Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.

Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737.

Lateral epicondylitis: comparing ultrasound-guided tenotomy with or without amniotic membrane allograft injection.

Aim: To evaluate the clinical response to augmenting ultrasound-guided tenotomy (USGT) with an amniotic membrane (AM) allograft injection. Design: Retrospective study. Materials & methods: Subjects underwent either a USGT (N = 16) or a combined USGT plus AM injection (N = 14). Results: Both groups demonstrated a significant reduction in pain from baseline starting after 2 weeks in the USGT plus AM group (p = 0.036) and after 8 weeks in the USGT group (p = 0.021). The reduction in pain was sustained for the entire duration of the study (52 weeks). There was no significant difference in pain levels at 26- or 52-week follow-up or patient satisfaction between the two groups. Conclusion: USGT with or without AM allograft injections results in a significant reduction in pain with high patient satisfaction.

The goal of this study was to determine if a single injection of an amniotic membrane (AM) tissue improves clinical outcomes for patients with chronic tennis elbow treated with ultrasound-guided tenotomy. Ultrasound-guided tenotomy involves using a cutting device to remove degenerative tissue with ultrasound-guidance to help tendon's healing process. An AM injection is thought to reduce inflammation in the surrounding tissue, provide growth factors that help with the tendon's healing process, and minimize painful scar formation. 30 patients were included in this study (16 ultrasound-guided tenotomy [USGT] and 14 USGT plus AM injection). Both groups showed improvement in pain levels compared with their baseline at the short-term follow-up, and this reduction in pain was sustained for 52 weeks. There were no long-term differences between the two groups at the 52 week follow-up in pain levels or satisfaction. Our findings suggest that USGT, with or without AM injection, is an effective method of treatment for chronic tennis elbow.

Regulatory Considerations of Orthobiologic Procedures.

The injection of biologic products for musculoskeletal pathologies is an emerging and promising field; however, dubious and unsafe uses for these products are often marketed. The Food and Drug Administration (FDA) has determined the need for varying degrees of regulation for these products for safety and efficacy. These regulations are frequently updated and federally enforced. As the regulatory landscape changes, clinicians using biologic products must stay informed to remain within the purview of the FDA. This article describes the current regulations of the most common products: platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and birth tissue products.

NSAIDs Reduce Therapeutic Efficacy of Mesenchymal Stromal Cell Therapy in a Rodent Model of Posttraumatic Osteoarthritis.

BACKGROUND: Intra-articular injections of human mesenchymal stromal cells (hMSCs) have shown promise in slowing cartilage degradation in posttraumatic osteoarthritis (PTOA). Clinical use of cell therapies for osteoarthritis has accelerated in recent years without sufficient scientific evidence defining best-use practices. Common recommendations advise patients to avoid nonsteroidal anti-inflammatory drug (NSAID) use before and after cell injection over concerns that NSAIDs may affect therapeutic efficacy. Recommendations to restrict NSAID use are challenging for patients, and it is unclear if patients are compliant. HYPOTHESIS: NSAIDs will reduce the efficacy of hMSC therapy in treating a preclinical model of PTOA. STUDY DESIGN: Controlled laboratory study. METHODS: Lewis rats underwent medial meniscal transection (MMT) surgery to induce PTOA or a sham (sham group) surgery that did not progress to PTOA. Rats received naproxen solution orally daily before (Pre-NSAID group) or after (Post-NSAID group) hMSC treatment, throughout the course of the experiment (Full-NSAID group), or received hMSCs without NSAIDs (No NSAID). Cartilage morphology and composition were quantified using contrast-enhanced micro-computed tomography and histology. Pain (secondary allodynia) was measured using a von Frey filament. RESULTS: Injection of hMSCs attenuated cartilage degeneration associated with MMT. hMSCs prevented proteoglycan loss, maintained smooth cartilage surfaces, reduced cartilage lesions, reduced mineralized osteophyte formation, and reduced pain by week 7. The Pre-NSAID group had decreased proteoglycan levels compared with the hMSC group, although there were no other significant differences. Thus, pretreatment with NSAIDs had minimal effects on the therapeutic benefits of hMSC injections. The Post-NSAID and Full-NSAID groups, however, exhibited significantly worse osteoarthritis than the hMSC-only group, with greater proteoglycan loss, surface roughness, osteophyte volume, and pain. CONCLUSION: Use of NSAIDs before hMSC injection minimally reduced the therapeutic benefits for PTOA, which included preservation of cartilage surface integrity as well as a reduction in osteophytes. Use of NSAIDs after injections, however, substantially reduced the therapeutic efficacy of cellular treatment. CLINICAL RELEVANCE: Our data support the clinical recommendation of avoiding NSAID use after hMSC injection but suggest that using NSAIDs before treatment may not substantially diminish the therapeutic efficacy of cell treatment.

Use of Bone Marrow Concentrate to Treat Pain and Musculoskeletal Disorders: An Academic Delphi Investigation.

BACKGROUND: Acute and degenerative musculoskeletal disorders are among the most common etiologies of disability worldwide. Recently, there has been interest in the field of regenerative medicine to bridge the gap between conservative and surgical management of these conditions. Autologous bone marrow concentrate is one type of injectate that has increased in popularity over the last few decades. Though there is promising evidence supporting its efficacy, standard of care practice guidelines to govern the appropriate use and implementation of such technology are currently lacking. OBJECTIVES: The aim of this article is to report findings from a survey administered using the Delphi technique to a group of physicians using bone marrow concentrate in practice to determine best practice consensus regarding optimization of patient safety and education. STUDY DESIGN: Delphi panel technique. SETTING: The study was first announced at a national meeting and continued remotely across the United States via 4 rounds of online surveys. METHODS: An initial panel of 30 expert members was convened and a 5-member steering committee was established. Four rounds of consensus questionnaires totaling 11 unique questions were distributed. Ten questions included a 5-point Likert scale from "Strongly Agree" to "Strongly Disagree," and one question had a selection of 5 options regarding minimum level of evidence required. The anonymized aggregate results of each round were shared with the group prior to voting in the subsequent round in accordance with the Delphi process. Consensus was defined as 80% agreement of the statements indicating either "Strongly Agree" or "Agree" for the 10 questions with the Likert Scale and 80% agreement among 2 of 5 choices in the question regarding levels of evidence. RESULTS: Three invited participants were excluded by the second round of questions due to lack of response in a timely manner, leaving 27 physicians queried. Nine of the 11 questions met criteria for > 80% consensus. Areas of agreement included importance of a treatment registry, candidacy grading, expanded informed consent, scientific accuracy in advertising, institutional review board approval for novel uses, performance of procedures by only licensed physicians or mid-level providers with direct physician oversight, use of image guidance for injections, data submission for publication in peer reviewed literature, and a minimum requirement of case-series level of evidence for use of bone marrow concentrate in musculoskeletal medicine. The 2 areas that did not meet criteria for consensus included online publishing of individual clinic data and standards around cell counting for dosing. LIMITATIONS: The Delphi panel of experts was convened on a voluntary basis rather than a nomination process. Our panel of experts were all physicians who use bone marrow concentrate in practice, therefore it is possible that a different panel of experts within other disciplines would reach different conclusions. CONCLUSIONS: There is significant consensus among a panel of physicians performing bone marrow concentrate injections regarding best practice guidelines for musculoskeletal conditions.

A Review of Current Management of Knee Hemarthrosis in the Non-Hemophilic Population.

The knee joint is one of the most frequently injured joints in the body, and the resulting injury may often lead to the presence of a bloody effusion, or hemarthrosis. The acute management of this condition can have long-lasting implications, and may ultimately result in the early onset of osteoarthritis in this population. Heme, a breakdown product of erythrocytes, and associated pro-inflammatory mediators, are known to have deleterious interactions with cartilage and synovium. The presence of blood in a joint following injury can precipitate these effects and accelerate the degenerative changes in the joint. Currently, there is no consensus on the optimal management of a traumatic knee joint injury with a hemarthrosis. Nontraumatic hemarthosis, seen most commonly in hemophilia patients, has a set of established guidelines that does not routinely recommend drainage of the joint. This article presents a rationale for joint aspiration to minimize the harmful effects of blood following traumatic hemarthrosis.

Identifiable Factors Associated With Acceptance Into Sports Medicine Fellowship Programs: A Brief Report.

OBJECTIVE: To identify factors associated with entry into primary care sports medicine (PCSM) fellowship programs. DESIGN: Primary care sports medicine fellowship directors (FDs) and fellowship faculty were surveyed regarding preferences for accepting applicants into their programs. SETTING: Survey study. PARTICIPANTS: Primary care sports medicine FDs and fellowship faculty. ASSESSMENT OF RISK FACTORS: Questions were designed to delineate factors [clinical experience, letters of recommendation (LOR), scholarship, service commitment, interview performance, etc] perceived to be associated with entry into PCSM fellowship (1-10 scale; 10 = highest value). Weighted mean ± SD were calculated for each question. MAIN OUTCOME MEASURES: Determination of most valued factors for entry into PCSM fellowship. RESULTS: Responses were provided by 242/2332 (10.4%) of the American Medical Society for Sports Medicine members, including 77 of 175 (44%) FDs. The top 3 factors for entry into PCSM fellowships for all respondents were as follows: interview performance (9.17 ± 1.13), LOR from SM fellowship faculty (8.20 ± 1.67), and high school game/event coverage (7.83 ± 1.70). Musculoskeletal ultrasound experience (4.50 ± 2.23) and residency training in pediatrics (4.58 ± 2.54), internal medicine (4.48 ± 2.44), emergency medicine (4.44 ± 2.59), and physical medicine and rehabilitation (4.40 ± 2.83) received the lowest scores. CONCLUSIONS: Applicants seeking entry into SM fellowships should prioritize performance during interviews, LOR from SM fellowship faculty, and team game/event coverage experiences.

Validity of Indirect Ultrasound Findings in Acute Anterior Cruciate Ligament Ruptures.

OBJECTIVES: Ultrasound (US) is increasingly being used as an extension of the physical examination on the sidelines, in training rooms, and in clinics. Anterior cruciate ligament (ACL) injury in sport is common, but the literature on US findings after acute ACL rupture is limited. Three indirect US findings of ACL rupture have been described, and this study assessed the validity of these indirect signs. METHODS: Patients with an acute knee injury (<6 weeks) underwent US examinations to determine whether there was evidence of a femoral notch sign, posterior cruciate ligament wave sign, or capsular protrusion sign. Ultrasound findings were compared to magnetic resonance imaging. RESULTS: Sixty-nine patients were included (53 with ACL tears and 16 control patients). The posterior cruciate ligament sign had the highest sensitivity (84.9%), and the notch sign had the highest specificity (93.8%). If 2 or 3 of the signs were positive, the sensitivity was 86.8%, and the specificity was 87.5%. CONCLUSIONS: A US examination is an easy-to-perform and noninvasive test, and the 3 indirect signs of an acute ACL tear had high positive predictive values ranging from 91.8% to 96.8%.

The role of rehabilitation after regenerative and orthobiologic procedures for the treatment of tendinopathy: a systematic review.

AIM: Significant variability exists in the literature, with no clear consensus to the optimal protocol after a regenerative procedure. Given this uncertainty, the authors systematically reviewed the literature cataloging the different variables that may influence outcomes. METHODS: Search was limited to randomized clinical trials and prospective cohort studies of regenerative procedures for the treatment of tendinopathy. Variables were predetermined, and included: cyrotherapy, pre- and post-procedure nonsteroidal anti-inflammatory drugs use, recommendations for alternative pain medications, immobilization and duration of rest. Variables were categorized based on the influence of the intervention on the three phases of healing. RESULTS: 749 studies were assessed for eligibility, and 60 studies were included. Significant variability existed in the literature. CONCLUSION: Despite the importance of rehabilitation after regenerative procedures, there is a paucity of evidence available to guide clinicians and highlights the need for additional validation.

Sphenopalatine Ganglion Block for Management of Refractory Chronic Posttraumatic Headaches After a Sport-Related Concussion.

Posttraumatic headaches (PTHs) are one of the most frequently reported symptoms after a sport concussion, and treatment options for chronic PTH are limited. In this report, we present a case of a 17-year-old boy with persistent PTH after a sport concussion successfully treated with an intranasal sphenopalatine block.

Ultrasound-Guided Elbow Procedures.

High-resolution ultrasonography can help clinicians visualize key anatomic structures of the elbow and guide periarticular and intra-articular injections. Historically, most procedures done around the elbow have been done using landmark guidance, and few studies have reported the accuracy of ultrasonography-guided injections in the elbow region. This article reviews common musculoskeletal disorders about the elbow that can be evaluated with ultrasonography, reviews the literature on ultrasonography-guided injections of the elbow region, and describes the senior author's preferred approach for the most commonly performed elbow region injections.

Treatment of tendinopathies with platelet-rich plasma.

Pain and dysfunction related to tendinopathy are often refractory to traditional treatments and offer a unique challenge to physicians, because no gold standard treatment exists. Injectable biologics may represent a new modality in conjunction with a multifaceted treatment approach. Platelet-rich plasma (PRP) injections are not associated with the systemic or tendon degradation risks of corticosteroids or the inherent risks of surgery. Studies are promising but have not been replicated with high-powered evidence at the clinical level. Further evidence to expand understanding of the role of PRP in the treatment of tendinopathy is needed.

The young adult spine in sports.

In summary, LBP is a common problem for the young adult athlete, with discogenic pain being the most common of all etiologies. Although rare, more serious etiologies such as tumor or infection should be included in the differential diagnosis until effectively ruled out. Regardless of the cause, nonoperative and conservative strategies should be the cornerstone of treatment, owing to the favorable natural history of most LBP etiologies. Short-term non-narcotic medications are helpful, and avoidance of bed rest is critical for the athletic population. Rehabilitation should focus on stabilization and strengthening of the core and pelvic muscle groups, and biomechanical imbalances should be addressed. Surgical intervention ought to be utilized as a last resort in this population. Return to play should be considered only when the athlete is pain free with full range of motion and daily medications have been discontinued. Careful monitoring of the training regimen should always be undertaken,especially with chronic pain or recurrent injuries.