Justin J. Mitchell

Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis.

BACKGROUND Intra-articular cellular therapy injections constitute an appealing strategy that may modify the intra-articular milieu or regenerate cartilage in the settings of osteoarthritis and focal cartilage defects. However, little consensus exists regarding the indications for cellular therapies, optimal cell sources, methods of preparation and delivery, or means by which outcomes should be reported. METHODS We present a systematic review of the current literature regarding the safety and efficacy of cellular therapy delivered by intra-articular injection in the knee that provided a Level of Evidence of III or higher. A total of 420 papers were screened. Methodological quality was assessed using a modified Coleman methodology score. RESULTS Only 6 studies (4 Level II and 2 Level III) met the criteria to be included in this review; 3 studies were on treatment of osteoarthritis and 3 were on treatment of focal cartilage defects. These included 4 randomized controlled studies without blinding, 1 prospective cohort study, and 1 retrospective therapeutic case-control study. The studies varied widely with respect to cell sources, cell characterization, adjuvant therapies, and assessment of outcomes. Outcome was reported in a total of 300 knees (124 in the osteoarthritis studies and 176 in the cartilage defect studies). Mean follow-up was 21.0 months (range, 12 to 36 months). All studies reported improved outcomes with intra-articular cellular therapy and no major adverse events. The mean modified Coleman methodology score was 59.1 ± 16 (range, 32 to 82). CONCLUSIONS The studies of intra-articular cellular therapy injections for osteoarthritis and focal cartilage defects in the human knee suggested positive results with respect to clinical improvement and safety. However, the improvement was modest and a placebo effect cannot be disregarded. The overall quality of the literature was poor, and the methodological quality was fair, even among Level-II and III studies. Effective clinical assessment and optimization of injection therapies will demand greater attention to study methodology, including blinding; standardized quantitative methods for cell harvesting, processing, characterization, and delivery; and standardized reporting of clinical and structural outcomes. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Meniscal Ramp Lesions Anatomy, Incidence, Diagnosis, and Treatment

Meniscal ramp lesions are more frequently associated with anterior cruciate ligament (ACL) injuries than previously recognized. Some authors suggest that this entity results from disruption of the meniscotibial ligaments of the posterior horn of the medial meniscus, whereas others support the idea that it is created by a tear of the peripheral attachment of the posterior horn of the medial meniscus. Magnetic resonance imaging (MRI) scans have been reported to have a low sensitivity, and consequently, ramp lesions often go undiagnosed. Therefore, to rule out a ramp lesion, an arthroscopic evaluation with probing of the posterior horn of the medial meniscus should be performed. Several treatment options have been reported, including nonsurgical management, inside-out meniscal repair, or all-inside meniscal repair. In cases of isolated ramp lesions, a standard meniscal repair rehabilitation protocol should be followed. However, when a concomitant ACL reconstruction (ACLR) is performed, the rehabilitation should follow the designated ACLR postoperative protocol. The purpose of this article was to review the current literature regarding meniscal ramp lesions and summarize the pertinent anatomy, biomechanics, diagnostic strategies, recommended treatment options, and postoperative protocol.

Opening- and Closing-Wedge Distal Femoral Osteotomy A Systematic Review of Outcomes for Isolated Lateral Compartment Osteoarthritis

Background: Lateral compartment osteoarthritis of the knee can be a challenging pathology in the younger, active population due to limited treatment options and high patient expectations. Distal femoral osteotomy (DFO) has been reported to be a potential treatment option. Purpose: To perform a systematic review on the survival, outcomes, and complications of DFO for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the literature was performed using the Cochrane Database of Systematic Reviews, the Cochrane Central Registry of Controlled Trials, PubMed, and MEDLINE from 1980 to present. Inclusion criteria were as follows: outcomes of opening- and closing-wedge DFOs performed for treatment of genu valgum with concomitant lateral compartment osteoarthritis of the knee, English language, minimum 2-year follow-up, and human studies. Data abstracted from the selected studies included type of osteotomy (opening vs closing), survival rate, patient-reported and radiographic outcomes, and complications. Results: Fourteen studies met the inclusion criteria and were considered for the review. A total of 9 closing-wedge and 5 opening-wedge DFO studies were included. All were retrospective studies and reported good to excellent patient-reported outcomes after DFO. Survival decreased with increasing time from surgery, with 1 study reporting a 100% survival rate at 6.5 years, compared with 21.5% at 20 years in another study. A low rate of complications was reported throughout the review. Conclusion: Highly heterogeneous literature exists for both opening- and closing-wedge DFOs for the treatment of isolated lateral compartment osteoarthritis with valgus malalignment. A mean survival rate of 80% at 10-year follow-up was reported, supporting that this procedure can be a viable treatment option to delay or reduce the need for joint arthroplasty. A low complication rate was observed, with symptomatic hardware being the most prevalent postoperative complication.

Anterolateral Ligament Reconstruction Technique: An Anatomic-Based Approach

Restoration of anteroposterior laxity after an anterior cruciate ligament reconstruction has been predictable with traditional open and endoscopic techniques. However, anterolateral rotational stability has been difficult to achieve in a subset of patients, even with appropriate anatomic techniques. Therefore, differing techniques have attempted to address this rotational laxity by augmenting or reconstructing lateral-sided structures about the knee. In recent years, there has been a renewed interest in the anterolateral ligament as a potential contributor to residual anterolateral rotatory instability in anterior cruciate ligament-deficient patients. Numerous anatomic and biomechanical studies have been performed to further define the functional importance of the anterolateral ligament, highlighting the need for surgical techniques to address these injuries in the unstable knee. This article details our technique for an anatomic anterolateral ligament reconstruction using a semitendinosus tendon allograft.

Delayed Anterior Cruciate Ligament Reconstruction in Young Patients With Previous Anterior Tibial Spine Fractures

Background: Avulsion fractures of the anterior tibial spine in young athletes are injuries similar to anterior cruciate ligament (ACL) injuries in adults. Sparse data exist on the association between anterior tibial spine fractures (ATSFs) and later ligamentous laxity or injuries leading to ACL reconstruction. Purpose: To better delineate the incidence of delayed instability or ACL ruptures requiring delayed ACL reconstruction in young patients with prior fractures of the tibial eminence. Study Design: Case series; Level of evidence, 4. Methods: We identified 101 patients between January 1993 and January 2012 who sustained an ATSF and who met inclusion criteria for this study. All patients had been followed for at least 2 years after the initial injury and were included for analysis after completion of a questionnaire via direct contact, mail, and/or telephone. If patients underwent further surgical intervention and/or underwent later ACL reconstruction, clinical records and operative reports pertaining to these secondary interventions were obtained and reviewed. Differences between categorical variables were assessed using the Fisher exact test. The association between time to revision ACL surgery and fracture type was assessed by Kaplan-Meier plots. The association between need for revision ACL surgery and age, sex, and mechanism of surgery was assessed using logistic regression. Results: Nineteen percent of all patients evaluated underwent delayed ACL reconstruction after a previous tibial spine fracture on the ipsilateral side. While there were a higher proportion of ACL reconstructions in type II fractures, there was not a statistically significant difference in the number of patients within each fracture group who went on to undergo later surgery (P = .29). Further, there was not a significant association between fracture type, sex, or mechanism of injury as it related to the progression to later ACL reconstruction. However, there was a significant association between age at the time of injury and progression to later ACL reconstruction (P = .02). For every year increase in age at the time of injury, the odds of going on to undergo delayed ACL reconstruction were greater by a factor of 1.3 (95% CI, 1.1-1.6). Conclusion: Although an ATSF is a relatively rare injury, our cohort of patients suggests that a subset of young patients with all types of tibial spine fractures will require later ACL reconstruction. There is a need to counsel patients that a delayed ACL rupture is a potential risk after an ATSF, especially as children approach skeletal maturity. Further patient follow-up and prospective studies are required.

Incidence of meniscal injury and chondral pathology in anterior tibial spine fractures of children.

Background: Pediatric avulsion fractures of the anterior tibial spine are injuries similar to anterior cruciate ligament injuries in adults. Sparse data exists on the association between anterior tibial spine fractures (ATSFs) and injury to the meniscus or cartilage of the knee joint in children. This research presents a retrospective review of clinical records, imaging, and operative reports to characterize the incidence of concomitant injury in cases of ATSFs in children. The purpose of this study was to better delineate the incidence of associated injuries in fractures of the anterior tibial spine in the pediatric population. Methods: We identified 58 patients who sustained an ATSF and met inclusion criteria for this study between 1996 and 2011. The subjects were separated by the Myers and McKeever classification into type I, II, and III fractures, and each of these were subclassified by associated injury pattern. Results: 59% of children with an ATSF had an associated soft tissue or other bony injury diagnosed by magnetic resonance imaging or arthroscopy. The most prevalent associated injuries were meniscal entrapment, meniscal tears, and chondral injury. We found no meniscal or chondral injury associated with type I fractures. Twenty-nine percent of type II injuries demonstrated meniscal entrapment, 33% showing meniscal tears. Seven percent demonstrated chondral injury. Forty-eight percent of type III fractures had entrapment, whereas 12% showed meniscal tears. Eight percent had a chondral injury. Conclusions: A majority (59%) of displaced ATSF had either concomitant meniscal, ligamentous, or chondral injury. This finding suggests that magnetic resonance imaging evaluation is an important aspect of the evaluation of these injuries, particularly in type II and type III patterns. To date, this study reports the largest number of patients to evaluate the specific question of concomitant injuries in ATSFs in the pediatric population. Level of Evidence: Level IV.

Outcomes After Biologically Augmented Isolated Meniscal Repair With Marrow Venting Are Comparable With Those After Meniscal Repair With Concomitant Anterior Cruciate Ligament Reconstruction

Background: Meniscal repair in the setting of anterior cruciate ligament (ACL) reconstruction has demonstrated superior outcomes compared with isolated meniscal repair. Limited evidence exists for the effects of biological augmentation in isolated meniscal repair, particularly as compared with meniscal repair with concomitant ACL reconstruction. Purpose/Hypothesis: The purpose of this study was to compare the outcomes and survivorship of meniscal repair in 2 cohorts of patients: meniscal repair with biological augmentation using a marrow venting procedure (MVP) of the intercondylar notch, and meniscal repair with concomitant ACL reconstruction. We hypothesized that the clinical outcomes and survivorship of meniscal repair with concomitant ACL reconstruction would be improved compared with meniscal repair with biological augmentation. Study Design: Cohort study; Level of evidence, 3. Methods: Inclusion criteria were skeletally mature patients aged ≥16 years who underwent inside-out meniscal repair and either a concomitant MVP of the intercondylar notch or ACL reconstruction. Patients were excluded from this study if they were skeletally immature, underwent meniscus root or radial tear repair, or underwent meniscal repair with concurrent ligamentous reconstruction not limited to the ACL. At the preoperative evaluation and a minimum 2 years after the index meniscal repair procedure, patients were administered a subjective questionnaire. Differences in outcome scores, survivorship, and failure rates between the cohorts were assessed. Failure was defined as reoperation with meniscectomy or revision meniscal repair. Results: There were 109 patients (52 female, 57 male) who met the inclusion criteria for this study. There were 37 knees in cohort 1 (isolated meniscal repair plus MVP) and 72 knees in cohort 2 (meniscal repair plus ACL reconstruction). The failure status was known in 95 patients, and patient-reported outcome scores were obtained in 89 (82%) patients. Both cohorts demonstrated a significant improvement in all outcome scores, and there was no significant difference in any of the preoperative or postoperative outcome measures. The overall failure rate was 9.5% (9/95). There were 4 (12.9%) failures in cohort 1 and 5 failures (7.8%) in cohort 2, with no significant difference in failures between the cohorts (P = .429). There was a significant association between failure and female sex (P = .001). Conclusion: The most important finding in this study was that there was no difference in outcomes in meniscal repair performed with biological augmentation using an MVP versus that performed concomitantly with ACL reconstruction. The similar outcomes reported for meniscal repair with an MVP and meniscal repair with ACL reconstruction may be partly attributed to biological augmentation.

Anatomic Posterolateral Corner Reconstruction

Posterolateral corner injuries represent a complex injury pattern, with damage to important coronal and rotatory stabilizers of the knee. These lesions commonly occur in association with other ligament injuries, making decisions regarding treatment challenging. Grade III posterolateral corner injuries result in significant instability and have poor outcomes when treated nonoperatively. As a result, reconstruction is advocated. A thorough knowledge of the anatomy is essential for surgical treatment of this pathology. The following technical note provides a diagnostic approach, postoperative management, and details of a technique for anatomic reconstruction of the 3 main static stabilizers of the posterolateral corner of the knee.

Intra-articular Implantation of Mesenchymal Stem Cells, Part 1: A Review of the Literature for Prevention of Postmeniscectomy Osteoarthritis

Osteoarthritis (OA) after a partial or total meniscectomy procedure is a common pathology. Because of the high incidence of meniscectomy in the general population, as well as the significant burden of knee OA, there is increasing interest in determining methods for delaying postmeniscectomy OA. Biological therapies, including mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and platelet-rich plasma (PRP), have been proposed as possible therapies that could delay OA in this and other settings. Several studies in various animal models have evaluated the effect of injecting MSCs into the knee joints of animals with OA induced either by meniscal excision with or without anterior cruciate ligament transection. When compared with control groups receiving injections without progenitor cells, short-term benefits in the experimental groups have been reported. In human subjects, there are limited data to determine the effect of biological therapies for use in delaying or preventing the onset of OA after a meniscectomy procedure. The purpose of this review is to highlight the findings in the presently available literature on the use of intra-articular implantation of MSCs postmeniscectomy and to offer suggestions for future research with the goal of delaying or treating early OA postmeniscectomy with MSCs.

Fresh Osteochondral Allograft Versus Autograft Twelve-Month Results in Isolated Canine Knee Defects

Background: Osteochondral autografts and allografts have been widely used in the treatment of isolated grade 4 articular cartilage lesions of the knee. However, there is a paucity of literature regarding the basic science investigating the direct comparison between fresh osteochondral allografts to autografts. Hypothesis: At 12 months, fresh osteochondral allografts are equal to autografts with respect to function, bony incorporation into host bone, and chondrocyte viability. Study Design: Controlled laboratory study. Methods: Eight adult mongrel dogs underwent bilateral hindlimb osteochondral graft implantation in the knee after creation of an acute Outerbridge grade 4 cartilage defect. One hindlimb of each dog knee received an autograft, and the contralateral knee received an allograft. All dogs were sacrificed at 12 months. Graft analysis included gross examination, radiographs, magnetic resonance imaging (MRI), biomechanical testing, and histology. Results: MRI demonstrated excellent bony incorporation of both autografts and allografts, except for 1 allograft that revealed partial incorporation. Histologic examination of cartilage showed intact hyaline appearance for both autografts and allografts, with fibrocartilage at the host-graft interface of both. Biomechanical testing demonstrated no significant difference between allografts and autografts (P = .76). Furthermore, no significant difference was observed between allografts and the native cartilage with biomechanical testing (P = .84). Conclusion: After 12 months from time of implantation, fresh osteochondral allograft tissue and autograft tissue in this study were not statistically different with respect to biomechanical properties, gross morphology, bony incorporation, or overall histologic characteristics. When compared with the previously reported 6-month incorporation rates, there was improved allograft and autograft incorporation at 12 months. Clinical Relevance: With no significant differences in gross examination, radiographs, MRI, biomechanical testing, or histology in the canine model, the use of allograft tissue to treat osteochondral defects may eliminate the morbidity associated with autograft harvest.