Advances in biological techniques for treatment of lumbar discogenic pain

Treatment of lumbar discogenic pain is based upon restoration of mechanical function and suppression of nociception within the intervertebral disc. The biophysical and pathologic basis of disc injury is reviewed with discussion of treatment modalities. Ablative intradiscal ethanol and restorative intradiscal fibrin appear promising. Intradiscal platelet-rich plasma is tantalizing, but unproven. Biochemical modification of anabolic-catabolic balance by intradiscal administration of growth factors including BMP-7 and GDF-5 in clinical trials, as well as multiple investigational pharmacologic moieties, is discussed. Successful use of intradiscal autologous and mesenchymal stem cells has been demonstrated for in animal models, but human experience is limited. Clinical considerations and risks of these treatments are discussed.     

Intradiscal methylene blue injection for the treatment of chronic discogenic low back pain

This article was a preliminary report of prospective clinical trial of a group of patients with chronic discogenic low back pain who met the criteria for lumbar interbody fusion surgery but were treated instead with an intradiscal injection of methylene blue (MB) for the pain relief. Twenty-four patients with chronic discogenic low back pain underwent diagnostic discography with intradiscal injection of MB. The principal criteria to judge the effectiveness included alleviation of pain, assessed by visual analog scale (VAS), and improvement in disability, as assessed with the Oswestry Disability Index (ODI) for functional recovery. The mean follow-up period was 18.2 months (range 12–23 months). Of the 24 patients, 21 (87%) reported a disappearance or marked alleviation of low back pain, and experienced a definite improvement in physical function. A statistically significant and clinically meaningful improvement in the changes in the ODI and the VAS scores were obtained in the patients with chronic discogenic low back pain (P=0.0001) after the treatment. The study suggests that the injection of MB into the painful disc may be a very effective alternative for the surgical treatment of chronic discogenic low back pain.     

Evaluation of transforaminal epidural steroid injections for discogenic axial lumbosacral back pain utilizing PROMIS as an outcome measure

Background contextDiscogenic lumbosacral back pain continues to present a challenging clinical entity with limited, controversial therapeutic options. No study to date has evaluated the efficacy of fluoroscopically guided transforaminal epidural steroid injections (TFESI) in a homogenous patient population with axial lumbosacral back pain from discogenic pathology utilizing strict, explicitly clinical and radiographic criteria. Additionally, there is a paucity of published data utilizing Patient Reported Outcome Measurement Information System (PROMIS) scores as an outcome measure for interventional spine procedures.PurposeEvaluate the therapeutic effect of TFESIs in a specific subset of patients with discogenic axial lumbosacral back pain. Investigate PROMIS as an outcome measure for interventional spine procedures targeting focal degenerative spinal pathology.Study design/settingRetrospective review of patients presenting to a multidisciplinary, tertiary academic spine center.Patient sampleThree thousand eight hundred eighty-one patients were screened for inclusion. A total of 26 patients with discogenic axial low back, based on strict clinical and radiographic criteria, underwent TFESIs. All patients had axial low back pain without radicular pain, ≥3 clinical features of discogenic pain, corroborative radiographic features of active discogenic pathology on lumbar spine magnetic resonance imaging without confounding spinal pathology.Outcome measuresPROMIS Pain Interference (PI) v1.1, PROMIS Physical Function (PF) v1.2/v2.0, and PROMIS Depression (D) v1.0 outcome scores were collected at baseline and postprocedure follow-up.MethodsQuery of an institutional, patient reported outcome database and subsequent retrospective review of electronic medical records was performed. Statistical analysis comparing baseline and postprocedural PROMIS outcome scores and correlation between these instruments was performed. Additionally, an exploratory investigation of minimal clinically important difference achievement rates was performed.ResultsAnalysis determined a statistically significant improvement in PROMIS PI (p=.017, 95% CI=?8.02 to ?1.82) and PROMIS PF (p=.003, 95% CI=0.91–8.72) scores after treatment with TFESIs. At post treatment time points, TFESI had medium effect size on pain (d=0.55) and function (d=0.59). Change in PROMIS D scores (p=.488, 95% CI ?1.74–3.54; d=.08) did not demonstrate statistical significance. Pearson correlation demonstrated a moderate negative correlation (r=?0.544, p=.004) between PROMIS PF with PROMIS PI. Correlation between PROMIS PF (r=?0.239, p=.24) and PROMIS PI (r=0.198, p=.33) with PROMIS D was not significant. Fourteen (53.8%) and 9 (34.6%) subjects achieved minimum clinically important difference (MCID) for PROMIS PI and PROMIS PF, respectively. Nine subjects (34.6%) achieved MCID for PROMIS D despite not otherwise reaching statistical significance otherwise.ConclusionsUtilizing PROMIS as an outcome measure, discogenic axial lumbosacral back pain patients appear to benefit from TFESI in terms of pain and physical function. This study contributes to the growing body of literature utilizing PROMIS scores in patients with clinical sequelae of degenerative spinal pathology; however, prospective studies are needed.     

In vitro and in vivo evaluation of discogenic cells,an investigational cell therapy for disc degeneration

BACKGROUND/CONTEXTDisc degeneration (DD) is a significant driver of low back pain and few treatments exist to treat the pain and disability associated with the disease.PURPOSEOur group has developed a method to generate therapeutic discogenic cells as a potential treatment for symptomatic DD. These cells are derived and modified from adult nucleus pulposus cells. In this study, we evaluated the characteristics, mode of action, and in vivo efficacy and safety of these cells prior to human clinical testing.STUDY DESIGNPrivately funded in vitro studies and in vivo preclinical models were used in this study.METHODSDiscogenic cells generated from different adult human donors were evaluated for surface marker expression profile, matrix deposition and tumorigenic potential. Discogenic cells were then injected subcutaneously into nude mice to assess cell survival and possible extracellular matrix production in vivo. Finally, a rabbit model of DD was used to evaluate the therapeutic potential of discogenic cells after disc injury.RESULTSWe found that discogenic cells have a consistent surface marker profile, are multipotent for mesenchymal lineages, and produce extracellular matrix consisting of aggrecan, collagen 1 and collagen 2. Cells did not show abnormal karyotype after culturing and did not form tumor-like aggregates in soft agar. After subcutaneous implantation in a nude mouse model, the human discogenic cells were found to have generated regions rich with extracellular matrix over the course of 4 months, with no signs of tumorigenicity. Intradiscal injection of human discogenic cells in a rabbit model of DD caused an increase in disc height and improvement of tissue architecture relative to control discs or injection of vehicle alone (no cells) with no signs of toxicity.CONCLUSIONSThis study demonstrates that intradiscal injection of discogenic cells may be a viable treatment for human degenerative disc disease. The cells produce extracellular matrix that may rebuild the depleting tissue within degenerating discs. Also, the cells do not pose any significant safety concerns.CLINICAL SIGNIFICANCEHuman clinical testing of discogenic cells combined with a sodium hyaluronate carrier is ongoing in multiple randomized, controlled, double-blinded studies in the United States (clinicaltrials.gov identifier NCT03347708) and Japan (clinicaltrials.gov identifier NCT03955315).     

亚甲兰注射治疗椎间盘源性腰痛的临床观察

目的选择一组符合行腰椎融合手术标准的慢性失能性椎间盘源性腰痛患者,给予腰椎椎间盘内注射亚甲蓝,观察其临床效果。方法回顾性分析2010年8月～2011年12月行亚甲蓝椎间盘内注射治疗的90例椎间盘源性腰痛病例。用疼痛视觉模拟量表(visual analog scale,VAS)评分和Oswestry功能障碍指数(Oswestry disability index,ODI)评估每个患者手术前后的腰痛情况和腰椎功能,以评价亚甲蓝注射疗效。结果患者术后随访时间为3～6个月。所有患者中,83例(92.2%)腰痛症状有明显改善或完全消失,80例(88.9%)腰椎功能明显改善。手术前后的VAS评分和ODI比较,差异具有统计学意义(P<0.01)。结论椎间盘内注射亚甲蓝是一种非常有效的治疗椎间盘源性腰痛的方法。     

Editorial Commentary: Injection of Platelet-Rich Plasma Appears Superior to Hyaluronic Acid and Adipose- or Bone-Derived Marrow Stem Cells for Knee Osteoarthritis

Injection therapy for knee osteoarthritis continues to be a controversial topic. Commonly accepted treatment options are corticosteroid and hyaluronic acid injections, but recently platelet-rich plasma also has been a promising biologic treatment option. Adipose and bone marrow–derived mesenchymal stem cells have been applied clinically, but there is no strong supporting evidence for their use. It is also currently unknown whether stem cells can regenerate cartilage. As there is no cure for painful knee osteoarthritis, injection therapy can provide symptom relief. Recent network meta-analyses suggest that platelet-rich plasma provides the best functional improvement and safety for knee osteoarthritis, and adipose-derived mesenchymal stem cells provide excellent pain relief. We must bear in mind that other network meta-analyses report different results, and a challenge of network meta-analysis is inconsistency that can lead to biased treatment effect estimates.     

HIZ与椎间盘造影在椎间盘源性腰痛诊断中的对比研究

目的对比MRI T2WI上HIZ（high intensity zone）与椎间盘造影对椎间盘源性腰痛的诊断价值。方法2006年9～2007年12月,对43例严重下腰痛患者进行MRI检查以及椎间盘造影术,对MRI T2WI存在HIZ表现的患者以及椎间盘造影阳性的患者进行回顾性分析。结果43例患者中,26例患者的31个节段有HIZ表现（60．5％,26／43）,其中17例造影阳性,阳性率为65．4％（17／26）;17例无HIZ表现的患者中4例造影阳性,阳性率为（23．5％,4／17）。43例患者中,共计21例患者23个节段造影阳性,阳性率为48．8％（21／43）。结论慢性下腰痛患者中HIZ对椎间盘源性腰痛有较高的提示作用,但确诊仍需椎间盘造影术予以明确。     

Nonoperative and Operative Soft-Tissue,Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Shoulder: An Orthoregeneration Network (ON) Foundation Review

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the shoulder including the rotator cuff tendons, glenohumeral articular cartilage, glenoid labrum, the joint capsule, and bone. Promising and established treatment modalities include hyaluronic acid (HA); platelet-rich plasma (PRP) and platelet rich concentrates (PRC); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs alternatively termed medicinal signaling cells and frequently, misleadingly labelled “mesenchymal stem cells”); MSC harvested from adipose, umbilical, or placental sources; factors including vascular endothelial growth factors (VEGF), basic fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGFβ), bone morphogenic protein (BMP), and matrix metalloproteinases (MMPs); prolotherapy; pulsed electromagnetic field therapy; microfracture and other marrow-stimulation techniques; biologic resurfacing using acellular dermal allografts, allograft Achilles tendons, allograft lateral menisci, fascia lata autografts, and porcine xenografts; osteochondral autograft or allograft); and autologous chondrocyte implantation (ACI). Studies involving hyaluronic acid, platelet rich plasma, and medicinal signaling cells of various origin tissues have shown mixed results to-date as isolated treatments and as surgical adjuncts. Despite varied results thus far, there is great potential for improved efficacy with refinement of current techniques and translation of burgeoning preclinical work.Level of EvidenceLevel V, expert opinion.     

The efficacy of repeat intradiscal electrothermal therapy

Nine consecutive patients with discogenic low back pain who obtained excellent pain relief from intradiscal electrothermal therapy were treated with a repeat procedure after the beneficial effects had diminished. Although 4 of 9 patients obtained > or =50% pain relief and were satisfied with the results, both the degree and duration of benefit were less pronounced than after the first procedure. Prospective studies are needed to identify the best candidates for repeat intradiscal electrothermal therapy.     

Human mesenchymal stem cells respond differentially to platelet preparations and synthesize hyaluronic acid in nucleus pulposus extracellular matrix

BACKGROUND CONTEXTIn recent years, autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have been used as treatments for disc-related pain. A better understanding of the effects of leukocyte-rich (LR) versus leukocyte poor (LP-) PRP on bone marrow derived human mesenchymal stem/progenitor cells (hMSCs) is likely to improve future research studies, clinical practice and care for patients with chronic discogenic back pain.PURPOSEThe primary aim of this study is to determine the effects of LR-PRP and LP-PRP on the proliferation and migration of hMSCs in pig nucleus pulposus (NP) extracellular matrix (ECM). The secondary aim is to characterize hMSC-dependent expression of the matrix remodeling enzymes metalloproteinases MMP-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinases TIMP-2, and to determine whether transplanted hMSCs can synthesize hyaluronic acid (HA).STUDY DESIGNControlled laboratory study.METHODSBone marrow-derived culture expanded hMSCs were seeded onto pig NP and cultured with LR-PRP, LP-PRP or serum/platelet releasate (PR). The same conditions without hMSCs were used as controls. hMSC proliferation, migration and dispersion was assessed via fluorescent microscopy, while HA synthesis, MMP-2, MMP-3, MMP-9, and TIMP-2 protein levels were assessed via enzyme linked immunosorbent assay. All funding was provided by a 501c(3) research foundation and does not have any commercial or sponsorship interests.RESULTSLP-PRP and PR cultures resulted in higher hMSC proliferation, migration, dispersion, and MMP-2 expression. LP-PRP cultures resulted in the highest HA production. LR-PRP cultures resulted in lower hMSC proliferation, negligible migration and dispersion, increased MMP-9 expression and lower HA production.CONCLUSIONSHuman bone marrow-derived hMSCs seeded onto pig NP ECM are capable of synthesizing HA, indicating a transition towards a NP cell phenotype. This process was most enhanced by LP-PRP and marked by increased hMSC proliferation, MMP-2 production, HA synthesis and reduced MMP-9 levels.CLINICAL SIGNIFICANCELP-PRP and PR, with or without hMSCs, may provide better outcomes than LR-PRP in lab investigations and clinical trials for discogenic pain. Bone marrow-derived hMSCs may hold promise as a treatment for disc degeneration.     

Biologic Therapies for the Treatment of Knee Osteoarthritis: An Updated Systematic Review

BackgroundUse of “orthobiologics” continues to expand for patients who have knee osteoarthritis (OA). We sought to perform a systemic review of biologic therapies relative to comparative groups, including the following: (1) platelet-rich plasma (PRP); (2) bone marrow–derived mesenchymal stem cells (BMSCs); (3) adipose-derived mesenchymal stem cells (ADSCs); and (4) amniotic-derived mesenchymal stem cells (AMSCs). We assessed the following: (1) study methodologies; (2) cell preparations and formulations; (3) patient-reported outcome scores (PROMs); and (4) structural changes.MethodsPubMed, Cochrane Library, and Embase databases were queried (2013-2021) to conduct a systematic review of biologic therapies for knee OA, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eighty-two studies were included: PRP (51); BMSC (15); ADSC (11); and AMSC (5). Study evaluations were made using the Modified Coleman Methodology Score. PROMs included the Western Ontario and McMaster Universities Arthritis Index and the Visual Analog Scale. Structural change evaluations included ultrasounds, radiographs, or magnetic resonance imaging.ResultsPRP comprised a majority of the studies (n = 51), most with “fair” to “good” Modified Coleman Methodology Score. Studies had variable cell preparations and formulations, with comparison study results leading to inconsistent PROMs, and structural changes. A limited number of studies were included for BMSC, ADSC, and AMSC, all with similar findings to PRP.ConclusionAvailable literature evaluating “orthobiologics” for knee OA remain nonsuperior to comparison cohorts. Higher level studies with larger sample sizes and improved methodologies are warranted to suggest differences. Despite a growth of “orthobiologics” in clinics, this updated systematic review highlights the uncertain efficacy for use in knee OA.     

Prevalence of COVID-19 among patients with chronic inflammatory rheumatic diseases treated with biologic agents or small molecules: A population-based study in the first two months of COVID-19 outbreak in Italy

ObjectiveThe aim of this study is to determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) among adult patients treated with biologic agents or small molecules for chronic inflammatory rheumatic diseases, in particular for chronic inflammatory arthritides.MethodsTo this end, a population-based study, in the province of Udine (466,700 inhabitants, with age > 15 years old, Friuli Venezia Giulia region, Italy) was planned. The primary outcome was the prevalence of COVID-19 in the first two months of the outbreak. All the rheumatic patients treated with biologic agents or small molecules in the last 6 months in our province were included (N = 1051).ResultsFrom February 29 to April 25, 2020, 4 adult patients (4/1051, i.e. 3.8/1000, 95% Confidence Interval 1.5–9.7/1000) were registered as swab test positive by PCR for COVID-19. Overall, a total of 47/1051 (4.5%) cases were tested for COVID-19 by PCR in the same period, and 15 of them due to symptoms compatible with COVID-19. In the general population, the prevalence was 937 cases/466700 (2/1000, 95% Confidence Interval 1.9–2.1/1000, P-value = 0.33, chi square test), and 20,179/466,700 (4.3%) swab tests for COVID-19 were performed.ConclusionThe risk of COVID-19 in rheumatic patients under biologic agents or small molecules does not appear different from that observed in the general population. Patients should be informed to safely proceed with their treatment and follow the rules for self-protection to COVID-19.     

Efficacy of duloxetine in patients with knee osteoarthritis or chronic low back pain with early pain reduction: An exploratory post-hoc analysis of Japanese phase 3, 1-year extension studies

BackgroundTwo previous phase 3, double-blind, randomized, placebo-controlled trials showed that duloxetine 60 mg/day for 14 weeks significantly improved pain and quality of life in Japanese patients with knee osteoarthritis or chronic low back pain. In their open-label extension studies, these improvements were maintained for ≥48 weeks. This post-hoc analysis assessed the relationship between initial response to duloxetine and long-term pain reduction and quality of life in patients with knee osteoarthritis or chronic low back pain.MethodsPatients (knee osteoarthritis: N = 43; chronic low back pain: N = 41) were subdivided based on extent of pain reduction from baseline to Week 4 of duloxetine (≥30%, 10–30%, or <10% reduction in Brief Pain Inventory-Severity average pain score). Outcome measures were changes from baseline for Brief Pain Inventory-Severity and Brief Pain Inventory-Interference at regular intervals up to Week 65.ResultsMean change from baseline in Brief Pain Inventory-Severity was greater in patients with ≥30% early pain reduction than in patients with <10% early pain reduction through Week 27 for both conditions, and also Weeks 47–65 for back pain. Compared with the <10% early pain reduction group, mean change from baseline in the average of seven Brief Pain Inventory-Interference domain scores was greater in the ≥30% or 10–30% early pain reduction groups for knee osteoarthritis (except Weeks 63–65), and in the ≥30% early pain reduction group for chronic low back pain through Week 19.ConclusionsThese results suggest that patients with knee osteoarthritis who respond well to duloxetine in the first month might experience sustained, long-term pain relief with generally greater quality-of-life improvement than patients with poor initial response. Patients with chronic low back pain who had strong initial response may experience a greater long-term pain relief, but not greater quality-of-life improvement, than patients with poor initial response.     

Intradiscal oxygen-ozone chemonucleolysis versus microdiscectomy for lumbar disc herniation radiculopathy: a non–inferiority randomized control trial

BACKGROUND CONTEXTLow back pain with or without radicular leg pain is an extremely common health condition significantly impacting patient's activities and quality of life. When conservative management fails, epidural injections providing only temporary relief, are frequently utilized. Intradiscal oxygen-ozone may offer an alternative to epidural injections and further reduce the need for microdiscectomy.PURPOSETo compare the non–inferiority treatment status and clinical outcomes of intradiscal oxygen-ozone with microdiscectomy in patients with refractory radicular leg pain due to single-level contained lumbar disc herniations.STUDY DESIGN / SETTINGMulticenter pilot prospective non–inferiority blocked randomized control trial conducted in three European hospital spine centers.PATIENT SAMPLEForty-nine patients (mean 40 years of age, 17 females/32 males) with a single-level contained lumbar disc herniation, radicular leg pain for more than six weeks, and resistant to medical management were randomized, 25 to intradiscal oxygen-ozone and 24 to microdiscectomy. 88% (43 of 49) received their assigned treatment and constituted the AS-Treated (AT) population.OUTCOME MEASURESPrimary outcome was overall 6-month improvement over baseline in leg pain. Other validated clinical outcomes, including back numerical rating pain scores (NRS), Roland Morris Disability Index (RMDI) and EQ-5D, were collected at baseline, 1 week, 1-, 3-, and 6-months. Procedural technical outcomes were recorded and adverse events were evaluated at all follow-up intervals.METHODSOxygen-ozone treatment performed as outpatient day surgeries, included a one-time intradiscal injection delivered at a concentration of 35±3 μg/cc of oxygen-ozone by a calibrated delivery system. Discectomies performed as open microdiscectomy inpatient surgeries, were without spinal instrumentation, and not as subtotal microdiscectomies. Primary analyses with a non–inferiority margin of -1.94-point difference in 6-month cumulative weighted mean leg pain NRS scores were conducted using As-Treated (AT) and Intent-to-Treat (ITT) populations. In post hoc analyses, differences between treatment groups in improvement over baseline were compared at each follow-up visit, using baseline leg pain as a covariate.RESULTSIn the primary analysis, the overall 6-month difference between treatment groups in leg pain improvement using the AT population was -0.31 (SE, 0.84) points in favor of microdiscectomy and using the ITT population, the difference was 0.32 (SE, 0.88) points in favor of oxygen-ozone. The difference between oxygen-ozone and microdiscectomy did not exceed the non–inferiority 95% confidence lower limit of treatment difference in either the AT (95% lower limit, -1.72) or ITT (95% lower limit, -1.13) populations. Both treatments resulted in rapid and statistically significant improvements over baseline in leg pain, back pain, RMDI, and EQ-5D that persisted in follow-up. Between group differences were not significant for any outcomes. During 6-month follow-up, 71% (17 of 24) of patients receiving oxygen-ozone, avoided microdiscectomy. The mean procedure time for oxygen-ozone was significantly faster than microdiscectomy by 58 minutes (p<.0010) and the mean discharge time from procedure was significantly shorter for the oxygen-ozone procedure (4.3±2.9 hours vs. 44.2±29.9 hours, p<.001). No major adverse events occurred in either treatment group.CONCLUSIONSIntradiscal oxygen-ozone chemonucleolysis for single-level lumbar disc herniations unresponsive to medical management, met the non–inferiority criteria to microdiscectomy on 6-month mean leg pain improvement. Both treatment groups achieved similar rapid significant clinical improvements that persisted and overall, 71% undergoing intradiscal oxygen-ozone were able to avoid surgery.     

Nonoperative and Operative Soft-Tissue and Cartilage Regeneration and Orthopaedic Biologics of the Knee: An Orthoregeneration Network (ON) Foundation Review

Orthoregeneration is defined as a solution for orthopedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and optimally, provide an environment for tissue regeneration. Options include: drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electro-magnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the knee, including symptomatic osteoarthritis and chondral injuries, as well as injuries to tendon, meniscus, and ligament, including the anterior cruciate ligament. Promising and established treatment modalities include hyaluronic acid (HA) in liquid or scaffold form; platelet-rich plasma (PRP); bone marrow aspirate (BMA) comprising mesenchymal stromal cells (MSCs), hematopoietic stem cells, endothelial progenitor cells, and growth factors; connective tissue progenitor cells (CTPs) including adipose-derived mesenchymal stem cells (AD-MSCs) and tendon-derived stem cells (TDSCs); matrix cell–based therapy including autologous chondrocytes or allograft; vitamin D; and fibrin clot. Future investigations should standardize solution preparations, because inconsistent results reported may be due to heterogeneity of HA, PRP, BMAC, or MSC preparations and regimens, which may inhibit meaningful comparison between studies to determine the true efficacy and safety for each treatment.     

Occupational driving as a risk factor for low back pain in active-duty military service members

Background contextAlthough occupational driving has been associated with low back pain, little has been reported on the incidence rates for this disorder.PurposeTo determine the incidence rate and demographic risk factors of low back pain in an ethnically diverse and physically active population of US military vehicle operators.Study design/settingRetrospective database analysis.Patient sampleAll active-duty military service members between 1998 and 2006.Outcome measuresLow back pain requiring visit to a health-care provider.MethodsA query was performed using the US Defense Medical Epidemiology Database for the International Classification of Diseases, Ninth Revision, Clinical Modification code for low back pain (724.20). Multivariate Poisson regression analysis was used to estimate the rate of low back pain among military vehicle operators and control subjects per 1,000 person-years, while controlling for sex, race, rank, service, age, and marital status.ResultsA total of 8,447,167 person-years of data were investigated. The overall unadjusted low back pain incidence rate for military members whose occupation is vehicle operator was 54.2 per 1,000 person-years. Compared with service members with other occupations, motor vehicle operators had a significantly increased adjusted incidence rate ratio (IRR) for low back pain of 1.15 (95% confidence interval [CI] 1.13–1.17). Female motor vehicle operators, compared with males, had a significantly increased adjusted IRR for low back pain of 1.45 (95% CI 1.39–1.52). With senior enlisted as the referent category, the junior enlisted rank group of motor vehicle operators had a significantly increased adjusted IRR for low back pain: 1.60 (95% CI 1.52–1.70). Compared with Marine service members, those motor vehicle operators in both the Army, 2.74 (95% CI 2.60–2.89), and the Air Force, 1.98 (95% CI 1.84–2.14), had a significantly increased adjusted IRR for low back pain. The adjusted IRRs for the less than 20-year and more than 40-year age groups, compared with the 30- to 39-year age group, were 1.24 (1.15–1.36) and 1.23 (1.10–1.38), respectively.ConclusionsMotor vehicle operators have a small but statistically significantly increased rate of low back pain compared with matched control population.     

椎间盘造影阴性在椎间盘源性腰痛诊断中的分析评价

[目的]通过对一组有典型椎间盘源性下腰痛症状和影像学表现但椎间盘造影阴性的患者进行前瞻性分析,观察椎间盘造影阴性是否能完全排除椎间盘源性下腰痛的诊断.[方法] 2008年6月～2011年2月连续诊治的具有典型椎间盘源性疼痛症状和影像学表现(Dallas V型)但椎间盘造影阴性的一组患者共59例,其中男16例,女43例;年龄36～ 51岁,平均43.8岁;病史6个月～4年,平均1.8年.将59例患者随机分为两组,实验组(29例)于造影剂注射完后于椎间隙再给予注射利多卡因10 mg和地塞米松2.5 mg的混悬液,对照组(30例)则不注射药物并结束造影.两组患者于椎间盘造影术术前、术中、术后行VAS及ODI评分并观察结果.[结果]实验组术后2周内可见VAS评分下降,与对照组相比有统计学意义(P＜0.01),术后第3周随访时两组间VAS评分无明显差别(P＞0.05).实验组中18例VAS评分下降的患者在术后第1、4、8周时进行VAS评分及ODI评分时均较术前明显改善(P＜0.01),在第12周随访时总体上VAS评分及ODI评分与术前比较无明显差别(P＞0.05),对照组患者VAS评分及ODI评分与术前比较均无明显差别(P＞0.05).[结论]本研究结果表明椎间盘造影阴性,但同时合并典型的症状和影像学表现时,并不能完全排除椎间盘源性疼痛的诊断.     

Allogeneic mesenchymal precursor cells treatment for chronic low back pain associated with degenerative disc disease: a prospective randomized,placebo-controlled 36-month study of safety and efficacy

BACKGROUND CONTEXT PURPOSEEvaluate the safety and efficacy of a single intradiscal injection of STRO-3+ adult allogeneic mesenchymal precursor cells (MPCs) combined with hyaluronic acid (HA) in subjects with chronic low back pain (CLBP) associated with degenerative disc disease (DDD) through 36-month follow-up.STUDY DESIGN/SETTINGA multicenter, randomized, controlled study conducted at 13 clinical sites (12 in the United States and 1 in Australia).SUBJECT SAMPLEA total of 100 subjects with chronic low back pain associated with moderate DDD (modified Pfirrmann score of 3–6) at one level from L1 to S1 for at least 6 months and failing 3 months of conservative treatment, including physical therapy were randomized in a 3:3:2:2 ratio to receive 6 million MPCs with HA, 18 million MPCs with HA, HA vehicle control, or saline control (placebo) treatment.OUTCOME MEASURESSubjects were clinically and radiographically evaluated at 1, 3, 6, 12, 24, and 36 months postinjection. Subject-reported outcomes including adverse events, LBP on a Visual Analog Scale (VAS), Oswestry Disability Index (ODI), SF-36 and Work Productivity and Activity Index were collected.METHODSClinical and radiographic measures were collected at each visit. All randomized subjects were included in the safety assessments and analyzed based on the treatment received. Safety assessments included assessments of AEs, physical and radiographic examinations and laboratory testing. Efficacy assessments evaluated changes in VAS, ODI, and modified Pfirrmann (MP) scores between all active and control groups, respectively. Assessments included least squares mean (Mean), LS mean change from baseline (Mean Change) and responder analyses in order to assess the clinical significance of observed changes from baseline. The population for efficacy assessments was adjusted for the confounding effects of post-treatment interventions (PTIs). This study was conducted under an FDA Investigational New Drug application sponsored and funded by Mesoblast.RESULTSThere were significant differences between the control and MPC groups for improvement in VAS and ODI. The PTI-corrected VAS and ODI Means and Mean Change analyses; the proportion of subjects with VAS ≥30% and ≥50% improvement from baseline; absolute VAS score ≤20; and ODI reduction ≥10 and ≥15 points from baseline showed MPC therapy superior to controls at various time points through 36 months. Additionally, the proportion of subjects achieving the minimally important change and clinically significant change composite endpoints for the MPC groups was also superior compared with controls at various time points from baseline to 36 months. There were no significant differences in change in MP score from baseline across the groups. There were also no statistically significant differences in change in modified MP score at the level above or below the level treated between study arms. Both the procedure and treatment were well tolerated and there were no clinical symptoms of immune reaction to allogeneic MPCs. There was a low rate of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events, and the rates of these events in the MPC groups were not significantly different from the control groups. One TEAE of severe back pain was possibly related to study agent and one TEAE of implantation site infection was considered to be related to the study procedure.CONCLUSIONSResults provide evidence that intradiscal injection of MPCs could be a safe, effective, durable, and minimally invasive therapy for subjects who have CLBP associated with moderate DDD.     

Percutaneous endoscopic laser annuloplasty for discogenic low back pain

BackgroundLaser-assisted spinal endoscopy (LASE) kit has been used for percutaneous intradiscal decompression to evaporate and shrink the posterior and central nucleus for improvement of leg and radicular pain due to contained disc herniation. Percutaneous endoscopic laser annuloplasty (PELA), a new minimally invasive technique, uses LASE to directly coagulate the inflamed disc granulation tissue associated with annular tears. The small diameter of the endoscope including Ho:YAG laser, irrigation, and light, plus the extreme posterolateral approach into the posterior annulus, enables one to minimize damage to normal nuclear tissue. The authors sought to demonstrate the safety and efficacy of PELA for controlling discogenic low back pain (DLBP) due to abnormal disc tissues, new vessels, and nerves in the central torn posterior annulus.MethodsClinical outcomes of PELA were investigated in patients having DLBP with an annulus-torn degenerative disc or contained disc herniation. Thirty patients treated at a single level and achieving a mean follow-up of 9.7 months were analyzed. Outcomes were assessed using the visual analog scale (VAS) for back pain, the Korean Oswestry Disability Index (KODI), and the modified Macnab's criteria.ResultsThe mean back pain VAS score improved from 8.0 to 2.4, and the mean KODI score improved from 79.0 to 22.4 (P < .001). Results by the modified Macnab's criteria also showed a good outcome, with a success rate of 90.0%. There were no serious complications observed during follow-up.ConclusionsPercutaneous endoscopic laser annuloplasty using the Ho:YAG laser provides favorable outcomes for carefully selected groups of patients with DLBP.