Thoracic Outlet Syndrome in the Pediatric and Young Adult Population.

PURPOSE: This study aimed to assess both nonsurgical and operative treatment outcomes of pediatric and young adult patients with thoracic outlet syndrome (TOS) at a tertiary care pediatric hospital. METHODS: A retrospective chart review of patients diagnosed with TOS, who were seen between January 2010 and August 2022 at a tertiary care pediatric hospital, was conducted. Collected pre- and postoperative data included symptoms, provocative testing (ie, Roo's, Wright's, and Adson's tests), participation in sports or upper-extremity activities, additional operations, and surgical complications. Assessment of operative treatment efficacy was based on pre- and post-provocative testing, pain, venogram results, alleviation of symptoms, and return to previous activity level 6 months after surgery. RESULTS: Ninety-six patients, (70 females and 26 males) with an average age at onset of 15 ± 4 (4-25) years, met the inclusion criteria for TOS. Among them, 27 had neurogenic TOS, 29 had neurogenic and vasculogenic TOS, 20 had vasculogenic TOS, 19 had Paget-Schroetter Syndrome, and one was asymptomatic. Twenty-six patients were excluded because of less than 6 months of follow-up. Of the remaining 70, 6 (8.6%) patients (4 bilateral and 2 unilateral) underwent nonoperative management with activity modification and physical therapy only, and one was fully discharged because of complete relief of symptoms. Sixty-four (90.1%) patients (45 bilateral and 19 unilateral) underwent surgery. A total of 102 operations were performed. Substantial improvements were observed in provocative maneuvers after surgery. Before surgery, 79.7% were involved in sports or playing musical instruments with repetitive overhead activity, and after surgery, 86.2% of these patients returned to their previous activity level. CONCLUSIONS: Few patients were successfully managed with nonoperative activity modification and physical therapy. In those requiring surgical intervention, first or cervical rib resection with scalenectomy using a supraclavicular approach provided resolution of symptoms with 86.2% of patients being able to return to presymptom sport or activity level. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Presentation and Management of the Pediatric Trigger Finger: A Multicenter Retrospective Cohort Study.

PURPOSE: Pediatric trigger finger (PTF) is an acquired condition that is uncommon and anatomically complex. Currently, the literature is characterized by a small number of retrospective case series with limited sample sizes. This investigation sought to evaluate the presentation, management, and treatment outcomes of PTF in a large, multicenter cohort. METHODS: A retrospective review of pediatric patients with a diagnosis of PTF between 2009 and 2020 was performed at three tertiary referral hospitals. Patient demographics, PTF characteristics, treatment strategies, and outcomes were abstracted from the electronic medical records. Patients and families also were contacted by telephone to assess the downstream persistence or recurrence of triggering symptoms. RESULTS: In total, 321 patients with 449 PTFs were included at a mean follow-up of 3.9 ± 4.0 years. There were approximately equal numbers of boys and girls, and the mean age of symptom onset was 5.4 ± 5.1 years. The middle (34.7%) and index (11.6%) fingers were the most and least commonly affected digits, respectively. Overall, PTFs managed operatively achieved significantly higher rates of complete resolution compared with PTFs managed nonsurgically (97.1% vs 30.0%). Seventy-five percent of PTFs that achieved complete resolution with nonsurgical management did so within 6 months, and approximately 90% did so within 12 months. Patients with multidigit involvement, higher Quinnell grade at presentation, or palpable nodularity were significantly more likely to undergo surgery. There was no significant difference in the rate of complete resolution between splinted versus not splinted PTFs or across operative techniques. CONCLUSIONS: Only 30% of the PTFs managed nonsurgically achieved complete resolution. Splinting did not improve resolution rates in children treated nonsurgically. In contrast, surgical intervention has a high likelihood of restoring motion and function of the affected digit. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

International Pediatric Multidisciplinary Management Using Telemedicine to Promote Equitable Care.

Objective: To evaluate the use of telemedicine as a collaboration tool between a pediatrician and subspecialists looking to address challenges, such as the lack of health care specialists, which are present in the Dominican Republic. Study design: During this 6-year study, 65 patients were evaluated by a medical team consisting of a local pediatrician and 17 subspecialists from a leading academic medical center in the Unites States. Patient's age ranged from 2 months to 16 years of age (mean 8 years old). The most common reasons for referral were masses or malignancies, vascular malformations, urogenital anomalies, stuttering, and cochlear implant programming. Results: A total of 39 out of 65 cases (60%) carried an initial diagnosis. Of the 65 cases, a change in medical management occurred in 92.31% of cases (60 cases). There was no change in medical diagnosis or treatment in 5 of 65 cases (8%). Conclusion: This protocol exhibited high patient satisfaction with the technology and platform and direct patient savings from transportation costs. It also demonstrated the importance of thorough diagnosis in providing appropriate treatment and solutions. Telemedicine use in comparable practices should be studied further to aid in the development of policies for the diagnosis and management of chronic illnesses that require referrals to subspecialists.

Bizarre Parosteal Osteochondromatous Proliferation (Nora Lesion) in Pediatric Phalanges.

Bizarre parosteal osteochondromatous proliferation, or Nora tumor, is an uncommon lesion affecting the tubular bones of the hands and feet. Normally arising from the cortical surface and periosteum of these bones, these lesions histologically consist of a hypercellular cartilaginous cap covering a bony stalk that is surrounded by ossified areas and spindle cell stroma. The differential diagnosis includes conditions involving the periosteum such as chondrosarcoma, parosteal osteosarcoma, osteochondroma, turret exostosis, and florid reactive periostitis. The only effective treatment is wide surgical excision; nevertheless, local recurrence rates are extremely high and may necessitate revision surgery. In the present study, we report 3 cases of Nora lesion located in the hand in pediatric patients. The diagnosis in these cases was challenging owing to their presenting symptoms and radiographic findings. The diagnosis was made based on characteristic findings noted on the radiographic images and was confirmed by histological examination following excision.

Humerus Rotation Has a Negligible Effect on Baumann Angle in a Wide Range of Rotational Positions.

BACKGROUND: Rotation of the humerus out of the coronal plane is presumed to alter the Baumann angle (BA) value. Identifying the rotational limits of the humerus at which the BA can be accurately and reliably measured will circumvent repeated radiographs and unnecessary exposure to radiation, may improve patient comfort, and save time and medical resources. METHODS: A retrospective chart review was performed to identify patients under the age of 18 who underwent an elbow computed tomography (CT) scan without any humeral pathology and with an open distal humeral physis. For each patient, a 3-dimensional (3D) computerized model was generated with 30% transparency to mimic a plain radiograph. These models were rotated in 10-degree increments and the BA was measured on each position. In addition, the measurements were taken on an anteroposterior radiograph for each patient. Analysis of variance and the Pearson tests were performed to locate differences and define associations. RESULTS: Fifteen 3D CT reconstructions were generated from 14 patients. The mean BA on the neutral position was found to be 72.2±3 degrees, which correlated with the 70.6±5.91 degrees measurement obtained on radiographs. The most extreme rotational positions on which the BA values were consistent with the neutral position values were +40 external rotation (70.97±7.01 degrees, P=1) and -70 degrees internal rotation (68.4±7.47 degrees, P=0.14). A negative correlation was found between the BA values and the extent at which the humerus was rotated from the neutral position. The variability of the BA between patients, implied by the SD of measurements on each position increased with increasing rotation from the neutral position (r=1, P<0.05). CONCLUSIONS: On the basis of 3D CT images, the BA is the most accurate when the arm is positioned at an exact anteroposterior position. It is reliable to measure the BA when the humerus is rotated no more than +40 degrees external rotation to -70 degrees internal rotation. This range of rotation can act as an "accurate zone" and help avoiding multiple radiographs. LEVEL OF EVIDENCE: Level III.

Performance of a Deep Neural Network Algorithm Based on a Small Medical Image Dataset: Incremental Impact of 3D-to-2D Reformation Combined with Novel Data Augmentation, Photometric Conversion, or Transfer Learning.

Collecting and curating large medical-image datasets for deep neural network (DNN) algorithm development is typically difficult and resource-intensive. While transfer learning (TL) decreases reliance on large data collections, current TL implementations are tailored to two-dimensional (2D) datasets, limiting applicability to volumetric imaging (e.g., computed tomography). Targeting performance enhancement of a DNN algorithm based on a small image dataset, we assessed incremental impact of 3D-to-2D projection methods, one supporting novel data augmentation (DA); photometric grayscale-to-color conversion (GCC); and/or TL on training of an algorithm from a small coronary computed tomography angiography (CCTA) dataset (200 examinations, 50% with atherosclerosis and 50% atherosclerosis-free) producing 245 diseased and 1127 normal coronary arteries/branches. Volumetric CCTA data was converted to a 2D format creating both an Aggregate Projection View (APV) and a Mosaic Projection View (MPV), supporting DA per vessel; both grayscale and color-mapped versions of each view were also obtained. Training was performed both without and with TL, and algorithm performance of all permutations was compared using area under the receiver operating characteristics curve. Without TL, APV performance was 0.74 and 0.87 on grayscale and color images, respectively, compared to 0.90 and 0.87 for MPV. With TL, APV performance was 0.78 and 0.88 on grayscale and color images, respectively, compared with 0.93 and 0.91 for MPV. In conclusion, TL enhances performance of a DNN algorithm from a small volumetric dataset after proposed 3D-to-2D reformatting, but additive gain is achieved with application of either GCC to APV or the proposed novel MPV technique for DA.

Outcomes of Spinal Accessory-to-Suprascapular Nerve Transfers for Brachial Plexus Birth Injury.

PURPOSE: The results of a spinal accessory nerve-to-suprascapular (SAN-SSN) nerve transfer for brachial plexus birth injuries (BPBIs) have thus far been presented only in limited case series. Our study evaluates the recovery of shoulder function of patients who underwent an SAN-SSN for BPBI as an isolated procedure or as part of a multinerve reconstruction (MNR) surgery. METHODS: We retrospectively reviewed the medical records of patients at a single institution who underwent an SAN-SSN after BPBI. Inclusion criteria were patients with both preoperative and a minimum 12-months postoperative active movement scale (AMS) scores. Patients for whom the primary surgery involved tendon transfers were excluded. The primary outcome measures were AMS scores for shoulder abduction, forward flexion, and external rotation and secondary outcomes included the need for further shoulder surgery to improve function. RESULTS: Seventy-three patients met the inclusion criteria. Forty-three patients (58.9%) obtained functional shoulder motion (AMS ≥ 6) of at least 1 of 3 planes (abduction/flexion/external rotation) following surgery, with 13 patients (17.8%) achieving full recovery of 1 of these shoulder motions against gravity (AMS = 7). Fifty-six patients (76.7%) did not undergo subsequent tendon transfers or corrective osteotomies to augment shoulder function. The MNR procedures were performed in 46 patients (63%), of whom 45.7% gained a functional recovery. In 27 patients for whom SAN-SSN nerve transfer was conducted in isolation, 81.5% gained functional shoulder motion. However, isolated SAN-SSNs were conducted at a later age than MNR procedures (13.2 vs 4.8 months) and had higher preoperative AMS scores. The anterior and posterior approaches for SAN-SSN were both found to be effective when used for SAN-SSN in BPBI. When the follow-up duration cutoff was set to 3 years, the outcomes were found to be superior. CONCLUSIONS: In 76.7% of the patients, SAN-SSN was able to recover function that was sufficient to prevent tendon transfers and corrective osteotomies. A cutoff of 3 postoperative years should be used as a benchmark for analyzing the results of this procedure. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A Bundled Payment Model for Pediatric Distal Radius Fractures: Defining an Episode of Care.

BACKGROUND: Distal radius fractures are the most common fracture of childhood, occurring in ∼1 per 100 children annually. Given the high incidence of these fractures, we explored feasibility of a bundled payment model. We determined the total treatment costs for each child and identified components of fracture management that contributed to variations in cost. METHODS: We retrospectively reviewed all hospital and physician costs related to the treatment of closed distal radius fractures at a large academic children's hospital. We included all children age 2 to 15 years treated by an orthopaedic surgeon for an isolated closed distal radius fracture between 2013 and 2015. We compared total treatment costs by fracture management approach. We then estimated the contribution of each component of fracture management to total treatment costs using linear regression. RESULTS: We identified 5640 children meeting the inclusion criteria, of which 4602 (81.6%) received closed treatment without manipulation, 922 (16.3%) underwent closed reduction in the clinic, emergency department, or radiology procedure suite, and 116 (2.1%) underwent treatment in the operating room. The median cost for closed treatment without manipulation was $1390 [interquartile range (IQR) 1029 to 1801], compared with $4263 (IQR, 3740 to 4832) for closed reduction and $9389 (IQR, 8272 to 11,119) for closed reduction and percutaneous pinning (P<0.001). In multivariable regression analysis, fracture management approach and use of the operating room environment were the largest cost drivers (P<0.001, R=0.88). Closed reduction in the clinic or emergency department added $894 (95% confidence interval, 819-969) to treatment costs, while closed reduction in the operating room added $5568 (95% confidence interval, 5224-6297). Location of the initial clinical evaluation, number of radiographic imaging series obtained, and number of orthopaedic clinic visits also contributed to total costs. CONCLUSIONS: Closed pediatric distal radius fractures treated without manipulation show small variations in treatment costs, making them well suited for bundled payment. Bundled payments for these fractures could reduce costs by encouraging adoption of existing evidence-based practices. LEVEL OF EVIDENCE: Level III-therapeutic.

Increasing Brace Treatment for Pediatric Distal Radius Buckle Fractures: Using Quality Improvement Methodology to Implement Evidence-based Medicine.

BACKGROUND: Multiple randomized trials have showed equivalent outcomes and improved patient/family satisfaction using a removable brace to treat pediatric distal radius buckle fractures (DRBF). We tested the hypothesis that we could use quality improvement (QI) methodology to increase the proportion of patients with DRBF treated with removable braces at 2 tertiary care orthopaedic clinics from a baseline of 34.8% to 80%. METHODS: Clinic billing records were reviewed monthly to determine treatment (brace vs. cast) of DRBF and tracked using control charts (p-chart). Balance measures including correct application of the diagnostic criteria and algorithm were monitored. Process measures including the number of follow-up visits, radiographs obtained, and total cost of treatment were collected. Baseline data were obtained over a 3-month period, followed by a 12-month period of interventions using Plan-Do-Study-Act cycles targeting both individuals and groups of providers. RESULTS: The proportion of DRBF treated in a brace increased from a combined baseline of 34.8% to a combined 84% at the end of the study period. Following intervention, 83% (15/18) of providers began using braces for a majority of patients (defined as >67%), with only 1 provider continuing to use casts 100% of the time. Patient preference was cited as the most common reason for use of cast treatment. There was a significant decrease in the number of radiographs obtained at 1 of 2 institutions. The charges for brace treatment averaged $630 less per patient than for cast treatment, leading to an estimated medical-cost savings of $205,000 following intervention. CONCLUSIONS: Implementation of brace treatment for pediatric DRBF using QI methodology resulted in a shift toward brace treatment in the majority of patients, leading to substantial medical and nonmedical cost savings. Although patient preference was cited as the most common reason for persistent cast treatment, the data show the use of cast treatment to be more dependent upon individual provider preference. LEVEL OF EVIDENCE: Level II-therapeutic.

Shielding a high-sensitivity digital detector from electromagnetic interference.

PURPOSE: To document a study in shielding a high-sensitivity digital mammography system detector from AC magnetic fields of magnitudes great enough to induce imaging artifacts. METHODS/MATERIALS: Preliminary evaluation of AC magnetic fields at a site designated for a digital breast tomosynthesis (DBT) system raised concerns that the magnetic component of electromagnetic interference (EMI) may be great enough to induce imaging artifacts. Subsequent measurements using digital detector arrays from two separate manufacturers verified this concern, and AC magnetic fields were mapped, spatially and temporally, throughout the area of concern. A simple shielding model was developed to elucidate the physics of extremely low-frequency (ELF) EMI shielding and independently verify a commercial group's proposed shielding design and installation. Postshielding measurements were performed to demonstrate that the EMI fields were reduced to acceptable levels. RESULTS: Preshielding measurements showed AC magnetic fields significantly exceeding manufacturers' tolerances for artifact-free imaging in DBT. Continuous measurements demonstrated that the EMI fields varied significantly over time. Some locations in the room routinely averaged above 30 mG and occasionally exceeded 100 mG. The source was attributed to an adjacent electrical supply room, and temporal changes of the EMI were attributed to variations of the building electrical loads. The proposed shielding primarily consisted of continuous aluminum (6.35 mm thickness) and was installed by a group specializing in electromagnetic field shielding. Postshielding measurements demonstrated that the EMI fields were significantly reduced, generally to less than 0.5 mG, and that the shielding effectively dampened the large variations due to dynamic building electrical loads. Subsequent installation and evaluation of a DBT system revealed no issues with imaging artifacts. CONCLUSIONS: The successful shielding of ELF EMI involves physical principles that are not commonly encountered by medical physicists. Modern high-sensitivity digital detectors may be successfully shielded against imaging artifacts with careful application of these principles.

Automated Critical Test Findings Identification and Online Notification System Using Artificial Intelligence in Imaging.

Purpose To evaluate the performance of an artificial intelligence (AI) tool using a deep learning algorithm for detecting hemorrhage, mass effect, or hydrocephalus (HMH) at non-contrast material-enhanced head computed tomographic (CT) examinations and to determine algorithm performance for detection of suspected acute infarct (SAI). Materials and Methods This HIPAA-compliant retrospective study was completed after institutional review board approval. A training and validation dataset of noncontrast-enhanced head CT examinations that comprised 100 examinations of HMH, 22 of SAI, and 124 of noncritical findings was obtained resulting in 2583 representative images. Examinations were processed by using a convolutional neural network (deep learning) using two different window and level configurations (brain window and stroke window). AI algorithm performance was tested on a separate dataset containing 50 examinations with HMH findings, 15 with SAI findings, and 35 with noncritical findings. Results Final algorithm performance for HMH showed 90% (45 of 50) sensitivity (95% confidence interval [CI]: 78%, 97%) and 85% (68 of 80) specificity (95% CI: 76%, 92%), with area under the receiver operating characteristic curve (AUC) of 0.91 with the brain window. For SAI, the best performance was achieved with the stroke window showing 62% (13 of 21) sensitivity (95% CI: 38%, 82%) and 96% (27 of 28) specificity (95% CI: 82%, 100%), with AUC of 0.81. Conclusion AI using deep learning demonstrates promise for detecting critical findings at noncontrast-enhanced head CT. A dedicated algorithm was required to detect SAI. Detection of SAI showed lower sensitivity in comparison to detection of HMH, but showed reasonable performance. Findings support further investigation of the algorithm in a controlled and prospective clinical setting to determine whether it can independently screen noncontrast-enhanced head CT examinations and notify the interpreting radiologist of critical findings. © RSNA, 2017 Online supplemental material is available for this article.

Eccentric Capitellar Ossification Limits the Utility of the Radiocapitellar Line in Young Children.

BACKGROUND: The radiocapitellar line (RCL) has long been used for the radiographic evaluation of elbow alignment. In children, the capitellar ossific nucleus serves as a proxy for the entire capitellum, but this substitution has not been verified. Using magnetic resonance imaging (MRI), we sought to understand how maturation of the ossific nucleus of the capitellum affects the utility of RCL throughout skeletal maturation of the elbow. METHODS: The RCL was drawn on coronal and sagittal MRIs in 82 children (43 boys, 39 girls; age range, 1 to 13 y) with at least 3 patients in each 1-year interval age group. The perpendicular distance of the RCL from the center of both the cartilaginous capitellum and the capitellar ossific nucleus was measured relative to its total width, and a percent offset for each measurement was calculated. Logarithmic regression analysis was performed to analyze the effect of age and sex on percent offset. RESULTS: The RCL reliably intersected with the central third of the cartilaginous capitellum at all ages in both planes. Although the RCL intersected with the ossified capitellum in all but 3 measurements, it intersected with the central third of the ossified capitellum less often in younger children in both sagittal (B=0.47, P<0.001) and coronal (B=0.31, P=0.002) planes. Percent offset decreased significantly with age in a logarithmic manner in both sagittal (r=0.57, P<0.001) and coronal (r=-0.47, P<0.001) planes. 95% confidence intervals predict that the sagittal plane RCL will accurately intersect the central third of the ossified capitellum by age 10 years in girls and age 11 years in boys but not in the coronal plane. CONCLUSIONS: Eccentric ossification of the capitellum explains RCL variability in young children. The RCL does not reliably intersect the central third of the ossified capitellum until ages 10 years in girls and 11 years in boys in the sagittal plane. The RCL should be used within its limitations in skeletally immature children and should be combined with advanced imaging if necessary.

MR imaging of capitellar ossification: a study in children of different ages.

BACKGROUND: The capitellar ossification center is used routinely to evaluate elbow alignment on radiography. However, whether capitellar ossification is central and concentric to support this practice is unknown. OBJECTIVE: To define the pattern of capitellar ossification at different ages of childhood. MATERIALS AND METHODS: This HIPAA-compliant study was IRB approved. MR imaging examinations from 81 children (ages 1-13 years, at least 3 boys and 3 girls in each age group) were included. We determined the center points of the ossified capitellum and the cartilaginous capitellum on the sagittal and coronal sequences that best showed differentiation between cartilage and bone. Percentage offset of the center of the ossified capitellum from the center of the cartilaginous capitellum was calculated in anterior-posterior, proximal-distal and medial-lateral dimensions, and compared across age groups and between genders. Linear regressions were used to ascertain the effect of age on percentage offset for all patients and for each gender. RESULTS: Capitellar ossification begins eccentrically with sagittal anterior proximal offset and coronal medial offset. With age, ossification proceeds posteriorly, distally and laterally. Percentage offset gradually diminishes with age. The ossified capitellum centralizes in the sagittal plane by 12-13 years. In the coronal plane, the capitellum ossifies medially beyond the proximal radioulnar joint and remains eccentric at 12-13 years. Centralization in boys lags in the anterior-posterior dimension. CONCLUSION: Capitellar ossification is an eccentric process, with lag in anterior-posterior centralization in boys. Medial offset persists at 12-13 years. Recognition of this eccentric ossification may allow for more accurate assessment of elbow alignment on radiographs, especially in younger children.

Pollicization and Pediatric Thumb Reconstruction.

Functional impairment, absence, or traumatic loss of the thumb is associated with considerable morbidity. A fully functioning thumb is estimated to account for 40% of hand function. An array of options exists for thumb reconstruction, and the intervention selected must be tailored to each individual patient. Pollicization is a powerful and elegant operation that can dramatically improve function for many patients. However, the surgeon and patient must be keenly aware that pollicization does not construct a "normal" thumb. Herein, we present a stepwise approach to treatment, including surgical nuances, alternatives to pollicization, complications, and outcomes.

Predictors for operative treatment in pediatric proximal third both-bone diaphyseal forearm fractures in children include age and translation, but not initial angulation.

Introduction: Proximal third diaphyseal fractures of the radius and ulna represent an onerous fracture pattern due to difficulty maintaining acceptable alignment with nonoperative management. Our aim was to identify the factors that increase the odds for a surgical treatment of these fractures. Recognizing these factors can raise awareness to patients who are more likely to require additional care and assist clinicians in counseling families, targeting treatment plans, and constructing follow-up protocols. We hypothesized that the age of the patient, the amount of initial fracture displacement, and the angulation of the fracture would predict the need for operative treatment. Methods: We retrospectively reviewed 276 proximal third diaphyseal forearm fractures at a single tertiary care institution. All patients underwent a nonoperative treatment trial, and if failed continued to surgery. Following a univariate analysis, we constructed a binary multivariate logistic regression model that included age, initial translation, and initial angulation to assess the association between the tested variables. Results: A regression model revealed that age (10 years and older, odds ratio: 8.2, 95% confidence interval: 3.9-17.24, p < 0.001) and radius translation of more than 100% (odds ratio: 7.06, 95% confidence interval: 2.69-18.52, p < 0.001) were associated with the need for surgical treatment. Initial fracture angulation lacked an association with a surgical treatment (odds ratio: 0.81 95% confidence interval: 0.38-1.74, p = 0.59). Conclusion: Age above 10 years and 100% initial translation of the radius fracture increased the odds for an ultimate decision to perform a surgery. Initial angulation, although often being the most remarkable radiographic feature, was not associated with a nonoperative treatment failure. We recommend an initial reduction attempt after counseling patients and their families that there is a high rate of conversion to operative treatment when the above features are met. Level of evidence: level III.

Effects of Altering Magnesium Metal Surfaces on Degradation In Vitro and In Vivo during Peripheral Nerve Regeneration.

In vivo use of biodegradable magnesium (Mg) metal can be plagued by too rapid a degradation rate that removes metal support before physiological function is repaired. To advance the use of Mg biomedical implants, the degradation rate may need to be adjusted. We previously demonstrated that pure Mg filaments used in a nerve repair scaffold were compatible with regenerating peripheral nerve tissues, reduced inflammation, and improved axonal numbers across a short-but not long-gap in sciatic nerves in rats. To determine if the repair of longer gaps would be improved by a slower Mg degradation rate, we tested, in vitro and in vivo, the effects of Mg filament polishing followed by anodization using plasma electrolytic oxidation (PEO) with non-toxic electrolytes. Polishing removed oxidation products from the surface of as-received (unpolished) filaments, exposed more Mg on the surface, produced a smoother surface, slowed in vitro Mg degradation over four weeks after immersion in a physiological solution, and improved attachment of cultured epithelial cells. In vivo, treated Mg filaments were used to repair longer (15 mm) injury gaps in adult rat sciatic nerves after placement inside hollow poly (caprolactone) nerve conduits. The addition of single Mg or control titanium filaments was compared to empty conduits (negative control) and isografts (nerves from donor rats, positive control). After six weeks in vivo, live animal imaging with micro computed tomography (micro-CT) showed that Mg metal degradation rates were slowed by polishing vs. as-received Mg, but not by anodization, which introduced greater variability. After 14 weeks in vivo, functional return was seen only with isograft controls. However, within Mg filament groups, the amount of axonal growth across the injury site was improved with slower Mg degradation rates. Thus, anodization slowed degradation in vitro but not in vivo, and degradation rates do affect nerve regeneration.

Nerve Regeneration with a Scaffold Incorporating an Absorbable Zinc-2% Iron Alloy Filament to Improve Axonal Guidance.

Peripheral nerve damage that results in lost segments requires surgery, but currently available hollow scaffolds have limitations that could be overcome by adding internal guidance support. A novel solution is to use filaments of absorbable metals to supply physical support and guidance for nerve regeneration that then safely disappear from the body. Previously, we showed that thin filaments of magnesium metal (Mg) would support nerve regeneration. Here, we tested another absorbable metal, zinc (Zn), using a proprietary zinc alloy with 2% iron (Zn-2%Fe) that was designed to overcome the limitations of both Mg and pure Zn metal. Non-critical-sized gaps in adult rat sciatic nerves were repaired with silicone conduits plus single filaments of Zn-2%Fe, Mg, or no metal, with autografts as controls. After seventeen weeks, all groups showed equal recovery of function and axonal density at the distal end of the conduit. The Zn alloy group showed some improvements in early rat health and recovery of function. The alloy had a greater local accumulation of degradation products and inflammatory cells than Mg; however, both metals had an equally thin capsule (no difference in tissue irritation) and no toxicity or inflammation in neighboring nerve tissues. Therefore, Zn-2%Fe, like Mg, is biocompatible and has great potential for use in nervous tissue regeneration and repair.

Hypoxia: a critical regulator of early human tendinopathy.

OBJECTIVES: To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes. METHODS: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining. RESULTS: Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis. CONCLUSION: Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders.