Faculty Bibliography

BACKGROUND:Despite the promising clinical results of autologous osteochondral transplantation in the treatment of osteochondral lesions of the talus, the occurrence of knee donor-site morbidity remains a concern. However, the proportion of patients experiencing donor-site morbidity is not well established because of important variations in estimates drawn by heterogeneous studies with loss to followup, often made at short-term (< 1 year). Therefore, both a meta-analysis of studies that assumed no patients lost to followup had donor-site morbidity and assumed all patients lost to followup had donor-site morbidity may help to estimate the true risk of donor-site morbidity. QUESTIONS/PURPOSES/OBJECTIVE:To evaluate the proportion of patients who developed knee donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus, by (1) meta-analysis of the proportion of patients experiencing donor-site morbidity in the best-case scenario as reported, in which no patients lost to followup were assumed to have donor-site morbidity and (2) meta-analysis of the percentage of patients who had donor-site morbidity in the worst-case scenario, in which all patients lost to followup were assumed to have donor-site morbidity and (3) present the characteristics of studies associated with the reporting of donor-site morbidity. METHODS:A systematic search of the PubMed, Embase and The Cochrane Library databases was performed from their inception to October 2017 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The inclusion criteria were clinical studies that reported knee donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus, mean followup ≥ 1 year, full-text studies published in a peer-review journal and written in English. Quality of evidence (Case Series Quality Appraisal Checklist), sample size, mean patient age, study design, mean followup time, and observed rate of knee donor-site morbidity were evaluated. Twenty-six studies with 915 ankles (904 patients) were included in the systematic review and meta-analysis. Approximately half of the included studies were of small cohort (n < 30, 12 studies), and 12 of 26 studies did not report at all on loss to followup. In the studies that reported loss to followup (14 of 26), a total of 32 patients (35 ankles) were reported lost. Random-effects models were used to estimate the risk of donor-site morbidity as between-study heterogeneity was determined to be high in both meta-analyses that assumed that no patients lost to followup experienced donor-site morbidity (I = 82.1%) and the one that assumed all patients lost to followup experienced donor-site morbidity (I = 88.7%). Multivariable metaregression was used to estimate the association between study characteristics and the observed proportion of patients who experienced of donor-site morbidity. If there was evidence of an association between a study characteristic and proportion, a subgroup analysis was performed. RESULTS:The estimated proportion of donor-site morbidity was 6.7% (95% confidence interval [CI], 2.8-11.8), assuming that no patients lost to followup experienced donor-site morbidity and 10.8% (95% CI, 4.8-18.3) assuming that all patients lost to followup experienced donor-site morbidity after a mean followup of 43.8 ± 24.7 months (range, 15.9-120 months). There was a negative association between study sample size and proportion of donor-site morbidity (β = -0.26; 95% CI, -0.39 to -0.12; p < 0.001 assuming that no patients lost to followup experienced donor-site morbidity and β = -0.31; 95% CI, -0.48 to -0.13; p < 0.001 assuming that all patients lost to followup experienced donor-site morbidity); that is, as study size increased, the proportion of patients reported with donor-site morbidity decreased. In larger studies (n ≥ 30), the estimated percentage of donor-site morbidity was 2.8% (95% CI, 1.2%-5.0%; I = 47.6%) assuming that no patients lost to followup experienced donor-site morbidity, and 5.0% (95% CI, 2.1%-9.0%; I = 74.5%) assuming all patients lost to followup experienced donor-site morbidity. High between-study heterogeneity (differences in methodology) could not be completely explained by variability in study sample size, mean patient age, design, or mean followup time, and may be attributable to other factors such as inconsistent definitions of donor-site morbidity. CONCLUSIONS:The estimated proportion of donor-site morbidity after autologous osteochondral transplantation for osteochondral lesion of the talus ranged from 6.7% to 10.8% in the current meta-analysis. However, subgroup analysis demonstrated that larger studies (n ≥ 30) estimated a lower donor-site morbidity risk (< 5.0%) than smaller studies (n < 30). This estimate should be interpreted in light of the fact that nearly half of the included studies did not report on loss to followup, and so their estimates of donor-site morbidity may be low. In addition, high between-study heterogeneity and the inclusion of predominantly retrospective studies with small sample sizes likely contributed to estimates that suffered from a high risk of bias, probably in favor of the surgical treatment being studied. LEVEL OF EVIDENCE/METHODS:Level IV, therapeutic study.

PURPOSE/OBJECTIVE:To review the basic science studies on platelet-rich plasma (PRP) for cartilage and determine whether there has been an improvement in methodology and outcome reporting that would allow for a more meaningful analysis regarding the mechanism of action and efficacy of PRP for cartilage pathology. METHODS:The PubMed/MEDLINE and EMBASE databases were screened in May 2017 with publication dates of January 2011 through May 2017 using the following key words: "platelet-rich plasma OR PRP OR autologous conditioned plasma (ACP) OR ACP AND cartilage OR chondrocytes OR chondrogenesis OR osteoarthritis OR arthritis." Two authors independently performed the search, determined study inclusion, and extracted data. Data extracted included cytology/description of PRP, study design, and results. RESULTS:Twenty-seven studies (11 in vitro, 13 in vivo, 3 in vitro and in vivo) met the inclusion criteria and were included in the study. All of the studies (100%) reported the method by which PRP was prepared. Two studies reported basic cytologic analysis of PRP, including platelet, white blood cell, and red blood cell counts (6.7%). Nine studies reported both platelet count and white blood cell count (30.0%). Twelve studies reported platelet count alone (40.0%). Nine studies (30.0%) made no mention at all as to the composition of the PRP used. PRP was shown to increase cell viability, cell proliferation, cell migration, and differentiation. Several studies demonstrated increased proteoglycan and type II collagen content. PRP decreased inflammation in 75.0% of the in vitro studies reporting data and resulted in improved histologic quality of the cartilage tissue in 75.0% of the in vivo studies reporting data. CONCLUSIONS:Although the number of investigations on PRP for cartilage pathology has more than doubled since 2012, the quality of the literature remains limited by poor methodology and outcome reporting. A majority of basic science studies suggest that PRP has beneficial effects on cartilage pathology; however, the inability to compare across studies owing to a lack of standardization of study methodology, including characterizing the contents of PRP, remains a significant limitation. Future basic science and clinical studies must at a minimum report the contents of PRP to better understand the clinical role of PRP for cartilage pathology. CLINICAL RELEVANCE/CONCLUSIONS:Establishing proof of concept for PRP to treat cartilage pathology is important so that high-quality clinical studies with appropriate indications can be performed.

Surgical techniques for the management of recalcitrant osteochondral lesions of the talus have improved; however, the poor healing potential of cartilage may impede long-term outcomes. Repair (microfracture) or replacement (osteochondral transplants) is the standard of care. Reparative strategies lead to production of fibrocartilage, which, compared with the native type II articular cartilage, has decreased mechanical and wear properties. The success of osteochondral transplants may be hindered by poor integration between grafts and host that results in peripheral cell death and cyst formation. These challenges have led to the investigation of biologic adjuvants to augment treatment. In vitro and in vivo models have demonstrated promise for cartilage regeneration by decreasing inflammatory damage and increasing the amount of type II articular cartilage. Further research is needed to investigate optimal formulations and time points of administration. In addition, clinical trials are needed to investigate the long-term effects of augmentation.

Background/UNASSIGNED:Lesion size is a major determinant of treatment strategy for osteochondral lesions of the talus (OLTs). Although magnetic resonance imaging (MRI) is commonly used in the preoperative evaluation of OLTs, the reliability of the MRI measurement compared with the arthroscopic measurement is unknown. Purpose/UNASSIGNED:To compare preoperative lesion size measured on MRI versus intraoperative lesion size measured during arthroscopy. Study Design/UNASSIGNED:Cohort study (diagnosis); Level of evidence, 2. Methods/UNASSIGNED:We retrospectively reviewed a consecutive series of patients treated with bone marrow stimulation for OLTs. The diameter of the lesion was measured at its widest point in 2 planes, and MRI measurements were compared with those made during arthroscopy using a custom-made graduated probe. Results/UNASSIGNED:= .05). Further, MRI overestimated coronal diameter in 48.9% (22/45) of ankles and underestimated in 26.7% (12/45) compared with the arthroscopic measurement. Similarly, sagittal plane MRI diameter measurements overestimated lesion size in 46.7% (21/45) of ankles and underestimated lesion size in 28.9% (13/45) compared with the arthroscopic findings. Conclusion/UNASSIGNED:In a majority of lesions, MRI overestimated OLT area and diameter compared with arthroscopy. Surgeons should be aware of the discrepancies that can exist between MRI and arthroscopic measurements, as these data are important in making treatment decisions and educating patients.

Regenerative cell therapies are emerging as promising treatments for numerous musculoskeletal conditions, including knee osteoarthritis (OA). Adipose-derived stem cells and possibly other adipose-based therapies have a greater chondrogenic potential than stem cells derived from bone marrow, and thus a lot of attention is being placed on them as potential regenerative agents in the treatment of knee OA. Several types of adipose-based therapies have good basic science and preclinical data supporting their translation to human therapeutic intervention. Cultured, adipose-derived stem cells appear to be good source of bioactive cells with convenient accessibility, relative abundance, and well-documented regenerative capacity. Non-culture expanded adipose-based therapy, in the forms of stromal vascular fraction and most recently micronized adipose tissue (MAT), have been utilized in patients to treat OA and other cartilage abnormalities with encouraging preliminary data. These adipose-based therapies have shown a lot of therapeutic potential; however, because of the regulatory restrictions on enzymatic isolation and cell expansion, only MAT is currently available in clinical practice in the United States. While no serious adverse reactions have been reported, adipose-derived therapies also have the potential for adverse reactions including inflammation and infection. The current review provides an update on the latest research and presents this evidence on the therapeutic potential of adipose-based therapies in the treatment of knee OA.

Residual symptoms often persist even after successful operative reduction and internal fixation (ORIF) of ankle fractures. Concurrent ankle arthroscopic procedures (CAAPs) have been proposed to improve clinical outcomes; however, a dearth of evidence is available supporting this practice. The purpose of the present study was to investigate the reoperation and complication rates after ORIF of ankle fractures with and without CAAPs. Reoperations and complications after ORIF of ankle fractures were identified using the PearlDiver database from January 2007 to December 2011. The CAAPs included bone marrow stimulation, debridement, synovectomy, and unspecified cartilage procedures. Reoperation procedures consisted of ankle fracture repeat fixation, arthroscopic procedures, osteochondral autograft transfers, and ankle arthrodesis. Of the 32,307 patients who underwent ankle fracture fixation, 248 received CAAP and 32,059 did not. No significant difference was found in the reoperation rate between the 2 groups (7.7% versus 8.6%; odds ratio 0.89; 95% confidence interval 0.55 to 1.42; p = .61). Of the 248 patients in the CAAP group, 19 (7.7%) underwent reoperation, of which 13 (68.4%) were arthroscopic debridement and 6 were either ankle refixation or osteochondral autograft transfer. For the non-CAAP group, 3021 reoperation procedures were performed, consisting of ankle refixation in 83.2%, arthroscopic procedures in 14.3%, and ankle arthrodesis in 2.5%. The complication rate in the non-CAAP group included wound dehiscence in 2.4%, wound surgery in 0.4%, deep vein thrombosis in 0.8%, and pulmonary embolism in 0.4%. No complications were detected in the CAAP group. Ankle fracture fixation with CAAPs did not increase the postoperative reoperation rate compared with ankle fracture fixation without CAAPs.

PURPOSE/OBJECTIVE:To clarify if the use of concentrated bone marrow aspirate (CBMA) would affect both postoperative functional outcomes and magnetic resonance imaging (MRI) outcomes compared with those of autologous osteochondral transplantation (AOT) alone; in addition, to assess the efficacy of CBMA reducing the presence of postoperative cyst formation following AOT in the treatment of osteochondral lesions of the talus. METHODS:Fifty-four (92%) of 59 eligible patients who underwent AOT between 2004 and 2008 were retrospectively assessed at a minimum of 5-year follow-up. Twenty-eight patients were treated with AOT and CBMA (AOT/CBMA group) and 26 patients were treated with AOT alone (AOT-alone group). Clinical outcomes were evaluated using the Foot and Ankle Outcome Scores (FAOS) and Short-Form 12 (SF-12) preoperatively and at final follow-up. Postoperative MRI was evaluated with the modified Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system. Cyst formation was also evaluated on postoperative MRI. RESULTS:The mean FAOS and SF-12 significantly improved in both the AOT/CBMA and AOT-alone groups, but there were no statistical differences between groups in FAOS (80.5 vs 75.5, P = .225) and SF-12 (71.1 vs 69.6, P = .756) at final follow-up. Additionally, there was no difference in the mean MOCART score (80.4 vs 84.3, P = .484); however, AOT/CBMA did result in a statistically lower rate of cyst formation (46.4% vs 76.9%, P = .022). No significant differences were found in the mean postoperative FAOS and SF-12 between patients with and without cysts postoperatively. CONCLUSIONS:CBMA reduced postoperative cyst occurrence rate in patients treated with AOT; however, CBMA did not result in significant differences in medium term functional outcomes and MOCART score in patients who underwent AOT. LEVEL OF EVIDENCE/METHODS:Level III, retrospective comparative trial.

With our aging population desiring to remain active, the incidence and costs associated with managing knee pain from both acute injury and symptomatic knee osteoarthritis continue to dramatically increase. Current treatment methods fall short with respect to their ability to improve the intra-articular environment and restore normal joint homeostasis. With increasing basic science and clinical evidence showing efficacy, cell-based therapies such as bone marrow concentrate (BMC) hold promise as a nonsurgical joint preserving treatment approach. BMC has inherent advantages over other treatments commonly used for various knee pathologies because it is a point-of-care orthobiologic product that uniquely and simultaneously delivers growth factors, anti-inflammatory proteins, and mesenchymal stem cells. There is increasing evidence for the use of BMC for repair of focal cartilage defects and for the treatment of generalized knee pain. However, continued high-quality studies are necessary for the clinical utility of BMC to be critically assessed with particular attention paid to appropriate patient selection, standardized aspiration, and processing and reporting of both functional and imaging-based outcomes.

Articular cartilage is a highly specialised connective tissue that serves to lubricate joint surfaces and distribute loads across the joint. Injury to articular cartilage is a significant cause of pain and dysfunction that may eventually lead to osteoarthritis or degenerative arthrosis. Management of these injuries is complicated by the complex architecture and poor vascularity of this tissue. The field of articular cartilage restoration has evolved rapidly over the past several decades and current techniques offer promising results. However, despite the fast pace of progress in the treatment and repair of articular cartilage injury, a clear gold standard in management has yet to emerge. Current techniques for managing cartilage injuries discussed in this review include bone marrow stimulation, osteochondral transplantation, chondrocyte implantation, cell-based transplantation, biological augmentation and scaffold-based therapies. Heterogeneity in study design, including surgical procedures, lesion and patient characteristics, cell collection, biologics preparation protocols and outcome measures limits interpretation of results presented in the literature. Therefore, standardisation across research protocols and collaboration among centres will be necessary. This state-of-the-art review' presents the indications and techniques for managing ankle articular cartilage lesions, as well as future directions and geographical differences in management.
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