Prathap Jayaram

Need for Proper Classification of PRP: Letter to the Editor

Dear Editor: It was with great interest that we reviewed the article by Cole et al published in the American Journal of Sports Medicine. More than a decade has passed since the initial use of platelet-rich plasma (PRP) for orthopaedic conditions, and controversies continue as to whether this treatment is effective for various conditions including chronic tendinopathy, ligament injuries, and articular cartilage lesions. As noted in the literature, a great deal of this controversy is related to the lack of standardization of what we refer to as ‘‘PRP.’’ As the science of PRP evolves, it has become apparent that not all PRP processing systems yield the same parameters, and final PRP injectates vary greatly. Due to these variations in PRP, terminology and classification have become imperative, and the most updated classification system has attempted to quantify PRP and determine appropriate dosing to improve objective outcome measures. From a biological standpoint, the characterization of the presence of cells (such as leukocytes) is a critical step, but many other parameters should be considered, such as the rate and quantity of platelet collection, the rate and quantity of leukocyte collection, and detailed composition of the cells during collection and centrifugation. The activation of the cell content during or after centrifugation is also important for the biological properties of these products. Other technical parameters should be considered as well, because they directly affect the possibility of using these techniques in daily clinical practice: These parameters include the size of the centrifuge; the duration, cost, and ergonomic properties of the preparation procedure; the final volume of product; and its form (liquid, light gel, or solid gel material). Although the study by Cole et al provides valuable data on PRP, the study fails to quantify the type of PRP used through any other classification system. The article fails to appropriately describe the dose of PRP provided (ie, the actual platelet count), which is a major flaw of the study. According to the data provided in the article, the platelet concentration is less than 2 times the baseline concentration of platelets in all the subjects injected. Given the normal range of platelet concentration in the average population of 100,000 to 400,000/mL, the subjects in this study would have received platelet concentrations of anywhere from 200,000 to 800,000/mL. This would be considered a low platelet concentration for the treatment of primary knee osteoarthritis given that other studies have demonstrated the efficacy of PRP at concentrations greater than 5 times the baseline. Another parameter that adds to the variability of PRP is the spin time. Cole et al chose a spin time of 5 minutes, which is less than the time supported by current practice and literature. The authors provide excellent background on the hyaluronic acid dosing profile but do not provide a proper dosing profile for the PRP arm; the novice reader looking at the title and conclusions of the study would thus be misled. The authors did not clarify whether their 3-mL blood draw was made through the same venous access as the 10-mL port for PRP preparation, thus not accurately accounting for platelet discrepancy. The report of the 2015 AOSSM Biologics Think Tank outlined that while PRP holds promise, 2 particular challenges must be met in order to advance the science: characterizing active elements in PRP injectate and finding the appropriate dosing regimen. The cytokine profile chosen by Cole et al was novel compared with profiles reported in the current PRP literature; however, only 2 of 10 catabolic parameters showed significance at one time point, and the paper did not disclose the variability in analysis of 2 mL of synovial sample. A wider panel of anabolic chemokines would have added valuable information in the context of anabolic-catabolic ratio. The study by Cole et al adds to the growing body of evidence regarding the safety profile of PRP. The paper highlights that this particular PRP product failed to show significance in the primary outcome (ie, Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain scale); however, multiple study endpoints demonstrated statistically significant differences and showed superiority of even this low-dose PRP product compared with hyaluronic acid, including reductions in visual analog scale (VAS) pain score and International Knee Documentation Committee (IKDC) knee evaluation scores at 24 and 52 weeks. Like several other studies examining PRP, the study by Cole et al is a prospective, double-blind, randomized controlled trial whose design appears to be at the highest level of science; however, the actual PRP product lacks an up-todate characterization. Thus, this article fails to advance the science regarding the PRP product used, its effect on osteoarthritis compared with hyaluronic acid, and its effect on various important synovial biochemical constituents found in patients who have osteoarthritis. We encourage the editors of AJSM and other journals of high scientific quality to require strict characterization of the PRP content prior to acceptance of future articles on this topic. This will greatly assist readers in properly assessing the scientific evidence of this treatment.

Orthobiologic Interventions Using Ultrasound Guidance

The application of regenerative therapies for the treatment of musculoskeletal conditions has emerged over the last decade with recent acceleration. These include prolotherapy, platelet-rich plasma, and mesenchymal stem cell therapy. These strategies augment the bodys innate physiology to heal pathologic processes. This article presents an overview of platelet-rich plasma and mesenchymal stem cell therapy for the treatment of musculoskeletal injuries. A brief literature review is included, as are techniques for the use of ultrasound guidance to assist with these procedures.

The Role of Low-Intensity Pulsed Ultrasound on Cartilage Healing in Knee Osteoarthritis: A Review

Ultrasound (US) is a therapeutic modality that has been used in the treatment of musculoskeletal conditions for decades. In recent years, there have been technological advancements using low‐intensity pulsed ultrasound (LIPUS) as a clinical modality. The purpose of this review was to critically examine the medical literature to determine the effects of LIPUS on the chondrogenic properties of knee osteoarthritis. A literature search of 3 major databases (PubMed, Scopus, and EMBASE) was performed. Two independent physician reviewers screened titles and abstracts, yielding a total of 18 relevant articles after the inclusion and exclusion criteria were applied. Results favored that LIPUS has a promising effect on the cellular elements in articular cartilage, specifically on chondrocytes in knee osteoarthritis. Although the use of LIPUS is encouraging based on basic science and preclinical data, there is a paucity of evidence with respect to humans. Consequently, there is insufficient evidence to recommend for or against LIPUS in clinical OA populations. We suggest future directions for research centered on LIPUS in both human and animal models to delineate the effect on the biologic properties of cartilage in knee osteoarthritis.

Musculoskeletal Injuries and Regenerative Medicine in the Elderly Patient

Regenerative medicine has gained increasing popularity in its clinical applications, particularly in the field of musculoskeletal medicine. Regenerative medicine, a broad term, can be thought of as a particular medical strategy that strives to rebuild and restore diseased tissue to normal physiologic tissue baseline. Simply put, regenerative strategies augment the bodys innate physiology to heal pathologic processes. This article focuses on specific regenerative strategies and the uses of them for common pathologies in the aging adult, including platelet-rich plasma, mesenchymal stem cells, viscosupplementation, and prolotherapy.

Iliocostal friction syndrome causing flank pain in a patient with a history of stroke with scoliosis and compensated Trendelenburg gait.

From the University of Medicine and Dentistry of New JerseyYNew Jersey Medical School, Newark (S. Patel, PJ, S. Portugal, TPS); and Kessler Institute for Rehabilitation, West Orange, New Jersey (S. Patel). Prathap Jayaram is now with the University of Maryland, Baltimore, MD. Salvador Portugal is now with SIRI Medical Associates/Catskill Physical Medicine and Pain Management and Bronx-Lebanon Hospital Center, Bronx, NY.

Bone Marrow–Derived and Adipose-Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review

Regenerative medicine in the context of musculoskeletal injury is a broad term that offers potential therapeutic solutions to restore or repair damaged tissue. The current focus in recent literature and clinical practice has been on cell based therapy. In particular, much attention has been centered on autologous bone marrow concentrate and adipose‐derived mesenchymal stem cells (MSCs) for cartilage and tendon disorders. This article provides an overview of MSC‐derived therapy and offers a comprehensive review of adipose‐ and bone marrow–derived MSC therapy in primary knee osteoarthritis.

Poster 193: A Rare Case of Hip Osteomyelitis in a Football Player: A Case Report

Disclosures: Kameron Bazmi: I Have No Relevant Financial Relationships To Disclose Case/Program Description: The patient is a right-handed male who was evaluated for left shoulder pain since 2016 while playing recreational football. He caught the ball with an outstretched left arm, but was tackled with players piling on top of him. He then complained of an electric sensation in the left arm. The pain persisted and gradually worsened and his primary care provider obtained an MRI that showed a left, full thickness rotator cuff tear. He was referred to an orthopedic surgeon for surgical repair. At this time, patient was reporting 6/10 pain over posterior left shoulder and anterior to the acromioclavicular joint. He denied radiating neck pain or weakness, however complained of some paresthesias of his left hand. Physical examination was significant for left scapular winging. Prior to surgery, he underwent a brachial plexus MRI, which showed no compressive lesions of the brachial plexus. The patient also had an electrodiagnostic study, which revealed evidence consistent with primarily a left moderate to severe long thoracic neuropathy with some features also suggestive of a left upper trunk brachial plexopathy. Setting: Outpatient clinic Results: Electromyography demonstrated at least 3+ positive sharp waves and fibrillation potentials with severely reduced recruitment and interference pattern in the serratus anterior, consistent with long thoracic neuropathy. Also, prolonged peak latency of the left lateral antebrachial cutaneous sensory nerve with reduced recruitment and interference pattern of the left supraspinatus and infraspinatus muscles. Discussion: Medial winging of the scapula occurs due to serratus anterior muscle dysfunction from long thoracic nerve palsy. Although rare, isolated long thoracic nerve neuropathies have been reported in sports such as tennis, archery, basketball and gymnastics, however this injury has not been reported during football. Conclusions: This case is evident that injuries sustained during football can be associated with isolated or primary injuries of the long thoracic nerve. Level of Evidence: Level V

Poster 34: Bone Marrow Derived vs Adipose Derived Mesenchymal Stem/Stromal Cell Therapy in Primary Knee Osteoarthritis: A Comprehensive Review

Disclosures: Genevieve Jacobs: I Have No Relevant Financial Relationships To Disclose Objective: It is essential but challenging that spinal cord injured (SCI) patients understand their injury and that they receive proper education early on in their hospital course. Using a quality improvement approach, this study was able to identify knowledge gaps seen in SCI patients and attempt to improve these gaps through education. We assessed patients before and after teaching and modified our tactic for education based on what we learned. Design: Quality Improvement Study Setting: Acute Rehabilitation Facility Participants: SCI patients Interventions: Nurses and physicians provided informal bedside training focusing on bowel, bladder, or skin issues. Education was accomplished during rounds or by nursing staff after rounds. Main Outcome Measures: Patients were interviewed before and after the week of education to assess if there was a change in patient understanding of self-care. Results: Based on a 3-topic interview prior to the week of informal patient education, 2/3rds were able to report how their bowel program was performed. 100% were able to describe their bladder program. Two-thirds were able to identify their skin checking technique. Following the intervention, there was no change in interview responses. We then modified our educational approach by designing a plan to provide formal, weekly, 10-minute seminars to patients on bowel, bladder, and skin issues. A 15-question survey to test patient knowledge was created to more objectively assess understanding. Conclusions: The goal of SCI patient education efforts should be to improve understanding and promote ownership of a patient’s injury. Using the Plan-Do-Study-Act tactic, an educational plan was designed in an attempt to enhance patient learning. The next step of this project is to implement the aforementioned formal seminars and utilize patient surveys to assess effectiveness of this approach. Level of Evidence: Level IV

Combinatorial Prg4 and Il-1ra gene therapy protects against hyperalgesia and cartilage degeneration in post-traumatic osteoarthritis

Osteoarthritis (OA) is a degenerative disease of synovial joints characterized by progressive loss of articular cartilage, subchondral bone remodeling, and intra-articular inflammation with synovitis that results in chronic pain and motor impairment. Despite the economic and health impacts, current medical therapies are targeted at symptomatic relief of OA and fail to alter its progression. Given the complexity of OA pathogenesis, we hypothesized that a combinatorial gene therapy approach, designed to inhibit inflammation with interleukin-1 receptor antagonist (IL-1Ra) while promoting chondroprotection using lubricin (PRG4), would improve preservation of the joint compared to monotherapy alone. Employing two surgical techniques to model mild, moderate and severe posttraumatic OA, we found that combined delivery of helper-dependent adenoviruses (HDVs), expressing IL-1Ra and PRG4, preserved articular cartilage better than either monotherapy in both models as demonstrated by preservation of articular cartilage volume and surface area. This improved protection was associated with increased expression of proanabolic and cartilage matrix genes together with decreased expression of catabolic genes and inflammatory mediators. In addition to improvements in joint tissues, this combinatorial gene therapy prolonged protection against thermal hyperalgesia compared to either monotherapy. Taken together, our results show that a combinatorial strategy is superior to monotherapeutic approaches for treatment of posttraumatic OA.

Poster 128 Efficacy of Low Intensity Pulsed Ultrasound in Knee Osteoarthritis: A Crticial Review

Disclosures: Abhishek Patel: I Have No Relevant Financial Relationships To Disclose Case/Program Description: A 54-year-old woman with a past medical history of heart failure secondary to familial cardiomyopathy on chronic cyclosporine immunosuppression as well as prednisone 5 mg daily referred to our outpatient clinic for left hip pain. Five weeks prior the patient was doing a “Hollywood Stretch” at her gym (sitting upright, right lower extremity fully extended, left lower extremity adducted over the right knee, knees and hips flexed, and adding a left body rotation). She heard a pop followed by significant left hip pain. She was able to bear weight but had significant left lateral thigh, hip and knee pain. Initial Xray evaluation showed no fractures in the ED. She was referred to orthopedic surgery. MRI was obtained which was read as a left rectus femoris tendon tear. She was advised conservative management with rest and physical therapy. She continued to have pain and was sent for a second MRI which confirmed rectus femoris tendon tear. She sought a second opinion and was diagnosed with iliotibial band tear based on further review of imaging. Nonsurgical management was indicated but the patient had persistent pain even after a second round of PT directed at the quadriceps. She also obtained a steroid injection to the area with exacerbation of her symptoms by her orthopedic surgeon. She was seen by a second orthopedic surgeon for another opinion and was recommended non-surgical management of what was seen as an IT band rupture. She referred herself to our clinic for pain management. On review of MRI our read revealed a rupture at the tensor fasciae latae/iliotibial band transition. We recommended regenerative therapy in the form of platelet rich plasma therapy and revised physical therapy. Setting: Outpatient Musculoskeletal/Pain Clinic. Results: The patient was hesitant to undergo PRP therapy given exacerbation of pain by the steroid injection she received by her surgeon. Thus a detailed physical therapy prescription was written focusing on range of motion, stretching, modalities, and progression to strengthening of the hip extensors, abductors, quadriceps, and knee extensors. On telephone followup the patient states that her pain has come down from a debilitating 8 on a 10 scale to a functional 4 on a 10 scale. She is able to tolerate walking without pain and is currently jogging. Discussion: Iliotibial band syndrome is a common diagnosis made in athletes, especially runners. These injuries are usually more distal where the Iliotibial Band inserts at Gerdy’s Tubercle (the lateral tubercle of the Tibia). However, proximal ruptures are uncommon. In this case, the patient likely had significant weakness in her iliotibial tract secondary from chronic steroid therapy. Though she was on a low dose, 5 mg daily, the patient had concurrent Cyclosporine use which is actually a CYP450 inhibitor and likely increased the bioavailability of prednisone which, too, is metabolized by the CYP450 family. Elevated levels of chronic steroid likely induced myopathy and muscle weakness at the Tensor Fasciae Lataecomplex resulting in IT band rupture during stretching. Given literature supporting plasma rich therapy for tendon healing and this was explained to her; however, she was reluctant to try any regenerative therapy after increased pain from her steroid injection. Physical therapy was encouraged but her prescription was revised and directed at hip stabilization and extensor/abductor strengthening. Conclusions: Proximal iliotibial band rupture, though more uncommon than distal tendonopathy at the tract, is still a diagnosis worth keeping in mind especially in patients on chronic steroid therapy. Caution should be taken in prescribing physical therapy or activity that may place added stress on the tract. Focus should be directed on strengthening the hip extensors, abductors, and quads in a progressive fashion to prevent such injuries. Gentle stretching and in a progressive and dynamic motion should be endorsed. Level of Evidence: Level V