Treatment of Degenerated Intervertebral Discs Using a Viable Disc Tissue Allograft for Chronic Discogenic Low Back Pain: A Randomized Controlled Trial Comparing Single-site Outcomes With Aggregate and Longer-Term Follow-Up Data

Background: Disruption of the internal structure of the nucleus pulposus commonly occurs with the development of painful degenerative lumbar disc disease. Supplementing disc tissue through autologous or allogeneic human cellular and tissue therapies has been tested in small sample clinical trials. A few investigators have reported substantial improvements in pain and function. A viable disc tissue allograft was developed to supplement tissue loss associated with intervertebral disc degeneration. Methods: We assessed results in a subgroup of patients from a large trial comparing this allograft with other treatments. A multicenter randomized controlled trial of 218 subjects with chronic low back pain secondary to degenerative disc disease was conducted. Patients were treated with the allograft, saline, or nonsurgical management and studied for 12 months. We assessed longer-term results in a single-site subgroup from this prospective trial.Results: At 12 months, subjects from the single-site subgroup who had been randomly assigned to the active allograft group (n=17) showed improvements in both mean Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) scores. There was an overall reduction of 28.69 points in the ODI and 33.06 points in the VAS. This was similar to the aggregate ODI and VAS scores of the active allograft group. At 24 months postprocedure, 9 of the 10 patients remaining in the active allograft group at the single study site had mean ODI and VAS score improvements of 28.23 and 36.13, respectively. A similar improvement in pain scores occurred in the 4 patients at 36 months with mean ODI and VAS score improvements from preoperative scores of 25.21 and 51.35, respectively.Conclusions: Clinically meaningful improvements demonstrated in this single-site analysis were comparable to the aggregate study population at 12 months. Longer-term results from this single site at 24 and 36 months suggested durability of viable disc tissue allograft supplementation for patients with discogenic back pain.Trial registration: The trial was retrospectively registered 17 October 2018 on www.clinicaltrials.gov (NCT03709901) and was approved by the Sterling Institutional Review Board, Atlanta, Georgia (IRB no. 5792).

Homologous Use of Umbilical Cord Tissue for Knee Pain

Context: Injection with homologously-used umbilical cord tissue allograft has not been adequately studied in patients suffering from knee pain. Objectives: The goal of this study is to determine if knee pain subjects who received cryopreserved umbilical cord tissue (UCT) injected into knee joints experience less knee pain, better function, decreased physical limitations, and reduction of medications (e.g., opiates, NSAIDs, and acetaminophen) over a 6-month period. Methods: Prior to initiation of this study, Institutional Review Board (IRB) approval was obtained. Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritic Index (WOMAC), and medication usage data were recorded for thirty (30) consenting knee pain subjects receiving UCT at a single site in the United States. Subject profile information was also gathered and utilized to gain further insight into any effects of age, gender, and BMI on pain improvement over time. Results: Mean resting VAS scores improved from 1.95 to 0.83 over 6 months (p<0.001), while mean VAS scores with activity improved from 6.28 to 2.87 (p<0.001) for the same period. There was no strong evidence of correlation found between gender and VAS scores (resting or with activity). However, there were statistically significant correlations found for both BMI vs. Pre-injection VAS with activity scores (r=0.402, p=.028) and Age vs. Pre-injection VAS with activity scores (r=0.434, p=.017). Mean WOMAC daily activity function scores improved from 44.7 to 18.5 over the same 6 months (p<.001). Overall, of the patients who used medications at the beginning of the study (18), 77.8% of them reduced or eliminated medication use. Conclusion: Analysis demonstrates that injection with UCT decreases pain, improves physical function, and allows for less medication use for at least 6 months.

Viable Disc Tissue Allograft Supplementation; One- and Two-level Treatment of Degenerated Intervertebral Discs in Patients with Chronic Discogenic Low Back Pain: One Year Results of the VAST Randomized Controlled Trial

Background: A viable disc tissue allograft has been developed to supplement tissue loss associated with degenerative lumbar disc disease and the development of chronic discogenic lower back pain. Objectives: Viable disc allograft was injected into painful degenerated discs to evaluate safety and determine whether it can improve pain and function. Study Design: Patients received an active treatment of allograft or saline, or continued with nonsurgical management (NSM). Prior to entering the study, patients had back pain for a minimum of 6 months before treatment that was recalcitrant to nonoperative treatment modalities. Standardized outcome measures were used to evaluate the patient’s condition before and after treatment. Primary endpoints included improvement in Oswestry Disability Index (ODI) and Visual Analog Scale of Pain Intensity (VASPI). Conventional radiographs and magnetic resonance imaging scans were used to assess disc space height and spinal alignment, and to determine the degree of disc degeneration. Patients were followed for one year after enrollment. The NSM group could cross over to the allograft group after 3 months. Setting: This multicenter trial was completed in outpatient surgical centers and office injection suites. A total of 218 patients with chronic low back pain secondary to single-level or 2-level degenerative disc disease were enrolled. Inclusion criteria included pretreatment VASPI >= 40 mm, ODI score >= 40 and symptoms present longer than 6 months. Patients were blinded and randomized to receive intradiscal injections of either viable disc allograft or saline. Patients randomized to the NSM group continued existing treatment. Patients were assessed at 6 and 12 months. Adverse events (AEs) were continually assessed. Methods: The VAST trial is a prospective, multicenter, blind, randomized clinical trial (RCT) for patients with single-level or 2-level degenerative lumbar disc disease. Results: At 12 months, clinically meaningful improvements in mean VASPI and ODI scores were achieved in the investigational allograft and saline groups. A responder analysis demonstrated a clinically meaningful reduction in ODI of >= 15 points at 12 months that was statistically significant; 76.5% of patients randomized to allograft were responders (P = 0.03) compared to 56.7% in the saline group. A responder group characterized by a ? 20 point reduction in pain at 12 months achieved a statistically significant reduction in pain compared to the saline group (P = 0.022). In the allograft group, 11 safety adverse events occurred in 141 patients (3.5%) and there were no persistently symptomatic AEs. Limitations: Limitations of this study include a comparison to saline that has been shown to be more representative of an active comparator as opposed to a placebo. In addition, 36 patients were lost to follow-up; this loss resulted in the saline and NSM/crossover groups being smaller than the predetermined group size to have an appropriately powered analysis. Conclusions: This large, prospective blinded RCT demonstrated safety and efficacy results indicating that viable disc tissue allograft may be a beneficial nonsurgical treatment for patients who have chronically painful lumbar degenerative discs. Further studies would be optimal to confirm efficacy Key words: Viable disc tissue allograft, discogenic back pain, allograft supplementation, degenerative disc disease, low back pain, intervertebral disc, intradiscal injection

Treatment of Degenerated Intervertebral Discs using a Viable Disc Tissue Allograft for Chronic Discogenic Low Back Pain: A Randomized Controlled Trial Comparing Single-Site Outcomes with Aggregate and Longer-term Follow-Up Data

BackgroundDisruption of the internal structure of the nucleus pulposus commonly occurs with the development of painful degenerative lumbar disc disease. Supplementing disc tissue through autologous or allogeneic human cellular and tissue therapies has been tested in small sample clinical trials. A few investigators have reported substantial improvements in pain and function. A viable disc tissue allograft was developed to supplement tissue loss associated with intervertebral disc degeneration. MethodsWe assessed results in a subgroup of patients from a large trial comparing this allograft with other treatments. A multicenter randomized controlled trial of 218 subjects with chronic low back pain secondary to degenerative disc disease was conducted. Patients were treated with the allograft, saline, or nonsurgical management and studied for 12 months. We assessed longer-term results in a single-site subgroup from this prospective trial.ResultsAt 12 months, subjects from the single-site subgroup who had been randomly assigned to the active allograft group (n=17) showed improvements in both mean Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) scores. There was an overall reduction of 28.69 points in the ODI and 33.06 points in the VAS. This was similar to the aggregate ODI and VAS scores of the active allograft group. At 24 months postprocedure, 9 of the 10 patients remaining in the active allograft group at the single study site had mean ODI and VAS score improvements of 28.23 and 36.13, respectively. A similar improvement in pain scores occurred in the 4 patients at 36 months with mean ODI and VAS score improvements from preoperative scores of 25.21 and 51.35, respectively.ConclusionsClinically meaningful improvements demonstrated in this single-site analysis were comparable to the aggregate study population at 12 months. Longer-term results from this single site at 24 and 36 months suggested durability of viable disc tissue allograft supplementation for patients with discogenic back pain.Trial registrationThe trial was retrospectively registered 17 October 2018 on www.clinicaltrials.gov (NCT03709901) and was approved by the Sterling Institutional Review Board, Atlanta, Georgia (IRB no. 5792).

Primary Dural Repair via an Endoscopic Endonasal Corridor: Preliminary Development of a 3D-Printed Model for Training

Objectives Endonasal suturing is an investigational method for dural repair that has been reported to decrease the incidence of cerebrospinal fluid fistula. This method requires handling of single-shaft instrumentation in the narrow endonasal corridor. In this study, we designed a low-cost, surgical model using three-dimensional (3D) printing technology to simulate dural repair through the endonasal corridor and subsequently assess the utility of the model for surgical training. Methods Using an Ultimaker 2+ printer, a 3D-printed replica of the cranial base and nasal cavity was fitted with tissue allograft to recapitulate the dural layer. Residents, fellows, and attending surgeons were asked to place two sutures using a 0-degree endoscope and single-shaft needle driver. Task completion time was recorded. Participants were asked to fill out a Likert scale questionnaire after the experiment. Results Twenty-six participants were separated into groups based on their prior endoscope experience: novice, intermediate, and expert. Twenty-one (95.5%) residents and fellows rated the model as “excellent” or “good” in enhancing their technical skills with endoscopic instrumentation. Three of four (75%) of attendings felt that the model was “excellent” or “good” in usefulness for training in dural suturing. Novice participants required an average of 11 minutes for task completion, as compared with 8.7 minutes for intermediates and 5.7 minutes for experts. Conclusion The proposed model appears to be highly effective in enhancing the endoscopic skills and recapitulating the task of dural repair. Such a low-cost model may be especially important in enhancing endoscopic facility in countries/regions with limited access to cadaveric specimens.