Intradiscal Leukocyte Rich Platelet Rich Plasma for Degenerative Disc Disease.

If we could choose a single non-fatal medical condition to find a better solution that would make the greatest impact on global health it would be a solution for degenerative disc disease (DDD) - the number one cause of chronic low back pain (CLBP).

Clinical outcomes following intradiscal injections of higher-concentration platelet-rich plasma in patients with chronic lumbar discogenic pain.

PURPOSE: This study aimed to assess clinical outcomes following intradiscal injections of higher-concentration (> 10 ×) platelet-rich plasma (PRP) in patients with chronic lumbar discogenic pain and to compare outcomes with a historical cohort. METHODS: This retrospective study included 37 patients who received intradiscal injections of higher-concentration (> 10 ×) PRP and had post-procedure outcomes data (visual numerical scale pain score, Functional Rating Index [FRI], and NASS Patient Satisfaction Index). Outcomes were compared to a historical cohort of 29 patients who received intradiscal injections of < 5X PRP. RESULTS: Pain and FRI scores significantly improved by 3.4 ± 2.5 and 46.4 ± 27.6, respectively, at 18.3 ± 13.3 months following intradiscal injections of > 10 × PRP (p < 0.001). These improvements were greater than those reported by the historical cohort (1.7 ± 1.6 and 33.7 ± 12.3; p = 0.004 and 0.016, respectively). Additionally, the satisfaction rate was higher in patients receiving > 10 × PRP compared to those receiving < 5 × PRP (81% vs. 55%; p = 0.032). CONCLUSIONS: Findings from this study suggest that clinical outcomes can be optimized by using PRP preparations that contain a higher concentration of platelets. Further research is needed to continue to optimize the composition of PRP used to treat patients with lumbar disc disease.

Risks of Intradiscal Orthobiologic Injections: A Review of the Literature and Case Series Presentation.

BACKGROUND: Intervertebral disc disease (IDD) is responsible for a large portion of back pain with historically suboptimal treatments for long-term improvement. IDD pathogenesis is thought to arise at a cellular and biochemical level, making biologically based injections an area of clinical interest. Although human studies have shown promise, emerging data suggest there may be risks inherent to such injections that were previously unrecognized. The aim of this review is to summarize the known risks to date and provide mitigation steps to reduce potential complications in the future. In addition, we present a small case series of serious adverse events (SAEs) from our clinical practice. METHODS: A literature review was performed to identify human intradiscal autologous biologic injection studies to date, including mesenchymal signaling cells (MSCs) and platelet-rich plasma (PRP) preparations, which were reviewed for complications. Cases of complication following intradiscal orthobiologic injection were identified from a single outpatient center and reviewed. RESULTS: Publications of MSC-based intradiscal injection documented 136 total patients treated with two SAEs reported, one infection and one progressive disc herniation. Publications of PRP intradiscal injection included 194 patients with one SAE reported. We also review three cases of previously unpublished SAEs, including one case of confirmed infection with Cutibacterium acnes (C acnes) and two presumed cases of discitis without pathogen confirmation. Bone marrow concentrate was the injectate in all three cases. CONCLUSIONS: Although biologic intradiscal injection shows promise for the treatment of discogenic back pain, there are inherent risks to be considered and mitigated. We currently recommend a leukocyte-rich PRP and a two-needle delivery technique coupled with intradiscal gentamicin to mitigate the risk of postinjection spondylodiscitis. Further research is needed using large registries to not only track clinical outcomes but also complication rates.

Infections Following Interventional Spine Procedures: A Systematic Review.

BACKGROUND: Interventional spine procedures, such as discography, epidural steroid injections (ESIs), facet joint procedures, and intradiscal therapies, are commonly used to treat pain and improve function in patients with spine conditions. Although infections are known to occur following these procedures, there is a lack of comprehensive studies on this topic in recent years. OBJECTIVES: To assess and characterize infections following interventional spine procedures. STUDY DESIGN: Systematic review. METHODS: Studies that were published from January 2010 to January 2020 and provided information on infections or infection rates following discography, ESIs, facet joint procedures, and intradiscal therapies were included. PubMed (Medline), EMBASE, and Cochrane Library databases were searched, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Infection data were extracted from included studies, and infection rates were calculated for each procedure type. Case reports and infection-only articles were not included in infection rate calculations. RESULTS: Seventy-two studies met the eligibility criteria and were included in the systematic review. The overall incidence of infection across all studies was 0.12% (231/200,588). The majority of studies (n = 51) were linked to ESIs. Infections related to ESIs were more common than those related to discography or facet joint procedures (0.13% [219/174,431] vs. 0% [0/269] or 0.04% [9/25,697], respectively). Intradiscal therapies had the highest calculated rate of infections (1.05%; 2/191). Quality assessments of the included studies ranged widely. LIMITATIONS: There was an abundance of case reports in comparison to other study designs; to minimize skewing of the analysis, case reports and infection-only articles were not included in the infection rate. Studies that reported combined infection data for multiple procedures could not be included. Many cohort studies and case series were of lower quality because of their retrospective nature. Additionally, the true incidence of infections related to these procedures is unknown because the majority of these infections often go unreported, and information on regions of the spine and procedure details are often lacking. CONCLUSIONS: Based on our systematic review, the risk of infections following interventional spine procedures appears to be low overall. More studies focusing on infectious complications with larger sample sizes are needed, particularly for intradiscal therapies, in which the microbiome may be an underlying cause of disc infection. To achieve a true incidence of the risk of infections with these procedures, large prospective registries that collect complication rates are necessary.

A retrospective analysis of a commercially available platelet-rich plasma kit during clinical use.

INTRODUCTION: Point-of-care analyses of platelet-rich plasma (PRP) are not routine in the orthopedic regenerative medicine field. Therefore, many physicians rely on the manufacturer's reported content for commercial preparation kits. This contributes to a knowledge gap between injectate content and patient outcome. OBJECTIVE: To assess whether the EmCyte PurePRP II 60-mL preparation kit returns PRP content that meets the manufacturer's expectations when used during routine clinical care for a heterogenous patient population, and to determine whether a change in PRP yield volume affects injectate content. Protocol A (exclusion of granulocytes and low hematocrit) and Protocol B (inclusion of granulocytes and higher hematocrit) were evaluated. DESIGN: Retrospective review. SETTING: Private practice. PARTICIPANTS: One hundred five patients (118 preparations) treated for orthopedic conditions over an 8-month period via PRP injection. Thirteen patients had two independently made preparations on different treatment days that qualified for analysis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Complete blood count (absolute counts and calculated fold enrichment from baseline of platelets, white blood cells, red blood cells, granulocytes, lymphocytes, monocytes; and hematocrit levels). Confounding variables included age, gender, and preparation yield volume. RESULTS: During routine clinical use, the cellular content of both Protocols A and B met or exceeded the manufacturer's expectations of platelet enrichment and granulocyte inclusion or exclusion. Hematocrit values were slightly higher than anticipated from Protocol A preparations. The modification of yield volume from 7 to 4 mL led to a significant difference in platelet enrichment without affecting absolute cell counts (2.88; 95% confidence interval [CI] 1, 4.76; P = .003). Both gender and age moderately affected the level of platelet enrichment from baseline but did not significantly affect absolute platelet counts. CONCLUSION: In the absence of widespread characterization, confirming the variation in commercial PRP kits during clinical use is crucial.

Cellular and Clinical Analyses of Autologous Bone Marrow Aspirate Injectate for Knee Osteoarthritis: A Pilot Study.

INTRODUCTION: Knee osteoarthritis (OA) is characterized by pain and functional deficits. Common conservative strategies include medications, physical therapy, and intra-articular injections. Recently, treatment using autologous cell injections has increased. OBJECTIVE: To characterize the cellular content of bone marrow aspirate (BMA) and to evaluate the effect of intra-articular autologous BMA injections in patients with mild knee OA. DESIGN: Prospective pilot observational study. SETTING: Academic institution. PATIENTS: Eleven patients with unilateral or bilateral mild knee OA (15 knees) were included in the cellular analysis. Ten patients (13 knees) were included in the overall (cellular and clinical) analysis. INTERVENTIONS: BMA was aspirated from patients' iliac crests and then injected intra-articularly under fluoroscopic and/or ultrasound guidance. BMA samples were analyzed using flow cytometry, colony forming unit (CFU) assays, and enzyme-linked immunosorbent assays. Questionnaires assessing pain and function were administered preinjection and at 1, 3, 6, and 12 months postinjection. Side effects and satisfaction were assessed. MAIN OUTCOME MEASURES: Total nucleated cell (TNC) concentration, mesenchymal stem cell (MSC) concentration, CFU count, and interleukin-1 receptor antagonist (IL-1Ra) concentration. RESULTS: BMA sample analyses revealed wide ranges in TNC concentration (173300-4 491 050 cells/mL), MSC concentration (0-500 cells/mL), CFUs (0-19), and IL-1Ra concentration (2806-29 394 pg/mL). Improvements in Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement were observed throughout the 12-month follow-up period (F[4,12] = 12.29, P < .001). Additionally, current, usual, best, and worst numerical rating scale pain scores significantly decreased over time (P < .001). Patient satisfaction was high (range: 8.1 ± 2.1-8.8 ± 1.9), and side effects were uncommon. CONCLUSIONS: The cellular content of BMA samples varied widely between patients and was lower than the anticipated yield reported by the device's manufacturer. However, intra-articular BMA injections for knee OA in a small pilot cohort appeared to be safe with potential therapeutic value. Larger, prospective, double-blinded studies are warranted.

Optimizing the safety of intradiscal platelet-rich plasma: an in vitro study with Cutibacterium acnes.

Aim: The most common risk associated with intradiscal injection of platelet-rich plasma (PRP) is discitis with Cutibacterium acnes. It is hypothesized that antimicrobial activity of PRP can be enhanced through inclusion of leukocytes or antibiotics in the injectate. Materials & methods: Multiple PRP preparations of varying platelet and leukocyte counts were co-cultured with C. acnes with or without cefazolin, with viable bacterial colony counts being recovered at 0, 4, 24 and 48 hours post-inoculation. Results: A direct correlation between C. acnes recovery and granulocyte counts were observed. Conclusion: We observed the greatest antimicrobial activity with the leukocyte-rich, high platelet PRP preparation combined with an antibiotic in the injectate. However, cefazolin did not completely clear the bacteria in this assay.

Treatment of symptomatic degenerative intervertebral discs with autologous platelet-rich plasma: follow-up at 5-9 years.

Aim: This study assessed pain and function at 5-9 years postinjection in a subset of patients who received intradiscal platelet-rich plasma (PRP) injections for moderate-to-severe lumbar discogenic pain. Patients & methods: All patients received injections of intradiscal PRP in a previous randomized controlled trial. Data on pain, function, satisfaction, and need for surgery were collected at one time point of 5-9 years postinjection and compiled with existing data. Results: In comparison to baseline, there were statistically significant improvements in pain and function (p < 0.001). All improvements were clinically significant. Six patients had undergone surgery during the follow-up period. Conclusion: This subset of patients demonstrated statistically and clinically significant improvements in pain and function at 5-9 years postinjection.

Spondylodiscitis due to Cutibacterium acnes following lumbosacral intradiscal biologic therapy: a case report.

A 40-year-old woman with a history of chronic low back pain underwent a fluoroscopically guided intradiscal platelet-rich plasma injection (PRP) at the L5-S1 level. She subsequently developed progressive low back pain, night sweats and decreased ability to ambulate. Laboratory work-up revealed elevated acute phase reactants and imaging revealed L5-S1 intervertebral disc and vertebral end-plate abnormalities highly suggestive of spondylodiscitis. Computed tomography-guided aspiration and biopsy cultures grew Cutibacterium acnes and the patient was subsequently treated with intravenous antibiotics without surgical management. To the best of our knowledge, this is the first published case of lumbar spondylodiscitis following an intradiscal PRP injection, and brings to the forefront several clinically relevant issues including the antimicrobial effects of PRP, the role of C. acnes in spine infections and the ideal treatment protocol for intradiscal biologics in order to minimize morbidity and optimize functional outcomes.

Fluoroscopically guided caudal epidural steroid injections for axial low back pain associated with central disc protrusions: a prospective outcome study.

PURPOSE: To determine if axial low back pain (LBP) associated with central disc protrusions can be improved by caudal epidural steroid injections (ESIs). METHODS: Adults with chronic (> 3 months) moderate-to-severe axial LBP with L4-5 and/or L5-S1 central disc protrusions were enrolled in this prospective study. Participants underwent caudal ESIs under standard-of-care practice. The numerical rating scale (NRS) pain score, modified North American Spine Society satisfaction, and Roland Morris Disability Questionnaire (RMDQ) were collected at one week, one month, three months, six months, and one year post-injection. Pre-injection magnetic resonance images were assessed by a musculoskeletal radiologist. RESULTS: Sixty-eight participants (42 males, 26 females) were analyzed. There were statistically significant improvements in all outcome measures at all follow-up time points, with the exception of NRS best pain at six months. Clinically significant improvements in outcomes were observed at various time points: at three months and one year for current pain; at one week, one month, three months, six months, and one year for worst pain; and at one month and one year for RMDQ. The proportion of satisfied participants ranged from 57 to 69% throughout the study. No adverse events were observed. CONCLUSIONS: This study demonstrated significant improvements in pain and function following caudal ESIs in a cohort of axial LBP with associated central disc protrusions. Further studies, including the use of randomized controlled trials, are needed to determine the ideal subset of candidates for this treatment and to explore additional applications that caudal ESIs may have for chronic LBP.

Percutaneous Rupture of Zygapophyseal Joint Synovial Cysts: A Prospective Assessment of Nonsurgical Management.

BACKGROUND: Although lumbar zygapophyseal joint synovial cysts are fairly well recognized, they are an uncommon cause of lumbosacral radicular pain. Nonoperative treatments include percutaneous aspiration of the cysts under computed tomography or fluoroscopic guidance with a subsequent corticosteroid injection. However, there are mixed results in terms of long-term outcomes and cyst reoccurrence. This study prospectively evaluates percutaneous ruptures of zygapophyseal joint (Z-joint) synovial cysts for the treatment of lumbosacral radicular pain. OBJECTIVES: Primary: To determine whether percutaneous rupture of symptomatic Z-joint synovial cysts leads to sustained improvements in radicular pain and function. Secondary: To assess the rates of cyst recurrence and progression to surgical intervention following percutaneous rupture of symptomatic Z-joint synovial cysts. DESIGN: Prospective cohort study. SETTING: Outpatient academic spine practice. PARTICIPANTS: Adults with primary radicular pain due to a facet synovial cyst. METHODS: Participants underwent fluoroscopically guided percutaneous Z-joint synovial cyst ruptures under standard-of-care practice. Data on pain, physical function, satisfaction, and progression to surgery were collected at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year after rupture. An intention-to-treat analysis was used for assessment of patient-reported outcome measures. MAIN OUTCOME MEASURES: The Numerical Rating Scale, Oswestry Disability Index, and modified North American Spine Society questionnaires were used to measure pain, function, and satisfaction with the procedure, respectively. RESULTS: Thirty-five participants were included in the study, and data were analyzed by an independent researcher. Statistically significant changes in Oswestry Disability Index were reported at 2 weeks, 3 months, and 1 year postintervention (P = .034, .040, and .039, respectively). A statistically and clinically significant relief of current pain was reported at 2 weeks (P = .025) and 6 weeks (P = .014) with respect to baseline. Patients showed significant improvements for best pain at 6 weeks with respect to baseline (P = .031). Patients' worst pain showed the greatest amount of improvement with clinically meaningful changes at all time points compared with baseline. Patient-reported satisfaction was found nearly 70% of the time at all time points. Forty percent (14/35) of participants required repeat cyst rupture, and 31% (11/35) required surgical interventions. CONCLUSIONS: There were statistically and clinically significant improvements in pain and function after percutaneous rupture of Z-joint synovial cysts. In addition, the outcomes support previous retrospective studies indicating that approximately 40% of patients will need surgery. This study provides further research to determine the utility of this procedure and to precisely define a subset of ideal candidates. LEVEL OF EVIDENCE: Level II.

Regenerative Treatments for Spinal Conditions.

A literature review of clinical and translational studies was performed to provide an overview of current concepts on regenerative treatments for spinal conditions, including platelet rich plasma and stem cell treatments to treat low back pain.

Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study.

BACKGROUND: Chronic low back pain due to disc degeneration represents a major social and economic burden worldwide. The current standard of care is limited to symptomatic relief and no current approved therapy promotes disc regeneration. Bone marrow-derived mesenchymal stem cells (MSCs) are easily accessible and well characterized. These MSCs are multipotent and exhibit great tissue regenerative potential including bone, cartilage, and fibrous tissue regeneration. The use of this cell-based biologic for treating protruding disc herniation and/or intervertebral disc degeneration is a promising therapeutic strategy, due to their known regenerative, immuno-modulatory and anti-inflammatory properties. METHODS: Five patients diagnosed with degenerative disc disease received an intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells (15.1-51.6 million cells) as part of a previous study. These patients were re-consented to participate in this study in order to assess long-term safety and feasibility of intra-discal injection of autologous, hypoxic cultured, bone marrow-derived mesenchymal stem cells 4-6 years post mesenchymal stem cell infusion. The follow-up study consisted of a physical examination, a low back MRI, and a quality of life questionnaire. RESULTS: Patients' lower back MRI showed absence of neoplasms or abnormalities surrounding the treated region. Based on the physical examination and the quality of life questionnaire, no adverse events were reported due to the procedure or to the stem cell treatment 4-6 years post autologous, hypoxic cultured mesenchymal stem cell infusion. All patients self-reported overall improvement, as well as improvement in strength, post stem cell treatment, and four out of five patients reported improvement in mobility. CONCLUSION: This early human clinical data suggests the safety and feasibility of the clinical use of hypoxic cultured bone marrow-derived mesenchymal stem cells for the treatment of lower back pain due to degenerative disc disorders and support further studies utilizing hypoxic cultured bone marrow-derived stem cells. The overall improvements reported are encouraging, but a larger double-blind, controlled, randomized clinical study with significant number of patients and implementation of validated endpoint measurements are next steps in order to demonstrate efficacy of this cell-based biologic.

Intradiscal platelet-rich plasma (PRP) injections for discogenic low back pain: an update.

PURPOSE: The aim of this article is to provide an overview of clinical and translational research on intradiscal platelet-rich plasma (PRP) as a minimally invasive treatment for discogenic low back pain. METHODS: A literature review of in vitro, in vivo, and clinical studies was performed. RESULTS: There is strong in vitro evidence that supports the use of intradiscal PRP for discogenic low back pain. There are also promising findings in select preclinical animal studies. A clinical study of 29 participants who underwent intradiscal PRP injections for discogenic low back pain found statistically and clinically significant improvements in pain and function through two years of follow-up. CONCLUSIONS: Intradiscal PRP is a safe and a possibly effective treatment for discogenic low back pain. Future studies are warranted to determine the best candidates for this treatment, what the optimal injectate is and what relationships exist between patient-reported outcomes and radiological findings.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

OBJECTIVE: To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. DESIGN: Prospective, double-blind, randomized controlled study. SETTING: Outpatient physiatric spine practice. PARTICIPANTS: Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. METHODS: Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. MAIN OUTCOME MEASURES: Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. RESULTS: Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. CONCLUSION: Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal treatment and the ideal cellular characteristics of the intradiskal PRP injectate.

Percutaneous intradiscal aspiration of a lumbar vacuum disc herniation: a case report.

We report a case of an 83-year-old gentleman presenting with acute low back pain and radicular left lower extremity pain after golfing. A magnetic resonance imaging (MRI) of the lumbar spine revealed a low-signal-density lesion compressing the L5 nerve. A computed tomography scan was then ordered, confirming an extra-foraminal disc protrusion at the L5-S1 level, containing a focus of gas that was compressing the left L5 nerve root and communicating with the vacuum disc at L5-S1. After a failed left L5 transforaminal epidural steroid injection, the patient was brought back for a percutaneous intradiscal aspiration of the vacuum disc gas. This resulted in immediate relief for the patient. A follow-up MRI performed 2 months after the procedure found an approximate 25% reduction in the size of the vacuum disc herniation. Six months after the procedure, the patient remains free of radicular pain. This case report suggests that a percutaneous aspiration of gas from a vacuum disc herniation may assist in the treatment of radicular pain.