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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.

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.

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.

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., Competing Interests: The authors declare no potential conflict of interest., (© 2020 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

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.

Objective: To determine whether maternal cardiovascular disease (CVD) risk factors predict preterm birth., Design: Case control., Setting: California hospitals., Participants: 868 mothers with linked demographic information and biospecimens who delivered singleton births from July 2009 to December 2010., Methods: Logistic regression analysis was employed to calculate odds ratios for the associations between maternal CVD risk factors before and during pregnancy (including diabetes, hypertensive disorders and cholesterol levels) and preterm birth outcomes., Primary Outcome: Preterm delivery status., Results: Adjusting for the other maternal CVD risk factors of interest, all categories of hypertension led to increased odds of preterm birth, with the strongest magnitude observed in the pre-eclampsia group (adjusted OR (aOR), 13.49; 95% CI 6.01 to 30.27 for preterm birth; aOR, 10.62; 95% CI 4.58 to 24.60 for late preterm birth; aOR, 17.98; 95% CI 7.55 to 42.82 for early preterm birth) and chronic hypertension alone for early preterm birth (aOR, 4.58; 95% CI 1.40 to 15.05). Diabetes (types 1 and 2 and gestational) was also associated with threefold increased risk for preterm birth (aOR, 3.06; 95% CI 1.12 to 8.41). A significant and linear dose response was found between total and low-density lipoprotein (LDL) cholesterol and aORs for late and early preterm birth, with increasing cholesterol values associated with increased risk (likelihood χ 2 differences of 8.422 and 8.019 for total cholesterol for late and early, and 9.169 and 10.896 for LDL for late and early, respectively). Receiver operating characteristic curves using these risk factors to predict late and early preterm birth produced C statistics of 0.601 and 0.686., Conclusion: Traditional CVD risk factors are significantly associated with an increased risk of preterm birth; these findings reinforce the clinical importance of integrating obstetric and cardiovascular risk assessment across the healthcare continuum in women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: The authors declare no competing interest.

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.

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.

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 2 , 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 2  = 0.43; CA4+: R 2  = 0.67) and indentation equilibrium modulus (Gd4+: R 2  = 0.48; CA4+: R 2  = 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 2  = 0.56, p < 0.05; Iox1-: R 2  = 0.31, p > 0.05) and indentation equilibrium modulus (Gd2-: R 2  = 0.38, p < 0.05; Iox1-: R 2  = 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., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Health care professionals and organizations have attempted to advance sound climate policies through educational efforts including conferences, symposia, webinars, and policy and scientific statements. Unfortunately, these approaches have failed to make a substantial impression on the public or elected officials. In view of rapid environmental degradation, our industry must urgently marshal every resource at its command to protect patients and communities. The power and influence of health care can offset pressures and retribution from entrenched fossil fuel interests. Ethically, the shared mission of our industry is saving lives, reducing suffering, and promoting the best possible health for all. We have the expertise and obligation to help reduce the health impacts of climate disruption. As leaders, we must move our organizations from passive concern to active engagement in fighting for a healthy future.

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.

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model., Design: Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.)., Results: Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (E eq ) (r = 0.79, P < 0.0001) and safranin-O histological score (r = -0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = -0.44, P < 0.0001) of bone. Mean [95% CI] cationic CECT attenuation at the impact site (2215 [1987, 2443] Hounsfield Units [HUs]) was lower than site-matched controls (2836 [2490, 3182] HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), E eq (r = 0.26, P = 0.025) and safranin-O histology score (r = -0.32, P = 0.0046)., Conclusions: Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: COMPETING INTERESTS M.W.G., M.W., and B.D.S. had a conflict of interest, as they owned shares in FlexBiomedical, Inc, a company that specializes in the design and development of biolubricants for OA treatment, as well as have grant funding from the NIH and Coulter Foundation.

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., (Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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.

Objective: Depletion of glycosaminoglycans (GAGs) and degradation of collagen network are early hallmarks of osteoarthritis (OA). Currently, there are no chondroprotective therapies that mitigate the loss of GAGs or effectively restore the collagen network. Recently, a novel polymeric cartilage supplement was described that forms a charged interpenetrating polymer network (IPN) reconstituting the hydrophilic properties of the extracellular matrix (ECM). To investigate the mechanism by which this hydrophilic IPN improves articular cartilage material properties, a finite element (FE) model is used to evaluate the IPN's effect on the fibrillar collagen network, nonfibrillar matrix, and interstitial fluid flow., Methods: Bovine osteochondral plugs were degraded with chondroitinase ABC to selectively decrease GAG content. Samples were mechanically tested before and after IPN treatment using unconfined testing geometry and stress-relaxation protocol. Every measurement was modeled separately using a fibril-reinforced poroviscoelastic FE model. Measurement replication was achieved by optimizing the following model parameters: initial and strain-dependent fibril network modulus (E f 0 , E f ε , respectively), nonfibrillar matrix modulus (E nf ), initial permeability (k 0 ) and strain-dependent permeability factor (M)., Results: Based on the FE model results, treatment of native and GAG depleted cartilage with the hydrophilic IPN increases the ECM stiffness and impedes fluid flow. The IPN did not alter the stiffness of fibrillary network. Cartilage permeability and the strain-dependent permeability factor decreased with increasing IPN w/v%., Conclusions: The IPN reconstitutes cartilage material properties primarily by augmenting the hydrophilic ECM. This reinforcement of the solid phase also affects the fluid phase reestablishing low permeability., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Articular cartilage lines the load-bearing surfaces of long bones and undergoes compositional and structural degeneration during osteoarthritis progression. Contrast enhanced microcomputed tomography (μCT) is being applied to a variety of preclinical models, including the mouse, to map structural and compositional properties in 3-D. The thinness (∼30-50 μm) and high cellularity of mouse articular cartilage presents a significant imaging challenge. Our group previously showed that mouse articular cartilage and proteoglycan (PG) content can be assessed by μCT with the ioxagalate-based contrast agent Hexabrix, but the voxel size used (6 μm) was deemed to be barely adequate. The objective of the present study is to assess the utility of a novel contrast agent, CA4+, to quantify mouse articular cartilage morphology and composition with high resolution μCT imaging (3 μm voxels) and to compare the sensitivity of CA4+ and Hexabrix to detect between-group differences. While both contrast agents are iodine-based, Hexabrix is anionic and CA4+ is cationic so they interact differently with negatively charged PGs. With CA4+, a strong correlation was found between non-calcified articular cartilage thickness measurements made with histology and μCT (R 2  = 0.72, p < 0.001). Cartilage degeneration-as assessed by loss in volume, thickness, and PG content-was observed in 34-week-old mice when compared to both 7- and 12-week-old mice. High measurement precision was observed with CA4+, with the coefficient of variation after repositioning and re-imaging samples equaling 2.8%, 4.5%, 7.4% and 5.9% for attenuation, thickness, volume, and PG content, respectively. Use of CA4+ allowed increased sensitivity for assessing PG content compared to Hexabrix, but had no advantage for measurement of cartilage thickness or volume. This improvement in imaging should prove useful in preclinical studies of cartilage degeneration and regeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2740-2748, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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.

Purpose: Limited research has been conducted on the non-medical out-of-pocket expenses (NOOPEs) incurred by families of children with chronic health conditions. The study objectives were to: 1) calculate the estimated NOOPEs incurred by families during hospitalization of their child, 2) identify predictors of high NOOPEs, and 3) assess the impact of the child's chronic health condition on the family's finances., Design and Methods: Prospective observational study. Parents were included if their child was 3-20years old, had severe, non-ambulatory cerebral palsy (CP), and scheduled for hip or spine surgery. Parents reported all NOOPEs incurred during their child's hospitalization using the Family Expense Diary. Families completed the subscales of the Impact on Family Scale and the Assessment of Caregivers Experience with Neuromuscular Disease. Descriptive and univariate and multiple hierarchical regression models were used in the analysis., Results: Fifty two parents participated. The total NOOPEs ranged from $193.00 to $7192.71 (M=$2001.92) per hospitalization representing an average of 4% of the family's annual earned income. Caregiver age (F=8.393, p<0.001), income (F=7.535, p<0.001), and distance traveled to the hospital (F=4.497, p=0.039) were significant predictors of high NOOPEs. The subscale scores indicated that a child's chronic health condition had a significant impact on family finances., Conclusions and Practice Implications: Hospitalization is associated with numerous NOOPEs that create additional financial demands for families caring for a child with severe CP. NOOPEs should be addressed when preparing families for their children's planned hospital admissions, especially those families of CSHCN who experience significant financial impacts secondary to their children's care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective The aim of this study was to investigate whether the concentration of the anionic contrast agent ioxaglate, as quantitated by contrast-enhanced computed tomography (CECT) using a clinical cone-beam CT (CBCT) instrument, reflects biochemical, histological, and biomechanical characteristics of articular cartilage imaged in an ex vivo, intact human knee joint. Design An osteoarthritic human cadaveric knee joint (91 years old) was injected with ioxaglate (36 mg I/mL) and imaged using CBCT over 61 hours of ioxaglate diffusion into cartilage. Following imaging, the joint surfaces were excised, rinsed to remove contrast agent, and compressive stiffness (equilibrium and instantaneous compressive moduli) was measured via indentation testing ( n = 17 sites). Each site was sectioned for histology and assessed for glycosaminoglycan content using digital densitometry of Safranin-O stained sections, Fourier transform infrared spectroscopy for collagen content, and morphology using both the Mankin and OARSI semiquantitative scoring systems. Water content was determined using mass change after lyophilization. Results CECT attenuation at all imaging time points, including those <1 hour of ioxaglate exposure, correlated significantly ( P < 0.05) with cartilage water and glycosaminoglycan contents, Mankin score, and both equilibrium and instantaneous compressive moduli. Early time points (<30 minutes) also correlated ( P < 0.05) with collagen content and OARSI score. Differences in cartilage quality between intrajoint regions were distinguishable at diffusion equilibrium and after brief ioxaglate exposure. Conclusions CECT with ioxaglate affords biochemical and biomechanical measurements of cartilage health and performance even after short, clinically relevant exposure times, and may be useful in the clinic as a means for detecting early signs of cartilage pathology.

Fast, nongenomic androgen actions have been described in various cell types, including neurons. However, the receptor mediating this cell membrane-initiated rapid signaling remains unknown. This study found a putative androgen receptor splice variant in a dopaminergic N27 cell line and in several brain regions (substantia nigra pars compacta, entorhinal cortex, and hippocampus) from gonadally intact and gonadectomized (young and middle-aged) male rats. This putative splice variant protein has a molecular weight of 45 kDa and lacks an N-terminal domain, indicating it is homologous to the human AR45 splice variant. Interestingly, AR45 was highly expressed in all brain regions examined. In dopaminergic neurons, AR45 is localized to plasma membrane lipid rafts, a microdomain involved in cellular signaling. Further, AR45 protein interacts with membrane-associated G proteins Gαq and Gαo. Neither age nor hormone levels altered AR45 expression in dopaminergic neurons. These results provide the first evidence of AR45 protein expression in the brain, specifically plasma membrane lipid rafts. AR45 presence in lipid rafts indicates that it may function as a membrane androgen receptor to mediate fast, nongenomic androgen actions., Competing Interests: Authors report no conflicts of interest.

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

Objective: Osteoarthritis (OA) is associated with increased articular cartilage hydraulic permeability and decreased maintenance of high interstitial fluid load support (IFLS) during articulation, resulting in increased friction on the cartilage solid matrix. This study assesses frictional response following in situ synthesis of an interpenetrating polymer network (IPN) designed to mimic glycosaminoglycans (GAGs) depleted during OA., Methods: Cylindrical osteochondral explants containing various interpenetrating polymer concentrations were subjected to a torsional friction test under unconfined creep compression. Time-varying coefficient of friction, compressive engineering strain, and normalized strain values (ε/ε eq ) were calculated and analyzed., Results: The polymer network reduced friction coefficient over the duration of the friction test, with statistically significantly reduced friction coefficients (95% confidence interval 14-34% reduced) at equilibrium compressive strain upon completion of the test (P = 0.015). A positive trend was observed relating polymer network concentration with magnitude of friction reduction compared to non-treated tissue., Conclusion: The cartilage-interpenetrating polymer treatment improves lubrication by augmenting the biphasic tissue's interstitial fluid phase, and additionally improves the friction dissipation of the tissue's solid matrix. This technique demonstrates potential as a therapy to augment tribological function of articular cartilage., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Osteoarthritis (OA) affects millions of people and results in weakened hyaline cartilage due to overloading. During joint articulation, hyaline cartilage must withstand high loads while maintaining low friction to prevent wear and tissue loss. Thus, cartilage compressive stiffness and the coefficient of friction are important indicators of the tissue's functional performance. These mechanical properties are often measured ex vivo using mechanical testing regimens, but arthroscopic handheld probes (e.g., for indentation testing, ultrasound, and optical coherence tomography) and noninvasive imaging modalities (e.g., magnetic resonance imaging and computed tomography) provide opportunities for either direct or indirect in vivo assessment of cartilage mechanical properties. In this review, we examine the application of these techniques for evaluating cartilage, with a focus on measuring mechanical properties for early-stage OA diagnosis. For each approach, we discuss the advantages, disadvantages, current and potential clinical utility, and promising technological improvement.

Study Design: A prospective longitudinal cohort., Objective: The objective of this study was to evaluate changes in caregivers' perceptions of health-related quality of life (HRQOL) and caregiver burden in children with severe cerebral palsy (CP) following spinal fusion., Summary of Background Data: Progressive scoliosis is common in nonambulatory children with CP; the utility of spine fusion has been long debated and prospective evaluations of patient reported outcomes are limited., Methods: Children 3 to 21 years old, gross motor classification system (GMFCS) IV-V CP, scheduled for spine fusion were enrolled consecutively from September 2011 to March 2014. Caregivers completed the CPCHILD and ACEND pre-operatively and at 6 weeks, 3, 6, 12, and 24 months postoperatively. Changes in CPCHILD and ACEND scores from preoperative to 1 and 2 years after surgery were assessed using paired t tests. Correlations between preoperative Cobb angle and CPCHILD and ACEND scores were evaluated using Pearson's correlation analysis., Results: Twenty-six GMFCS IV-V CP patients with severe scoliosis treated with spine fusion were included. Mean age was 14 years, 50% male, and 46% had instrumentation to the pelvis. Average preoperative Cobb angle was 68.9° (SD 25.68) with an average improvement of 76%. The CPCHILD score increased by 9.8 points above baseline [95% confidence interval (95% CI): 3.4-16.2] at 1 year postoperatively (P = 0.005). However, at 2 years, the CPCHILD score regressed to baseline (P = 0.40). ACEND scores did not change from baseline scores at 1-year (P = 0.09) and 2-year (P = 0.72) follow-up, reflecting that caregiver burden is little changed by spine fusion. There was no correlation between preoperative Cobb angle and CPCHILD score (P = 0.52) or ACEND score (P = 0.56) at 1-year or 2-year follow-up (P = 0.69, P = 0.90). Children with Cobb angle ≤75° experienced more improvement 1 year after surgery than children with Cobb angle >75°., Conclusion: HRQOL improves 1 year following spine fusion but regresses to baseline after 2 years. Caregiver burden was unchanged following spine fusion., Level of Evidence: 2.

Background: The Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT) is a new clinical assessment for children and youth from birth through 20 years of age., Objective: To determine the discriminant validity of the PEDI-CAT according to the Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) in children with cerebral palsy (CP)., Design: A prospective convenience cross-sectional sample of 101 school-age children with CP was stratified by GMFCS level., Methods: Participants were excluded if they underwent recent surgery (<6 months). Receiver operating characteristics curve analysis was used to quantify the discriminant validity of the PEDI-CAT domains to distinguish the level of independence in fine and gross motor function. General linear modeling was used to assess discriminant ability across all GMFCS and MACS levels., Results: Mean age was 11 years, 11 months (SD 3.7). Mobility and Daily Activities domains exhibited excellent discriminant validity distinguishing between ambulatory and nonambulatory participants [area under the curve (AUC) = 0.98 and 0.97, respectively] and the Daily Activities domain exhibited excellent discriminant validity distinguishing between independent and dependent hand function (AUC = 0.93). All PEDI-CAT domains were able to discriminate between ambulatory (GMFCS levels I-III) or nonambulatory (GMFCS levels IV-V) as well as manually independent (MACS levels I-II) or manually dependent functional levels (MACS levels III-V) ( P < .001)., Limitations: Our convenience cross-sectional sample included school-age children with primarily Caucasian, middle-income parents and may not be representative of other cultural, socioeconomic backgrounds. Not all participants had a MACS level assigned, however, no differences were found in PEDI-CAT scores between those with and without MACS scores., Conclusions: These results demonstrate that the PEDI-CAT is a valid outcome instrument for measuring functional abilities in children with CP, able to differentiate across fine and gross motor functional levels., (© 2017 American Physical Therapy Association)

The biochemical and histopathological techniques used to investigate meniscal content and structure are destructive and time-consuming. Therefore, this study evaluated whether contrast-enhanced computed tomography (CECT) attenuation and contrast agent flux using the iodinated contrast agents CA4+ and ioxaglate correlate with the glycosaminoglycan (GAG) content/distribution and water content in human menisci. The optimal ioxaglate and CA4+ contrast agent concentrations for mapping meniscal GAG distribution were qualitatively determined by comparison of CECT color maps with Safranin-O stained histological sections. The associations between CECT attenuation and GAG content, CECT attenuation and water content, and flux and water content at various time points were determined using both contrast agents. Depth-wise analyses were also performed through each of the native surfaces to examine differences in contrast agent diffusion kinetics and equilibrium partitioning. The optimal concentrations for GAG depiction for ioxaglate and CA4+ were ≥80 and 12 mgI/ml, respectively. Using these concentrations, weak to moderate associations were found between ioxaglate attenuation and GAG content at all diffusion time points (1-48 h), while strong and significant associations were observed between CA4+ attenuation and GAG content as early as 7 h (R 2  ≥ 0.67), being strongest at the equilibrium time point (48 h, R 2  = 0.81). CECT attenuation for both agents did not significantly correlate with water content, but CA4+ flux correlated with water content (R 2  = 0.56-0.64). CECT is a promising, non-destructive imaging technique for ex vivo assessment of meniscal GAG concentration and water content compared to traditional biochemical and histopathological methods. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1018-1028, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health., Introduction: Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN., Methods: In this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m 2 . Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes., Results: BSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, p diff  = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; p diff  = 0.01). Serum OC did not change in either group (p > 0.70)., Conclusions: Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.

Severe os odontoideum causing ventral brainstem compression is a rare and difficult entity to treat. It is generally accepted that severe os odontoideum causing ventral brainstem compression and neurological deficits warrants surgical treatment. This often requires both anterior and posterior procedures. Anterior approaches to the craniocervical junction are fraught with complications, including infection and risk of injury to neurovascular structures. External traction systems traditionally require long-term bedrest. The authors report 2 cases of severe ventral brainstem compression secondary to displaced os odontoideum and describe their use of extended preoperative halo vest traction to reduce the severe kyphosis and improve neurological function, followed by posterior occipitocervical fusion. Postoperatively both patients showed remarkable improvements in their neurological function and kyphotic deformity. Preoperative halo vest traction combined with posterior occipitocervical fusion appears to be a safe and effective method to treat brainstem compression by severe os odontoideum. It allows for adequate decompression of ventral neural structures and improvement of neurological function, but it is not hindered by the risks of anterior surgical approaches and does not restrict patients to strict bedrest as traditional traction systems. This method of halo vest traction and posterior-only approaches may be transferable to other cervical instability issues with both anterior and posterior pathologies.

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.

Background: The primary aim of this study was to evaluate the relationship of the migration percentage (a radiographic metric quantifying hip displacement) in children with Gross Motor Function Classification System (GMFCS) level-IV or V cerebral palsy and spastic hip dysplasia to the acetabular index and the health-related quality of life (HRQOL) as measured with the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) before and after reconstructive hip surgery., Methods: In a prospective cohort study (n = 38), the migration percentage, acetabular index, and CPCHILD scores were analyzed using the Pearson correlation analysis immediately before reconstructive hip surgery and at 6 weeks and 3, 6, 12, and 24 months after the surgery. Subgroup analysis was used to compare patients who had a preoperative migration percentage of ≥50% with those who had a preoperative migration percentage of <50% and to compare the acetabular index between patients who had a pelvic osteotomy and those who had not. Linear mixed models were used to analyze changes in the migration percentage, acetabular index, and CPCHILD scores over time., Results: The preoperative migration percentage negatively correlated with the preoperative CPCHILD score (r = -0.50; p = 0.002). This relationship continued throughout the follow-up period such that, for each additional 1% correction in migration percentage, the CPCHILD total score increased by 0.2 point (p < 0.001). There was no correlation between the acetabular index and CPCHILD total score before or after surgery (p = 0.09 to 0.71). The preoperative CPCHILD total scores differed between the migration-percentile groups (mean difference = 13 points; 95% confidence interval = 3.3 to 22.8; p = 0.01). However, after hip surgery, the CPCHILD score improved similarly for both groups., Conclusions: These data support the effectiveness of reconstructive hip surgery for the treatment of spastic hip dysplasia to improve the HRQOL of non-ambulatory children with severe cerebral palsy., Level of Evidence: Prospective Level IV. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation., Methods: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial., Results: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0% to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial., Conclusions: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747., (© 2016 American Heart Association, Inc.)

Mouse models of osteoarthritis (OA) are commonly used to study the disease's pathogenesis and efficacy of potential treatments. However, measuring the biochemical and mechanical properties of articular cartilage in these models currently requires destructive and time-consuming histology and mechanical testing. Therefore, we examined the feasibility of using contrast-enhanced CT (CECT) to rapidly and non-destructively image and assess the glycosaminoglycan (GAG) content. Using three ex vivo C57BL/6 mouse tibial plateaus, we determined the time required for the cationic contrast agent CA4+ to equilibrate in the cartilage. The whole-joint coefficient of friction (μ) of 10 mouse knees (some digested with Chondroitenase ABC to introduce variation in GAG) was evaluated using a modified Stanton pendulum. For both the medial and lateral tibial plateau cartilage of these knees, linear regression was used to compare the equilibrium CECT attenuations to μ, as well as each side's indentation equilibrium modulus (E) and Safranin-O determined GAG content. CA4+ equilibrated in the cartilage in 30.9 ± 0.95 min (mean ± SD, tau value of 6.17 ± 0.19 min). The mean medial and lateral CECT attenuation was correlated with μ (R(2)  = 0.69, p < 0.05), and the individual medial and lateral CECT attenuations correlated with their respective GAG contents (R(2)  ≥ 0.63, p < 0.05) and E (R(2)  ≥ 0.63, p < 0.05). In conclusion, CECT using CA4+ is a simple, non-destructive technique for three-dimensional imaging of ex vivo mouse cartilage, and significant correlations between CECT attenuation and GAG, E, and μ are observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1130-1138, 2016., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Unlabelled: This study investigated the degree of acetabular and femoral remodeling after isolated varus derotation osteotomy (VDRO) in children with cerebral palsy. This retrospective review investigated 56 children (103 hips) who underwent VDROs for spastic hip displacement between 1994 and 2007. The average age of the patients at surgery was 7.7 years and the follow-up duration was 7.8 years (range 5-11 years). The acetabular index showed a significant linear decrease (P<0.001), with children of less than 6 years showing the greatest correction (P<0.001). VDRO without pelvic osteotomy does result in a mild improvement in acetabular dysplasia over time, with greater rates of correction found in children of less than 6 years old., Level of Evidence: Therapeutic Study - Level IV.

Incorporation of an interpenetrating polymer network into an existing single polymer network enables augmentation of the original substrate's mechanical properties, and translation of this concept from purely synthetic materials to natural-synthetic hybrid systems provides the opportunity to reinforce mechanical properties of bulk biological substrates. In many disease states, the mechanical properties of bodily tissues deteriorate rendering them prone to further material failure. Herein, a tissue-supplementing technique is described in which an interpenetrating biomimetic hydrogel is polymerized in situ throughout cartilage tissue. The treatment restores the inferior compressive properties of osteoarthritic cartilage to that of healthy cartilage, preferentially localizing to weaker regions of tissue. Furthermore, the treatment technique preserves cartilage under harsh articulation conditions, showing promise as a materials-based treatment for early-stage osteoarthritis., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Controversy continues regarding the appropriate assessment of fracture risk in long bone lesions affected by disseminated malignancy., Questions/purposes: The purpose of this ongoing Musculoskeletal Tumor Society-sponsored, multi-institutional prospective cross-sectional clinical study is to compare CT-based structural rigidity analysis (CTRA) with physician-derived Mirels scoring for predicting pathologic fracture in femoral bone lesions. We hypothesized CTRA would be superior to Mirels in predicting fracture risk within the first year based on (1) sensitivity, specificity, positive predictive value, and negative predictive value; (2) receiver operator characteristic (ROC) analysis; and (3) fracture prediction after controlling for potential confounding variables such as age and lesion size., Methods: Consented patients with femoral metastatic lesions were assigned Mirels scores by the individual enrolling orthopaedic oncologist based on plain radiographs and then underwent CT scans of both femurs with a phantom of known density. The CTRA was then performed. Between 2004 and 2008, six study centers performed CTRA on 125 patients. The general indications for this test were femoral metastatic lesions potentially at risk of fracture. The enrolling physician was allowed the choice of prophylactic stabilization or nonsurgical treatment, and the local treating oncology team along with the patient made this decision. Of those 125 patients, 78 (62%) did not undergo prophylactic stabilization and had followup sufficient for inclusion, which was fracture through the lesion within 12 months of CTRA, death within 12 months of CTRA, or 12-month survival after CTRA without fracture, whereas 15 (12%) were lost to followup and could not be studied here. The mean patient age was 61 years (SD, 14 years). There were 46 women. Sixty-four of the lesions were located in the proximal femur, 13 were in the diaphysis, and four were distal. Osteolytic lesions prevailed (48 lesions) over mixed (31 lesions) and osteoblastic (15 lesions). The most common primary cancers were breast (25 lesions), lung (14 lesions), and myeloma (11 lesions). CTRA was compared with Mirels based on sensitivity/specificity analysis, ROC, and fracture prediction by multivariate analysis. For the CTRA, reduction greater than 35% in axial, bending, or torsional rigidities at the lesion was considered at risk for fracture, whereas a Mirels score of 9 or above, as suggested in the original manuscript, was used as the definition of impending fracture., Results: CTRA provided higher sensitivity (100% versus 66.7%), specificity (60.6% versus 47.9%), positive predictive value (17.6% versus 9.8%), and negative predictive value (100% versus 94.4%) compared with the classic Mirels definition of impending fracture (≥ 9), although there was considerable overlap in the confidence intervals. ROC curve analysis found CTRA to be better than the Mirels score regardless of what Mirels score cutoff was used. After controlling for potential confounding variables including age, lesion size, and Mirels scores, multivariable logistic regression indicated that CTRA was a better predictor of fracture (likelihood ratio test = 10.49, p < 0.001)., Conclusions: CT-based structural rigidity analysis is better than Mirels score in predicting femoral impending pathologic fracture. CTRA appears to provide a substantial advance in the accuracy of predicting pathological femur fracture over currently used clinical and radiographic criteria., Level of Evidence: Level III, diagnostic study.

Background: There is a need to improve the prediction of fracture risk for patients with metastatic bone disease. CT-based rigidity analysis (CTRA) is a sensitive and specific method, yet its influence on clinical decision-making has never been quantified., Questions/purposes: What is the influence of CTRA on providers' perceived risk of fracture? (2) What is the influence of CTRA on providers' treatment recommendations in simulated clinical scenarios of metastatic bone disease of the femur? (3) Does CTRA improve interobserver agreement regarding treatment recommendations?, Methods: We conducted a survey among 80 academic physicians (orthopaedic oncologists, musculoskeletal radiologists, and radiation oncologists) using simulated vignettes of femoral lesions presented as three separate scenarios: (1) no CTRA input (baseline); (2) CTRA input suggesting increased risk of fracture (CTRA+); and (3) CTRA input suggesting decreased risk of fracture (CTRA-). Participants were asked to rate the patient's risk of fracture on a scale of 0% to 100% and to provide a treatment recommendation. Overall response rate was 62.5% (50 of 80)., Results: When CTRA suggested an increased risk of fracture, physicians perceived the fracture risk to be slightly greater (37% ± 3% versus 42% ± 3%, p < 0.001; mean difference [95% confidence interval {CI}] = 5% [4.7%-5.2%]) and were more prone to recommend surgical stabilization (46% ± 9% versus 54% ± 9%, p < 0.001; mean difference [95% CI] = 9% [7.9-10.1]). When CTRA suggested a decreased risk of fracture, physicians perceived the risk to be slightly decreased (37% ± 25% versus 35% ± 25%, p = 0.04; mean difference [95% CI] = 2% [2.74%-2.26%]) and were less prone to recommend surgical stabilization (46% ± 9% versus 42% ± 9%, p < 0.03; mean difference [95% CI] = 4% [3.9-5.1]). The effect size of the influence of CTRA on physicians' perception of fracture risk and treatment planning varied with lesion severity and specialty of the responders. CTRA did not increase interobserver agreement regarding treatment recommendations when compared with the baseline scenario (κ = 0.41 versus κ = 0.43, respectively)., Conclusions: Based on this survey study, CTRA had a small influence on perceived fracture risk and treatment recommendations and did not increase interobserver agreement. Further work is required to properly introduce this technique to physicians involved in the care of patients with metastatic lesions. Given the number of preclinical and clinical studies outlining the efficacy of this technique, better education through presentations at seminars/webinars and symposia will be the first step. This should be followed by clinical trials to establish CTRA-based clinical guidelines based on evidence-based medicine. Increased exposure of clinicians to CTRA, including its underlying methodology to study bone structural characteristics, may establish CTRA as a uniform guideline to assess fracture risk., Level of Evidence: Level III, economic and decision analyses.

Aim: The aim of this study was to evaluate changes in caregivers' perceptions of health-related quality of life (HRQOL) and caregiver impact in children with severe, non-ambulatory cerebral palsy after orthopedic surgery to correct hip or spine deformities., Method: A prospective longitudinal cohort study (n=44) design was used to measure changes before and after surgery. Caregivers completed the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) and the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Data collection was between February 2011 and February 2014. Caregivers were included if their child was 3 to 25 years old, had cerebral palsy in Gross Motor Function Classification System levels IV and V, and was scheduled for orthopedic surgery. Analysis of variance with repeated measures was used to assess changes before and at four time points after surgery., Results: Forty-four caregivers participated. Caregivers' perceptions of their child's HRQOL demonstrated an improvement from baseline to 12 months (p<0.001). Patients who had spine surgery demonstrated a steady improvement over time, whereas patients who had hip surgery had a decrease at 6 weeks followed by steady improvement. Improvements were noted in five of six of the CPCHILD domains, with no changes in the quality of life domain. No changes were noted in any of the ACEND domains., Interpretation: Caregivers report an improvement in a variety of domains of HRQOL 1 year after orthopedic surgery., (© 2015 Mac Keith Press.)

Background: The purpose of this study was to evaluate mid-term results of proximal femoral varus derotation osteotomy (VDRO) in children with cerebral palsy and determine what effect age, Gross Motor Function Classification System (GMFCS) level, and surgeon volume had on surgical success., Methods: We analyzed a cohort of children with cerebral palsy who underwent VDRO for hip displacement at a tertiary-level pediatric hospital between 1994 and 2007. Age, sex, GMFCS level, preoperative radiographic parameters, previous botulinum toxin administration or soft-tissue release, adjunctive pelvic osteotomy, the performance of bilateral surgery at the index VDRO, and surgeon volume (the number of procedures performed) were recorded. Results were analyzed via univariate and multivariate analyses for association with the need for revision hip surgery. Kaplan-Meier survivorship curves were generated, determining the time from index surgery to failure (defined as the need for subsequent surgical procedures on the hip and/or pelvis, or a hip migration percentage of >50% at the time of final follow-up), and were further stratified according to osseous versus soft-tissue revision., Results: A total of 567 VDROs were performed in 320 children (mean age [and standard deviation], 8.2 ± 3.8 years). The mean follow-up was 8.3 years (range, three to eighteen years). Of the initial 320 patients, 117 (37%) were considered to have had failure. Multivariate Cox regression analysis confirmed that younger age at surgery (p < 0.001), increased GMFCS level (p = 0.01), and lower annual surgical hip volume (p = 0.02) were significant independent predictors of any type of surgical revision. Furthermore, soft-tissue release at VDRO was protective against revision (p = 0.02). Five-year survivorship analysis revealed a 92% success rate for children classified as GMFCS levels I and II compared with a 76% success rate for those of GMFCS level V (p < 0.01)., Conclusions: This study demonstrated a 37% failure rate after VDRO in children with cerebral palsy. Older age, lower GMFCS level, and increased surgeon volume were strong predictors of surgical success., (Copyright © 2015 by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis., Design: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline μCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties., Results: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60)., Conclusion: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have future use as a platform to evaluate treatment effectiveness.

A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

Purpose: To identify factors associated with an increased risk of fractures in Long-Gap Esophageal Atresia (LGEA) patients. Following implementation of a risk-stratified program, we hypothesized a reduction in fracture incidence within this potentially high-risk population., Methods: A retrospective review of LGEA-patients admitted between 2005 and 2014 was conducted. Symptomatic fractures with radiographic confirmation were defined as events. Univariate and multivariable analysis evaluated factors including admission weight-for-age z-score, primary versus secondary Foker process (FP), weight at Foker Stage I, days and episodes of paralysis, number of parenteral nutrition (PN) days, cumulative dose of loop diuretics adjusted for body weight and days exposed, and exposure to non-loop diuretics. A fracture-prevention protocol was initiated in 2012; incidence was evaluated pre and post-intervention., Results: Fifty-nine patients met inclusion criteria. Twenty-three (39%) patients in the entire cohort incurred at least one fracture during their hospitalization utilizing the Foker process. Given this high percentage, a targeted fracture-prevention protocol was initiated in 2012. Fracture incidence decreased from 48% prior to the protocol to 21% following the protocol ( P  = 0.046). Several variables that were associated with an increased risk of fractures on univariate analysis included prior esophageal anastomosis attempt ( P  = 0.008), number of separate episodes of paralysis ( P  = 0.002), exposure to non-loop diuretics ( P  = 0.006), cumulative loop diuretic dose ( P  < 0.001), as well as cumulative loop diuretic over days exposed ( P  < 0.001). Intensive care unit (ICU) stay ( P  = 0.002) and total length of hospitalization ( P  < 0.001) were also significantly longer among patients with a fracture. Number of separate episodes of paralysis was the only independent risk factor for the development of a fracture; patients having more than 3 episodes of paralysis had an estimated risk of fracture 15 times higher than those patients paralyzed only once or twice (O.R. 15.87, 95% C.I.: 1.47-171.23, P  = 0.008)., Conclusion: Episodes of paralysis appeared to be the most significant risk factor for fractures in patients with LGEA who underwent the Foker procedure. The incidence of symptomatic fractures decreased significantly following implementation of a standardized protocol in this series of LGEA patients with continued prospective evaluation.