Association of Posterior Tibial Slope With Outcomes After Multiligamentous Knee Reconstruction for Knee Dislocation Grades 2 to 4.

Background: Patients with isolated anterior cruciate ligament (ACL) reconstruction have demonstrated an increased risk of ACL graft failure and lower patient-reported outcome (PRO) scores when increased posterior tibial slope (PTS) is present. However, there is a paucity of literature evaluating the effect of PTS on outcomes after combined bicruciate multiligamentous knee reconstruction. Purpose: To determine whether differences exist for graft failure rates or PRO scores based on PTS after combined bicruciate multiligamentous knee reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: All patients who underwent combined ACL and posterior cruciate ligament (PCL) reconstruction between 2000 and 2020 at our institution were identified. Exclusion criteria were age <18 years, knee dislocation grade 5 injuries, concomitant osteotomy procedures, and <2 years of clinical follow-up. Demographic and outcomes data were collected from our prospectively gathered multiligamentous knee injury database. Lysholm and International Knee Documentation Committee (IKDC) scores were analyzed in relation to PTS. Outcomes were compared for patients with a PTS above and below the mean for the total cohort, PTS >12° versus <12°, positive versus negative Lachman test at follow-up, and positive versus negative posterior drawer test at follow-up. Results: A total of 98 knees in 98 patients were included in the study, with a mean clinical follow-up of 5.1 years (median, 4.6 years; range, 2-16 years). The mean PTS was 8.7° (range, 0.4°-16.9°). Linear regression analysis showed no significant correlation between PTS and IKDC or Lysholm scores. Patients with a PTS above the mean of 8.7° trended toward lower IKDC (P = .08) and Lysholm (P = .06) scores. Four patients experienced ACL graft failure and 5 patients experienced PCL graft failure. There were no differences in graft failure rates or PRO scores for patients with a PTS >12°. Patients with a positive Lachman test trended toward higher PTS (9.6° vs 8.5°, P = .15). Conclusion: In this series of bicruciate multiligamentous knee reconstructions at midterm follow-up, no differences in graft failures, complications, reoperations, revisions, or PRO scores based on PTS were identified. Patients with a positive Lachman test were found to have a slightly higher PTS, although this did not reach statistical significance.

Outcomes of Lateral Meniscal Oblique Radial Tear Repair Compared With Intact Meniscus After ACL Reconstruction: A Cohort Study.

Background: Recently, the posterior horn lateral meniscal oblique radial tear (LMORT) was identified in 12% of acute anterior cruciate ligament (ACL) injuries. However, patient-reported outcomes for repair of this relatively common tear have not been reported. Purpose: To determine the minimum 2-year functional outcomes after LMORT repair at the time of ACL reconstruction (ACLR) compared to a matched cohort of patients who underwent isolated ACLR (iACLR). Study Design: Cohort study; Level of evidence, 3. Methods: Included were 100 patients (mean age at surgery, 21 years; range, 13-45 years) who underwent primary ACLR between 2010 and 2018. The mean follow-up period was 4.1 ± 2.0 years (range, 2.0-9.2 years). A total of 50 patients with surgically repaired LMORT type 3 or type 4 lesions, defined as partial or complete tears >10 mm from the root (LMORT group) were matched 1:1 based on age, date of surgery, and graft choice with 50 patients who underwent iACLR (iACLR group). The postoperative outcomes were compared between groups using the International Knee Documentation Committee subjective score (sIKDC) and the Tegner activity scale. An updated medical history was obtained via the electronic medical record to determine any subsequent complications and reoperations. Results: There was 1 ACL graft failure in each group as well as 5 (10%) reoperations per group. None of the patients in the LMORT group necessitated a lateral meniscal revision repair or partial meniscectomy. The LMORT and iACLR groups reported comparable sIKDC scores (92.5 ± 6.8 vs 91.9 ± 8.2, respectively; P = .712) as well as Tegner scores (6.7 ± 1.8 vs 6.6 ± 1.8, respectively; P = .910) at final follow-up. No failures of the LMORT repairs were reported. Conclusion: The study findings demonstrated that reoperations, graft failure rates, patient-reported outcomes, and patient activity levels at ≥2 years after type 3 and 4 LMORT repairs at the time of ACLR compared favorably with those of a matched cohort of patients who underwent iACLR with intact meniscus.

Meniscal Extrusion: Diagnosis, Etiology, and Treatment Options.

PURPOSE OF REVIEW: The concept of meniscal extrusion has recently been recognized as a hallmark of meniscus dysfunction. This review examines contemporary literature regarding the pathophysiology, classification, diagnosis, treatment, and future directions for investigation regarding meniscus extrusion. RECENT FINDINGS: Meniscus extrusion, defined as >3 mm of radial displacement of the meniscus, leads to altered knee biomechanics and accelerated knee joint degeneration. Meniscus extrusion has been associated with degenerative joint disease, posterior root and radial meniscal tears, and acute trauma. Meniscus centralization and meniscotibial ligament repair have been proposed as techniques to address meniscal extrusion with promising biomechanical, animal model, and early clinical reports. Further studies on the epidemiology of meniscus extrusion and associated long-term nonoperative outcomes will help to elucidate its role in meniscus dysfunction and resultant arthritic development. Understanding and appreciation for the anatomic attachments of the meniscus will help to inform future repair techniques. Long-term reporting on the clinical outcomes of meniscus centralization techniques will yield insights into the clinical significance of meniscus extrusion correction.

Genetic Risk Factors for End-Stage Hip Osteoarthritis Treated With Total Hip Arthroplasty: A Genome-wide Association Study.

BACKGROUND: Although a genetic component to hip osteoarthritis (OA) has been described, focused evaluation of the genetic components of end-stage disease is limited. We present a genomewide association study for patients undergoing total hip arthroplasty (THA) to characterize the genetic risk factors associated with end-stage hip osteoarthritis (ESHO), defined as utilization of the procedure. METHODS: Patients who underwent primary THA for hip OA were identified in a national patient data repository using administrative codes. Fifteen thousand three hundred and fifty-five patients with ESHO and 374,193 control patients were identified. Whole genome regression of genotypic data for patients who underwent primary THA for hip OA corrected for age, sex, and body mass index (BMI) was performed. Multivariate logistic regression models were used to evaluate the composite genetic risk from the identified genetic variants. RESULTS: There were 13 significant genes identified. Composite genetic factors resulted in an odds ratio 1.04 for ESHO (P < .001). The effect of genetics was lower than that of age (Odds Ratio (OR): 2.38; P < .001) and BMI (1.81; P < .001). CONCLUSION: Multiple genetic variants, including 5 novel loci, were associated with end-stage hip OA treated with primary THA. Age and BMI were associated with greater odds of developing end-stage disease when compared to genetic factors.

Genome-Wide Association Study of Adhesive Capsulitis Suggests Significant Genetic Risk Factors.

BACKGROUND: Adhesive capsulitis of the shoulder involves loss of passive range of motion with associated pain and can develop spontaneously, with no obvious injury or inciting event. The pathomechanism of this disorder remains to be elucidated, but known risk factors for adhesive capsulitis include diabetes, female sex, and thyroid dysfunction. Additionally, transcriptional profiling and pedigree analyses have suggested a role for genetics. Identification of elements of genetic risk for adhesive capsulitis using population-based techniques can provide the basis for guiding both the personalized treatment of patients based on their genetic profiles and the development of new treatments by identification of the pathomechanism. METHODS: A genome-wide association study (GWAS) was conducted using the U.K. Biobank (a collection of approximately 500,000 patients with genetic data and associated ICD-10 [International Classification of Diseases, 10th Revision] codes), comparing 2,142 patients with the ICD-10 code for adhesive capsulitis (M750) to those without. Separate GWASs were conducted controlling for 2 of the known risk factors of adhesive capsulitis-hypothyroidism and diabetes. Logistic regression analysis was conducted controlling for factors including sex, thyroid dysfunction, diabetes, shoulder dislocation, smoking, and genetics. RESULTS: Three loci of significance were identified: rs34315830 (in WNT7B; odds ratio [OR] = 1.28; 95% confidence interval [CI], 1.22 to 1.39), rs2965196 (in MAU2; OR = 1.67; 95% CI, 1.39 to 2.00), and rs1912256 (in POU1F1; OR = 1.22; 95% CI, 1.14 to 1.31). These loci retained significance when controlling for thyroid dysfunction and diabetes. The OR for total genetic risk was 5.81 (95% CI, 4.08 to 8.31), compared with 1.70 (95% CI, 1.18 to 2.36) for hypothyroidism and 4.23 (95% CI, 2.32 to 7.05) for diabetes. CONCLUSIONS: The total genetic risk associated with adhesive capsulitis was significant and similar to the risks associated with hypothyroidism and diabetes. Identification of WNT7B, POU1F1, and MAU2 implicates the Wnt pathway and cell proliferation response in the pathomechanism of adhesive capsulitis. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Characterization of Genetic Risk of End-Stage Knee Osteoarthritis Treated with Total Knee Arthroplasty: A Genome-Wide Association Study.

BACKGROUND: End-stage knee osteoarthritis (OA) is a highly debilitating disease for which total knee arthroplasty (TKA) serves as an effective treatment option. Although a genetic component to OA in general has been described, evaluation of the genetic contribution to end-stage OA of the knee is limited. To this end, we present a genome-wide association study involving patients undergoing TKA for primary knee OA to characterize the genetic features of severe disease on a population level. METHODS: Individuals with the diagnosis of knee OA who underwent primary TKA were identified in the U.K. Biobank using administrative codes. The U.K. Biobank is a data repository containing prospectively collected clinical and genomic data for >500,000 patients. A genome-wide association analysis was performed using the REGENIE software package. Logistic regression was also used to compare the total genetic risk between subgroups stratified by age and body mass index (BMI). RESULTS: A total of 16,032 patients with end-stage knee OA who underwent primary TKA were identified. Seven genetic loci were found to be significantly associated with end-stage knee OA. The odds ratio (OR) for developing end-stage knee OA attributable to genetics was 1.12 (95% confidence interval [CI], 1.10 to 1.14), which was lower than the OR associated with BMI (OR = 1.81; 95% CI, 1.78 to 1.83) and age (OR = 2.38; 95% CI, 2.32 to 2.45). The magnitude of the OR for developing end-stage knee OA attributable to genetics was greater in patients <60 years old than in patients ≥60 years old (p = 0.002). CONCLUSIONS: This population-level genome-wide association study of end-stage knee OA treated with primary TKA was notable for identifying multiple significant genetic variants. These loci involve genes responsible for cartilage development, cartilage homeostasis, cell signaling, and metabolism. Age and BMI appear to have a greater impact on the risk of developing end-stage disease compared with genetic factors. The genetic contribution to the development of severe disease is greater in younger patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Management of Chondral Defects Associated with Patella Instability.

Cartilage defects of the patellofemoral joint are commonly found in association with patellar instability owing to abnormal biomechanics. Strategies to address chondral defects of the patellofemoral joint secondary to instability should first address causes of recurrent instability. Most patellofemoral chondral defects associated with instability are less than 2 cm2 and do not generally require intervention beyond chondroplasty. Larger defects of the patella and/or the trochlea can be repaired with osteochondral or surface cartilage repair.

Prevalence of Cannabidiol Use in Patients With Spine Complaints: Results of an Anonymous Survey.

BACKGROUND: Cannabidiol (CBD) is a cannabis derivative that has been popularized as a medicinal product with analgesic and anti-inflammatory effects. Given the anecdotal observations that several patients have reported use of CBD for spine-related pain, this study was designed to characterize CBD consumption patterns and perceived effects in patients with spine-related complaints. METHODS: The study design was a cross-sectional survey. Over a 4-week period, an anonymous paper survey was administered to all patients presenting for evaluation by 1 of 9 spine surgeons at a single institution. Surveys were given upon registration for the office visit and collected by the office manager or nurse before evaluation by the surgeon. Patients were included regardless of surgical status (ie, preoperative, postoperative, or nonoperative) or region of pathology (lumbar, thoracic, or cervical). The survey consisted of multiple-choice questions on patient patterns of CBD use. RESULTS: Out of 300 surveys, 214 (71%) were completed. CBD use for spine-related pain was reported by 54 (25.2%) patients. CBD was initially used for potential relief of back pain (66.7%), neck pain (37.0%), leg pain (35.2%), and/or arm pain (9.3%). Users also sought improvements in insomnia (25.9%) and mood (18.5%). Oil was the most popular formulation (64.8%). CBD was most often consumed 2-5 times (40.7%) or 6-10 times (31.5%) per week. The most common source of initial recommendation for CBD was friends or family (75.9%). Reported benefits were pain relief (46.3%), improved sleep (33.3%), and reduced anxiety (20.4%); however, 24.1% of patients reported no benefit from CBD use. The most reported side effect was fatigue (7.4%). Most users (63.0%) would recommend CBD to a friend for pain relief. CONCLUSION: CBD is already used by many patients, and further high-quality research on this supplement is essential. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: CBD is a commonly used by spine patients as an off label treatment.

Wdpcp regulates cellular proliferation and differentiation in the developing limb via hedgehog signaling.

BACKGROUND: Mice with a loss of function mutation in Wdpcp were described previously to display severe birth defects in the developing heart, neural tube, and limb buds. Further characterization of the skeletal phenotype of Wdpcp null mice was limited by perinatal lethality. RESULTS: We utilized Prx1-Cre mice to generate limb bud mesenchyme specific deletion of Wdpcp. These mice recapitulated the appendicular skeletal phenotype of the Wdpcp null mice including polydactyl and limb bud signaling defects. Examination of late stages of limb development demonstrated decreased size of cartilage anlagen, delayed calcification, and abnormal growth plates. Utilizing in vitro assays, we demonstrated that loss of Wdpcp in skeletal progenitors lead to loss of hedgehog signaling responsiveness and associated proliferative response. In vitro chondrogenesis assays showed this loss of hedgehog and proliferative response was associated with decreased expression of early chondrogenic marker N-Cadherin. E14.5 forelimbs demonstrated delayed ossification and expression of osteoblast markers Runx2 and Sp7. P0 growth plates demonstrated loss of hedgehog signaling markers and expansion of the hypertrophic zones of the growth plate. In vitro osteogenesis assays demonstrated decreased osteogenic differentiation of Wdpcp null mesenchymal progenitors in response to hedgehog stimulation. CONCLUSIONS: These findings demonstrate how Wdpcp and associated regulation of the hedgehog signaling pathway plays an important role at multiple stages of skeletal development. Wdpcp is necessary for positive regulation of hedgehog signaling and associated proliferation is key to the initiation of chondrogenesis. At later stages, Wdpcp facilitates the robust hedgehog response necessary for chondrocyte hypertrophy and osteogenic differentiation.

Open Reduction and Internal Fixation of Patella Fracture With Contoured Dorsal Plating.

SUMMARY: In this article, we present a novel patella fixation technique using a low-profile highly contoured dorsal mini-fragment locking plate. This procedure is ideally indicated in patients with fracture patterns that are transverse without significant comminution. Long-term clinical studies are being performed to evaluate the effectiveness of this surgical technique.

Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing.

Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.

Stem Cells in Skeletal Tissue Engineering: Technologies and Models.

This review surveys the use of pluripotent and multipotent stem cells in skeletal tissue engineering. Specific emphasis is focused on evaluating the function and activities of these cells in the context of development in vivo, and how technologies and methods of stem cell-based tissue engineering for stem cells must draw inspiration from developmental biology. Information on the embryonic origin and in vivo differentiation of skeletal tissues is first reviewed, to shed light on the persistence and activities of adult stem cells that remain in skeletal tissues after embryogenesis. Next, the development and differentiation of pluripotent stem cells is discussed, and some of their advantages and disadvantages in the context of tissue engineering are presented. The final section highlights current use of multipotent adult mesenchymal stem cells, reviewing their origin, differentiation capacity, and potential applications to tissue engineering.

Cleavage of mispaired heteroduplex DNA substrates by numerous restriction enzymes.

The utility of restriction endonucleases as a tool in molecular biology is in large part due to the high degree of specificity with which they cleave well-characterized DNA recognition sequences. The specificity of restriction endonucleases is not absolute, yet many commonly used assays of biological phenomena and contemporary molecular biology techniques rely on the premise that restriction enzymes will cleave only perfect cognate recognition sites. In vitro, mispaired heteroduplex DNAs are commonly formed, especially subsequent to polymerase chain reaction amplification. We investigated a panel of restriction endonucleases to determine their ability to cleave mispaired heteroduplex DNA substrates. Two straightforward, non-radioactive assays are used to evaluate mispaired heteroduplex DNA cleavage: a PCR amplification method and an oligonucleotide-based assay. These assays demonstrated that most restriction endonucleases are capable of site-specific double-strand cleavage with heteroduplex mispaired DNA substrates, however, certain mispaired substrates do effectively abrogate cleavage to undetectable levels. These data are consistent with mispaired substrate cleavage previously reported for Eco RI and, importantly, extend our knowledge of mispaired heteroduplex substrate cleavage to 13 additional enzymes.