Symptomatic Lumbar Degenerative Disc Disease Research Articles

Allogeneic Disc Progenitor Cells Safely Increase Disc Volume and Improve Pain, Disability, and Quality of Life in Patients With Lumbar Disc Degeneration-Results of an FDA-Approved Biologic Therapy Randomized Clinical Trial.

Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease. Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells (N = 20), high-dose cells (N = 20), vehicle alone (N = 10), or placebo (N = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment. At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, P = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, P = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, P = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm3 (P = 0.028) at 52 weeks and 402.1 mm3 (P = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle (n = 1) or placebo (n = 3) groups, none treatment related. High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection. NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.

Association of TaqI (rs731236) Polymorphism of Vitamin D Receptor Gene with Lumbar Degenerative Disc Disease

Lumbar degenerative disc disease (LDDD) significantly contributes to low back pain, with a complicated etiology involving genetic and environmental facts. The aim of study was to investigate the association between the TaqI (rs731236) polymorphism of the vitamin D receptor (VDR) gene with LDDD. In total, 248 patients with symptomatic LDDD and 146 control subjects were examined. The evaluation of clinical features of patients with LDDD comprised radiodiagnostic magnetic resonance imaging, neurologic examinations, pain scores including the visual analog scale (VAS), and disability investigation with Oswestry Disability Index (ODI). Genotyping of the VDR gene polymorphism was conducted using polymerase chain reaction-based methods. Individuals of the LDDD group who were VDR TaqI AA genotype carriers were significantly greater than the other group (P= 0.014), whereas those with GG genotype were significantly lower (P= 0.028) in the patient group. In addition, VAS and ODI scores were significantly lower in the GG genotype carrier group, whereas AA genotype carriers had the greatest scores (P= 0.004). Carrying the G allele decreased the risk of LDDD 1.7 times (P= 0.014) and carrying the A allele enhanced the risk 1.8 times (P= 0.028). Moreover, G-allele carriers had significantly lower VAS (P= 0.002) and ODI scores (P < 0.0001). VDR TaqI (rs731236) GG genotype and G allele have protective potential, whereas the AA genotype and A allele are risk factors for LDDD. The findings reveal a statistically significant association of the TaqI (rs731236) polymorphism of VDR gene polymorphism with LDDD. This result highlights the potential role of genetic factors in developing LDDD and suggests avenues for future research in genetic screening and personalized treatment strategies.

40. Disc progenitor cell therapy improves pain, disability, and quality of life for patients with lumbar disc degeneration: results of an FDA-approved clinical trial

BACKGROUND CONTEXT Allogeneic disc progenitor cells derived from adult intervertebral disc tissue have demonstrated both immunomodulatory and regenerative properties in preclinical animal studies. This includes the ability to increase aggrecan and collagen production and restore disc histology. These cells have the potential to impact the pathophysiology of degenerative disc disease (DDD) and lead to lasting pain relief and improved quality of life for patients with symptomatic DDD. PURPOSE To report the results of an FDA-approved clinical trial of injectable allogeneic disc progenitor cells and a viscous carrier for the treatment of DDD vs carrier and saline controls. STUDY DESIGN/SETTING A randomized, double-blind, placebo-controlled study at 13 clinical sites. PATIENT SAMPLE Sixty subjects (mean age 38, 60% male) were enrolled. OUTCOME MEASURES Subjects were assessed using validated safety and efficacy parameters including low-back pain visual analog scale (VAS), Oswestry Disability Index (ODI) and EQ-5D. METHODS Subjects with early to moderate, symptomatic lumbar DDD were randomized to one of four treatment groups and received single intradiscal injections of either low-dose cells (3,000,000cells/mL; N=20), high-dose cells (9,000,000cells/mL; N=20), vehicle alone (N=10) or placebo (N=10). Subject outcomes were assessed over 52 weeks. RESULTS VAS scores in the high-dose cell group were statistically significantly improved over baseline at weeks 12 (-54.53% [-69.46, -39.60], p=0.0056), 26 (-50.94% [-66.10, -35.78], p=0.0140), and 52 (-62.79% [90% CI -77.13, -48.46], p=0.0005). The vehicle group achieved statistical significance in VAS at week 52 only (-52.83% [90%CI -74.73, -30.92], p=0.0443). Mean pain VAS improved from baseline after treatment but only achieved statistical significance at week 26 with low-dose cells (-48.49% [90% CI -61.03, -35.94], p=0.0101) and saline (-50.13% [-65.24, -35.02], p=0.0206); neither demonstrated statistical significance at week 52. Further analysis showed that only the high-dose cell group showed reduction from baseline in back pain VAS that was statistically significantly greater than a minimum clinically important difference (MCID) of -20mm at week 52 (-39.8 [-50.0, -29.6], p=0.0001). Only the high-dose cell group exhibited an improvement from baseline in ODI score at week 52 that was statistically significantly greater than a MCID of -10 points (-24.3[-31.2, -17.5], p <0.0001) and an EQ-5D index score that was statistically significantly greater than a MCID of 0.08 (0.194 [0.139, 0.250], p <0.0001). CONCLUSIONS High-dose allogeneic disc progenitor cells produced meaningful, statistically significant improvements in back pain VAS, ODI and EQ-5D at one-year post-intradiscal injection. FDA DEVICE/DRUG STATUS IDCT - Injectable Discogenic Cell Therapy (Investigational/Not Approved) Allogeneic disc progenitor cells derived from adult intervertebral disc tissue have demonstrated both immunomodulatory and regenerative properties in preclinical animal studies. This includes the ability to increase aggrecan and collagen production and restore disc histology. These cells have the potential to impact the pathophysiology of degenerative disc disease (DDD) and lead to lasting pain relief and improved quality of life for patients with symptomatic DDD. To report the results of an FDA-approved clinical trial of injectable allogeneic disc progenitor cells and a viscous carrier for the treatment of DDD vs carrier and saline controls. A randomized, double-blind, placebo-controlled study at 13 clinical sites. Sixty subjects (mean age 38, 60% male) were enrolled. Subjects were assessed using validated safety and efficacy parameters including low-back pain visual analog scale (VAS), Oswestry Disability Index (ODI) and EQ-5D. Subjects with early to moderate, symptomatic lumbar DDD were randomized to one of four treatment groups and received single intradiscal injections of either low-dose cells (3,000,000cells/mL; N=20), high-dose cells (9,000,000cells/mL; N=20), vehicle alone (N=10) or placebo (N=10). Subject outcomes were assessed over 52 weeks. VAS scores in the high-dose cell group were statistically significantly improved over baseline at weeks 12 (-54.53% [-69.46, -39.60], p=0.0056), 26 (-50.94% [-66.10, -35.78], p=0.0140), and 52 (-62.79% [90% CI -77.13, -48.46], p=0.0005). The vehicle group achieved statistical significance in VAS at week 52 only (-52.83% [90%CI -74.73, -30.92], p=0.0443). Mean pain VAS improved from baseline after treatment but only achieved statistical significance at week 26 with low-dose cells (-48.49% [90% CI -61.03, -35.94], p=0.0101) and saline (-50.13% [-65.24, -35.02], p=0.0206); neither demonstrated statistical significance at week 52. Further analysis showed that only the high-dose cell group showed reduction from baseline in back pain VAS that was statistically significantly greater than a minimum clinically important difference (MCID) of -20mm at week 52 (-39.8 [-50.0, -29.6], p=0.0001). Only the high-dose cell group exhibited an improvement from baseline in ODI score at week 52 that was statistically significantly greater than a MCID of -10 points (-24.3[-31.2, -17.5], p <0.0001) and an EQ-5D index score that was statistically significantly greater than a MCID of 0.08 (0.194 [0.139, 0.250], p <0.0001). High-dose allogeneic disc progenitor cells produced meaningful, statistically significant improvements in back pain VAS, ODI and EQ-5D at one-year post-intradiscal injection.

26. Clinical outcome of lumbar hybrid surgery in a consecutive series of patients including long-term follow-up

<h3>BACKGROUND CONTEXT</h3> Many patients with symptomatic lumbar degenerative disc disease (DDD) are affected at more than one level. When nonoperative treatment fails to provide adequate relief, multilevel surgery may be considered. Lumbar total disc replacement (TDR) was introduced as an option to fusion. Some disc levels are not amenable to TDR and fusion is preferable at that level. Hybrid surgery, involving TDR at one level and fusion at the adjacent segment, has been introduced as an option to fusing multiple levels. <h3>PURPOSE</h3> The purpose of this study was to investigate the long-term clinical outcome of patients undergoing lumbar hybrid surgery for treating symptomatic lumbar DDD at more than one level. <h3>STUDY DESIGN/SETTING</h3> The study was a retrospective record review combined with a mailing and/or telephone calls to patients to collect current outcome data. <h3>PATIENT SAMPLE</h3> A consecutive series of 296 patients undergoing lumbar hybrid surgery was identified beginning with the first case experience in 2005. All patients were treated for painful disc degeneration unresponsive to nonoperative care and were at least two years postoperative. <h3>OUTCOME MEASURES</h3> The primary outcome measures were visual analog scales (VAS) separately assessing back and leg pain, and the Oswestry Disability Index (ODI). Data on re-operations were also collected. <h3>METHODS</h3> General descriptive data, surgical data and outcomes were collected for the consecutive series of hybrid patients. For patients who had not been seen recently in the clinic, mailing and/or telephone calls were conducted to collect VAS, ODI, and re-operation data. <h3>RESULTS</h3> The mean follow-up duration was 71.4 months with a maximum of 196 months. A total of 649 levels were operated with TDR implanted in 318 levels and 331 levels undergoing either stand-alone ALIF or combined anterior/posterior fusion. The most common combination for hybrid surgery was TDR at L4-5 and fusion at L5-S1. The mean blood loss was 99.1 ml. There were statistically significant improvements (p <0.001) in the mean values of all three clinical <h3>OUTCOME MEASURES</h3> VAS back pain scores improved from 6.7 to 3.2; VAS leg pain scores improved from 4.2 to 2.0; and ODI scores improved from 45.7 to 25.4. There were no significant differences in the pain and function scores for patients with minimum 10-year follow-up vs those with shorter follow-up duration. Re-operation occurred in 16.2% of patients. The most common reason for re-operation was the removal of painful posterior instrumentation at the fusion level of the hybrid (31.3% of re-operations; 6.1% of the study group). Re-operations involving the TDR level occurred in 9 patients (3.0%). These included 3 cases of TDR migration, 1 posterior fusion for facet joint arthrosis, 4 patients underwent decompression at the TDR and fusion levels, and one patient underwent re-operations at both hybrid levels related to multilevel deformity. One patient reported multiple re-operations on the returned mailing, but insufficient detail was provided to determine the procedure(s) performed. <h3>CONCLUSIONS</h3> The results of this study support that for many patients with symptomatic DDD arising from more than one disc, hybrid surgery is a viable surgical option. Significant improvement was demonstrated in pain and function scores with no difference in scores among patients with more than 10-year follow-up. The most commonly occurring re-operation was removal of painful posterior fixation, unrelated to the TDR. <h3>FDA DEVICE/DRUG STATUS</h3> Charite, ProDisc-L, activL (Not approved for this indication)

Predictors of long-term clinical outcomes in adult patients after lumbar total disc replacement: development and validation of a prediction model.

Long-term outcomes of single-level lumbar arthroplasty are understood to be very good, with the most recent Investigational Device Exemption (IDE) trial showing a < 5% reoperation rate at the close of the 7-year study. This post hoc analysis was conducted to determine whether specific patients from the activL IDE data set had better outcomes than the mean good outcome of the IDE trial, as well as to identify contributing factors that could be optimized in real-world use. Univariable and multivariable logistic regression models were developed using the randomized patient set (n = 283) from the activL trial and used to identify predictive factors and to derive risk equations. The models were internally validated using the randomized patient set and externally validated using the nonrandomized patient set (n = 52) from the activL trial. Predictive power was assessed using area under the receiver operating characteristic curve analysis. Two factors were significantly associated with achievement of better than the mean outcomes at 7 years. Randomization to receive the activL device was positively associated with better than the mean visual analog scale (VAS)-back pain and Oswestry Disability Index (ODI) scores, whereas preoperative narcotics use was negatively associated with better than the mean ODI score. Preoperative narcotics use was also negatively associated with return to unrestricted full-time work. Other preoperative factors associated with positive outcomes included unrestricted full-time work, working manual labor after index back injury, and decreasing disc height. Older age, greater VAS-leg pain score, greater ODI score, female sex, and working manual labor before back injury were identified as preoperative factors associated with negative outcomes. Preoperative BMI, VAS-back pain score, back pain duration ≥ 1 year, SF-36 physical component summary score, and recreational activity had no effect on outcomes. Lumbar total disc replacement for symptomatic single-level lumbar degenerative disc disease is a well-established option for improving long-term patient outcomes. Discontinuing narcotics use may further improve patient outcomes, as this analysis identified associations between no preoperative narcotics use and better ODI score relative to the mean score of the activL trial at 7 years and increased likelihood of return to work within 7 years. Other preoperative factors that may further improve outcomes included unrestricted full-time work, working manual labor despite back injury, sedentary work status before back injury, and randomization to receive the activL device. Tailoring patient care before total disc replacement may further improve patient outcomes.

Surgical outcomes of patients with degenerative lumbar disc disease post-IntraSPINE® device fixation: Three-year prospective study

Background: Lumbar degenerative disc disease is one of the most common conditions associated with chronic low back pain. IntraSPINE® is a novel inter-laminar device that allows more physiological rocking-type movements in flexion and extension. Aim: To evaluate the results of patients with symptomatic Lumbar degenerative disc disease treated with an IntraSPINE® device and followed up over a 3-year period. Materials and Methods: A Prospective longitudinal research study involving patients with imaging-confirmed Lumbar degenerative disc disease in whom conservative treatment was unsuccessful. Outcome measures were changes over baseline score on the Oswestry Disability Index (ODI), and low back and radicular pain assessed at 6, 12, 24 and 36 months postoperatively. Overall success, a composite outcome that included key safety and clinical considerations, was assessed. Secondary outcomes included satisfaction with symptoms, employment status and post-surgery medical interventions. To compare differences in longitudinal clinical score patterns over 36 months, a mixed-effect model ANCOVA with repeated measurements was performed, with adjustment for low back and radicular pain score and ODI score at baseline. Results: 231 patients were recruited and 180 completed the study. A significant improvement in ODI score (p=0.0597), as well as in VAS (Visual Analogue Scale) scores for back (p= 0.0228) and leg pain (p&lt;0.0001) was observed during the follow-up. For ODI score, the mean percentage decrease from inclusion to month 36 was 64.5%. These scores were respectively 66.2% for radicular pain and 46.4% for low back pain. In 73% of cases, surgery was considered successful. 89% of working patients returned to work and 68% of patients were very satisfied at month 12. Only four patients presented intraoperative complications.

267. The impact of preventative multimodal analgesia on postoperative opioid requirement and pain control in patients undergoing lumbar fusions

BACKGROUND CONTEXT Preventive multimodal analgesia (PMA) addresses multiple sources and pathways of acute and chronic pain by interfering with peripheral and central sensitization and should provide a way to achieve safer and more effective pain management with reduced opioid medication use. PURPOSE The main objectives of this study were to determine the impact of PMA on postoperative opioid requirements and analgesic effectiveness in patients undergoing lumbar fusion surgery. STUDY DESIGN/SETTING A prospective observational study with a historical reference group was performed. PATIENT SAMPLE The study compared postoperative opioid requirement and analgesic effect in a total of 103 patients undergoing elective, one- or two-level transforaminal lumbar interbody fusion (TLIF) surgeries for symptomatic lumbar degenerative disc disease. The PMA patient group included 52 consecutive patients who received 1000 mg of acetaminophen, 300 – 900 mg of gabapentin, and 200 – 400 mg of celecoxib 1 hour before the procedure. The reference group included 51 patients who received 15 mg of morphine-equivalent dose (MED) preoperatively. OUTCOME MEASURES Postoperative opioid requirement and pain scores. METHODS Multiple linear regression was used to evaluate the influence of PMA on pain, MED and acetaminophen use over 4 postoperative days (PODs), while controlling for all variables likely to influence these outcomes, including age, gender, baseline opioid use, duration of surgery, postoperative intrathecal morphine use and administration of muscle relaxants and anticonvulsants. RESULTS The differences in opioid requirement and postoperative pain scores were statistically significant on all four postoperative days. The effect size varied from -0.54 to -0.99 for the postoperative opioid requirement and from -0.59 to -1.16 for postoperative pain indicating that these measures were reduced by about ½ to 1 standard deviation in the PMA patient group. CONCLUSIONS PMA is a highly effective method for postoperative pain management in patients undergoing lumbar fusion surgeries, which not only improves pain control, but also reduces opioid requirement. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

81. Seven-year results of a randomized controlled IDE trial for lumbar artificial discs in single-level degenerative disc

BACKGROUND CONTEXT The activL artificial disc received Food and Drug Administration approval in 2015 based on 2-year follow-up data. PURPOSE To compare the 7-year safety and efficacy of the activL® artificial disc with ProDisc-L total disc replacement (TDR) in the treatment of patients with symptomatic single-level lumbar degenerative disc disease (DDD). Study Design/Setting Prospective, randomized, multicenter IDE. Patient Sample A total of 206 patients who underwent single-level lumbar arthroplasty with either Activ L or Prodisc L. OUTCOME MEASURES ODI, SF-36, VAS, complications, re-operations. METHODS Eligible patients presented with symptomatic, single-level, lumbar DDD who failed ≥6 months of nonsurgical management. At entry, 283 patients were randomly allocated to treatment with activL (n=218) or ProDisc-L (n=65) TDR. At 7-years follow-up, a total of 206 patients (activL: 160, ProDisc-L: 46) were available for analysis. RESULTS The activL group was non-inferior compared to the ProDisc-L group in the primary composite end point at 7 years (p=0.0369). Relative to baseline, significant reductions in visual analog scale (VAS) back/leg pain severity as well as improvements in Oswestry Disability Index (ODI) and SF36 Questionnaire were observed in both treatment groups at 7 years. The activL group showed significantly better range of motion for flexion-extension (FE) rotation, disc height/angle and higher proportion of patients without heterotopic ossification, compared with ProDisc-L. Freedom from a serious adverse event through 7 years was 62% in activL patients and 43% in ProDisc-L patients (log-rank p=0.011). Significant reduction in narcotic usage compared to baseline were observed in both treatment groups over time, with 0% of TDR patients using narcotics at 7 years. Freedom from reoperation was high for TDR patients at 95%. Patients who experienced improvements in radiographic (FE rotation, FE translation, lateral rotation), VAS leg pain, ODI, and SF36 measures at 2 years were more likely to experience improvements at 7 years. CONCLUSIONS Long-term evidence supports TDR as safe and efficacious treatment for lumbar DDD. The results demonstrated short-term benefits of TDR are maintained at 7 years, with patients no longer requiring narcotic use. The next generation activL Artificial Disc is more effective at preserving range of motion compared to first generation TDR (ProDisc-L) and offers an improved safety profile. Other primary and secondary outcomes are similar between disc designs. FDA DEVICE/DRUG STATUS Activ L (Approved for this indication), Prods L (Approved for this indication)

Evaluation of DIAM™ Spinal Stabilization System for lower lumbar disc degenerative disease: A randomized, prospective, single-site study

ObjectiveTo determine the efficacy of DIAM Spinal Stabilization System compared with nonoperative treatment for patients with low back pain and lower lumbar disc degenerative disease. MethodsA single center collected prospective outcomes data on 38 patients randomized to an interspinous device or non-operative treatment for symptomatic lumbar degenerative disc disease with treatment crossover allowed at 6 months. ResultsAt all postoperative timepoints out to 2-years, statistically significant improvements in ODI and back pain scores were observed with the interspinous device. Clinically significant improvements (ODI >15-point improvement) were seen in 87.5% of DIAM patients at 2-years postoperatively. A high cross-over rate was noted from the non-operative cohort to the operative group (12 of 15) due to continued pain with nonoperative care. Additionally, 80% of patients receiving the DIAM implant reported a >15-point ODI reduction from pre-surgical scores at 2-year follow-up. ConclusionThe DIAM device demonstrates improvement in ODI and Back Pain scores maintained out to a 2-year follow-up timepoint and performed superior to conventional nonoperative treatment regimens commonly used in low back pain.

Treatment outcome of quality of life and clinical symptoms in patients with symptomatic lumbar degenerative disc diseases: which treatment modality is superior?

This was to assess the quality of life and clinical symptoms before and after treatment of patients with symptomatic lumbar degenerative disc disease (LDDD). It was also to determine the superior treatment for well-selected patients: conservative versus surgical treatment. Prospective interventional analytical study. We studied 160 adult symptomatic patients aged 31-60years with diagnosis of LDDD who were enrolled between May 2016 and November 2017. Their pre- and post-treatment clinical symptoms and signs and quality of life were studied using the Oswestry disability index (ODI). The data was analysed using SPSS version 24. One hundred fifty-three adult patients aged 31 to 60years completed the study. The male-to-female ratio was 1:1.5 while the symptom duration ranged between one and 14years. The treatment modalities were medical (46%), epidural steroid injection (26%) and operative treatment (28%). The responses to the treatment were worsened symptoms (10.5%), no improvement (13.1%), moderate/slight improvement (27.5%) and significant improvement (49%). There were statistically significant improvements (p value < 0.05) in clinical symptoms, sign and ODI at six months after treatment. Surgical treatment was superior to all other form of care. This study showed significant improvement in outcome among the participants in different treatment modalities with surgical treatment being the superior. We recommend surgical treatment for well-selected adult patients with symptomatic LDDD and assessment of quality of life and clinical symptoms before and after treatment.

Lumbar Total Disc Replacement by the Lateral Approach–Up to 10 Years Follow-Up

This study aimed to analyze radiologic and clinical results with a minimum 5 years follow-up (FUP) of lateral lumbar total disc replacement for the treatment of symptomatic lumbar degenerative disc disease. We performed a prospective, single-center, clinical, and radiologic study. Patients were treated with lumbar total disc replacement (extreme lateral total disc replacement) by a lateral transpsoas approach. From 2005 to 2012, 60 patients were enrolled (31 male, 29 female; total, 66 levels; average age, 42.8 years [standard deviation (SD), 9.7 years, range, 22-64 years]; mean body mass index, 26.0 [SD, 3.4]). Clinical end points included visual analog scale and Oswestry Disability Index questionnaires, complications, and reoperation. Radiographic end points included heterotopic ossification (McAfee classification), adjacent level disease, and prosthesis migration or subluxation. The mean surgical duration was 122 minutes (SD, 45 minutes) with mean 58 mL (SD, 21 mL) of estimated blood loss. No intraoperative complication occurred. The exceptions were 1 patient with postanesthesia apnea and 2 patients with quadriceps motor deficit (resolved within 4 months with physiotherapy). Of 60 patients, 9 were missed to FUP and 51 (85%) were enrolled in the study, with mean FUP of 92 months (range, 60-122 months). In total, 5 levels (9%; 5 of 55) required to be fused. Both removal of the prostheses and interbody fusion were performed by the lateral transpsoas approach. One patient experienced CrCo allergy (at 2 months); 4 experienced persistent pain from different causes (at 7, 9, 24, and 88 months). Five patients (10%) presented with progression at adjacent levels and 2 (4%) required surgery. One patient required sacroiliac fusion at 63 months. There were no complications during the retrieval surgeries. One partial disc migration occurred but the patient refused retrieval. There was no bone bridging in 9% of the discs (grade 0 heterotopic ossification): grade I, 22%; grade II, 31%; grade III, 20%; grade IV (fusion), 18%. Most heterotopic ossification cases (93%) occurred in the lateral aspect of the disc space, and mostly at the contralateral side of the surgical approach. Patient-reported outcomes significantly improved (P < 0.01) at the last FUP. Visual analog scale back pain score was preoperatively 8.5, early postoperatively 2.5, and at last FUP 3.1. Oswestry Disability Index was preoperatively 55%, early postoperatively 31%, and at last FUP 21%. This study presents mid-term to long-term results of extreme lateral total disc replacement artificial disc for the treatment of lumbar degenerative disease, with fast mobilization, sustained pain relief, and improved physical function. Despite the low rate of ALDis, some discs evolved to ankyloses and others were retrieved. Lumbar artificial disc replacement by the lateral approach seems to be a safe and effective treatment.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P63. Pain-related safety outcomes seven years following lumbar total disc replacement in mobile core devices versus constrained core devices

BACKGROUND CONTEXT Total disc replacement (TDR) is an alterative to fusion for treating patients with disabling discogenic back pain. While several studies report significant improvements in overall back pain following TDR, some patients may experience recurring episodes of pain in the lumbar and/or lower extremities. Competing lumbar disc arthroplasty devices include a mobile core device versus a constrained core device. Long-term follow up (>7 years) from investigational device trials is now available to better assess long-term outcomes with arthroplasty with the two device types. PURPOSE To evaluate pain-related adverse events in patients 7years following single-level total disc replacement at L4–L5 or L5–S1 with either a mobile core disc (MCD) or a constrained core device (CCD) to determine if implant design is associated with increased pain serious adverse effects at 7-year follow-up. STUDY DESIGN/SETTING This post-hoc analysis of a multicenter, prospective, randomized, controlled, investigational device exemption trial included patients with symptomatic lumbar degenerative disc disease at L4–L5 or L5–S1. PATIENT SAMPLE The patients had lumbar arthroplasty surgery with either an MCD (n=218) or CCD (n=65) implant and were randomized prior to surgery in the IDE study. OUTCOME MEASURES The study reviewed events deemed to be serious adverse events in a FDA IDE study. METHODS This post-hoc analysis of a multicenter, prospective, randomized, controlled, investigational device exemption trial included patients with symptomatic lumbar degenerative disc disease at L4–L5 or L5–S1. Pain related adverse events (AE) at 7years post implantation for TDRs as a class and by device type (MCD vs. CCD) are reported. RESULTS Of the reported AEs, 23% (N=327) were categorized as pain of the lumbar and/or lower extremities: lumbar only (7%), lumbar and bilateral lower leg (5%), and lumbar and unilateral lower leg (3%). Patients presenting with AEs reported an average of two pain related AEs at 7years post-op. Of the pain related AEs, 11% were device related, 8% were procedure related and 9% were serious AEs (SAEs). Onset of the first pain related SAE occurred on average at 49days (range: 0–118 days) and 395days (range: 0–2,728 days) following CCD and MCD implantation, respectively (p=.21). Overall, the majority of pain related SAEs were classified as severe (69%). A greater proportion of patients implanted with the CCD device presented with severe SAEs (88%) compared to patients with MCD (61%; p=.17). At the 7-year follow-up, over half of the SAEs occurring in MCD patients were resolved (56%) while the SAEs in CCD patients remained mostly unresolved (75%; p=.14). CONCLUSIONS While the rate of pain related AEs were the same between patients implanted with an MCD or CCD implant, there were observed differences in the quality of SAEs between the two TDR devices. On average, the first pain related SAE in MCD patients occurred approximately 1 year after CCD patients. Furthermore, a smaller proportion of SAEs were severe and a greater proportion was resolved by the 7-year follow-up appointment with MCD versus CCD implanted patients.

Friday, September 28, 2018 1:00 PM–2:30 PM abstracts: achieving lumbar interbody fusion: 197. Expandable graft-containing fabric mesh system for single-level lumbar interbody stabilization: 1-year clinical and radiographic results from a prospective clinical IDE trial

BACKGROUND CONTEXT Interbody fusion with rigid cages are commonly employed in the surgical treatment of medically-refractory degenerative disc disease and spondylolisthesis. However, they require a certain degree of soft-tissue dissection and bone removal to accommodate placement of the cage. The SCOUT study is an on-going FDA IDE trial (clinicaltrials.gov NCT #: NCT02347410, IDE: G140140) investigating the safety and efficacy of a novel device for lumbar interbody fusion. It is exploring the use of an expandable bone graft-containing fabric mesh for use as the interbody spacer, a device that can be deployed through a delivery portal only 8mm in diameter. PURPOSE To report on 12-month follow-up data on patients participating in the SCOUT trial. STUDY DESIGN/SETTING Multiinstitutional prospective single-arm trial. PATIENT SAMPLE Skeletally mature adults, aged 21 to 80, with single-level symptomatic lumbar degenerative disc disease (levels L2–S1) requiring interbody fusion surgery. OUTCOME MEASURES Patient-reported satisfaction, VAS low back pain scores, ODI, and radiographic fusion rates at 12-month follow-up. METHODS All patients underwent either a MIS-TLIF or an open PLIF approach (determined by surgeon preference), and all received supplemental pedicle screw fixation. All patients had a minimum Visual Analogue Score (VAS) of 40mm (0-100 mm scale) and a minimum Oswestry Disability Index (ODI) of 40. All patients had a BMI RESULTS At most recent follow-up, 84 patients had undergone surgery, with 60 completing 6-month follow-up and 29 completing 12-month follow-up. Intraoperative and perioperative characteristics remained favorable in terms of estimated blood loss (mean: 129±150 cc), operative time (mean: 161±53 minutes), and length of stay (2.3±1.1 days). At twelve-month follow-up, all 29 patients (100%) demonstrated radiographic fusion, as defined by evidence of bridging bone on CT scan by two independent radiologists. Twenty of 29 patients (69%) reported “Excellent” satisfaction with their surgery and seven (24%) reported “Good” satisfaction. Compared to a baseline VAS low back pain score of 73.0±16.6 (Mean±SD) and baseline ODI of 54.0±12.1, there were significant improvements at both 6-months (VAS: 24.1±25.7, ODI: 25.3±20.4, p CONCLUSIONS At twelve-month follow-up, there are encouraging clinical and radiographic results for the use of an expandable fabric mesh device for lumbar interbody fusion. There is potential for such a system to provide good fusion and pain relief while minimizing tissue disruption.

The Incidence and Association of Mental Depression with Symptomatic Lumbar Degenerative Disc Disease and Treatment Outcome

Study Design: Prospective analytical study. Objectives: The aim was to determine the association between mental depression and symptomatic Lumbar Degenerative Disc Disease (LDDD) in patients with no previous background of mental disorder. We also aimed at determining the incidence of mental depressions in patients with LDDD and the effects of the treatment on the mental depression. Methodology: One hundred and sixty patients with no prior history of mental or behavioral disorders who presented with low back pains arising from LDDD and met inclusion criteria were studied. The clinical findings and Depression Screening Test pro-forma were completed for each. The extracted information was analyzed using Statistical Package for Social Science (SPSS) version 24.0. The statistical significance was set at P < 0.05. Results: One hundred and fifty-three patients completed the study, with a male to female ratio of 1:1.5 and the mean age of the patients was 48.5 years. The marital status was 4.4% single, 86.9% married, 3.8% divorce/separate and 5% widow/widower. Their levels of education were: no formal education (10.00%), primary school level (8.10%), secondary level (27.50%) and Tertiary level (54.40%). Conclusions: This study showed the incidence of mental depression in 32% of the patients with LDDD. We also noted a statistically significant relationship between symptomatic LDDD and level of mental depression with significant improvement in the level of depression at 6th month after treatment. Hence, assessment of the patients’ mental health is important in the management of LDDD.

Defining the Ideal Lumbar Total Disc Replacement Patient and Standard of Care.

: Lumbar total disc replacement, now in use since 2004, was determined by the panel to be a standard of care for the treatment of symptomatic single-level lumbar degenerative disc disease in the active patient subpopulation as outlined by the investigational device exemption study criteria. The large body of evidence supporting this statement, including surgeons' experiences, was presented and discussed. Consensus statements focusing on decision-making criteria reflected that efficacy, long-term safety, clinical outcomes with validated measures, and cost-effectiveness should form the basis of decision-making by payers. Diagnostic challenges with lumbar degenerative disc disease patients were discussed among the panel, and it was concluded that although variably used among surgeons, reliable tools exist to appropriately diagnose discogenic back pain.

Prediction based on preoperative opioid use of clinical outcomes after transforaminal lumbar interbody fusions

OBJECTIVE Opioid analgesics have become some of the most prescribed drugs in the world, despite the lack of long-term studies evaluating the benefits of opioid medications versus their risks associated with chronic use. In addition, long-term opioid use may be associated with worse long-term clinical outcomes. The primary objective of this study was to evaluate whether preoperative opioid use predicted inferior clinical outcomes among patients undergoing transforaminal lumbar interbody fusion (TLIF) for symptomatic lumbar degenerative disc disease. METHODS The authors of this observational study prospectively enrolled 93 patients who underwent 1-level to 2-level TLIFs in 2011-2014; the patient cohort was divided into 2 groups according to preoperative opioid use or no such use. Visual analog scale (VAS) scores for low-back pain and leg pain, Oswestry Disability Index scores, and the scores of the mental component summary (MCS) and physical component summary (PCS) on the 36-Item Short Form Health Survey were used to assess pain, disability, and health-related quality of life outcomes, respectively. The clinical scores for the 2 groups were determined preoperatively and at a 12-month follow-up examination. RESULTS In total, 60 (64.5%) patients took prescribed opioid medications preoperatively. Compared with those not taking opioids preoperatively, these patients had significantly higher VAS scores for low-back pain (p = 0.016), greater disability (p = 0.013), and lower PCS scores (p = 0.03) at the 12-month follow-up. The postoperative MCS scores were also significantly lower (p = 0.035) in the opioid-use group, but these lower scores were due to significantly lower baseline MCS scores in this group. A linear regression analysis did not detect opioid dose-related effects on leg and back pain, disability, and MCS and PCS scores, suggesting that poorer outcomes are not significantly correlated with higher opioid doses taken by the patients. CONCLUSIONS The use of opioid medications to control pain before patients underwent lumbar fusion for degenerative lumbar conditions was associated with less favorable clinical outcomes postoperatively. This is the first study that has demonstrated this association in a homogeneous cohort of patients undergoing TLIF; this association should be studied further to evaluate the conclusions of the present study. Clinical trial registration no.: NCT01406405 ( clinicaltrials.gov ).

Mini Anterior Lumbar Interbody Fusion: One Year Follow up for a Novel Device

Introduction This study is a prospective cohort observational trial, to evaluate the ROI-A (Radiolucent Open Implant-ALIF) and VerteBRIDGE plate construct, in the treatment of symptomatic lumbar degenerative disc disease. The principal advantage of anterior approach is that the risks associated with exploration of the spinal canal through a posterior approach can be avoided and damage to the muscles of the back is eliminated. The anterior approach offers superior visualization of the disc space itself, and can be done without disruption of the otherwise healthy posterior elements. The Mini ALIF retroperitoneal approach facilitates rapid patient recovery. Materials and Methods The ROI-A (Radiolucent Open Implant-ALIF) is made from PEEK (Polyetheretherketone), a medical grade plastic, and two metallic anchoring plates, marketed as VerteBridge, which provide both stability at the site of desired bony fusion and fixation of the implant to the vertebrae adjacent to the interbody device. Inclusion Criteria: 18 patients between the ages 31 and 65 years of age; Disc disease between L2-S1; Patients may have up to grade I spondylolisthesis or retrolesthesis at the involved site; Maximum two diseased vertebral motion segments to be instrumented; Has had no more than two previous non-fusion surgeries to the lumbar soine at the same level(s); Has failed to respond to an appropriate attempt at conservative treatment. Exclusion Criteria: More than two vertebral motion segments involved; Prior anterior, retroperitoneal approach; Has had previous anterior instrumented fusion at the proposed operative level; Higher than grade I spondylolisthesis or retrolisthesis at the involved level(s); Has reported active malignancy, localized or systemic infection; Morbid obesity, as defined by NIH Clinical Guidelines Body Mass Index (BMI &gt; 40); Patients with a diagnosis of osteoporosis, osteopenia, Paget's or other metabolic bone disease; Patients who smoke more than 1 pack per day; Has an active workers compensation claim relative to the involved part. Outcome Measures: Subjects are evaluated clinically pre-operatively, 6 weeks and 12 months post op by the pain questionnaire (VAS), and function questionnaire (ODI); The radiological measures included the segmental lordosis, integrity of the construct, and presence of bridging bone; Fusion success is defined as presence of bridging bone, and postoperative intervertebral motion at 12 months which is less than 5 degrees, via manual radiographic angular measurements (Cobb Method) of the implanted level(s) on flexion and extension radiographs at the 12 month follow up visit. Results The VAS has improved from an average of 9 preop to an average of 2 postop. ODI score has reduced an average 30 points from preop measurement. 83% (15 patients) went on bony fusion at the radiological assessment 12 month post op. None of the patients underwent revision, removal of implant, supplemented fixation, or re-operation. One patient developed mechanical ileus for 48 hours postop, resolved with NG tube. Conclusion Mini anterior inter-body fusion is a valid option when treating degenerative/discogenic back pain, the ROI-A implant is a safe and simple, with satisfactory results up to 12 month, according to our pilot study.

Intradiscal Injection of YH14618, a First-in-Class Disease-Modifying Therapy, Reduces Pain and Improves Daily Activity in Patients with Symptomatic Lumbar Degenerative Disc Disease

Intradiscal Injection of YH14618, a First-in-Class Disease-Modifying Therapy, Reduces Pain and Improves Daily Activity in Patients with Symptomatic Lumbar Degenerative Disc Disease

Does fusion increase the incidence of adjacent segment disease in patients with symptomatic lumbar degenerative disk disease?

This is a retrospective cohort study. It was conducted to compare the incidence of adjacent segment disease (ASD) in patients who have undergone fusion for treatment of lumbar degenerative disk disease and patients who were treated conservatively to determine if fusion increases the risk of adjacent segment disease. Previous case series have indicated that fusion increases the risk of ASD. The eligible population included patients without previous spinal surgery who were evaluated for symptomatic lumbar degenerative disk disease. The study population underwent lumbar fusion with instrumentation. The control population consisted of patients with the same diagnosis who were managed conservatively. ASD was defined as new symptoms of radiculopathy, referable to a different anatomical level of the spine. There were 83 patients with a mean follow-up of 4.3 years including 42 males and 41 females. There were 24 patients who underwent fusion (“fusion”) and 59 patients who were managed nonoperatively (“nonsurgery”). A total of 22 patients reported new symptoms of radiculopathy after a mean 6.5 years. There was no statistically significant difference in the incidence of new radiculopathy between the groups (fusion 17% vs. nonsurgery 30%, P = 0.27). Six patients underwent surgery for symptoms different than their initial complaint after a mean disease-free interval of 7.5 years. There was no statistically significant difference in the incidence of additional surgery between the groups (fusion 4% vs. nonsurgery 8%, P = 0.67). There was no statistically significant difference in mean period before reoperation in patients who underwent fusion (7.8 years) vs. nonsurgery (7.5 years). In conclusion, among a population of patients with symptomatic lumbar degenerative disk disease, there was no difference in incidence of new spinal symptoms (according to a newly-created questionnaire to define ASD) or rates of operation in patients who underwent fusion compared to nonoperative treatment. These findings challenge the commonly held observation that adjacent segment disease is directly attributable to fusion. Further study is warranted to determine whether fusion increases the incidence of degeneration at adjacent spinal segments.

Autogenous Point of Care Bone Marrow Concentrate (BMC) for the Treatment of Lumbar Degenerative Disc Disease: IRB Controlled Prospective Study

Current treatment options for moderate to severe symptomatic lumbar degenerative disc disease include fusion or conservative therapy. The use of autogenous BMC may provide a nonsurgical option for this condition. This is the first report of the safety and feasibility for using autogenous BMC in treating lumbar DDD.