Accurate prediction of lumbar microdecompression level with an automated MRI grading system.

OBJECTIVE: Lumbar spine MRI interpretations have high variability reducing utility for surgical planning. This study evaluated a convolutional neural network (CNN) framework that generates automated MRI grading for its ability to predict the level that was surgically decompressed. MATERIALS AND METHODS: Patients who had single-level decompression were retrospectively evaluated. Sagittal T2 images were processed by a CNN (SpineNet), which provided grading for the following: central canal stenosis, disc narrowing, disc degeneration, spondylolisthesis, upper/lower endplate morphologic changes, and upper/lower marrow changes. The grades were used to calculate an aggregate score. The variables and the aggregate score were analyzed for their ability to predict the surgical level. For each surgical level subgroup, the surgical level aggregate scores were compared with the non-surgical levels. RESULTS: A total of 141 patients met the inclusion criteria (82 women, 59 men; mean age 64 years; age range 28-89 years). SpineNet did not identify central canal stenosis in 32 patients. Of the remaining 109, 96 (88%) patients had a decompression at the level of greatest stenosis. The higher stenotic grade was present only at the surgical level in 82/96 (85%) patients. The level with the highest aggregate score matched the surgical level in 103/141 (73%) patients and was unique to the surgical level in 91/103 (88%) patients. Overall, the highest aggregate score identified the surgical level in 91/141 (65%) patients. The aggregate MRI score mean was significantly higher for the L3-S1 surgical levels. CONCLUSION: A previously developed CNN framework accurately predicts the level of microdecompression for degenerative spinal stenosis in most patients.

Elution properties of a resorbable magnesium phosphate cement.

OBJECTIVE: This study tests the elution capabilities of a magnesium phosphate cement (MPC). Study objectives were to quantify the passive release of magnesium ions from MPC and to assess the effects of antibiotic-loaded MPC on bacterial growth and osteoblast viability. METHODS: MPC constructs were created and incubated in fetal bovine serum (FBS). At 2, 4, and 17 weeks, a sample was collected for magnesium ion concentration analysis. Control and vancomycin-loaded (vanc) MPC beads were also created. Zone of inhibition was measured after incubating beads on Staphylococcus aureus agar plates for 24 h. Osteoblasts were seeded onto control and vanc beads and cultured for 9 days. Metabolic activity was measured via a resazurin assay. ANOVA with Tukey HSD post-hoc tests and t-tests were performed. RESULTS: Magnesium ions were eluted at 2 and 4-week time points without significant difference, but demonstrated a significant spike at the 17-week time point. Zones of inhibition for the bacterial species was observed for Vanc-MPC beads, but not control beads. No cytotoxic effects on osteoblasts were noted. CONCLUSION: MPC has potential to improve bone regeneration based on its ability to passively elute magnesium. Additionally, antibiotic-loaded MPC inhibits bacterial growth while avoiding osteoblast cytotoxicity.

Use of a Novel Magnesium-Based Resorbable Bone Cement for Augmenting Anchor and Tendon Fixation.

The aim of this study was to assess the efficacy and safety of a novel magnesium-based resorbable bone cement (OsteoCrete, Bone Solutions Incorporated) for anchor and tendon fixation. Cadaveric humeral testing involved straight pull-to-failure of rotator cuff suture anchors; OsteoCrete was injected through one anchor, and a second anchor served as the uninjected control. Testing was conducted 15 minutes post-injection. A canine preclinical model was used to evaluate the safety of the following parameters: Rotator cuff repair: A double-row technique was used to repair transected infraspinatus tendons; OsteoCrete was injected through both anchors in one limb, and the contralateral limb served as the uninjected control. Biceps tenodesis: The transected biceps tendon was implanted into a proximal humeral socket with a transcortical button; OsteoCrete was injected into the socket of one limb, and a screw was used for final fixation in the contralateral control limb. Nondestructive biomechanical testing and histologic assessment were performed after 12 weeks. OsteoCrete-augmented anchors showed significantly higher load-to-failure compared to that with uninjected controls. In cadaveric humeri with reduced bone quality, OsteoCrete increased the mean load-to-failure by 99%. Within the preclinical model, there were no complications or statistically significant biomechanical/histologic differences between the techniques. OsteoCrete has the potential for safely providing improved suture anchor and tissue fixation in patients with poor bone or tissue quality.

Impact of Clinical Presentation on Imaging Evaluation to Direct Effective Treatment Strategies.

A multitude of musculoskeletal disorders of the knee are commonly encountered in clinical practice. Ensuring an accurate diagnosis can be challenging. It is critical to establish a thoughtful and systematic approach to assessing the patient using history and physical exam followed by appropriate imaging studies. The physical exam may be complicated due to various test maneuvers designed to help make the diagnosis. It is also important to understand the limitations of each physical exam maneuver. When appropriate, imaging is obtained to help make the diagnosis and guide treatment. There are various imaging examinations to choose from when evaluating the knee, including X-rays, computed tomography, magnetic resonance imaging, and ultrasound. An algorithmic approach to choosing the best imaging study is often helpful to avoid unnecessary costs and burden to the patients. The combination of a thorough clinical assessment and appropriate imaging examinations will result in accurate diagnosis, which directs proper treatment.

Meniscal biology in health and disease.

The knee is a fascinating yet complex joint. Researchers and clinicians agree that the joint is an organ comprised of highly specialized intrinsic and extrinsic tissues contributing to both health and disease. Key to the function and movement of the knee are the menisci, exquisite fibrocartilage structures that are critical structures for maintaining biological and biomechanical integrity of the joint. The biological/physiological functions of the menisci must be understood at the tissue, cellular and even molecular levels in order to determine clinically relevant methods for assessing it and influencing it. By investigating normal and pathological functions at the basic science level, we can begin to translate data to patients. The objective of this article is to provide an overview of this translational pathway so that progression toward improved diagnostic, preventative, and therapeutic strategies can be effectively pursued. We have thoroughly examined the pathobiological, biomarker, and imaging aspects of meniscus research. This translational approach can be effective toward optimal diagnosis, prevention, and treatment for the millions of patients who suffer from meniscal disorders each year.

BioCartilage Improves Cartilage Repair Compared With Microfracture Alone in an Equine Model of Full-Thickness Cartilage Loss.

BACKGROUND: Microfracture (MFx) remains a dominant treatment strategy for symptomatic articular cartilage defects. Biologic scaffold adjuncts, such as particulated allograft articular cartilage (BioCartilage) combined with platelet-rich plasma (PRP), offer promise in improving clinical outcomes as an adjunct to MFx. PURPOSE: To evaluate the safety, biocompatibility, and efficacy of BioCartilage and PRP for cartilage repair in a preclinical equine model of full-thickness articular cartilage loss. STUDY DESIGN: Controlled laboratory study. METHODS: Two 10-mm-diameter full-thickness cartilage defects were created in 5 horses in the trochlear ridge of both knees: one proximal (high load) and another distal (low load). Complete blood counts were performed on each peripheral blood and resultant PRP sample. In each horse, one knee received MFx with BioCartilage + PRP, and the other knee received MFx alone. Horses were euthanized at 13 months. Outcomes were assessed with serial arthroscopy, magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), and histology. Statistics were performed using a mixed-effects model with response variable contrasts. RESULTS: No complications occurred. PRP generated in all subjects yielded an increase in platelet fold of 3.8 ± 4.7. Leukocyte concentration decreased in PRP samples by an average fold change of 5 ± 0.1. The overall International Cartilage Repair Society repair score in both the proximal and distal defects was significantly higher (better) in the BioCartilage group compared with MFx (proximal BioCartilage: 7.4 ± 0.51, MFx 4.8 ± 0.1, P = .041; distal BioCartilage: 5.6 ± 0.98, MFx 2.6 ± 1.5, P = .022). BioCartilage-treated proximal defects demonstrated improved histologic scores for repair-host integration (BioCartilage, 96 ± 9; MFx, 68 ± 18; P = .02), base integration (BioCartilage, 100 ± 0; MFx, 70 ± 37; P = .04), and formation of collagen type II (BioCartilage, 82 ± 8; MFx, 58 ± 11; P = .05) compared with the positive control. On MRI, T2 relaxation time was significantly shorter (better) in the superficial region of BioCartilage-treated distal defects compared with MFx (P = .05). There were no significant differences between BioCartilage and MFx on micro-CT analysis. CONCLUSION: BioCartilage with PRP safely improved cartilage repair compared with MFx alone in an equine model of articular cartilage defects up to 13 months after implantation. CLINICAL RELEVANCE: The 1-year results of BioCartilage + PRP suggest that homologous allograft tissue provides a safe and effective augmentation of traditional MFx.

Identification of Novel Synovial Fluid Biomarkers Associated with Meniscal Pathology.

The menisci are integral components within the knee for ensuring optimal joint function. The overall goal of this study was to identify proteomic markers of meniscal disease within synovial fluid samples obtained from control knees versus knees affected with varying degrees of meniscal injury and osteoarthritis. Joint fluid samples were collected before the patient underwent an arthroscopic knee procedure or total knee arthroplasty. Normal controls included patients younger than 30 years with no history of anterior cruciate ligament, posterior cruciate ligament, or meniscal injury. A total of 21 joint fluid aspirates were analyzed using mass spectrometry, and a total of 296 proteins were identified. Among these, 50 proteins were determined to be of interest as potential biomarkers based on initial analysis and known functions in articular metabolism. Further statistical analysis comparing protein concentrations among clinical groups identified 13 proteins with significant differences between at least two of the patient cohorts. These data provide novel information for the investigation of synovial fluid biomarkers and treatment strategies for meniscal pathology.

Identification of Synovial Fluid Biomarkers for Knee Osteoarthritis and Correlation with Radiographic Assessment.

Osteoarthritis (OA) is a costly and debilitating condition that is typically not diagnosed early enough to prevent progression of disease. The purpose of this study was to evaluate synovial fluid from knees with and without OA for potential markers of joint inflammation and degradation and to correlate these findings with radiographic severity of disease. With Institutional Review Board approval, synovial fluid samples were collected before the patient undergoing total knee arthroplasty. Control knees (n = 3) were patients younger than 30 years of age with no history of anterior cruciate ligament, posterior cruciate ligament, or meniscal injury, and no surgical history for either knee. Weight-bearing, anterior-posterior radiographic views were used to determine radiographic OA severity using the modified Kellgren and Lawrence scale. Synovial fluid samples from 18 patients (21 knees) were analyzed using a multiplex assay. Matrix metalloproteinase (MMP)-1 (p < 0.001), interleukin (IL)-6 (p < 0.013), IL-8 (p < 0.024), and Chemokine (C-C motif) ligand 5 (CCL5) (p < 0.006) were significantly higher in the synovial fluid of OA patients compared with normal patients. The radiographic score was significantly higher in patients with OA compared with normal knees (p < 0.002). MMP-1 had a moderate positive correlation with MMP-2, IL-6, IL-8, and CCL5. IL-6 had a strong positive correlation with IL-8 and a moderate positive correlation with MMP-2. Monocyte chemotactic protein 1 had a moderate positive correlation with IL-6 and a strong positive correlation with IL-8. Radiographic scores had a strong positive correlation with IL-6 and IL-8 and a moderate positive correlation with MCP-1. These data provide novel and clinically relevant information for the investigation of synovial fluid biomarkers for knee OA.

Characterization of Meniscal Pathology Using Molecular and Proteomic Analyses.

The meniscus is a complex tissue and is integral to knee joint health and function. Although the meniscus has been studied for years, a relatively large amount of basic science data on meniscal health and disease are unavailable. Genomic and proteomic analyses of meniscal pathology could greatly improve our understanding of etiopathogenesis and the progression of meniscal disease, yet these analyses are lacking in the current literature. Therefore, the objective of this study was to use microarray and proteomic analyses to compare aged-normal and pathologic meniscal tissues. Meniscal tissue was collected from the knees of five patient groups (n = 3/group). Cohorts included patients undergoing meniscectomy with or without articular cartilage pathology, patients undergoing total knee arthroplasty with mild or moderate-severe osteoarthritis, and aged-normal controls from organ donors. Tissue sections were collected from the white/white and white/red zones of posterior medial menisci. Expression levels were compared between pathologic and control menisci to identify genes of interest (at least a ×1.5 fold change in expression levels between two or more groups) using microarray analysis. Proteomics analysis was performed using mass spectrometry to identify proteins of interest (those with possible trends identified between the aged-normal and pathologic groups). The microarray identified 157 genes of interest. Genes were categorized into the following subgroups: (1) synthesis, (2) vascularity, (3) degradation and antidegradation, and (4) signaling pathways. Mass spectrometry identified 173 proteins of interest. Proteins were further divided into the following categories: (1) extracellular matrix (ECM) proteins; (2) proteins associated with vascularity; (3) degradation and antidegradation proteins; (4) cytoskeleton proteins; (5) glycolysis pathway proteins; and (6) signaling proteins. These data provide novel molecular and biochemical information for the investigation of meniscal pathology. Further evaluation of these disease indicators will help researchers develop algorithms for diagnostic, therapeutic, and prognostic strategies related to meniscal disorders.

Characterization of knee meniscal pathology: correlation of gross, histologic, biochemical, molecular, and radiographic measures of disease.

Meniscal pathology is an extremely prevalent problem, which inevitably leads to osteoarthritis and associated pain, swelling, and disability. Relatively little data are available regarding the molecular, biochemical, and histologic aspects of meniscal disease. This study characterizes meniscal pathology in the presence of symptomatic osteoarthritis and correlates clinical and basic science data in an attempt to delineate clinically relevant mechanisms of disease. Twenty-seven knees from 23 patients who underwent total knee arthroplasty comprised the affected group and 6 aged nonsymptomatic knees were used as controls. All meniscal tissues were harvested and subjectively scored for gross and histologic pathology. Biochemical analyses were performed to determine glycosaminoglycan (GAG) content, collagen (hydroxyproline) content, and water content. Real-time polymerase chain reaction analysis was conducted for genes involved in synthesis (collagens [col] 1, 2, 3, and 6), degradation (matrix metalloproteinases [MMP-1, -2, -3, -13]), and angiogenesis (vascular endothelial growth factor). Weight-bearing, anterior-posterior radiographic views were used to determine joint space measurements for lateral and medial compartments, and were subjectively scored for osteoarthritic changes. Data were compared for statistically significant differences and to determine the presence and strength of correlations among variables assessed. Affected menisci had significantly higher gross and histologic pathology scores compared with control menisci. Affected menisci had significantly higher water, proteoglycan, and collagen content compared with control menisci. Col 1, 3, and 6 gene expression levels for the affected group were significantly increased compared with controls. MMP-13 expression was significantly increased for the affected group. MMP-2 and -3 expression levels were significantly lower in the affected group compared with controls. The affected group had significantly more joint space narrowing and higher radiographic scores for medial compared with lateral compartments. Several strong and moderately strong correlations were present between variables. These data suggest that in vitro measures of meniscal pathology have potential value for understanding disease mechanisms and predicting clinical disease.

MRI versus ultrasonography to assess meniscal abnormalities in acute knees.

While magnetic resonance imaging (MRI) is often considered the "gold standard" diagnostic imaging modality for detection of meniscal abnormalities, it is associated with misdiagnosis in as high as 47% of cases, is costly, and is not readily available to a large number of patients. Ultrasonographic examination of the knee has been reported to be an effective diagnostic tool for this purpose with the potential to overcome many of the shortcomings of MRI. The purpose of this study is to determine the clinical usefulness of ultrasonography for diagnosis of meniscal pathology in patients with acute knee pain and compare its diagnostic accuracy to MRI in a clinical setting. With Institutional Review Board approval, patients (n = 71) with acute knee pain were prospectively enrolled with informed consent. Preoperative MRI (1.5 T) was performed on each affected knee using the hospital's standard equipment and protocols and read by faculty radiologists trained in musculoskeletal MRI. Ultrasonographic assessments of each affected knee were performed by one of two faculty members trained in musculoskeletal ultrasonography using a 10 to 14 MHz linear transducer. Arthroscopic evaluation of affected knees was performed by one of three faculty orthopedic surgeons to assess and record all joint pathology, which served as the reference standard for determining presence, type, and severity of meniscal pathology. All evaluators for each diagnostic modality were blinded to all other data. Data were collected and compared by a separate investigator to determine sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), correct classification rate (CCR), likelihood ratios (LR[+] and LR[-]), and odds ratios. Preoperative ultrasonographic assessment of meniscal pathology was associated with Sn = 91.2%, Sp = 84.2%, PPV = 94.5%, NPV = 76.2%, CCR = 89.5%, LR(+) = 5.78, and LR(-) = 0.10. Preoperative MRI assessment of meniscal pathology was associated with Sn = 91.7%, Sp = 66.7%, PPV = 84.6%, NPV = 80.0%, CCR = 81.1%, LR(+) = 2.75, and LR(-) = 0.13. Ultrasonography was two times more likely than MRI to correctly determine presence or absence of meniscal pathology seen arthroscopically in this study. Ultrasonography is a useful tool for diagnosis of meniscal pathology with potential advantages over MRI. Based on these data and available portable equipment, ultrasonography could be considered for use as a point-of-injury diagnostic modality for meniscal injuries.