Surgeon Performance as a Predictor for Patient-Reported Outcomes After Arthroscopic Partial Meniscectomy.

Background: Surgeon performance has been investigated as a factor affecting patient outcomes after orthopaedic procedures to improve transparency between patients and providers. Purpose/Hypothesis: The purpose of this study was to identify whether surgeon performance influenced patient-reported outcomes (PROMs) 1 year after arthroscopic partial meniscectomy (APM). It was hypothesized that there would be no significant difference in PROMs between patients who underwent APM from various surgeons. Study Design: Case-control study; Level of evidence, 3. Methods: A prospective cohort of 794 patients who underwent APM between 2018 and 2019 were included in the analysis. A total of 34 surgeons from a large multicenter health care center were included. Three multivariable models were built to determine whether the surgeon-among demographic and meniscal pathology factors-was a significant variable for predicting the Knee injury and Osteoarthritis Outcome Score (KOOS)-Pain subscale, the Patient Acceptable Symptom State (PASS), and a 10-point improvement in the KOOS-Pain at 1 year after APM. Likelihood ratio (LR) tests were used to determine the significance of the surgeon variable in the models. Results: The 794 patients were identified from the multicenter hospital system. The baseline KOOS-Pain score was a significant predictor of outcome in the 1-year KOOS-Pain model (odds ratio [OR], 2.1 [95% CI, 1.77-2.48]; P < .001), the KOOS-Pain 10-point improvement model (OR, 0.57 [95% CI, 0.44-0.73), and the 1-year PASS model (OR, 1.42 [95% CI, 1.15-1.76]; P = .002) among articular cartilage pathology (bipolar medial cartilage) and patient-factor variables, including body mass index, Veterans RAND 12-Item Health Survey-Mental Component Score, and Area Deprivation Index. The individual surgeon significantly impacted outcomes in the 1-year KOOS-Pain mixed model in the LR test (P = .004). Conclusion: Patient factors and characteristics are better predictors for patient outcomes 1 year after APM than surgeon characteristics, specifically baseline KOOS-Pain, although an individual surgeon influenced the 1-Year KOOS-Pain mixed model in the LR test. This finding has key clinical implications; surgeons who wish to improve patient outcomes after APM should focus on improving patient selection rather than improving the surgical technique. Future research is needed to determine whether surgeon variability has an impact on longer-term patient outcomes.

Evaluation of Health Care Disparities in Patients With Anterior Cruciate Ligament Injury: Does Race and Insurance Matter?

Background: It is unknown whether race- or insurance-based disparities in health care exist regarding baseline knee pain, knee function, complete meniscal tear, or articular cartilage damage in patients who undergo anterior cruciate ligament reconstruction (ACLR). Hypothesis: Black patients and patients with Medicaid evaluated for ACLR would have worse baseline knee pain, worse knee function, and greater odds of having a complete meniscal tear. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A cohort of patients (N = 1463; 81% White, 14% Black, 5% Other race; median age, 22 years) who underwent ACLR between February 2015 and December 2018 was selected from an institutional database. Patients who underwent concomitant procedures and patients of undisclosed race or self-pay status were excluded. The associations of race with preoperative Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale, KOOS Function subscale, and intraoperatively assessed complete meniscal tear (tear that extended through both the superior and the inferior meniscal surfaces) were determined via multivariate modeling with adjustment for age, sex, insurance status, years of education, smoking status, body mass index (BMI), meniscal tear location, and Veterans RAND 12-Item Health Survey Mental Component Score (VR-12 MCS). Results: The 3 factors most strongly associated with worse KOOS Pain and KOOS Function were lower VR-12 MCS score, increased BMI, and increased age. Except for age, the other two factors had an unequal distribution between Black and White patients. Univariate analysis demonstrated equal baseline median KOOS Pain scores (Black, 72.2; White, 72.2) and KOOS Function scores (Black, 68.2; White, 68.2). After adjusting for confounding variables, there was no significant difference between Black and White patients in KOOS Pain, KOOS Function, or complete meniscal tears. Insurance status was not a significant predictor of KOOS Pain, KOOS Function, or complete meniscal tear. Conclusion: There were clinically significant differences between Black and White patients evaluated for ACLR. After accounting for confounding factors, no difference was observed between Black and White patients in knee pain, knee function, or complete meniscal tear. Insurance was not a clinically significant predictor of knee pain, knee function, or complete meniscal tear.

Failure Rate and Clinical Outcomes of Anterior Cruciate Ligament Reconstruction Using Autograft Hamstring Versus a Hybrid Graft.

PURPOSE: To compare the revision rate and subjective outcome measures of autograft hamstring versus a soft tissue hybrid graft combining both autograft hamstring and tibialis allograft for isolated anterior cruciate ligament (ACL) reconstruction. METHODS: A single-center retrospective, nonrandomized, comparative study of isolated ACL reconstruction revision rates for subjects who underwent arthroscopic reconstruction of the ACL using autograft hamstring or a soft tissue hybrid graft using both autograft hamstring and tibialis allograft was performed. Patients with isolated ACL tears were included and underwent anatomic single-bundle reconstruction using an independent tunnel drilling technique and a minimum of 24 months' follow-up. The primary outcome assessed was the presence or absence of ACL rerupture. Secondary clinical outcomes consisted of the International Knee Documentation Committee, University of California at Los Angeles (UCLA) ACL quality of life assessment, and the visual analog pain scale. RESULTS: Between February 2010 and April 2013, 95 patients with isolated ACL tears between ages 18 and 40 met the inclusion criteria and were enrolled. Seventy-one autograft hamstring and 24 soft tissue hybrid graft ACL reconstructions were performed during the course of this study. The follow-up period was 24 to 32 months (mean 26.9 months). There were no statistically significant differences in patient demographics or Outerbridge classification. No statistically significant differences in ACL retears (5.6% auto, 4.2% hybrid; P = .57) were found between groups. Clinical International Knee Documentation Committee and UCLA ACL quality of life assessment improvement scores revealed no statistically significant differences in autograft and hybrid graft reconstructions (41 ± 11, 43 ± 13; P = .65) (38 ± 11, 40 ± 10; P = .23). The mean pain level decreased from 8.1 to 2.8 in the autograft group and 7.9 to 2.5 in the hybrid group (P = .18). CONCLUSIONS: The use of a hybrid soft tissue graft has a comparable rerupture rate and clinical outcome to ACL reconstruction using autograft hamstring. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Hybrid Graft Anterior Cruciate Ligament Reconstruction: A Predictable Graft for Knee Stabilization.

Trauma to the anterior cruciate ligament (ACL) is a season-ending injury and involves months of activity modification and rehabilitation. The annual incidence of ACL tears in the United States is approximately 200,000, which allows for a broad range of individualized treatment options. Various surgical techniques, including transtibial and independent tunnel drilling, allograft and autograft tissue, and various implants, have been described in the literature. This article describes the indications and technique for a hybrid soft tissue graft for ACL reconstruction. Autologous grafts eliminate the risk of disease transmission and have recently been shown to have a lower rerupture rate, particularly in younger, active patients; however, the harvesting of autologous hamstring grafts carries a risk of donor-site morbidity, iatrogenic injury of the graft, and inadequate graft size. In contrast to a traditional autologous soft tissue graft, the hybrid graft allows for graft size customization for a desired reconstruction, especially in cases where autograft hamstrings may be iatrogenically damaged or of inadequate size when harvested. The goal of a hybrid graft ACL reconstruction is to provide a favorable-sized graft with clinical outcomes comparable with autologous soft tissue grafts. In contrast to a traditional autologous soft tissue graft, this technique provides another option in the event of unforeseen deficiencies or complications associated with harvesting and preparation of the autologous gracilis and semitendinosis soft tissue graft.

Biomechanical analysis of posterior cruciate ligament reconstruction with aperture femoral fixation.

The goal of this study was to determine whether single-tunnel-double-bundle-equivalent posterior cruciate ligament (PCL) reconstruction using an aperture femoral fixation device better replicated normal knee kinematics than single-bundle reconstruction. Eight fresh-frozen human cadaver knees underwent arthroscopically assisted PCL reconstruction and were examined with a robotic testing system to assess knee joint kinematics under combinations of applied internal, neutral, and external rotational tibial torque and anteroposterior translational forces at 0°, 30°, 60°, 90°, and 120° flexion. Three conditions were tested: (1) intact PCL; (2) single-tunnel PCL reconstruction with anterolateral and posteromedial bundle fixation at 90°/90° (single bundle); and (3) 90°/0° (double-bundle equivalent), respectively. Posterior tibial translation was the primary outcome measure. Compared with the intact knee, double-bundle-equivalent reconstruction under external tibial torque allowed greater posterior translation across the flexion arc as a whole (P=.025) and at 30° flexion (P=.027) when results were stratified by flexion angle. No other kinematic differences were found with single-bundle or double-bundle-equivalent fixation, including mediolateral translation and both coupled and isolated tibial rotation (P>.05). Single-bundle PCL reconstruction closely approximated native knee rotational and translational kinematics, whereas double-bundle-equivalent reconstruction permitted increased posterior translation with applied external tibial torque, particularly at lower flexion angles. Single-bundle PCL reconstruction provides knee stability similar to the intact condition, making it a practical alternative to conventional double-bundle PCL reconstruction. The authors found that double-bundle-equivalent reconstruction provided no advantage to justify its clinical use.

Mouse growth and differentiation factor-5 protein and DNA therapy potentiates intervertebral disc cell aggregation and chondrogenic gene expression.

BACKGROUND CONTEXT: Growth and differentiation factor-5 (GDF-5)-deficient mice showed abnormalities in intervertebral disc (IVD) structure and extracellular matrix. Adenovirus-mediated GDF-5 delivery can promote the growth of rabbit disc cells. PURPOSE: The aim of the present study was to investigate the effect of recombinant GDF-5 protein and GDF-5 complementary DNA (cDNA) on the metabolism of IVD cells. STUDY DESIGN: The effects of recombinant GDF-5 protein and GDF-5 cDNA on mouse IVD cells will be evaluated in vitro. METHODS: Mouse disc cells in vitro were treated with recombinant GDF-5 protein. Mouse GDF-5 cDNA was cloned into an expression vector and was used to transfect mouse disc cells in vitro. Therapy with GDF-5 protein and cDNA was assessed by measuring cell proliferation, proteoglycan production, and extracellular matrix gene expression. RESULTS: Biochemical assays revealed an elevated sulfated glycosaminoglycan (GAG)/DNA ratio in mouse IVD cells that were cultured in the presence of various concentrations of mouse GDF-5(mGDF-5) protein. Real-time reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that treating the cells with GDF-5 protein increased the expression of the collagen Type II and aggrecan genes in a dose-dependent manner but decreased matrix metalloproteinase (MMP)-3 gene expression. Immunohistochemistry showed an increase in the aggregation of mouse IVD cells that were treated with mGDF-5 in culture compared with the control group. The mouse GDF-5 gene was successfully cloned into an expression plasmid vector, and GDF-5 protein production was confirmed by Western blot analysis. Type II collagen and aggrecan gene expression by the cells increased significantly in the cells that were transfected by nucleofection with the GDF-5 plasmid compared with cells that were transfected with a control plasmid. CONCLUSIONS: This is the first report of the cloning of the mouse GDF-5 gene and use of the nucleofection method to transfer DNA into IVD cells. The data suggest that both recombinant protein and the cDNA forms of GDF-5 can increase the expression of genes for extracellular matrix proteins in mouse IVD cells. Future attempts at gene therapy to treat degenerative disc disease with a novel ex vivo gene transfer technique are needed to develop a therapy that would alleviate the condition of patients with clinically relevant axial spine pain.

An adenosine A2A receptor agonist reduces interleukin-8 expression and glycosaminoglycan loss following septic arthrosis.

The purpose of this study was to determine whether an adenosine A(2A) receptor agonist (ATL146e) might augment the current treatment regimen of antibiotics plus irrigation and debridement to prevent the arthritic effects associated with joint sepsis. Staphylococcus aureus bacteria were injected into knees of rabbits, which were divided into 4 treatment groups (12 rabbits per group): no treatment, ATL146e only, antibiotics only, or antibiotics plus ATL146e. Analysis at days 1, 3, and 7 consisted of gross joint appearance, synovial fluid, serum, histologic, immunohistochemical, and biochemical analysis. Synovial fluid cultures at day 7 were negative in all antibiotic and antibiotic plus ATL146e treated knees indicating clearance of bacteria. Average WBC counts from synovial fluid aspirates significantly decreased with treatment of antibiotics alone and antibiotics plus ATL146e. Treatment with antibiotics plus ATL146e significantly decreased the Interleukin-8 content when compared to other treatment groups (p<0.001) indicating inflammatory response suppression. Histologic grading resulted in notably improved scores in the antibiotics plus ATL146e group compared to other treatment groups (p < or =0.001). Glycosaminoglycan assay values were significantly greater in the ATL146e plus antibiotics group compared to the untreated control group (p<0.04) indicating chondroprotection. The results of this study indicate that administration of an adenosine A(2A) agonist in combination with antibiotic therapy diminishes joint WBC chemotaxis and reduces joint inflammation, while not compromising the clearance of intraarticular bacteria in a rabbit model. Early bacterial clearance with modulation of the inflammatory response appears to prevent the early degradative effects of joint sepsis.

Collagen and proteoglycan abnormalities in the GDF-5-deficient mice and molecular changes when treating disk cells with recombinant growth factor.

STUDY DESIGN: A magnetic resonance image, histologic, biochemical, and gene expression study was conducted to characterize the effects of growth and development factor-5 (GDF-5) deficiency on the health of the intervertebral disc. OBJECTIVE: To determine the effect of GDF-5 deficiency on extracellular matrix and gene expression on the intervertebral disc. SUMMARY OF BACKGROUND DATA: Developmental and degenerative changes in intervertebral disc are not fully understood. Molecular abnormalities and spontaneous mutations that lead to the deficiency in a normal protein have been useful in understanding the function of certain molecules and the role they play in the structure and health of certain tissues. Although the role of GDF-5 in the disc has not been elucidated, this factor may have an important role in the disc as a result of the well-documented effect of GDF-5 in other chondrogenic tissues. METHODS.: Intervertebral discs of 20-week-old GDF-5 (-/-) and (+/+) mice were examined radiographically, histologically, biochemically, and with gene expression studies. Cells isolated from GDF-5-deficient mouse discs were treated with recombinant GDF-5 and gene expression was subsequently analyzed. RESULTS: GDF-5 (-/-) mice demonstrated significantly lower T2-weighted signal intensity in the central region of their lumbar discs, and disc histology revealed loss of the normal lamellar architecture of the anulus fibrosus and a shrunken, disorganized nucleus pulposus. Biochemical analysis revealed decreased proteoglycan content but no appreciable change in total collagen content of the discs. Significant downregulation of both aggrecan and type II collagen mRNA, without an appreciable change in type I collagen expression, was noted on gene expression studies. Recombinant GDF-5 treatment of disc cells from the GDF-5-deficient mice resulted in a dose-dependent upregulation of the aggrecan and type II collagen genes. CONCLUSION: The intervertebral disc is markedly affected by GDF-5 deficiency. This relatively simple (single gene) system with a known molecular defect may be useful in studies designed to define the response of the intervertebral disc to treatment with growth factor in vivo.

Split-line pattern and histologic analysis of a human osteochondral plug graft.

The split-line pattern of collagen fibers in articular cartilage is oriented according to weight-bearing stresses. The importance of aligning the split-line pattern of articular cartilage in human osteochondral plug grafts relative to the surrounding cartilage has been proposed but not evaluated clinically. The purpose of this case report is to compare the articular split-line pattern with the histologic analysis of a specimen obtained from a patient who underwent an osteochondral plug transfer procedure with subsequent conversion to joint arthroplasty. The fresh osteochondral section obtained at total knee arthroplasty, including the area treated 18 months earlier with an osteochondral plug transfer, was fixed in formalin. Split-lines were demonstrated on the surface using a needle dipped in India ink. After decalcification and paraffin embedding, the specimen was sectioned and stained with Safranin O and fast green for histologic analysis. The split-line pattern of the anterior portion of the graft was oriented parallel to the resident cartilage; however, collagen orientation was divergent (approximately 30 degrees oblique) to the surrounding cartilage near the posterior portion of the graft. It was at this margin that further resident articular degeneration was noted despite the plug articular surface remaining relatively intact. Although bony incorporation of the plug occurred, there was a residual chondral cleft at the graft-host interface. Our report suggests that an osteochondral plug transfer can survive despite a slightly divergent collagen split-line pattern of plug relative to the resident articular bed. Perhaps more important to the clinical outcome is the selection of true focal, traumatic lesions rather than lesions degenerative in etiology, no matter how focal they appear.

In vivo bioluminescent imaging of virus-mediated gene transfer and transduced cell transplantation in the intervertebral disc.

STUDY DESIGN: Work presented here used a small animal model to demonstrate the feasibility and usefulness of in vivo bioluminescent imaging to studying degenerative disc disease. OBJECTIVES: To determine the utility of in vivo bioluminescent imaging to monitor the temporal and spatial expression of genetically modified cells within the intervertebral disc of a rodent model. SUMMARY OF THE BACKGROUND DATA: Noninvasive imaging of genetically engineered cells in the spine has the advantage of allowing events to be tracked without killing the animal and can be used to follow the time course of a particular therapy. Results are presented on the use of Sprague-Dawley rats in experimental studies in which the luciferase reporter gene was delivered to the lumbar intervertebral disc through adenovirus-mediated or cell-based transfer techniques to demonstrate the feasibility to monitor gene expression noninvasively over time. METHODS: Tissue culture, disc surgery, and in vivo bioluminescent imaging were used. The intervertebral disc of the rat was either injected in situ with an adenovirus containing the luciferase reporter gene or implanted with fat, bone marrow or intervertebral disc cells transduced ex vivo and contained in a bioresorbable carrier. Results were assessed with in vivo bioluminescent imaging at several time points. CONCLUSION: Data from 11 animals were obtained with imaging up to 14 days. To our knowledge, this is the first description of in vivo bioluminescence imaging to study spinal conditions. We have characterized the relative expression of three cell types transduced with the Ad-luc virus by ex vivo transfection followed by cell implantation in the rat spine and compared them to one another and to direct infection of Ad-luc adenovirus in situ. Our results demonstrate the feasibility of tracing genetically altered cells in the spine. This technique has the potential to be used to noninvasively track the fate and expression of therapeutic genes within the spine of small animals used in disc research.

Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist.

We assessed the efficacy of a new adenosine A2A agonist ATL146e, a potent inhibitor of white blood cell chemotaxis, to reduce cartilage damage in the treatment of septic arthrosis. A live septic arthrosis model was created using Staphylococcus aureus in rabbit knees. Animals were divided into five treatment groups: (1) untreated infected control, (2) antibiotics control, and antibiotics plus ATL146e for (3) 24, (4) 48, or (5) 72 h and assessed at 1, 4, and 7 days. Knees in all ATL146e treated animals exhibited no detectable effusion, and histologic examination revealed near normal cartilage and diminished synovial inflammatory response. Synovial WBC counts decreased with the addition of ATL146e when compared to infected and antibiotic controls. Histologic grading of osteochondral specimens demonstrated improved scores for animals treated with ATL146e compared to infected (p<0.00004) and antibiotics controls (p<0.05). Analysis of glycosaminoglycan content revealed significantly decreased loss of articular cartilage following infection in the ATL146e groups when compared to infected (p<0.03) and antibiotics controls (p<0.05). Addition of an adenosine A2A agonist to antibiotic therapy decreases joint inflammation and articular cartilage destruction without compromising bacterial clearance in rabbit knees following intraarticular bacterial infection. The use of adenosine agonists selective to the A2A receptor to augment conventional treatment of joint sepsis may be chondroprotective and ultimately help prevent arthrosis.