Safety and Osteointegration of Titanium Screws Coated with a Fibroblast Growth Factor-2-Calcium Phosphate Composite Layer in Non-Human Primates: A Pilot Study.

Spinal instrumentation surgery for older patients with osteoporosis is increasing. Implant loosening may occur due to inappropriate fixation in osteoporotic bone. Developing implants that achieve stable surgical results, even in osteoporotic bone, can reduce re-operation, lower medical costs, and maintain the physical status of older patients. Fibroblast growth factor-2 (FGF-2) promotes bone formation; thus, coating pedicle screws with an FGF-2-calcium phosphate (FGF-CP) composite layer is hypothesized to enhance osteointegration in spinal implants. We designed a long-term implantation pilot study that estimated the safety and bone-forming efficacy of pedicle screws coated with an FGF-CP composite layer in cynomolgus monkeys. Titanium alloy screws, either uncoated (controls) or aseptically coated with an FGF-CP composite layer, were implanted in the vertebral bodies of six female adult cynomolgus monkeys (three monkeys per group) for 85 days. Physiological, histological, and radiographic investigations were performed. There were no serious adverse events, and no radiolucent areas were observed around the screws in either group. The bone apposition rate in the intraosseous region was significantly higher in the FGF-CP group than in the controls. Moreover, as analyzed by Weibull plots, the bone formation rate of the FGF-CP group exhibited a significantly higher regression line slope than the control group. These results demonstrated that there was significantly less risk of impaired osteointegration in the FGF-CP group. Our pilot study suggests that FGF-CP-coated implants could promote osteointegration, be safe, and reduce the probability of screw loosening.

Clinical Trial for the Safety and Feasibility of Pedicle Screws Coated with a Fibroblast Growth Factor-2-Apatite Composite Layer for Posterior Cervical Fusion Surgery.

To solve the instrument loosening problem, we developed a fibroblast growth factor-2-calcium phosphate composite layer as a novel coating material to improve screw fixation strength. The primary aim of the present study was to demonstrate the safety and feasibility of screws coated with the FGF-2-calcium phosphate composite layer for posterior instrumented surgery of the cervical spine. The trial design was a single-arm, open-label, safety and feasibility study. Patients receiving fusion of the cervical spine from C2 (or C3) to C7 (or T1) were recruited. The primary endpoint to confirm safety was any screw-related adverse events. Seven patients who underwent posterior fusion surgery of the cervical spine were enrolled in the present study. The coated pedicle screws were inserted bilaterally into the lowest instrumented vertebrae. There was only one severe adverse event unrelated with the coated screw. Three out of the fourteen coated screws showed loosening. The present results prove the safety and feasibility of pedicle screws coated with the FGF-2-calcium phosphate composite layer for fusion surgery in the cervical spine. This is the first step to apply this novel surface coating in the field of spine surgery.

Safety of terminally gamma-ray-sterilized screws coated with fibroblast growth factor 2-calcium phosphate composite layers in non-human primates.

Screws coated with fibroblast growth factor 2 (FGF-2)-calcium phosphate (CP) composite layers exhibit enhanced soft tissue and bone formation and angiogenesis because of the biological activity of FGF-2. Furthermore, the mitogenic activity of the FGF-2 within the composite layers remains unchanged after gamma-ray sterilization, which may improve the storage stability prior to clinical use. However, the in vivo safeties of these screws as spinal implants remain unknown. Here, a randomized controlled trial, involving non-human primates, investigated the safety of using FGF-2-CP composite layer-coated screws after either gamma-ray sterilization or aseptic processing. Titanium alloy screws coated with FGF-2-CP composite layers and subjected to either gamma-ray sterilization at 25 kGy (GS group) or aseptic storage (AS group) were implanted into the vertebral bodies of two cynomolgus monkeys exceeding 12 weeks (day 99). Physiological, histological, and radiographic investigations were performed to evaluate the safeties of the screws. There were no serious adverse events, such as surgical site infection, significant loss of body weight, or abnormal blood test results. No radiolucent areas were observed around the screws from the GS or AS group throughout the study. In the intraosseous region, no significant differences were observed in bone and fibrous tissue apposition rates and rate of bone formation between the two groups (p = 0.49, 0.77, and 0.11, respectively). Neither tumor lesions nor accumulation of lymphocytes and neutrophils were observed in either group. Our data suggest that FGF-2-CP composite layer-coated screws subjected to terminal gamma-ray sterilization are as safe as those fabricated in aseptic processing.

Development of a quantitative method to evaluate pedicle screw loosening after spinal instrumentation using digital tomosynthesis.

BACKGROUND: In general, the diagnosis of pedicle screw (PS) loosening is evaluated qualitatively based on the presence of a radiolucent area around the implant wider than 1 mm on plain radiographs and computed tomography (CT). Digital tomosynthesis is a novel imaging technology that can acquire reconstructed tomographic images of patients in different postures with relatively low radiation. In this study, PS loosening is evaluated quantitatively by measuring the PS displacement angle in the vertebrae using digital tomosynthesis. METHODS: We evaluated 41 patients who underwent posterior spinal fusion surgery using PS. The 72 pedicle screws at the cranial end of the fused segments were evaluated. The patients were divided in two groups, one with PS loosening (7 patients, 12 screws) and the other without PS loosening (34 patients, 60 screws), based on conventional CT findings. All patients underwent tomosynthesis in two different postures during a single CT session. RESULTS: The displacement angles of the PS in patients in a lying position and in a standing position were measured using selected slices of the same cross-sectional view from digital tomosynthesis. The displacement angle was significantly greater in the PS loosening group (5.7°) than in the group without PS loosening (0.6°) (p<0.01). Based on the ROC analysis, the optimal cut-off value of the PS displacement angle for identification of loosened screws was 1.7° with a sensitivity of 100% and specificity of 93% (AUC = 0.98). CONCLUSIONS: This new method using digital tomosynthesis has the potential to aid diagnosis of PS loosening quantitatively and more accurately than conventional evaluations.

Preoperative Evaluation and Surgical Simulation for Osteochondritis Dissecans of the Elbow Using Three-Dimensional MRI-CT Image Fusion Images.

We used our novel three-dimensional magnetic resonance imaging-computed tomography fusion images (3D MRI-CT fusion images; MCFIs) for detailed preoperative lesion evaluation and surgical simulation in osteochondritis dissecans (OCD) of the elbow. Herein, we introduce our procedure and report the findings of the assessment of its utility. We enrolled 16 men (mean age: 14.0 years) and performed preoperative MRI using 7 kg axial traction with a 3-Tesla imager and CT. Three-dimensional-MRI models of the humerus and articular cartilage and a 3D-CT model of the humerus were constructed. We created MCFIs using both models. We validated the findings obtained from the MCFIs and intraoperative findings using the following items: articular cartilage fissures and defects, articular surface deformities, vertical and horizontal lesion diameters, the International Cartilage Repair Society (ICRS) classification, and surgical procedures. The MCFIs accurately reproduced the lesions and correctly matched the ICRS classification in 93.5% of cases. Surgery was performed as simulated in all cases. Preoperatively measured lesion diameters exhibited no significant differences compared to the intraoperative measurements. MCFIs were useful in the evaluation of OCD lesions and detailed preoperative surgical simulation through accurate reproduction of 3D structural details of the lesions.

Novel method for selecting slices of the same cross-sectional view from digital tomosynthesis for monitoring posterior spinal instrumentation.

BACKGROUND: A method to evaluate pedicle screw loosening on digital tomosynthesis images is yet to be established owing to lack of methods for selecting slices of the same cross-sectional view. We aimed to develop an objective method for selecting slices of the same cross-sectional view on digital tomosynthesis images. METHODS: First, an objective method of pixel selection was developed by measuring the size of glass disk and titanium alloy screw on digital tomosynthesis images followed by comparison with the actual sizes. Second, a method for selecting slices of the same cross-sectional view was explored on a bone model with posterior spinal instrumentation using the screw centerline and rod curvature as indicators of the same cross section. The angle between the screw centerline and rod was calculated to verify the accuracy in obtaining the same cross-sectional view. Third, the method for selecting slices of the same cross-sectional view was applied to six patients after posterior lumbar spinal instrumentation. RESULTS: The pixel selection method enabled objective determination of a pixel on the peripheral lines of objects with an error as low as 200 µm in distance measurements on titanium alloy and glass. The mean differences of rod-screw angles between two slices were less than 1° and were not statistically significant in the bone model and patient images. CONCLUSION: A method for selecting slices of the same cross-sectional view on digital tomosynthesis images was successfully developed. This method can enable objective and quantitative evaluations of pedicle screw loosening.

A novel three-dimensional MRI-CT image fusion technique for precise preoperative evaluation and treatment of capitellar osteochondritis dissecans.

OBJECTIVES: We developed a novel method to create three-dimensional magnetic resonance imaging-CT (3D MRI-CT) fusion images for detailed lesion evaluation and surgical simulation in capitellar osteochondritis dissecans (COCD). This study aimed to clarify its usefulness. METHODS: We enrolled 12 boys with COCD (mean age, 13.8 years) and preoperatively constructed 3D models of the humerus and articular cartilage from MR images obtained with a 3-T imager. For better visualization of the articular cartilage outline, we applied 7 kg of axial traction to the elbow during MRI. We also constructed a 3D model of the humerus from CT images. 3D MRI-CT fusion images were created using both models. The average distance difference between two corresponding points as per the 3D CT and 3D MRI models of the humerus was evaluated. Using the 3D MRI-CT fusion images, we measured longitudinal and transverse lesion diameters; evaluated articular cartilage fissures and defects, articular surface deformities, and the International Cartilage Repair Society (ICRS) classification; and validated the results using intraoperative findings. RESULTS: The mean average distance difference was 0.75 mm. The 3D MRI-CT fusion images accurately reproduced lesion conditions in every case and correctly predicted the ICRS classification with 100% accuracy. Preoperatively measured longitudinal and transverse lesion diameters were not significantly different from intraoperative measurements (p = 0.79, 0.32 respectively). CONCLUSION: 3D MRI-CT fusion images provide a detailed evaluation of COCD lesion severity by presenting the exact positional relationship between the articular cartilage and subchondral bone. KEY POINTS: • We developed a novel method to create three-dimensional magnetic resonance imaging-computed tomography (3D MRI-CT) fusion images for the evaluation of capitellar osteochondritis dissecans. • 3D MRI-CT fusion images enabled the accurate prediction of lesions and provided a detailed evaluation of lesion severity by presenting the exact positional relationship between the articular cartilage and subchondral bone.

C5 pure motor spinal cord injury: A case with a rare manifestation of cervical spinal cord injury.

We report an extremely rare case showing a fifth cervical spine (C5) level pure motor cervical spinal cord injury (SCI). A 55-year-old-man lost consciousness and fell into a bathtub. Immediately after regaining consciousness, the patient had right arm drop alone. He was referred to our department for investigation of right arm drop 4 months later. Neurological examination revealed motor weakness of the right deltoid muscle. MRI of the cervical spine revealed a C3-4 level central disc herniation compressing the spinal cord. An electromyogram study revealed bilateral neurogenic discharges in the deltoid, supraspinatus and infraspinatus muscles. We diagnosed a C5 segmental pure motor SCI. We chose conservative therapy for the present patient. At the latest follow-up visit, the patient showed modest recovery of motor weakness. Although it is unusual, this case illustrates the possibility that C5 segmental pure motor palsy can occur as one of the manifestations of cervical SCI.

Intraoperative Local Administration of Platelet-Rich Plasma (PRP) during Neurolysis Surgery for the Treatment of Digital Nerve Crush Injury.

The digital nerves are important for normal hand function. In addition to conventional therapies such as neurolysis, direct repair, and auto/allografts, new treatments administering growth factors and cells for promoting nerve regeneration exist. Platelet-rich plasma (PRP), an autologous product with proven therapeutic effects for musculoskeletal disorders, is a new treatment option for peripheral nerve injury. We hypothesized that PRP could stimulate healing of digital nerve injuries. In the current case report, intraoperative local administration of PRP was performed during neurolysis surgery for a healthy 28-year-old woman with digital nerve crush injury. Five weeks postinjury, surgery was performed due to severe uncontrollable neuropathic pain and no sensory nerve action potential derivation of the index finger. Therapeutic effects were assessed by physical examination, visual analog scale for pain, and nerve conduction study. Postoperatively, early neuropathic pain relief and good functional recovery were obtained with no PRP-related adverse events. This case report demonstrates the therapeutic potential of intraoperative PRP to enhance the healing process of nerve crush injury in the acute phase and to decrease the neuropathic pain, thus enhancing healing of peripheral nerve crush injury.

Disruption of Flexor Tendon after Intrasheath Triamcinolone Acetonide Injection for Trigger Digits: Two Case Reports.

We experienced two cases of flexor tendons rupture after triamcinolone acetate (TA) injection for trigger finger. A 45-year-old man underwent injection of 40 mg of TA and 1 mL of 1% lidocaine solution into his little finger. While playing golf 3 months after the injection, he heard a popping sound, and was unable to flex it. A 57-year-old female nurse had undergone injection of 40 mg of TA and 1 mL of 1% lidocaine solution into her thumb twice at a 2-month interval. Two months after the second injection, she was unable to flex it. Both cases had high concentrated TA injection at trigger digits. The present and previous cases illustrate that when TA is injected into trigger digits, the dose should be low, the safety interval should be long, and refuse injection into the tendon proper.

Anatomical Variations of the Extensor Carpi Ulnaris Groove: A New Computed Tomography-based Evaluation.

BACKGROUND: This study aimed to develop a classification that precisely describes the extensor carpi ulnaris (ECU) groove morphology. METHODS: Reconstructed axial plane computed tomography scans of the wrists of 200 patients were reviewed. Three groups of groove shape were created based on the position of the deepest point: deviated to the ulnar side (Type U), in the middle of the groove (Type M), and deviated to the radial side (Type R). Groove depth, width, carrying angle, and radius of the curvature were measured using the Picture Archiving and Communication System in a slice in which the ulnar head was the largest. RESULTS: Type U was present in 88 patients (44%), Type M in 74 patients (37%), and Type R in 38 patients (19%). The average depth, width, carrying angle, and radius of curvature were 2.2 mm, 9.2 mm, 135.8° and 7.0 mm, respectively. Depth, width, and carrying angle were normally distributed. Both depth and width were statistically correlated with the carrying angle; groove depth and width were not correlated. ECU groove shape and depth showed excellent intra- and inter-observer reliabilities; the reliabilities for the width were poor. Therefore, depth subgroups were defined using cutoffs of ±2 standard deviations (SD): d1 (≤-2 SD), ≤1.0 mm; d2 (±SD), 1.1-3.3 mm; and d3 (≥+2 SD), ≥3.4 mm. The 200 wrists were classified as follows: 0.5% Ud1, 40.2% Ud2, 1.3% Ud3, 0.8% Md1, 38.3% Md2, 0.8% Md3, 1.5% Rd1, 16.4% Rd2, and 0.2% Rd3. CONCLUSIONS: The detailed morphology of the ECU groove was classified using three major types and depth subgroups. The Type R ECU groove, which lacks a medial bony buttress, might be more prone to ECU-related injuries. This classification helps to understand the ECU tendon-related injury pathologies and may provide valuable information for treatment decisions; however, further research is necessary.

Lipofibromatous Hamartoma of the Median and Ulnar Nerves at the Ipsilateral Wrist.

Lipofibromatous hamartoma (LFH) is a rare condition of the peripheral nerves that typically affects the median nerve. To the best of our knowledge, this is the first report of LFH of both, the median and ulnar nerves, at the wrist of a 63-year-old female patient. The patient presented to our hospital with a 40-year history of pain, numbness, and dysesthesia affecting all fingers of her left hand. Atrophy of the thenar muscles and the first dorsal interosseous was observed upon physical examination. Imaging studies and a surgery revealed that the patient's median and ulnar nerves were significantly enlarged, confirming the LFH diagnosis. The patient's dysesthesia and numbness improved after Carpal tunnel and Guyon canal release, and her pinch ability improved after opponensplasty. LFH has been known to be solitary, typically affecting median nerve, but it must be noted that the tumor may affect multiple nerves like in our case.

Fabella Syndrome as an Uncommon Cause of Posterolateral Knee Pain after Total Knee Arthroplasty: A Case Report and Review of the Literature.

The fabella is a sesamoid bone that is located in the lateral head of the gastrocnemius muscle and has been identified on magnetic resonance imaging in 31% of Japanese people. In the present case, a 65-year-old woman experienced posterolateral knee pain, accompanied by a clicking "sound" during active knee flexion, after undergoing total knee arthroplasty for knee osteoarthritis. Eight months of conservative therapy failed to produce an improvement, with progressive osteoarthritic change of the fabella identified on plain radiography. Based on this evidence, a diagnosis of fabella syndrome was made and the patient underwent a fabellectomy. Fabellectomy provided immediate resolution of posterolateral knee pain and the clicking sound with knee flexion, with the patient remaining symptom-free 18 months after fabellectomy and with no limitations in knee function. Fabellectomy eliminated symptoms in all of five case reports that have been previously published and is regarded as an effective first choice for treating fabella syndrome after total knee arthroplasty.