Vasili Karas

Platelet-Rich Plasma: A Milieu of Bioactive Factors

Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.

The Anti-inflammatory and Matrix Restorative Mechanisms of Platelet-Rich Plasma in Osteoarthritis

Background: Intra-articular (IA) treatment with platelet-rich plasma (PRP) for osteoarthritis (OA) results in improved patient-reported pain and function scores. Purpose: To measure the effects of PRP and high molecular weight hyaluronan (HA) on the expression of anabolic and catabolic genes and on the secretion of nociceptive and inflammatory mediators from OA cartilage and synoviocytes. Study Design: Controlled laboratory study. Methods: Synovium and cartilage harvested from patients undergoing total knee arthroplasty were co-cultured with media of PRP or HA. Tumor necrosis factor–α (TNF-α), interleukin-6 (IL-6), and IL-1β were measured in the media by enzyme-linked immunosorbent assay. Hyaluronan synthase–2 (HAS-2), matrix metalloproteinase–1 (MMP-1), MMP-13, and TNF-α genes were measured in synoviocytes by reverse transcription polymerase chain reaction (RT-PCR). Collagen type I α1 (COL1A1), COL2A1, aggrecan (ACAN), and MMP-13 gene expression were measured in cartilage by quantitative RT-PCR. Results: Media TNF-α concentration was decreased in PRP and HA compared with control cultures (PRP = 6.94 pg/mL, HA = 6.39 pg/mL, control = 9.70 pg/mL; P ≤ .05). Media IL-6 concentration was decreased in HA compared with PRP and control (HA = 5027 pg/mL, PRP = 5899 pg/mL, control = 5613 pg/mL; P ≤ .05). Media IL-1β was below detectable concentrations (<0.1 pg/mL) in all samples. Synoviocyte MMP-13 expression was decreased in PRP compared with HA and control (PRP = 10.1, HA = 12.8, control = 13.5; P ≤ .05). Synoviocyte HAS-2 expression was increased in PRP compared with HA and control (PRP = 12.1, HA = 9.8, control = 8.7; P ≤ .05). Cartilage ACAN expression was increased in PRP compared with HA, but neither was different from control (PRP = 8.8, HA = 7.7, control = 7.6; P ≤ .05); COL1A1 expression was increased in HA compared with PRP, but neither was different from control (PRP = 14.9, HA = 13.5, control = 12.9; P ≤ .05). Neither platelet nor leukocyte concentration had a significant effect on outcome measurements (gene or protein expression data) in cartilage or synoviocytes (P > .05). Conclusion: Both PRP and HA treatments of OA joint tissues result in decreased catabolism, but PRP treatment also resulted in a significant reduction of MMP-13, an increase in HAS-2 expression in synoviocytes, and an increase in cartilage synthetic activity compared with HA. These results indicate that PRP acts to stimulate endogenous HA production and decrease cartilage catabolism. Platelet-rich plasma showed similar effects as HA in the suppression of inflammatory mediator concentration and expression of their genes in synoviocytes and cartilage. Clinical Relevance: The antinociceptive and anti-inflammatory activities of PRP support its use in OA joints to reduce pain and modulate the disease process. This study supports further clinical investigations of IA PRP for the treatment of OA.

Outcomes of type II superior labrum, anterior to posterior (SLAP) repair: Prospective evaluation at a minimum two-year follow-up

HYPOTHESIS Patients with type II superior labrum, anterior to posterior (SLAP) lesions will have improved function and decreased pain at a minimum of 2 years after arthroscopic SLAP repair using bioabsorbable suture anchor fixation. MATERIALS AND METHODS The study population consisted of 48 patients who underwent arthroscopic SLAP repair. Subjective shoulder scores, range of motion, and strength (postoperative only) were assessed preoperatively and at a minimum of 2 years postoperatively. RESULTS At an average of 3.4 years after surgery, statistically significant improvement was seen in American Shoulder and Elbow Surgeons score, University of California, Los Angeles score, Simple Shoulder Test scores, Constant activities of daily living, visual analog scale for pain, and Short Form-12 Health Survey physical outcome scores. Improvements were made in forward flexion, abduction, external rotation, and internal rotation. Subgroup analysis of nonathletes, nonoverhead athletes, recreational overhead athletes, and collegiate overhead athletes showed preoperative to postoperative improvements in subjective outcomes scores. Overhead laborers and nonlaborers also showed preoperative to postoperative improvements in subjective shoulder scores. DISCUSSION No differences were seen between the outcomes of nonathletes, nonoverhead athletes, recreational overhead athletes, and collegiate overhead athletes, suggesting that SLAP type II repair is successful independent of the patients vocation or sport. CONCLUSION These results show that arthroscopic SLAP repair of type II lesions with bioabsorbable suture anchors provides a significant improvement in functional capacity and pain relief.

An Epidemiologic Analysis of Clinical Practice Guidelines for Non-Arthroplasty Treatment of Osteoarthritis of the Knee

PURPOSE To analyze the current practice patterns of non-arthroplasty treatment of knee osteoarthritis (OA) and to assess the impact of the American Academy of Orthopaedic Surgeons clinical practice guidelines on the management of OA of the knee, particularly as they relate to the use of arthroscopic treatment. METHODS The United Healthcare Database (2004-2009, 11 million patients, 216 million records) was used for the study and was searched using Boolean language for International Classification of Diseases, Ninth Edition, Clinical Modification and Current Procedural Terminology, fourth revision codes. A reference group was defined as patients treated with knee arthroplasty in 2009 and diagnosed with knee OA in the same record. Clinical practice patterns in the 5 years preceding arthroplasty were analyzed in this group. RESULTS The reference group consisted of 12,806 patients undergoing total knee arthroplasty in 2009 with a documented diagnosis of OA at the time of surgery, with prior nonoperative treatment strategies analyzed during the preceding 5 years (2004-2009); 10.0% of patients were prescribed physical therapy specific to OA, 2.6% received an unloader brace, 0.52% underwent acupuncture, 43.5% were administered intra-articular corticosteroids, and 15.4% received viscosupplementation injections. During the 5 years before arthroplasty, 2,505 patients (19.6%) underwent arthroscopy and debridement/lavage, 35% of whom did not have a diagnosis code for mechanical pathology. Within 1 year of knee arthroplasty, 2,028 of the 2,505 knee arthroscopies (80.9%) were performed. CONCLUSIONS The findings show that significant gaps do exist between the evidence-based American Academy of Orthopaedic Surgeons recommendations and actual practice patterns in the United States between 2004 and 2009. LEVEL OF EVIDENCE Level IV, diagnostic study.

Interobserver and Intraobserver Reliability of the Goutallier Classification Using Magnetic Resonance Imaging Proposal of a Simplified Classification System to Increase Reliability

Background: The Goutallier classification of fatty infiltration of the rotator cuff was developed for use in axial computed tomography arthrography. Now the Goutallier classification is being used with magnetic resonance imaging (MRI). Not only is there debate on the validity of the use of this system in MRI, but current literature is unclear as to the clinical use of the Goutallier classification. Hypothesis: There will be significant inter- and intraobserver variability of the Goutallier classification grading system for patients with chronic rotator cuff tears. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: An online database consisting of 35 single MRI images from 35 patients with chronic rotator cuff tears was designed and sent to members of the American Shoulder and Elbow Society. Surgeons were asked to identify the stage of rotator cuff fatty infiltration using the Goutallier classification system. Thirty surgeons responded and completed the survey in its entirety. At a minimum of 2 months later, 28 of the 30 initial respondents completed evaluations of the same online database. The responding surgeons were divided dichotomously according to their demographics and the interobserver reliability of the groups compared. A kappa analysis was performed to determine inter- and intraobserver reliability using 95% confidence intervals (95% CIs). A simplified 3-tiered classification was proposed combining Goutallier grades 0 and 1 as well as grades 2 and 3. Results: Statistical analysis of all respondent data demonstrated moderate intraobserver variability with a κ value of 0.56 (95% CI, 0.53-0.60). In addition, moderate interobserver variability was shown with a κ value of 0.43 (range, 0.16-0.74). With the simplified classification, intraobserver reliability was 0.70 (95% CI, 0.66-0.74) and interobserver reliability was 0.61 (range, 0.21-0.87). Correlation analysis showed no correlation with the presence or absence of fellowship training or board certification with either the Goutallier classification or the proposed modification (P > .05). Sports versus shoulder/elbow fellows had statistically better intraobserver variability (κ = 0.63 vs 0.50) with the Goutallier classification. Years in practice was negatively correlated with the level of agreement for both classifications (–r value, P < .05). The number of rotator cuff repairs performed per year negatively correlated with the level of agreement in the proposed modification only (r = −0.44, P = .022). Percent of practice dedicated to the shoulder did not correlate significantly with either classification (P > .05). Conclusion: There is significant inter- and intraobserver variability observed among experienced shoulder surgeons using the Goutallier classification for assessing fatty infiltration of the rotator cuff muscles after chronic rotator cuff tears. Respondents were more likely to agree with themselves than with other respondents. A simplification of the MRI classification system is proposed that takes into consideration the variability determined by this study.

Complications of Bioabsorbable Suture Anchors in the Shoulder

The development of the suture anchor has played a pivotal role in the transition from open to arthroscopic techniques of the shoulder. Various suture anchors have been manufactured that help facilitate the ability to create a soft tissue to bone repair. Because of reported complications of loosening, migration, and chondral injury with metallic anchors, bioabsorbable anchors have become increasingly used among orthopaedic surgeons. In this review, the authors sought to evaluate complications associated with bioabsorbable anchors in or about the shoulder and understand these in the context of the total number of bioabsorbable anchors placed. In 2008, 10 bioabsorbable anchor–related complications were reported to the US Food and Drug Administration. The reported literature complications of bioabsorbable anchors implanted about the shoulder include glenoid osteolysis, synovitis, and chondrolysis. These potential complications should be kept in mind when forming a differential diagnosis in a patient in whom a bioabsorbable anchor has been previously used. These literature reports, which amount to but a fraction of the total bioabsorbable anchors implanted in the shoulder on a yearly basis, underscore the relative safety and successful clinical results with use of bioabsorbable suture anchors. Product development continues with newer composites such as PEEK (polyetheretherketone) and calcium ceramics (tricalcium phosphate) in an effort to hypothetically create a mechanically stable construct with and improve biocompatibility of the implant. Bioabsorbable anchors remain a safe, reproducible, and consistent implant to secure soft tissue to bone in and about the shoulder. Meticulous insertion technique must be followed in using bioabsorbable anchors and may obviate many of the reported complications found in the literature. The purpose of this review is to provide an overview of the existing literature as it relates to the rare complications seen with use of bioabsorbable suture anchors in the shoulder.

Arthroscopic Repair of Full-Thickness Rotator Cuff Tears With and Without Acromioplasty Randomized Prospective Trial With 2-Year Follow-up

Background: Acromioplasty is commonly performed during arthroscopic rotator cuff repair, but its effect on short-term outcomes is debated. Purpose: To report the short-term clinical outcomes of patients undergoing arthroscopic repair of full-thickness rotator cuff tears with and without acromioplasty. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: Patients undergoing arthroscopic repair of full-thickness rotator cuff tears were randomized into acromioplasty or nonacromioplasty groups. The Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES) score, Constant score, University of California–Los Angeles (UCLA) score, and Short Form–12 (SF-12) health assessment were collected along with physical examination including range of motion and dynamometer strength testing. Intraoperative data including tear size, repair configuration, and concomitant procedures were recorded. Follow-up examination was performed at regular intervals up to 2 years. Preoperative imaging was reviewed to classify the acromial morphologic type, acromial angle, and lateral acromial angulation. Results: A total of 114 patients were initially enrolled in the study, and 95 (83%; 43 nonacromioplasty, 52 acromioplasty) were available for a minimum 2-year follow-up. There were no significant differences in baseline characteristics, including number of tendons torn, repair configuration, concomitant procedures, and acromion type and angles. Within groups, there was a significant (P < .001) improvement in all functional outcome scores from preoperatively to all follow-up time points, including 2 years, for the nonacromioplasty and acromioplasty groups (ASES score: 55.1-91.5, 48.8-89.0; Constant score: 48.3-75.0, 51.9-78.7, respectively). There were no significant differences in functional outcomes between nonacromioplasty and acromioplasty groups or between subjects with different acromial features at any time point. Conclusion: The results of this study demonstrate no difference in clinical outcomes after rotator cuff repair with or without acromioplasty at 2 years postoperatively.

Articular and Meniscal Pathology Associated with Primary Anterior Cruciate Ligament Reconstruction

BACKGROUND The abnormal kinematics, contact pressures, and repeated episodes of instability observed in chronic anterior cruciate ligament (ACL) deficiency suggest that these patients may be predisposed to early degenerative changes and associated pathologies such as meniscal tears and chondral injury. Injury to the cartilage and associated structures at the time of ACL rupture, in combination with the inflammatory mediators released at the time of injury, may create irreversible damage to the knee despite restoration of normal knee kinematics with an ACL reconstruction. HYPOTHESIS Patients undergoing acute ACL reconstruction have a higher incidence of lateral meniscal tears and less severe chondral changes when compared with patients undergoing late ACL reconstruction. Older patients likely have a higher incidence of chondral and meniscal pathology compared with younger patients. METHODS A retrospective chart review of a single surgeons ACL practice over 20 years was performed. A surgical data packet was used to record patient demographics, location, grade, and number of chondral injuries as well as location and pattern of meniscal injuries at the time of ACL reconstruction. Patients (N = 709) were divided into three subgroups according to their time from injury to surgery; acute (less than 4 weeks, N = 121), subacute (4 to 8 weeks, N = 146), and chronic (8 weeks or more, N = 442). RESULTS Older patients had a higher incidence of more severe chondral grade and number of chondral injuries at the time of ACL reconstruction. Patients undergoing surgery more than 8 weeks after injury had a statistically significant more severe chondral grade in the medial compartment when compared with those that had surgery less than 8 weeks after injury. A similar observation was not found in the lateral compartment. With regard to meniscal pathology, full-thickness medial meniscal tears were likely to be bucket-type tears regardless of the chronicity of the injury. Similarly, full-thickness lateral meniscal tears were more often flap-type tears independent of the time interval between injury and surgery. Partial-thickness tears were common both medially and laterally. CONCLUSIONS Patients age and chronicity of ACL tear greater than 8 weeks are both significant factors in medial compartment chondral pathology. Patients with delayed reconstruction may have greater associated pathology.

Hyaluronic Acid Versus Platelet-Rich Plasma A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis

Background: The use of platelet-rich plasma (PRP) for the treatment of osteoarthritis (OA) has demonstrated mixed clinical outcomes in randomized controlled trials when compared with hyaluronic acid (HA), an accepted nonsurgical treatment for symptomatic OA. Biological analysis of PRP has demonstrated an anti-inflammatory effect on the intra-articular environment. Purpose: To compare the clinical and biological effects of an intra-articular injection of PRP with those of an intra-articular injection of HA in patients with mild to moderate knee OA. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 111 patients with symptomatic unilateral knee OA received a series of either leukocyte-poor PRP or HA injections under ultrasound guidance. Clinical data were collected before treatment and at 4 time points across a 1-year period. Synovial fluid was also collected for analysis of proinflammatory and anti-inflammatory markers before treatment and at 12 and 24 weeks after treatment. Several measures were used to assess results: (1) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; (2) International Knee Documentation Committee (IKDC) subjective knee evaluation, visual analog scale (VAS) for pain, and Lysholm knee score; and (3) difference in intra-articular biochemical marker concentrations. Results: There were 49 patients randomized to treatment with PRP and 50 randomized to treatment with HA. No difference was seen between the groups in the primary outcome measure (WOMAC pain score). In the secondary outcome measure, linear contrasts identified a significantly higher IKDC score in the PRP group compared with the HA group at 24 weeks (mean ± standard error [SE], 65.5 ± 3.6 vs 55.8 ± 3.8, respectively; P = .013) and at final follow-up (52 weeks) (57.6 ± 3.37 vs 46.6 ± 3.76, respectively; P = .003). Linear contrasts also identified a statistically lower VAS score in the PRP group versus the HA group at 24 weeks (mean ± SE, 34.6 ± 3.24 vs 48.6 ± 3.7, respectively; P = .0096) and 52 weeks (44 ± 4.6 vs 57.3 ± 3.8, respectively; P = .0039). An examination of fixed effects showed that patients with mild OA and a lower body mass index had a statistically significant improvement in outcomes. In the biochemical analysis, differences between groups approached significance for interleukin-1β (mean ± SE, 0.14 ± 0.05 pg/mL [PRP] vs 0.34 ± 0.16 pg/mL [HA]; P = .06) and tumor necrosis factor α (0.08 ± 0.01 pg/mL [PRP] vs 0.2 ± 0.18 pg/mL [HA]; P = .068) at 12-week follow-up. Conclusion: We found no difference between HA and PRP at any time point in the primary outcome measure: the patient-reported WOMAC pain score. Significant improvements were seen in other patient-reported outcome measures, with results favoring PRP over HA. Preceding a significant difference in subjective outcomes favoring PRP, there was a trend toward a decrease in 2 proinflammatory cytokines, which suggest that the anti-inflammatory properties of PRP may contribute to an improvement of symptoms. Registration: ClinicalTrials.gov (Identifier: NCT02588872).

Assessment of glenoid chondral healing: comparison of microfracture to autologous matrix-induced chondrogenesis in a novel rabbit shoulder model.

BACKGROUND Management of glenohumeral arthrosis in young patients is a considerable challenge, with a growing need for non-arthroplasty alternatives. The objectives of this study were to develop an animal model to study glenoid cartilage repair and to compare surgical repair strategies to promote glenoid chondral healing. METHODS Forty-five rabbits underwent unilateral removal of the entire glenoid articular surface and were divided into 3 groups--untreated defect (UD), microfracture (MFx), and MFx plus type I/III collagen scaffold (autologous matrix-induced chondrogenesis [AMIC])--for the evaluation of healing at 8 weeks (12 rabbits) and 32 weeks (33 rabbits) after injury. Contralateral shoulders served as unoperated controls. Tissue assessments included 11.7-T magnetic resonance imaging (long-term healing group only), equilibrium partitioning of an ionic contrast agent via micro-computed tomography (EPIC-μCT), and histologic investigation (grades on International Cartilage Repair Society II scoring system). RESULTS At 8 weeks, x-ray attenuation, thickness, and volume did not differ by treatment group. At 32 weeks, the T2 index (ratio of T2 values of healing to intact glenoids) was significantly lower for the MFx group relative to the AMIC group (P = .01) whereas the T1ρ index was significantly lower for AMIC relative to MFx (P = .01). The micro-computed tomography-derived repair tissue volume was significantly higher for MFx than for UD. Histologic investigation generally suggested inferior healing in the AMIC and UD groups relative to the MFx group, which exhibited improvements in both integration of repair tissue with subchondral bone and tidemark formation over time. DISCUSSION Improvements conferred by AMIC were limited to magnetic resonance imaging outcomes, whereas MFx appeared to promote increased fibrous tissue deposition via micro-computed tomography and more hyaline-like repair histologically. The findings from this novel model suggest that MFx promotes biologic resurfacing of full-thickness glenoid articular injury.