A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis.

OBJECTIVE: To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. METHODS: Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). RESULTS: BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. CONCLUSIONS: To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

High Incidence of Intra-articular Injuries With Segond Fractures of the Tibia in the Pediatric and Adolescent Population.

BACKGROUND: Segond fractures (avulsion fractures of the proximal lateral tibia) are highly associated with anterior cruciate ligament (ACL) tears in adult patients. This large case series of pediatric Segond fractures describes the associated intra-articular knee injuries to determine if these fractures have a high incidence of ACL tears or its equivalent injury in young patients. METHODS: Institutional review board approved retrospective study at a tertiary children's hospital of patients under 19 years who were diagnosed with a Segond fracture between 2009 and 2019 was conducted. Demographics, clinical data, imaging features, associated injuries, and treatment information were collected. RESULTS: Fifty-three patients (44 males and 9 females) with median age 15.4 (11.8 to 19) years with Segond fractures of the proximal tibia on radiographic imaging were included. Diagnosis of associated injuries was established based on clinical examination, radiology report, and arthroscopic findings. Median Segond fracture size was 2.0×9.0 mm measured on standard anteroposterior knee radiographs. Magnetic resonance imaging (MRI) was obtained in 49/53 (92.5%) patients. Associated injuries included ACL tears (39 patients, 73.6%), tibial spine fractures (9, 17.0%), and other injuries (5, 9.4%). 37/53 (69.8%) patients had meniscal injury. Three (5.7%) patients sustained multiligament injuries. All associated injuries were confirmed by either MRI/computerized tomography or direct operative examination. Among Segond fractures found with ACL tears, 12 (30.8%) were contact injuries, 30 (76.9%) were sports injuries. In associated tibial spine fractures, 7 (78%) injuries were contact in nature and were sports related. There was a statistically significant difference (P=0.013) in age, patients with tibial spine fractures (median 13.6 y) being younger than those with ACL tears (median 15.4 y). 12/53 (22.6%) had associated articular cartilaginous injuries, 3 of which were treated surgically. Overall, 81.1% of patients were treated operatively for associated intra-articular injuries. CONCLUSIONS: This large case series of Pediatric Segond fractures suggests a high association with intra-articular injuries, specifically, ACL tears and its equivalent injury, that is, tibial spine fractures, the later more common in the younger patient population. An MRI is recommended in patients with a Segond fracture for characterizing the exact intra-articular injury to help plan the appropriate management. LEVEL OF EVIDENCE: Level IV-prognostic.

Chemoprotection with botulinum toxin following proximal hamstring-Ischial tuberosity avulsion fracture repair: Running title: Chemoprotection for hamstring avulsion fractures.

INTRODUCTION: Surgical treatment for avulsion injuries of the proximal hamstrings has gained increasing popularity over the past decade. Despite good outcomes, early failures have been noted and have been attributed to slipping and falling, postoperative muscle spasm, or early mobilization. In a recent review of hamstring repair rehabilitation protocols, it was shown that there is marked variability in post-operative management. Post-operative bracing with limiting knee extension and hip flexion is the standard of care in most early rehabilitation protocols. Braces with limitation of hip flexion and knee locked in 900 flexion can be awkward, cumbersome and create fall risk.Chemoprotection has more recently been proposed to be an alternative approach to prevent tendon repair failure and controlled mobilization which has been shown to be superior to complete immobilization. We present the first case series of the use of botulinum toxin for chemo-protection of the proximal hamstring ischial avulsion repair, demonstrating its safety and efficacy. METHODS: Retrospective case series at a tertiary children's hospital which included patients <18 years of age who underwent interventional treatment for proximal hamstring avulsion injuries of the ischium utilizing botulinum toxin as a chemoprotective agent. Data collected included demographic data, injury and treatment details, imaging, post-operative rehabilitation and return to activity. Descriptive statistical analysis was conducted. RESULTS: Five male patients with mean age 14 years (12-17) were included in the study. All were sports related non-contact injuries. Radiographs showed displaced avulsion fractures in all 5 patients. All patients had failed conservative management initially; mean time to surgery from initial injury was 34.4 weeks. 4 patients underwent open reduction and internal fixation (ORIF), 1 patient with less displacement had bone marrow aspirate (BMA) injection; all had chemoprotection using botulinum toxin injected in the hamstrings. No patient required hip immobilization or knee immobilization locked to 90°. We elected to use a brace locked at 20° knee flexion in 2/5 patients. All patients underwent supervised physical therapy and achieved symmetric knee range of motion (ROM). Post-operative radiographs confirmed healing of the avulsion fracture in all 5 patients and they all returned to previous level of activity at mean 32 weeks (21-43) from surgery. None of the patients had a hamstring re-injury at mean follow up of 27 months (11-42). CONCLUSION: Our case series is the first in literature that shows the safety and efficacy of chemoprotection with botulinum toxin for the post-operative management of avulsion injuries of proximal hamstrings, by minimizing the need for cumbersome bracing and allowing controlled motion during physical therapy.