Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up.

BACKGROUND: Surgical repair is recommended for the treatment of high-grade partial and full thickness rotator cuff tears, although evidence shows surgery is not necessarily superior to non-surgical therapy. The purpose of this study was to compare percutaneous orthobiologic treatment to a home exercise therapy program for supraspinatus tears. METHODS: In this randomized-controlled, crossover design, participants with a torn supraspinatus tendon received either 'BMC treatment', consisting of a combination of autologous bone marrow concentrate (BMC) and platelet products, or underwent a home exercise therapy program. After three months, patients randomized to exercise therapy could crossover to receive BMC treatment if not satisfied with shoulder progression. Patient-reported outcomes of Numeric Pain Scale (NPS), Disabilities of the Arm, Shoulder, and Hand, (DASH), and a modified Single Assessment Numeric Evaluation (SANE) were collected at 1, 3, 6, 12, and 24 months. Pre- and post-treatment MRI were assessed using the Snyder Classification system. RESULTS: Fifty-one patients were enrolled and randomized to the BMC treatment group (n = 34) or the exercise therapy group (n = 17). Significantly greater improvement in median ΔDASH, ΔNPS, and SANE scores were reported by the BMC treatment group compared to the exercise therapy group (-11.7 vs -3.8, P = 0.01; -2.0 vs 0.5, P = 0.004; and 50.0 vs 0.0, P < 0.001; respectively) after three months. Patient-reported outcomes continued to progress through the study's two-year follow-up period without a serious adverse event. Of patients with both pre- and post-treatment MRIs, a majority (73%) showed evidence of healing post-BMC treatment. CONCLUSIONS: Patients reported significantly greater changes in function, pain, and overall improvement following BMC treatment compared to exercise therapy for high grade partial and full thickness supraspinatus tears. TRIAL REGISTRATION: This protocol was registered with www. CLINICALTRIALS: gov (NCT01788683; 11/02/2013).

A Randomized Controlled Trial of the Treatment of Rotator Cuff Tears with Bone Marrow Concentrate and Platelet Products Compared to Exercise Therapy: A Midterm Analysis.

Injectable regenerative therapies such as bone marrow concentrate (BMC) and platelet-rich plasma (PRP) may represent a safe alternative in the treatment of rotator cuff tears. This is a midterm review of a randomized, crossover trial comparing autologous BMC and platelet product injections versus exercise therapy in the treatment of partial and full-thickness supraspinatus tears. Patients enrolled into the study were between 18 and 65 years of age presenting to an outpatient orthopedic clinic with partial to full thickness, nonretracted supraspinatus tendon tears. Enrolled patients were randomized to either ultrasound-guided autologous BMC with PRP and platelet lysate (PL) percutaneous injection treatment or exercise therapy. Patients could cross over to BMC treatment after at least 3 months of exercise therapy. Patients completed the Disability of the Arm, Shoulder and Hand (DASH) scores as the primary outcome measure. Secondary outcomes included the numeric pain scale (NPS), a modified Single Assessment Numeric Evaluation (SANE), and a blinded MRI review. At this midterm review, results from 25 enrolled patients who have reached at least 12-month follow-up are presented. No serious adverse events were reported. Significant differences were seen in patient reported outcomes for the BMC treatment compared to exercise therapy at 3 and 6 months for pain, and for function and reported improvement (SANE) at 3 months (p < .05). Patients reported a mean 89% improvement at 24 months, with sustained functional gains and pain reduction. MRI review showed a size decrease of most tears post-BMC treatment. These findings suggest that ultrasound-guided BMC and platelet product injections are a safe and useful alternative to conservative exercise therapy of torn, nonretracted supraspinatus tendons. This trial is registered with NCT01788683.

Bone Marrow Concentrate (BMC) Therapy in Musculoskeletal Disorders: Evidence-Based Policy Position Statement of American Society of Interventional Pain Physicians (ASIPP).

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine. OBJECTIVES: The aim of this review is to describe the current regulatory guidelines set in place by the FDA, specifically the terminology around "minimal manipulation" and "homologous use" within Regulation 21 CFR Part 1271, and specifically how this applies to the use of BMC in interventional musculoskeletal medicine. METHODS: The methodology utilized here is similar to the methodology utilized in preparation of multiple guidelines employing the experience of a panel of experts from various medical specialties and subspecialties from differing regions of the world. The collaborators who developed these position statements have submitted their appropriate disclosures of conflicts of interest. Trustworthy standards were employed in the creation of these position statements. The literature pertaining to BMC, its effectiveness, adverse consequences, FDA regulations, criteria for meeting the standards of minimal manipulation, and homologous use were comprehensively reviewed using a best evidence synthesis of the available and relevant literature. RESULTS/Summary of Evidence: In conjunction with evidence-based medicine principles, the following position statements were developed: Statement 1: Based on a review of the literature in discussing the preparation of BMC using accepted methodologies, there is strong evidence of minimal manipulation in its preparation, and moderate evidence for homologous utility for various musculoskeletal and spinal conditions qualifies for the same surgical exemption. Statement 2: Assessment of clinical effectiveness based on extensive literature shows emerging evidence for multiple musculoskeletal and spinal conditions. • The evidence is highest for knee osteoarthritis with level II evidence based on relevant systematic reviews, randomized controlled trials and nonrandomized studies. There is level III evidence for knee cartilage conditions. • Based on the relevant systematic reviews, randomized trials, and nonrandomized studies, the evidence for disc injections is level III. • Based on the available literature without appropriate systematic reviews or randomized controlled trials, the evidence for all other conditions is level IV or limited for BMC injections. Statement 3: Based on an extensive review of the literature, there is strong evidence for the safety of BMC when performed by trained physicians with the appropriate precautions under image guidance utilizing a sterile technique. Statement 4: Musculoskeletal disorders and spinal disorders with related disability for economic and human toll, despite advancements with a wide array of treatment modalities. Statement 5: The 21st Century Cures Act was enacted in December 2016 with provisions to accelerate the development and translation of promising new therapies into clinical evaluation and use. Statement 6: Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders and spine. With mixed results, these therapies are greatly outpacing the evidence. The reckless publicity with unsubstantiated claims of beneficial outcomes having putative potential, and has led the FDA Federal Trade Commission (FTC) to issue multiple warnings. Thus the US FDA is considering the appropriateness of using various therapies, including BMC, for homologous use. Statement 7: Since the 1980's and the description of mesenchymal stem cells by Caplan et al, (now called medicinal signaling cells), the use of BMC in musculoskeletal and spinal disorders has been increasing in the management of pain and promoting tissue healing. Statement 8: The Public Health Service Act (PHSA) of the FDA requires minimal manipulation under same surgical procedure exemption. Homologous use of BMC in musculoskeletal and spinal disorders is provided by preclinical and clinical evidence. Statement 9: If the FDA does not accept BMC as homologous, then it will require an Investigational New Drug (IND) classification with FDA (351) cellular drug approval for use. Statement 10: This literature review and these position statements establish compliance with the FDA's intent and corroborates its present description of BMC as homologous with same surgical exemption, and exempt from IND, for use of BMC for treatment of musculoskeletal tissues, such as cartilage, bones, ligaments, muscles, tendons, and spinal discs. CONCLUSIONS: Based on the review of all available and pertinent literature, multiple position statements have been developed showing that BMC in musculoskeletal disorders meets the criteria of minimal manipulation and homologous use. KEY WORDS: Cell-based therapies, bone marrow concentrate, mesenchymal stem cells, medicinal signaling cells, Food and Drug Administration, human cells, tissues, and cellular tissue-based products, Public Health Service Act (PHSA), minimal manipulation, homologous use, same surgical procedure exemption.

Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis.

This study aimed to determine whether autologous orthobiologic tissue source affects pain and functional outcomes in patients with symptomatic knee osteoarthritis (OA) who received microfragmented adipose tissue (MFAT) or bone marrow aspirate concentrate (BMAC) injection. We retrospectively reviewed prospectively collected data from patients who received BMAC or MFAT injection for symptomatic knee OA. Patients completed baseline and follow-up surveys. Each survey included the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, Emory Quality of Life (EQOL) questionnaire, and Visual Analog Scale (VAS) for pain. The follow-up responses were compared with baseline for all patients and between BMAC and MFAT groups. A total of 110 patients met inclusion criteria, with 76 patients (BMAC 41, MFAT 35) and 106 knees (BMAC 58, MFAT 48) having appropriate follow-up data. The BMAC group included 17 females and 24 males, with a mean age of 59 ± 11 years. The MFAT group included 23 females and 12 males, with a mean age of 63 ± 11 years. Minimum follow-up time was 0.5 years. Mean follow-up time was 1.80 ± 0.88 years for BMAC and 1.09 ± 0.49 years for MFAT. Both groups had significant improvement in EQOL, VAS, and all KOOS parameters preprocedure versus postprocedure (p < .001). There was not a significant difference when comparing postprocedure scores between groups (p = .09, .38, .63, .94, .17, .15, .70, respectively). These data demonstrate significant improvement in pain and function with both MFAT and BMAC injections in patients with symptomatic knee OA without a significant difference in improvement when comparing the two autologous tissue sources. Stem Cells Translational Medicine 2019;8:1149-1156.

Recurrent discitis in the acute rehab setting: a case report.

INTRODUCTION: Discitis is an infection of the intervertebral disc space that can lead to paralysis, sepsis, epidural abscess, or other life-threatening complications if left untreated and may sometimes present with limited laboratory abnormalities to clue a diagnosis. CASE PRESENTATION: We present a case of a 67-year-old female in an acute rehabilitation setting who had presenting symptoms of sudden unexplained back pain refractory to pain control. She had a previous history of discitis and multiple failed knee replacement surgeries secondary to MSSA infections. Although vitals and basic labs were within normal limits, we recognized the clinical presentation as an indicator to order inflammatory markers (CPR and ESR), which were elevated compared to levels on admission, and subsequently ordered imaging and blood cultures to detect a case of recurrent worsening discitis. DISCUSSION: We highlight the presentation of recurrent discitis and necessary low threshold needed to detect such recurrence in patients with a previous history of discitis that have sudden unexplained back pain with no other usual physical or laboratory indicators of infection.

A historical study of appendicular fractures in veterans with traumatic chronic spinal cord injury: 2002-2007.

OBJECTIVE: Describe the incidence and distribution of appendicular fractures in a cohort of veterans with spinal cord injury (SCI). DESIGN: Retrospective, observational study of fractures in veterans with a chronic traumatic SCI. SETTING: The Veterans Health Administration (VA) healthcare system. PARTICIPANTS: Veterans included in the VA Spinal Cord Dysfunction Registry from Fiscal Years (FY) FY2002-FY2007. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Description of fractures by site and number. Mortality at one year following incident fracture among men with single vs. multiple fractures. RESULTS: Male and female veterans sustained incident fractures with similar observed frequency (10.5% vs 11.5%). The majority of fractures occurred in the lower extremities for both men and women. In men, a complete extent of injury (compared to incomplete) was associated with 41% greater relative risk (RR) of incident fracture (RR 1.41, 95% confidence interval [1.17, 1.70]) among those with tetraplegia, but not paraplegia. Furthermore, many men (33.9%, n = 434) sustained multiple fractures over the course of the study. There were no differences in mortality between men who sustained a single fracture and those who had multiple fractures. CONCLUSIONS: The extent of injury may be an important predictor of fracture risk for male veterans with tetraplegia. Once a fracture occurs, male veterans with SCI appear to be at high risk for additional fractures.