Intervertebral disc human nucleus pulposus cells associated with back pain trigger neurite outgrowth in vitro and pain behaviors in rats.

Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing human nucleus pulposus cells (NPCs), generated by certain conditions in degenerating discs, that was associated with the onset of discogenic back pain. Single-cell transcriptomic analysis of human tissues showed a strong correlation between a specific cell subtype and the pain condition associated with the human degenerated disc, suggesting that they are pain-triggering. The application of IVD degeneration-associated exogenous stimuli to healthy NPCs in vitro recreated a pain-associated phenotype. These stimulated NPCs activated functional human iPSC-derived sensory neuron responses in an in vitro organ-chip model. Injection of stimulated NPCs into the healthy rat IVD induced local inflammatory responses and increased cold sensitivity and mechanical hypersensitivity. Our findings reveal a previously uncharacterized pain-inducing mechanism mediated by NPCs in degenerating IVDs. These findings could aid in the development of NPC-targeted therapeutic strategies for the clinically unmet need to attenuate discogenic LBP.

Perioperative Complications Following Spine Surgery in Adult Patients with Achondroplasia.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the common types of complications and their risk factors during spine surgery in patients with achondroplasia. METHODS: A retrospective review was performed of medical records of adult achondroplasia patients who underwent spine surgery at our institution between 2007 and 2021. Inclusion criteria were achondroplasia and age >16 years. Surgical encounters were evaluated for durotomy, postoperative neurologic deficit, wound compromise, medical complications, and return to the operating room. Statistical analysis included evaluation of relationships across complications and fisher exact test applied to bivariate/categorical variables and t-test/ANOVA for continuous variables. Multivariable analysis using logistic regression was performed to account for patient characteristics. RESULTS: Fifty-five patients with achondroplasia underwent 95 surgeries. Forty-nine percent of the surgeries involved a complication. These included durotomy (33.7%), neurologic deficit (11.6%), wound compromise (6.3%), and other medical complications (6.3%). Thirteen percent of surgeries required return to the operating room. The greatest number of complications occurred in thoracolumbar region (60.0%) compared to cervicothoracic (18.2%) and craniocervical junction (33.3%). Chronologically later surgical encounters had decreased complications and durotomies only occurred in thoracolumbar surgeries (45.7%). CONCLUSIONS: Adult patients with achondroplasia undergoing surgery chronologically later in this set of consecutive patients were at a decreased risk for complications. Thoracolumbar surgeries were at the greatest risk for durotomies. Male sex was a risk factor for durotomy, while age was a risk factor for neurologic deficit. The potential for adverse surgical events should be considered when evaluating patients with achondroplasia for spine surgery. .

Outpatient Versus Inpatient Anterior Lumbar Spine Surgery: A Multisite, Comparative Analysis of Patient Safety Measures.

BACKGROUND: The frequency and complexity of spinal surgery performed in an ambulatory surgery center (ASC) is increasing. However, safety and efficacy data of most spinal procedures adapted to the ASC are sparse and have focused on anterior cervical surgery. The purpose of this study was to compare the 90-day complication and readmission rates of anterior lumbar spine surgery performed in an ASC or inpatient setting. METHODS: We performed a retrospective comparative analysis of 226 consecutive anterior lumbar surgeries (283 levels treated) completed in an ASC (n = 124) or in an inpatient tertiary care hospital (n = 102) over a 3-year period. These included anterior lumbar interbody fusion (ALIF), artificial disc replacement (ADR), and hybrids. Patients undergoing simultaneous or staged posterior procedures within 3 months were excluded. Patient demographics and surgical parameters between the two surgical settings were compared. Ninety-day medical complications and readmission rates were assessed. One-way analysis of variance and Chi-square analysis were used. A P value of less than .05 was considered statistically significant. RESULTS: The two study groups had similar baseline characteristics. While there was a trend toward fewer complications, reoperations, and readmissions for the ASC cohort, the differences were not statistically significant. There were 7 intraoperative complications (5.6% minor vascular injury) in the inpatient cohort and 0 in the ASC cohort. The overall 90-day postoperative complication rate was 5.6% for the inpatient cohort and 0.9% for the ASC cohort. The 90-day readmission rate was 1.9% in the ASC cohort and 1.6% in the inpatient cohort. The 90-day reoperation rate was 0.8% for the inpatient cohort and 0% in the ASC cohort. The average hospital stay was 2.3 ± 1.5 days for the inpatient cohort. CONCLUSION: The 90-day readmission rates were lower for outpatients than for inpatients, while the complication and reoperation rates were similar. Our results demonstrate that anterior lumbar procedures, including single-level and multilevel ALIF, ADR, and hybrid procedures, can be performed safely in an ASC. This has significant cost savings implications for the ASC setting.

NF-κB inhibitor, NEMO-binding domain peptide attenuates intervertebral disc degeneration.

BACKGROUND CONTEXT: Nonphysiological mechanical loading and inflammation are both critically involved in intervertebral disc (IVD) degeneration, which is characterized by an increase in cytokines and matrix metalloproteases (MMPs) in the nucleus pulposus (NP). This process is known to be mediated by the NF-κB pathway. CLINICAL SIGNIFICANCE: Current clinical treatments for IVD degeneration focus on the alleviation of symptoms rather than targeting the underlying mechanism. Injection of an NF-κB inhibitor may attenuate the progression of IVD degeneration. PURPOSE: To investigate the ability of the NF-κB inhibitor, NEMO binding domain peptide (NBD), to alter IVD degeneration processes by reducing IL-1ß- and mechanically-induced cytokine and MMP levels in human nucleus pulposus cells in vitro, and by attenuating IVD degeneration in an in vivo rat model for disc degeneration. STUDY DESIGN: Experimental in vitro and animal model. PATIENT SAMPLE: Discarded specimens of lumbar disc from 21 patients, and 12 Sprague Dawley rats. OUTCOME MEASURES: Gene and protein expression, cell viability, µMRI and histology. METHODS: IL-1ß-prestimulated human nucleus pulposus cells embedded into fibrin constructs were loaded in the Flexcell FX-5000 compression system at 5 kPa and 1 Hz for 48 hours in the presence and absence of NBD. Unloaded hNPC/fibrin constructs served as controls. Cell viability in loaded and unloaded constructs was quantified, and gene and protein expression levels determined. For in vivo testing, a rat needle disc puncture model was employed. Experimental groups included injured discs with and without NBD injection and uninjured controls. Levels of disc degeneration were determined via µMRI, qPCR and histology. Funding sources include $48,874 NASS Young Investigator Research Grant and $119,174 NIH 5K01AR071512-02. There were no applicable financial relationships or conflicts of interest. RESULTS: Mechanical compression of hNPC/fibrin constructs resulted in upregulation of MMP-3 and IL-8. Supplementation of media with 10 µM NBD during loading increased cell viability, and decreased MMP-3 gene and protein levels. IVD injury in rat resulted in an increase in MMP-3, IL-1ß and IL-6 gene expression. Injections of 250 µg of NBD during disc injury resulted in decreased IL-6 gene expression. µMRI analysis demonstrated a reduction of disc hydration in response to disc needle injury, which was attenuated in NBD-treated IVDs. Histological evaluation showed NP and AF lesion in injured discs, which was attenuated by NBD injection. CONCLUSIONS: The results of this study show NBD peptide's capacity to reduce IL-1ß- and loading-induced MMP-3 levels in hNPC/fibrin constructs while increasing the cells' viability, and to attenuate IVD degeneration in rat, involving downregulation of IL-6. Therefore, NBD may be a potential therapeutic agent to treat IVD degeneration.

Radiographic Analysis of the Lumbosacral Juncture: Is There a Critical Sacral Angle for Total Disc Replacement?

STUDY DESIGN: Retrospective review of a patient cohort through a prospective study. PURPOSE: To determine whether there are correlations between radiographic measurements, including sacral slope (SS) and pelvic incidence (PI), and self-reported clinical outcomes among single-level L5/S1 ProDisc-L patients. OVERVIEW OF LITERATURE: The lumbosacral juncture presents unique biomechanical challenges with respect to artificial disc replacement (ADR) because of its orientation and consequential shear loading. Reports of inferior outcomes at L5/S1 compared to those of the outcomes at the levels above, including increased facet joint pain, suggest a relationship with the sacral inclination at L5/S1. METHODS: Plain standing lateral radiographs of 71 patients (age, 26-65 years) who underwent ADR at L5/S1 for degenerative disc disease were reviewed. SS and PI were measured based on pretreatment and initial follow-up standing films. Patient's average adjusted self assessments included the Oswestry disability index and visual analog scale for pain 2 years after ADR. Correlation coefficients were computed to evaluate relationships between radiographic parameters and clinical outcomes. Analysis of covariance was used to evaluate multivariate relationships among factors, including radiographic parameters, body mass index (BMI), and clinical outcomes. RESULTS: SS and PI values were obtained from 71 patients. The average SS was 33.3° and average PI was 39.9°. At the 24-month follow-up, no significant correlations (p≥0.05) were observed between radiographic parameters and clinical outcomes. BMI, age, and sex did not explain any variability in the relationships between clinical outcomes and SS and PI. CONCLUSIONS: We reviewed a large range of SS angles and found no associations between SS, PI, or BMI and clinical outcomes after ADR at L5/S1. These preliminary results demonstrate that ADR provided maintainence of pain relief and functional improvement for a wide range of SS angles, suggesting that steeper angles are not a contraindication for ADR.

Effects of Shinbaro pharmacopuncture in sciatic pain patients with lumbar disc herniation: study protocol for a randomized controlled trial.

BACKGROUND: Lumbar disc herniation is a major cause of sciatica and low back pain and imposes a heavy burden on both individual and society. While use of pharmacopuncture, a combined form of acupuncture and herbal medicine, for lumbar disc herniation is widespread in Korea and China, there is a paucity of research. METHODS/DESIGN: This study is the protocol for a three-armed, randomized, patient, physician, and assessor-blinded controlled pilot study. Sixty patients with severe non-acute sciatic pain diagnosed with lumbar disc herniation (NRS ≥ 5, onset between 4 weeks and 6 months) will be recruited and randomized 20 each to the Shinbaro pharmacopuncture (pharmacopuncture with acupuncture), acupuncture, and usual care groups, respectively. The 2 acupuncture groups will receive 2 sessions/week of acupuncture alone or with pharmacopuncture for 4 weeks (total 8 sessions), and the usual care group will receive conventional medication 2-3 times/day and physical therapy 2 sessions/week over 4 weeks (total 8 sessions). The initial acupuncture physician will administer acupuncture at 5 acupoints (GB30, BL40, BL25, BL23, GB34) in the 2 acupuncture groups, and mark an additional acupoint. A second acupuncture physician will administer pharmacopuncture to the marked acupoint in the pharmacopuncture group, and acupuncture in the acupuncture group during acupuncture needle retention. The second physician will administer acupuncture and pharmacopuncture in a similar manner in terms of advice and manual stimulation to maintain patient-blinding, treat the patient out of view of the initial physician, remove the additional acupuncture needle immediately, and cover the area with adhesive bandage to maintain physician-blinding. The primary endpoint will be at 5 weeks post-randomization, and the primary outcome will be Visual Analog Scale (VAS) of sciatic pain. Secondary outcomes will be VAS of low back pain, Numeric Rating Scale (NRS) of low back pain and sciatic pain, ODI, SF-36, EQ-5D, and PGIC. Post-treatment evaluations will take place 5, 7, 9, and 12 weeks after randomization. DISCUSSION: This trial will evaluate the comparative clinical effectiveness of pharmacopuncture for severe non-acute sciatic pain patients diagnosed with lumbar disc herniation with usual care of conventional medicine and that of Korean medicine (acupuncture), monitor its safety, and serve as basis for a large-scale, multicenter trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02384928 , registered 27 February 2015.

Access strategies for revision in anterior lumbar surgery.

STUDY DESIGN: Sixty-two consecutive patients undergoing anterior lumbar revision surgery from February 2000 to September 2007 were evaluated for approach strategies and complications. OBJECTIVE: To determine the incidence of complications in these patients and to make recommendations on future revisions based on the results obtained. SUMMARY OF BACKGROUND DATA: Only 2 articles exist in the literature that address this situation and they have widely varying results in a small number of patients. This larger series may help give more certainty to the expectations for complications in patients undergoing revision anterior lumbar surgery. METHODS: A concurrent database was maintained on these 62 consecutive patients. Preoperative strategies were evaluated and complications were tabulated as they occurred and later analyzed to arrive at recommendations for future similar cases. RESULTS: Twenty-three patients had the same level revised and 39 patients had adjacent levels operated on. There were 3 venous injuries (4.8%), 3 arterial injuries (4.8%), and 1 ureteral injury (1.6%). All 3 arterial injuries occurred while approaching L3-L4 after L4 to S1 prior fusion or disc replacement. All 3 venous injuries and the ureteral injury occurred while approaching a previously operated level or levels. Six of these patients had the injuries repaired and the procedures completed with full recovery. One L5-S1 revision had the procedure aborted after a venous injury. There were no deaths. CONCLUSION: Although the incidence of complications in revisions is much greater than for index cases, the actual percentage of venous, arterial, and ureteral complications is certainly acceptable for patients who must have this type of surgery. Only very experienced access surgeons should attempt revision surgery.

Results of the prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of the ProDisc-L total disc replacement versus circumferential fusion for the treatment of 1-level degenerative disc disease.

STUDY DESIGN: A prospective, randomized, multicenter, Food and Drug Administration-regulated Investigational Device Exemption clinical trial. OBJECTIVE: To evaluate the safety and effectiveness of the ProDisc-L (Synthes Spine, West Chester, PA) lumbar total disc replacement compared to circumferential spinal fusion for the treatment of discogenic pain at 1 vertebral level between L3 and S1. SUMMARY OF BACKGROUND DATA: As part of the Investigational Device Exemption clinical trial, favorable single center results of lumbar total disc replacement with the ProDisc-L have been reported previously. METHODS: Two hundred eighty-six (286) patients were treated on protocol. Patients were evaluated before and after surgery, at 6 weeks, 3, 6, 12, 18, and 24 months. Evaluation at each visit included patient self-assessments, physical and neurologic examinations, and radiographic evaluation. RESULTS: Safety of ProDisc-L implantation was demonstrated with 0% major complications. At 24 months, 91.8% of investigational and 84.5% of control patients reported improvement in the Oswestry Low Back Pain Disability Questionnaire (Oswestry Disability Index [ODI]) from preoperative levels, and 77.2% of investigational and 64.8% of control patients met the > or =15% Oswestry Disability Index improvement criteria. Overall neurologic success in the investigational group was superior to the control group (91.2% investigational and 81.4% control; P = 0.0341). At 6 weeks and 3 months follow-up time points, the ProDisc-L patients recorded SF-36 Health Survey scores significantly higher than the control group (P = 0.018, P = 0.0036, respectively). The visual analog scale pain assessment showed statistically significant improvement from preoperative levels regardless of treatment (P < 0.0001). Visual analog scale patient satisfaction at 24 months showed a statistically significant difference favoring investigational patients over the control group (P = 0.015). Radiographic range of motion was maintained within a normal functional range in 93.7% of investigational patients and averaged 7.7 degrees. CONCLUSIONS: ProDisc-L has been found to be safe and efficacious. In properly chosen patients, ProDisc-L has been shown to be superior to circumferential fusion by multiple clinical criteria.

Computed tomography assessment of the accuracy of in vivo placement of artificial discs in the lumbar spine including radiographic and clinical consequences.

STUDY DESIGN: Prospective cohort study of 52 patients who had undergone artificial lumbar disc replacement. OBJECTIVES: To evaluate the implantation accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis migration, and the clinical consequences of implant position. SUMMARY OF BACKGROUND DATA: Accuracy of spinal prosthesis implantation has not been evaluated rigorously, especially with a mini-incision approach. It is unknown if the inexact placement of a mobile device in the spine has any biomechanical, radiographic, or clinical repercussions. METHODS: A total of 52 consecutive patients were treated using standard methods of disc implantation with an intervertebral prosthesis. Computed tomography scans were performed within 3 days and again at 6 to 24 months. An independent radiologist analyzed the images for prosthesis position, rotation, migration, and facet changes. Results were compared with clinical outcome, measured by the Visual Analog Scale and Oswestry Disability Index. RESULTS: Deviation of the prosthesis from the center position was under 1.2 mm, and rotation off of midline was under 12 degrees. Follow-up CT scans showed no migration or facet changes. Regression analysis showed no correlation of prosthesis position with clinical outcome. CONCLUSIONS: Current prosthetic disc implantation methods, with minimally invasive access techniques, are relatively accurate. Although there can be deviation of the prosthesis from ideal placement, no repercussions were attributable.

Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment.

STUDY DESIGN: A retrospective study of patients who underwent 1-3-level kyphoplasty procedures at a single institute. OBJECTIVE: To examine and compare the effects of single and multilevel kyphoplasty procedures on local versus overall sagittal alignment of the spine. SUMMARY OF BACKGROUND DATA: Cement augmentation has been a safe and effective method in the treatment of symptomatic vertebral compression fractures (VCFs). In addition to providing rapid pain relief, balloon tamp kyphoplasty has reduced acute fractures, allowed controlled cement placement under lower pressure, and resulted in improvement of deformity. The restoration of normal overall spinal sagittal alignment in the elderly patient with a VCF and kyphotic deformity has obvious benefits. Although significant correction of local kyphosis (fractured vertebra) has been reported in the literature, to our knowledge, there have been no reports on whether this leads to an improved overall sagittal alignment. METHODS: A total of 65 consecutive patients with symptomatic VCFs who underwent 1-3-level kyphoplasty procedures were included in the study. Preoperative and postoperative radiographs were analyzed to quantify local and overall spinal sagittal alignment correction. Preoperative and postoperative vertebral heights at the fractured levels were also measured and categorized into anterior, middle, or posterior vertebral heights. RESULTS: Measurements revealed that kyphoplasty reduced local kyphotic deformity at the fractured vertebra by an average of 7.3 degrees (63% of preoperative kyphosis). This result did not translate to similar correction in overall sagittal alignment. In fact, angular correction decreased to 2.4 degrees (20% of preoperative kyphosis at fractured level) when measured 1 level above and below. The angular correction further decreased to 1.5 degrees and 1.0 degrees (13% and 8% of preoperative kyphosis at fractured level), respectively, at spans of 2 and 3 levels above and below. Average height gain was highest in the middle of the vertebral body (39% increase) compared to the anterior or posterior edges (19% and 3% increases, respectively). With multilevel kyphoplasty procedures, higher angular gains were seen over more vertebrae compared to the 7.3 degrees for a single-level kyphoplasty: 7.8 degrees over 2 levels and 7.7 degrees over 3 levels for 2 and 3-level kyphoplasty procedures, respectively. Kyphoplasty was able to achieve higher angular reduction in thoracic versus lumbar fractures (8.5 vs. 6.4 degrees, P < 0.01). The angular correction was also better maintained over adjacent segments in the thoracic spine. CONCLUSION: The majority of kyphosis correction by kyphoplasty is limited to the vertebral body treated. The majority of height gained after kyphoplasty occurs in the midbody. Higher correction over longer spans of the spine can be achieved with multilevel kyphoplasty procedures, in proportion to the number of levels addressed. Notwithstanding its well-published clinical efficacy, it is unrealistic to expect a 1 or 2-level kyphoplasty to improve significantly the overall sagittal alignment after VCFs.