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Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

Boakye, Lorraine A; Ross, Keir A; Pinski, John M; Smyth, Niall A; Haleem, Amgad M; Hannon, Charles P; Fortier, Lisa A; Kennedy, John G
AIM/OBJECTIVE:To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-β1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS:Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-β1 was then assessed. RESULTS:Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10(-4), 3.1 × 10(-4) and 7.3 × 10(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10(-6)) overall for each post-operative time point and ROI. CONCLUSION/CONCLUSIONS:Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.
PMID: 26716092
ISSN: 2218-5836
CID: 3524352

Platelet-Rich Plasma in the Animal Long-Bone Model: An Analysis of Basic Science Evidence

Gianakos, Arianna; Zambrana, Lester; Savage-Elliott, Ian; Lane, Joseph M; Kennedy, John G
Platelet-rich plasma (PRP) has been suggested as an adjunct to aid in long-bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of PRP in the treatment of bone pathology. The PubMed/MEDLINE and EMBASE databases were screened using the following search criteria: "(Platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP) AND (bone OR osteocytes OR osteogenesis OR nonunion OR delayed union)." Studies were included if they fulfilled the following criteria: (1) studied the effect of PRP or a similar concentrated platelet product, defined as a blood product with platelet concentration elevated to higher than baseline; (2) established a control with which to compare PRP; (3) were published in a peer-reviewed journal; and (4) looked specifically at animal long-bone models. All review articles and clinical studies, including randomized controlled trials and case series, were excluded from the review. Studies examining the effects of PRP on bones of animals with confounding pathology were excluded. In studies that contained additional treatment variables, only the portion of the experiment that compared PRP directly with the control were evaluated. Data were then extracted with a standardized table. The search yielded 29 articles for inclusion. Seventy-two percent of the studies reported platelet concentrations. Eighty-nine percent of studies reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. One hundred percent showed significant increase in bone formation on radiographs in the PRP group. Eighty percent of studies reported a significant increase in bone area on microcomputed tomography. One hundred percent of studies showed a higher torsional stiffness for the PRP-treated defects. In the in vivo studies evaluated, PRP confers several beneficial effects on animal long-bone models. Proof of concept for PRP as a biologic adjunct in long-bone models has been determined.
PMID: 26652328
ISSN: 1938-2367
CID: 3524302

The effect of concentrated bone marrow aspirate in operative treatment of fifth metatarsal stress fractures; a double-blind randomized controlled trial

Weel, Hanneke; Mallee, Wouter H; van Dijk, C Niek; Blankevoort, Leendert; Goedegebuure, Simon; Goslings, J Carel; Kennedy, John G; Kerkhoffs, Gino M M J
BACKGROUND:Fifth metatarsal (MT-V) stress fractures often exhibit delayed union and are high-risk fractures for non-union. Surgical treatment, currently considered as the gold standard, does not give optimal results, with a mean time to fracture union of 12-18 weeks. In recent studies, the use of bone marrow cells has been introduced to accelerate healing of fractures with union problems. The aim of this randomized trial is to determine if operative treatment of MT-V stress fractures with use of concentrated blood and bone marrow aspirate (cB + cBMA) is more effective than surgery alone. We hypothesize that using cB + cBMA in the operative treatment of MT-V stress fractures will lead to an earlier fracture union. METHODS/DESIGN/METHODS:A prospective, double-blind, randomized controlled trial (RCT) will be conducted in an academic medical center in the Netherlands. Ethics approval is received. 50 patients will be randomized to either operative treatment with cB + cBMA, harvested from the iliac crest, or operative treatment without cB + cBMA but with a sham-treatment of the iliac crest. The fracture fixation is the same in both groups, as is the post-operative care.. Follow up will be one year. The primary outcome measure is time to union in weeks on X-ray. Secondary outcome measures are time to resumption of work and sports, functional outcomes (SF-36, FAOS, FAAM), complication rate, composition of osteoprogenitors in cB + cBMA and cost-effectiveness. Furthermore, a bone biopsy is taken from every stress fracture and analysed histologically to determine the stage of the stress fracture. The difference in primary endpoint between the two groups is analysed using student's t-test or equivalent. DISCUSSION/CONCLUSIONS:This trial will likely provide level-I evidence on the effectiveness of cB + cBMA in the operative treatment of MT-V stress fractures. TRIAL REGISTRATION/BACKGROUND:Netherlands Trial Register (reg.nr NTR4377 ).
PMID: 26290323
ISSN: 1471-2474
CID: 3524242

Arthroscopic Treatment for Anterior Ankle Impingement: A Systematic Review of the Current Literature

Zwiers, Ruben; Wiegerinck, Johannes I; Murawski, Christopher D; Fraser, Ethan J; Kennedy, John G; van Dijk, C Niek
PURPOSE/OBJECTIVE:To provide a comprehensive overview of the clinical outcomes of arthroscopic procedures used as a treatment strategy for anterior ankle impingement. METHODS:A systematic literature search of the Medline, Embase (Classic), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases was performed. Studies that met the following inclusion criteria were reviewed: studies reporting outcomes of arthroscopic treatment for anterior ankle impingement; studies reporting on more than 20 patients; a study population with a minimum age of 18 years; and studies in the English, Dutch, German, Italian, or Spanish language. Two reviewers independently performed data extraction. Extracted data consisted of population characteristics, in addition to both primary and secondary outcome measures. The Downs and Black scale was used to assess the methodologic quality of randomized and nonrandomized studies included in this review. RESULTS:Twenty articles were included in this systematic review. Overall, good results were found for arthroscopic treatment in patients with anterior ankle impingement. In the studies that reported patient satisfaction rates, high percentages of good to excellent satisfaction were described (74% to 100%). The percentages of patients who would undergo the same procedure again under the same circumstances were also high (94.3% to 97.5%). Complication rates were low (4.6%), particularly with respect to major complications (1.1%). The high heterogeneity of the included studies made it impossible to compare the results of the studies, including between anterolateral impingement and anteromedial impingement. CONCLUSIONS:Arthroscopic treatment for anterior ankle impingement appears to provide good outcomes with respect to patient satisfaction and low complication rates. However, on the basis of the findings of this study, no conclusion can be made in terms of the effect of the type of impingement or additional pathology on clinical outcome. LEVEL OF EVIDENCE/METHODS:Level IV, systematic review of Level II and IV studies.
PMID: 25801044
ISSN: 1526-3231
CID: 3524172

Functional Outcomes of Tibialis Posterior Tendoscopy With Comparison to Magnetic Resonance Imaging

Gianakos, Arianna L; Ross, Keir A; Hannon, Charles P; Duke, Gavin L; Prado, Marcelo P; Kennedy, John G
BACKGROUND: The purpose of the current study was to report functional outcomes of tendoscopy for treatment of tibialis posterior tendon pathology as well as compare its diagnostic capability with magnetic resonance imaging (MRI). METHODS: Clinical records and MRI of 12 patients who underwent tendoscopy of the tibialis posterior tendon (TPT) were retrospectively reviewed. Mean follow-up was 31 months (range, 26-43 months). Preoperative MRI findings were compared with tendoscopic findings to assess the diagnostic agreement between each modality. Functional outcomes were assessed using the Foot and Ankle Outcome Score (FAOS) and Short Form-12 (SF-12) General Health Questionnaire pre- and postoperatively. Mean patient age was 43 years (range, 17-63 years). Mean duration of preoperative symptoms was 15.5 months (range, 3-36 months). RESULTS: Pathologies addressed via tendoscopy included tenosynovitis, tendinosis, stenosis, tendon subluxation, and partial thickness tear (via mini-arthrotomy). Preoperative MRI findings were in agreement with tendoscopic findings in 8 of 12 cases (67%). Tendoscopy diagnosed and allowed access for treating pathology that was missed on MRI in the remaining four cases. The FAOS improved from a mean preoperative score of 58 (range, 36-78) to a mean postoperative score of 81 (range, 44-98) (P < .01). The SF-12 score improved from a mean preoperative score of 34 (range, 13-51) to a mean postoperative score of 51 (range, 21-76) (P = .01). CONCLUSIONS: Although MRI is considered an effective imaging technique for tendon pathology, tendoscopy may be a more sensitive diagnostic tool. Tendoscopy was an effective minimally invasive tool to diagnose and treat tibialis posterior tendon pathology resulting in functional improvements in the short-term for early stage TPT dysfunction. Further studies comparing tendoscopy with traditional open approaches are warranted. LEVEL OF EVIDENCE: Level IV Case Series.
PMID: 25759276
ISSN: 1071-1007
CID: 1494942

Investigating the Relationship Between Ankle Arthrodesis and Adjacent-Joint Arthritis in the Hindfoot. A Systematic Review [Correction]

Ling, J S; Smyth, N A; Fraser, E J; Hogan, M V; Seaworth, C M; Ross, K A; Kennedy, J G
PMID: 25948528
ISSN: 1535-1386
CID: 4065492

Anterolateral tibial osteotomy for accessing osteochondral lesions of the talus in autologous osteochondral transplantation: functional and t2 MRI analysis

Gianakos, Arianna L; Hannon, Charles P; Ross, Keir A; Newman, Hunter; Egan, Christopher J; Deyer, Timothy W; Kennedy, John G
BACKGROUND:Autologous osteochondral transplantation (AOT) is a primary treatment strategy for large or cystic osteochondral lesions of the talus (OLT) or a secondary replacement strategy after failed bone marrow stimulation. The technique requires perpendicular access to the talar dome, which is often difficult to obtain for posterior or lateral lesions. Traditional methods to access these areas have required disruption of the syndesmotic complex with concern over osteotomy reduction, malalignment, and ligament disruption. An alternate to these traditional methods of access is an anterolateral tibial osteotomy. The purpose of this study was to report functional and magnetic resonance imaging (MRI) outcomes in a series of patients that underwent AOT for treatment of an OLT via an anterolateral tibial osteotomy. METHODS:Records of patients that underwent an anterolateral tibial osteotomy for AOT were retrospectively reviewed. Pre- and postoperative Foot and Ankle Outcome Scores (FAOS) and demographic data were recorded. Magnetic resonance observation of cartilage repair tissue (MOCART) was used to assess morphologic state of tibial cartilage at the repair site of the osteotomy. Quantitative T2 mapping MRI was analyzed in the superficial and deep cartilage layers of the repair site of the osteotomy and in adjacent normal cartilage to serve as control tissue. Seventeen patients with a mean age of 36.9 (range, 17-76) years underwent anterolateral tibial osteotomy with a mean follow-up of 64 (range, 29 to 108) months. MOCART data were available in 9 of 17 patients, and quantitative T2 mapping was available in 6 patients. RESULTS:FAOS significantly improved from an average 39.2 (range, 14 to 66) out of 100 points preoperatively to 81.2 (range, 19 to 98) postoperatively (P < .01). The average MOCART score was 73.9 out of 100 points (range, 40 to 100). Quantitative T2 analysis demonstrated relaxation times that were not significantly different from the normal native cartilage in both the deep half and superficial half of interface repair tissue (P > .05). CONCLUSION/CONCLUSIONS:This study demonstrated that the anterolateral tibial osteotomy was a reasonable alternative for accessing centrolateral or posterolateral OLT for AOT with limited morbidity associated with the osteotomy. The evidence demonstrated adequate osteotomy and cartilaginous healing with improvement in functional outcome scores at medium-term follow-up. LEVEL OF EVIDENCE/METHODS:Level IV, retrospective case series.
PMID: 25576475
ISSN: 1944-7876
CID: 3524152

Investigating the relationship between ankle arthrodesis and adjacent-joint arthritis in the hindfoot: a systematic review

Ling, Jeffrey S; Smyth, Niall A; Fraser, Ethan J; Hogan, MaCalus V; Seaworth, Christine M; Ross, Keir A; Kennedy, John G
BACKGROUND:Ankle arthrodesis traditionally has been regarded as the treatment of choice for many patients with end-stage ankle arthritis. However, a major reported risk of ankle arthrodesis is adjacent-joint degeneration. There are conflicting views in the literature as to the causative link between ankle arthrodesis and progression to adjacent-joint arthritis. Recent studies have challenged the causative link between arthrodesis and adjacent-joint arthritis, purporting that preexisting adjacent-joint arthritis is present in many patients. The aim of the present study was to systematically review the available literature to determine if there is sufficient evidence to support either hypothesis. METHODS:A literature search of the EMBASE and PubMed/MEDLINE databases (1974 to present) was performed. A total of twenty-four studies were included for review. The studies were reviewed, and the relevant information was extracted, including research methodology, postoperative outcomes in the adjacent joints of the foot, and whether pre-arthrodesis radiographs and medical records were available for analysis. RESULTS:The twenty-four manuscripts included eighteen clinical studies, five biomechanical studies, and one gait-analysis study. The majority of biomechanical studies showed altered biomechanics in the fused ankle; however, there was no clear consensus as to whether these findings were causes of adjacent-joint arthritis. In studies assessing clinical outcomes, the reported prevalence of subtalar joint arthritis ranged from 24% to 100% and the prevalence of talonavicular and calcaneocuboid arthritis ranged from 18% to 77%. Correlation between imaging findings of arthritis in adjacent joints and patient symptoms was not established in a number of the clinical studies reviewed. CONCLUSIONS:There is no true consensus in the literature as to the effects of ankle arthrodesis on biomechanics or whether ankle arthrodesis leads to adjacent-joint arthritis. Similarly, a correlation between postoperative imaging findings and clinical presentation in this cohort of patients has not been conclusively demonstrated.
PMID: 25788309
ISSN: 1535-1386
CID: 3524162

Bone Marrow Stimulation and Biological Adjuncts for Treatment of Osteochondral Lesions of the Talus

Ross, Keir A.; Robbins, Justin; Easley, Mark E.; Kennedy, John G.
Osteochondral lesions of the talus (OLT) frequently occur after ankle sprain or fracture. Although there has been a growing interest in OLT treatment recently, the pathology has been recognized for hundreds of years. Yet there is a lack of consensus as to the most effective treatment strategy. Because of a lack of vasculature and the relative hypocellularity of articular cartilage, OLT are difficult to treat. Arthroscopic bone marrow stimulation (BMS) has become a commonly used method of treating smaller, primary OLT because of technical simplicity, the advantages of minimally invasive access, and cost-effectiveness. Results of BMS are good in the short-tomidterm with high overall success rates reported in the literature. However, the fibrocartilagenous repair tissue formed after BMS confers inferior biological and mechanical properties compared with native hyaline cartilage. Poorer outcomes have also been demonstrated in large and uncontained talar shoulder lesions. Subchondral bone compaction and thermal necrosis with drilling may be the cause for concern. There is also evidence of high rates of cracks and fissuring in fibrocartilage and inadequate integration with native cartilage postoperatively. Furthermore, there is a lack of long-term BMS outcome data available. Concerns with BMS have prompted investigation of biological adjuncts that could potentially improve the quality of BMS repair tissue and form a more hyaline-like repair. Arthroscopic BMS has much promise for the future but long-term, high-level studies are required. Enhancement of BMS with biological adjuncts and improved surgical instrumentation has the potential to improve cartilage repair and outcomes.
ISI:000218261900009
ISSN: 1536-0644
CID: 3522712

Osteochondral Autologous Transfer and Bulk Allograft for Biological Resurfacing of Large Osteochondral Lesions of the Talus

Robbins, Justin; Ross, Keir A.; Kennedy, John G.; Easley, Mark E.
Osteochondral lesions of the talus that have previously undergone surgical management or involve the shoulder region of the talus require methods other than microfracture for treatment. For those lesions that have failed microfracture and do not involve the shoulder of the talus, osteochondral autologous transfer is our preferred treatment of choice. Perpendicular access to the lesion, often by osteotomy, is required for this technique. For those osteochondral lesions of the talus that involve the shoulder of the talus, structural allograft is indicated. This article describes our technique for osteochondral autologous transfer and structural allograft implantation.
ISI:000218261900008
ISSN: 1536-0644
CID: 3522702