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356


The biology of ewing sarcoma

Ross, Keir A; Smyth, Niall A; Murawski, Christopher D; Kennedy, John G
Objective. The goal of this study was to review the current literature on the biology of Ewing's sarcoma, including current treatments and the means by which an understanding of biological mechanisms could impact future treatments. Methods. A search of PubMed and The Cochrane Collaboration was performed. Both preclinical and clinical evidence was considered, but specific case reports were not. Primary research articles and reviews were analyzed with an emphasis on recent publications. Results. Ewing sarcoma is associated with specific chromosomal translocations and the resulting transcripts/proteins. Knowledge of the biology of Ewing sarcoma has been growing but has yet to significantly impact or produce new treatments. Localized cases have seen improvements in survival rates, but the same cannot be said of metastatic and recurrent cases. Standard surgical, radiation, and chemotherapy treatments are reaching their efficacy limits. Conclusion. Improving prognosis likely lies in advancing biomarkers and early diagnosis, determining a cell(s) of origin, and developing effective molecular therapeutics and antiangiogenic agents. Preclinical evidence suggests the utility of molecular therapies for Ewing sarcoma. Early clinical results also reveal potential for novel treatments but require further development and evaluation before widespread use can be advocated.
PMID: 23346417
ISSN: 2090-5661
CID: 3523962

Anatomic lateral ligament reconstruction in the ankle: a hybrid technique in the athletic population

Kennedy, John G; Smyth, Niall A; Fansa, Ashraf M; Murawski, Christopher D
BACKGROUND:Anatomic and checkrein tenodesis reconstruction techniques have been described as a means of treatment for chronic lateral ligament instability in the ankle. The current article describes a hybrid procedure using the most advantageous concepts of both techniques for use when insufficient normal ligament remains to fashion a direct repair of the anterior talofibular ligament (ATFL). PURPOSE/OBJECTIVE:The authors report the results at a minimum 1-year follow-up of 57 patients who underwent a hybrid anatomic lateral ligament reconstruction technique in the ankle. STUDY DESIGN/METHODS:Case series; Level of evidence, 4. METHODS:Fifty-seven patients underwent a hybrid anatomic lateral ligament reconstruction procedure under the care of the senior author. All patients were assessed preoperatively and postoperatively using the Foot and Ankle Outcome Score (FAOS) and Short Form-12 (SF-12) outcome score. The mean patient age at the time of surgery was 28 years (range, 17-65 years), including 39 male and 18 female patients. The mean follow-up time was 32 months (range, 12-47 months). RESULTS:The FAOS improved from 58 points preoperatively to 89 points postoperatively (P < .01). The SF-12 score improved from 48 points before surgery to 80 points at final follow-up (P < .01). All patients achieved mechanical stability at final clinical follow-up; 7 patients (12%) demonstrated functional instability. Functional instability was found to significantly influence not returning to sport at the previous level. CONCLUSION/CONCLUSIONS:This hybrid anatomic lateral ligament reconstruction technique using a peroneus longus autograft to substitute the native ATFL provides an alternative to anatomic reconstruction when direct repair is not possible.
PMID: 22879402
ISSN: 1552-3365
CID: 3523932

Critical defect size for osteochondral lesions of the talus: letter to the editor [Letter]

Hannon, Charles P; Murawski, Christopher D; Smyth, Niall A; Kennedy, John G
PMID: 22941577
ISSN: 1552-3365
CID: 3523942

The lateral dorsal cutaneous branch of the sural nerve: clinical importance of the surgical approach to proximal fifth metatarsal fracture fixation

Fansa, Ashraf M; Smyth, Niall A; Murawski, Christopher D; Kennedy, John G
BACKGROUND:Fractures of the proximal fifth metatarsal are one of the most common forefoot injuries encountered by orthopaedic surgeons in sports medicine. The percutaneous surgical approach to Jones fracture fixation and corresponding anatomy has received little attention in the literature to date. PURPOSE/OBJECTIVE:To describe in detail the location of the lateral dorsal cutaneous nerve (LDCN) and its branches relative to the base of the fifth metatarsal and to the standard lateral approach. STUDY DESIGN/METHODS:Descriptive laboratory study. METHODS:Ten fresh-frozen cadaveric foot specimens were used for this study. Specimens were dissected at the lateral aspect of the foot over the proximal fifth metatarsal, and the LDCN and its branches were identified. The distance of the LDCN to the superior border of the peroneus brevis tendon (PBT) was measured relative to standard reference points in all specimens, and the presence of an anastomotic branch was noted. A set of vertical and horizontal reference lines were also constructed to determine whether the LDCN or its branches would be compromised by a standard lateral approach. RESULTS:The LDCN was superficial (ie, lateral) and inferior to the superior border of the PBT in all specimens and at all reference points. A bifurcation of the LDCN was present in 8 specimens, located an average of 18 mm posterior and 11 mm dorsal to the base of the fifth metatarsal. The dorsolateral branch and dorsomedial branch of the LDCN each intersected with the base of the fifth metatarsal horizontal line and vertical line, respectively, indicating potential compromise of the nerve with a standard lateral surgical approach. CONCLUSION/CONCLUSIONS:The standard lateral approach to the base of the fifth metatarsal carries a higher risk for surgical injury to the LDCN. A "high and inside" approach that remains superior to the superior border of the PBT is anatomically safe and may decrease the chance of intraoperative nerve injury and irritation postoperatively.
PMID: 22679294
ISSN: 1552-3365
CID: 3523902

Establishing proof of concept: Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

Smyth, Niall A; Murawski, Christopher D; Haleem, Amgad M; Hannon, Charles P; Savage-Elliott, Ian; Kennedy, John G
Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative (microfracture) or replacement (autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration, with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.
PMID: 22816065
ISSN: 2218-5836
CID: 3523912

Platelet-rich plasma as a biological adjunct to the surgical treatment of osteochondral lesions of the talus

Smyth, NA; Fansa, AM; Murawski, CD; Kennedy, John G
Platelet-rich plasma (PRP) has become an increasingly utilized biological adjunct in orthopedics, particularly in sports medicine. Cartilage repair is one such application for which PRP has been utilized. Osteochondral lesions of the talus are common athletic injuries, and they present a difficult clinical problem in part because of the poor biological environment of cartilage healing. The current authors' are investigating the use of PRP with reparative and restorative techniques, including arthroscopic bone marrow stimulation and autologous osteochondral transplantation, respectively. The hypothesis is that the bioactive molecules and growth factors contained within PRP will stimulate a healing response for the differentiation of fibrocartilage such that it resembles a more hyaline-like microstructure, in addition to enhancing bony incorpoaration. In addition to these anabolic pathways, there is also recent evidence to suggest that PRP may inhibit the catabolic processes of arthritis. This article presents the indications and treatment strategy for using PRP in the surgical treatment of osteochondral lesions of the talus
ORIGINAL:0013327
ISSN: 1536-0644
CID: 3702422

Autologous osteochondral transplantation of the talus partially restores contact mechanics of the ankle joint

Fansa, Ashraf M; Murawski, Christopher D; Imhauser, Carl W; Nguyen, Joseph T; Kennedy, John G
BACKGROUND:Autologous osteochondral transplantation procedures provide hyaline cartilage to the site of cartilage repair. It remains unknown whether these procedures restore native contact mechanics of the ankle joint. PURPOSE/OBJECTIVE:This study was undertaken to characterize the regional and local contact mechanics after autologous osteochondral transplantation of the talus. STUDY DESIGN/METHODS:Controlled laboratory study. METHODS:Ten fresh-frozen cadaveric lower limb specimens were used for this study. Specimens were loaded using a 6 degrees of freedom robotic arm with 4.5 N·m of inversion and a 300-N axial compressive load in a neutral plantar/dorsiflexion. An osteochondral defect was created at the centromedial aspect of the talar dome and an autologous osteochondral graft from the ipsilateral knee was subsequently transplanted to the defect site. Regional contact mechanics were analyzed across the talar dome as a function of the defect and repair conditions and compared with those in the intact ankle. Local contact mechanics at the peripheral rim of the defect and at the graft site were also analyzed and compared with the intact condition. A 3-dimensional laser scanning system was used to determine the graft height differences relative to the native talus. RESULTS:The creation of an osteochondral defect caused a significant decrease in force, mean pressure, and peak pressure on the medial region of the talus (P = .037). Implanting an osteochondral graft restored the force, mean pressure, and peak pressure on the medial region of the talus to intact levels (P = .05). The anterior portion of the graft carried less force, while mean and peak pressures were decreased relative to intact (P = .05). The mean difference in graft height relative to the surrounding host cartilage for the overall population was -0.2 ± 0.3 mm (range, -1.00 to 0.40 mm). Under these conditions, there was no correlation between height and pressure when the graft was sunken, flush, or proud. CONCLUSION/CLINICAL RELEVANCE/CONCLUSIONS:Placement of the osteochondral graft in the most congruent position possible partially restored contact mechanics of the ankle joint. Persistent deficits in contact mechanics may be due to additional factors besides graft congruence, including structural differences in the donor cartilage when compared with the native tissue.
PMID: 21868691
ISSN: 1552-3365
CID: 3523882

The Treatment of Osteochondral Lesions of the Talus with Autologous Osteochondral Transplantation and Bone Marrow Aspirate Concentrate: Surgical Technique

Kennedy, John G; Murawski, Christopher D
OBJECTIVE:To present the functional results after autologous osteochondral transplantation with bone marrow aspirate concentrate in 72 patients, while placing an emphasis on the surgical technique. METHODS:Between 2005 and 2009, 72 patients underwent autologous osteochondral transplantation under the care of the senior author. The mean patient age at the time of surgery was 34.19 years (range, 16-85 years). All patients were followed for a minimum of 1 year after surgery. The mean follow-up time was 28.02 months (range, 12-64 months). Patient-reported outcome measures were taken preoperatively and at final follow-up using the Foot and Ankle Outcome Score (FAOS) and Short Form-12 (SF-12) general health questionnaire. Identical questionnaires were used in all instances. RESULTS:The mean FAOS scores improved from 52.67 points preoperatively to 86.19 points postoperatively (range, 71-100 points). The mean SF-12 scores also improved from 59.40 points preoperatively to 88.63 points postoperatively (range, 52-98 points). Three patients reported donor site knee pain after surgery, and one patient required the decompression of a cyst that developed beneath the graft site approximately 2 years after the index procedure. CONCLUSION/CONCLUSIONS:Autologous osteochondral transplantation is a reproducible and primary treatment strategy for large osteochondral lesions of the talus.
PMID: 26069591
ISSN: 1947-6035
CID: 3524212

Prolongation of T2 Stratification after Microfracture Does Not Indicate Normal Cartilage

Murawski, Christopher D; Kennedy, John G
PMID: 26069599
ISSN: 1947-6035
CID: 3524222

Percutaneous internal fixation of proximal fifth metatarsal jones fractures (Zones II and III) with Charlotte Carolina screw and bone marrow aspirate concentrate: an outcome study in athletes

Murawski, Christopher D; Kennedy, John G
BACKGROUND:Internal fixation is a popular first-line treatment method for proximal fifth metatarsal Jones fractures in athletes; however, nonunions and screw breakage can occur, in part because of nonspecific fixation hardware and poor blood supply. PURPOSE/OBJECTIVE:To report the results from 26 patients who underwent percutaneous internal fixation with a specialized screw system of a proximal fifth metatarsal Jones fracture (zones II and III) and bone marrow aspirate concentrate. STUDY DESIGN/METHODS:Case series; Level of evidence, 4. METHODS:Percutaneous internal fixation for a proximal fifth metatarsal Jones fracture (zones II and III) was performed on 26 athletic patients (mean age, 27.47 years; range, 18-47). All patients were competing at some level of sport and were assessed preoperatively and postoperatively using the Foot and Ankle Outcome Score and SF-12 outcome scores. The mean follow-up time was 20.62 months (range, 12-28). Of the 26 fractures, 17 were traditional zone II Jones fractures, and the remaining 9 were zone III proximal diaphyseal fractures. RESULTS:The mean Foot and Ankle Outcome Score significantly increased, from 51.15 points preoperatively (range, 14-69) to 90.91 at final follow-up (range, 71-100; P < .01). The mean physical component of the SF-12 score significantly improved, from 25.69 points preoperatively (range, 6-39) to 54.62 at final follow-up (range, 32-62; P < .01). The mean mental component of the SF-12 score also significantly improved, from 28.20 points preoperatively (range, 14-45) to 58.41 at final follow-up (range, 36-67; P < .01). The mean time to fracture healing on standard radiographs was 5 weeks after surgery (range, 4-24). Two patients did not return to their previous levels of sporting activity. One patient experienced a delayed union, and 1 healed but later refractured. CONCLUSION/CONCLUSIONS:Percutaneous internal fixation of proximal fifth metatarsal Jones fractures, with a Charlotte Carolina screw and bone marrow aspirate concentrate, provides more predictable results while permitting athletes a return to sport at their previous levels of competition, with few complications.
PMID: 21212308
ISSN: 1552-3365
CID: 3523872