin, Austin, Texas 5Department of Orthopaedic Surgery, Boston Children's Hospital, Boston, Massachusetts.

Research is a foundational component of an orthopaedic residency. It fosters intellectual curiosity and pursuit of excellence, while teaching discipline and the scientific method. These are the key principles for careers in both community-based practice and academia. Currently, no consensus exists on how to best engage residents and support their research endeavors. In 2014, the American Academy of Orthopaedic Surgeons Board of Specialty Societies Research and Quality Committee convened a Clinician-Scientist Collaboration Workgroup. The workgroup's task was to identify barriers to clinical and basic science research, and to propose feasible recommendations to overcome these barriers. Herein, we have compiled the opinions of various stakeholder constituencies on how to foster scholarly pursuits during an orthopaedic residency. These opinions reflect the workgroup's conclusions that research is directly and indirectly influenced by funding, departmental support, and mentorship, and that early exposure and dedicated time to pursue scholarly activities may have a positive impact on lifelong research interests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2106/JBJS.16.01502DOI Listing
November 2017
-->