Publications by authors named "Arash Sharafat Vaziri"

14 Publications

  • Page 1 of 1

Evaluation of TAK-242 (Resatorvid) Effects on Inflammatory Status of Fibroblast-like Synoviocytes in Rheumatoid Arthritis and Trauma Patients.

Iran J Allergy Asthma Immunol 2021 Aug 7;20(4):453-464. Epub 2021 Aug 7.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis )RA( pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients.
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August 2021

Role of Fibroblast Activation Protein Alpha in Fibroblast-like Synoviocytes of Rheumatoid Arthritis.

Iran J Allergy Asthma Immunol 2021 Jun 6;20(3):338-349. Epub 2021 Jun 6.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran AND Inflammation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.
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http://dx.doi.org/10.18502/ijaai.v20i3.6335DOI Listing
June 2021

Low post-arthroplasty infection rate is possible in developing countries: long-term experience of local vancomycin use in Iran.

J Orthop Surg Res 2021 Mar 17;16(1):199. Epub 2021 Mar 17.

Department of Orthopaedic Surgery, Shahid Beheshti Hospital, Babol University of Medical Sciences, Babol, Mazandaran, Iran.

Background: Utilizing intrawound vancomycin powder in TKA surgery has yielded rather contrasting results in the current literature. Furthermore, CDC criteria, although effective in general, are not specifically designed for post-TKA infections. Here, we present a 7-year experience of vancomycin use in primary TKA in a high-volume tertiary knee center in Iran. Also, new criteria are proposed to detect suspected superficial post-TKA infections.

Methods: This is a retrospective analysis of primary total knee arthroplasties performed in a tertiary knee center, from March 2007 to December 2018, by a single senior knee surgeon. All patients with follow-up periods of less than 1 year were excluded from the study. Since March 2011, all patients received vancomycin (powder, 1 g) before water-tight closure of the joint capsule. A comparison was made between this group and historical control subjects (operated from March 2007 to March 2011).

Results: Altogether, 2024 patients were included in the study. The vancomycin and the control groups included 1710 and 314 cases respectively. Patients were mostly women (male to female ratio, 1 to 4), with a mean age of 65.20 (SD = 10.83) years. In the vancomycin group, the rate of suspected SII (1.87%) and PJI (0.41%) was significantly lower than the control group (P = 0.002).

Conclusions: Our experience shows that application of local vancomycin during TKA surgery could be a reasonable infection prevention measure, although prospective randomized studies are required to evaluate its efficacy.
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http://dx.doi.org/10.1186/s13018-021-02344-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968172PMC
March 2021

Transformation of fibroblast-like synoviocytes in rheumatoid arthritis; from a friend to foe.

Auto Immun Highlights 2021 Feb 5;12(1). Epub 2021 Feb 5.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Swelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs' phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.
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http://dx.doi.org/10.1186/s13317-020-00145-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863458PMC
February 2021

Safety and efficacy of engineered tissue composed of silk fibroin/collagen and autologous chondrocytes in two patients with cartilage defects: A pilot clinical trial study.

Knee 2020 Oct 27;27(5):1300-1309. Epub 2020 Jul 27.

Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran. Electronic address:

Background: The objective of this pilot clinical trial study was to evaluate safety and effectiveness of the newly engineered tissue composed of autologous chondrocytes and collagen/fibroin scaffold in repair of osteochondral defects.

Methods: We implemented a pilot clinical study in two patients with knee osteochondral lesions using engineered tissue composed of scaffold and autologous chondrocytes. Patients were clinically evaluated using the International Repair Cartilage Society score and magnetic resonance imaging (MRI) for one year.

Results: Improved clinical outcomes and objective scores indicated a normal or nearly normal knee in both patients. International Knee Documentation Committee score was upgraded from 34.5 at baseline to 72.4 in the first patient, and 28.7 to 81.6 in the second patient. Visual analogue scale, showing the suffering pain score, was lowered from 8 to 0 in both patients, Western Ontario and McMaster Universities Osteoarthritis Index score representing the physical ability of the patients was changed from 68.1 to 87.1 in Patient 1 and 58.3 to 87.1 in Patient 2, the knee function score, related to the functional ability of the knee, was improved from 70 to 100 in the first patient and from 45 to 91 in the second patient. MRI showed great coverage and integration of the graft in patients, with no effusion, decreased edema and cartilage formation signals.

Conclusions: The functional and clinical outcomes alongside MRI data showed promising results for regenerating osteochondral defects. A randomized clinical trial study is required to confirm feasibility of this novel engineered tissue in repair of osteochondral defects.
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http://dx.doi.org/10.1016/j.knee.2020.06.015DOI Listing
October 2020

Loop-Post Construct, A Novel Technique for Medial Meniscus Root Repair.

Arch Bone Jt Surg 2020 Jul;8(4):545-549

Department of Orthopedics, Tehran University of Medical Sciences, Tehran, Iran.

Surgical reattachment of medial meniscus posterior root tear (MMPRT) with transtibial sutures can delay the presence of medial knee joint compartment osteoarthritis. Most suture configurations are placed five mm away from the torn margin in the meniscal substance which is already degenerated and may decrease the pull out strengths of repair construct. The number of meniscus penetration may also be important considering meniscus tissue damage with more complex suture techniques impose the risk of suture cut out through the meniscus substance. We introduce our loop postsuture construct technique which is simple, cheap and reproducible.
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http://dx.doi.org/10.22038/abjs.2020.44187.2209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443071PMC
July 2020

Two-stage Total Knee Arthroplasty for Treatment of Surgical Failure of Septic Arthritis in Degenerative Knee Joints.

Arch Bone Jt Surg 2020 Jul;8(4):524-530

Department of Orthopedics, Tehran University of Medical Sciences, Tehran, Iran.

Background: The ultimate goal of the treatment of infectious knee arthritis is to protect the articular cartilage from adverse effects of infection. Treatment, however, is not always hundred percent successful and has a 12% failure rate. Persistent infection is more likely to happen in elderly patients and those with underlying joint diseases, particularly osteoarthritis. Eradication of infection and restoration of function in the involved joint usually are not possible by conventional treatment strategies. There are few case series reporting two-stage primary knee arthroplasty as the salvage treatment of the septic degenerative knee joint; however, the treatment protocol remains to be elucidated.

Methods: Based on a proposed approach, patients with failure of common interventions for treatment of septic knee arthritis and underlying joint degeneration were treated by two-stage TKA and intervening antibiotic loaded static cement spacer. Suppressive antibiotic therapy was not prescribed after the second stage.

Results: Complete infection eradication was achieved with mean follow up of 26 months. All cases were balanced with primary total knee prosthesis. The knee scores and final range of motions were comparable to other studies.

Conclusion: The two-stage total knee replacement technique is a good option for management of failure of previous surgical treatment in patients with septic arthritis and concomitant joint degeneration. Our proposed approach enabled us to use primary prosthesis in all of our patients with no need for suppressive antibiotic therapy.
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http://dx.doi.org/10.22038/abjs.2020.43184.2178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443076PMC
July 2020

Sonography: a sensitive and specific method for detecting trochlear cartilage pathologies.

J Ultrasound 2020 Sep 10;23(3):259-263. Epub 2020 Jun 10.

Department of Orthopaedic Surgery, Shariati Hospital, Tehran University of Medical Sciences, Jalal Street, Tehran, Iran.

Purpose: MRI is now the modality of choice for evaluating articular cartilage. Nevertheless, it has some general drawbacks. Some patients cannot undergo MRI, and in others US scan could be the first examination and cartilage should be evaluated. Ultrasound could be a useful method for detecting trochlear cartilage low-grade lesions. In this study, our goal was to evaluate the efficacy of ultrasonography in detecting these lesions.

Methods: All patients referred to our hospital, from July 2018 to July 2019, who were arthroscopic candidates due to sport-related pathologies, underwent ultrasound scan 1 day prior to surgery. Ultrasound assessment was performed by an expert radiologist, with a 13-MHz probe, located transversely proximal to the patella in different degrees of knee flexion to assess trochlear lesion grade and thickness. Arthroscopic examination of all patients was performed by an experienced orthopedic knee surgeon (second author). Sensitivity and specificity of ultrasound were calculated.

Results: A total of 48 patients were involved in the study with a mean age of 33.2 years (SD: 9.7), between 19 and 51 years of age. Patients were 81% male (39 patients). The sensitivity of ultrasound in grading of trochlear cartilage lesion was 100%, meanwhile its specificity was 88.2% (30 cases had normal cartilage while this figure was 34 in arthroscopy).

Conclusion: Sonography is a low-cost, accessible diagnostic tool with high sensitivity and specificity for early detection of trochlear cartilage pathologies. It can play an important role as an outpatient diagnostic workup in patients with anterior knee pain.
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http://dx.doi.org/10.1007/s40477-020-00488-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441103PMC
September 2020

Epigenetics in rheumatoid arthritis; fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease.

Immunol Cell Biol 2020 03 26;98(3):171-186. Epub 2020 Jan 26.

Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Rheumatoid arthritis (RA) is characterized by immune dysfunctions and chronic inflammation that mainly affects diarthrodial joints. Genetics has long been surveyed in searching for the etiopathogenesis of the disease and partially clarified the conundrums within this context. Epigenetic alterations, such as DNA methylation, histone modifications, and noncoding RNAs, which have been considered to be involved in RA pathogenesis, likely explain the nongenetic risk factors. Epigenetic modifications may influence RA through fibroblast-like synoviocytes (FLSs). It has been shown that FLSs play an essential role in the onset and exacerbation of RA, and therefore, they may illustrate some aspects of RA pathogenesis. These cells exhibit a unique DNA methylation profile in the early stage of the disease that changes with disease progression. Histone acetylation profile in RA FLSs is disrupted through the imbalance of histone acetyltransferases and histone deacetylase activity. Furthermore, dysregulation of microRNAs (miRNAs) is immense. Most of these miRNAs have shown an aberrant expression in FLSs that are involved in proliferation and cytokine production. Besides, dysregulation of long noncoding RNAs in FLSs has been revealed and attributed to RA pathogenesis. Further investigations are needed to get a better view of epigenetic alterations and their interactions. We also discuss the role of these epigenetic alterations in RA pathogenesis and their therapeutic potential.
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http://dx.doi.org/10.1111/imcb.12311DOI Listing
March 2020

An evaluation of the use of a lateral wedged insole and a valgus knee brace in combination in subjects with medial compartment knee osteoarthritis (OA).

Assist Technol 2021 03 4;33(2):87-94. Epub 2019 Apr 4.

Orthopedic surgery department, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of).

: The aim of this study was to evaluate the effect (6 weeks) of the use of a knee brace and a lateral wedge insole, both in isolation and combined, on the knee adduction moment (KAM), pain levels, kinematics (velocity, stride length, cadence), knee ROM, function, and satisfaction in patients with knee osteoarthritis (OA).: Twenty-one patients with medial compartment knee OA were participated in this study. A relatively light three-point valgus knee brace (VB) and full length custom-made lateral wedge insole with arch support were prepared for each subject. Patients divided into three groups at random.: The use of a custom fit valgus brace with lateral edge insole concurrently can reduce a greater peak KAM than use in isolation (30%). In addition, the use of both interventions can improve walking velocity, cadence, and reduce levels of pain in patients with medial compartment OA.: All parameters except stride length and KAM in comparison with first day of wearing interventions improved significantly in the combined, concurrent usage group. The use of a lateral wedge insole and a valgus knee brace in combination can improve the kinetic and kinematic parameters in patients with medial compartment knee OA.
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http://dx.doi.org/10.1080/10400435.2019.1595788DOI Listing
March 2021

Arthroscopic ablation of an osteoid osteoma of the elbow: a case series with a minimum of 18 months' follow-up.

J Shoulder Elbow Surg 2017 May 22;26(5):e122-e127. Epub 2017 Feb 22.

Joint Reconstruction Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Arthroscopic excision of an osteoid osteoma was first reported in the knee joint; since then, there have been several reports of arthroscopic excisions in the knee, shoulder, and elbow, with inconclusive outcomes because of a limited number of cases. The aim of this prospective study was to evaluate the medium-term functional effects of arthroscopic ablation in cases of an osteoid osteoma around the elbow.

Methods: We treated osteoid osteoma of the elbow through arthroscopic ablation in 10 patients. The arthroscopic resection procedure was performed 23 ± 9 months (range, 12-36 months) after initial symptoms. At the preoperative examination and last follow-up examination, the elbow flexion-extension and forearm supination-pronation ranges of motion were measured. The patients were assessed by the Mayo Elbow Performance Score, the visual analog scale for the elbow and wrist, and the Quick Disabilities of the Arm, Shoulder, and Hand score. Finally, the patients' general satisfaction was assessed.

Results: The postoperative elbow flexion-extension range of motion was significantly higher compared with range of motion before surgery (P = .001; r = 0.86). According to the Mayo Elbow Performance Score, the average score increased significantly at the final follow-up examination. The mean preoperative and final Quick Disabilities of the Arm, Shoulder, and Hand scores were 47 ± 14 and 1.6 ± 2.8, respectively (P < .001). All patients were satisfied with the operation result.

Conclusion: According to the results of our study, arthroscopic ablation is a safe and efficient method of treatment for osteoid osteoma of the elbow, with a fast rehabilitation time.
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http://dx.doi.org/10.1016/j.jse.2017.01.010DOI Listing
May 2017

Femoral Condyle Fracture during Revision of Anterior Cruciate Ligament Reconstruction: Case Report and a Review of Literature.

Arch Bone Jt Surg 2015 Apr;3(2):137-40

Sohrab Keyhani MD Orthopedic Department, Akhtar Hospital, Shahid-Beheshti University of Medical Sciences, Tehran, Iran.

A rare and devastating complication following anterior cruciate ligament (ACL) revision reconstruction is femoral fracture. A 35-year old male soccer player with a history of ACL tear from one year ago, who underwent arthroscopic ACL reconstruction and functioned well until another similar injury caused ACL re-rupture. Revision of ACL reconstruction was performed and after failure of graft tension during the pumping, a fluoroscopic assessment showed a femoral condyle fracture. The patient referred to our knee clinic and was operated on in two stages first fixation of the fracture and then ACL re-revision after fracture healing was complete. Not inserting multiple guide pins, keeping a safe distance from the posterior cortex and giving more attention during graft tensioning, especially in revision surgeries, are all small points that can reduce the risk of fracture during the revision of ACL reconstruction.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4468616PMC
April 2015

Surgical treatment of pectoralis major tendon rupture (outcome assessment).

Asian J Sports Med 2014 Jun;5(2):129-35

Department of Orthopedic Surgeon, Booshehr University of Medical Sciences, Booshehr, Iran.

Purpose: Rupture of pectoralis major (PM) occurs most commonly as a result of an indirect mechanism associated with extensive tension on a maximally contracted muscle. Patients with PM tendon ruptures, classically present a history of sudden severe pain in arm and shoulder at the time of injury. Treatment options vary from conservative to operative. In cases with total or near-total injuries, surgical treatment by anatomic repair is generally advised, since conservative treatment may lead to poor results. The present paper reports 24 cases of surgically-treated ruptured PM while assessing the results.

Methods: Between 2005 and 2010, 32 cases of unilaterally distal ruptured PM were surgically treated by the same surgeon and same technique, in two teaching hospitals of Tehran University of Medical Sciences. All cases were followed postoperatively by physical examination and functional criteria.

Results: Since eight of the cases were lost from follow up, 24 cases were followed for at least one year. According to modified Kakwani system, 6 of our patients (25%) rated as excellent, 15 cases(62.5%) rated as good, 2 cases (8.33%) rated as fair and 1 case (4.1%) rated as poor.

Conclusion: In conclusion, we see that 87.5% of the patients had good to excellent results, according to modified Kakwani classification, after one year of follow up. So it seems that surgical repair of the pectoralis major ruptures will help the patients to return to their previous activities more frequently and we believe, to achieve better functional outcome. Meticulous surgical technique and attention to rehabilitation program are more important than delay in surgery.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4374614PMC
June 2014

Evidence-based status of osteochondral cylinder transfer techniques: a systematic review of level I and II studies.

Arthroscopy 2014 Apr;30(4):497-505

Tehran University of Medical Science and Shariati Hospital, Tehran, Iran.

Purpose: Our purpose was to examine the Level I and II evidence for the use of osteochondral cylinder transfer technique (OCT) for cartilage repair.

Methods: A literature search was carried out for Level I and II evidence studies on cartilage repair using the PubMed database. All the studies that involved OCT were identified. Only Level I and II studies that compared OCT to other modalities of treatment such as microfracture (MF) and autologous chondrocyte implantation (ACI) were selected.

Results: A total of 8 studies matched the selection criteria with 2 Level I and 6 Level II studies. Four studies compared OCT with MF, 3 compared OCT with ACI, and one compared all 3 techniques. Of 3 studies, 4 came from a single center. Mean age of patients ranged from 24 to 33 years, and mean follow-up ranged from 9 to 124 months. The studies from the single center showed superior results from OCT over MF, especially in younger patients, with one study having long-term follow-up of 10 years. They also showed an earlier return to sports. The size of the lesions were small (average < 3 cm(2)). The 4 other independent studies did not show any difference between OCT and ACI, with one study showing inferior outcome in the OCT group. Magnetic resonance imaging (MRI) showed good osseous integration of the osteochondral plugs to the subchondral bone. Histologic examination showed that there was hyaline cartilage in the transplanted osteochondral plugs but no hyaline cartilage between the plugs.

Conclusions: From the studies of a single center, OCT had an advantage over MF in younger patients with small chondral lesions. Comparison of outcomes between OCT and ACI showed no significant difference in 2 studies and contrasting results in another 2 studies. There was insufficient evidence for long-term results for OCT.

Level Of Evidence: Level II, systematic review of Level I and II studies.
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http://dx.doi.org/10.1016/j.arthro.2013.12.023DOI Listing
April 2014
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