Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects.

Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs.

The Effects of Preoperative Epidural Steroid Injection on Pseudarthrosis Following Lumbar Fusion: A Retrospective Cohort Study.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The goal of this study is to evaluate the effects of preoperative lumbar epidural steroid injection on the rate of pseudarthrosis following lumbar spine fusion surgery. SUMMARY OF BACKGROUND DATA: Epidural corticosteroids help to reduce nerve root edema and suppress proinflammatory cytokines in patients with radiculopathy. Corticosteroids may inhibit bone formation and reduce bone matrix synthesis rates. Thus, there is concern that corticosteroids may reduce lumbar fusion capability, potentially resulting in increased rates of symptomatic pseudarthrosis. MATERIALS AND METHODS: We identified all patients who underwent 1-level or 2-level lumbar fusion surgery between 2018 and 2022. Patients were categorized into one of 3 groups: no preoperative epidural steroid injection (ESI) history (group 0), preoperative ESI within 90 days of surgery (group 1), or most recent ESI >90 days before surgery (group 2). The primary outcome of this study was pseudarthrosis. Binominal regression analyses were performed to determine the relationships between potential risk factors (sex, age, body mass index, smoking history, diabetes status, history of systemic steroid use, preoperative ESI, perioperative intravenous steroid administration, type of surgery, and postoperative ESI within 6 mo) and the development of postoperative pseudarthrosis. RESULTS: A total of 446 patients were included in this study. Of those, 106 patients (23.7%) did not have a preoperative ESI (group 0), 132 patients (29.5%) had an ESI within 90 days of surgery (group 1), and 208 patients (46.6%) had their most recent ESI >90 days before surgery (group 2). The overall incidence of pseudarthrosis following lumbar fusion was 8.7% (39 of 446). Although the incidence of pseudarthrosis following ESI at any time point was higher than in our control cohort (group 0), this difference was not statistically significant. CONCLUSIONS: This study found no increased risk of postoperative pseudarthrosis in patients who underwent 1-level or 2-level lumbar fusions after preoperative ESI. LEVEL OF EVIDENCE: Level III.

Complications of the Prone Transpsoas Lateral Lumbar Interbody Fusion for Degenerative Lumbar Spine Disease: A Multicenter Study.

BACKGROUND AND OBJECTIVES: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a novel technique for degenerative lumbar spine disease. However, there is a paucity of information in the literature on the complications of this procedure, with all published data consisting of small samples. We aimed to report the intraoperative and postoperative complications of PTP in the largest study to date. METHODS: A retrospective electronic medical record review was conducted at 11 centers to identify consecutive patients who underwent LLIF through the PTP approach between January 1, 2021, and December 31, 2021. The following data were collected: intraoperative characteristics (operative time, estimated blood loss [EBL], intraoperative complications [anterior longitudinal ligament (ALL) rupture, cage subsidence, vascular and visceral injuries]), postoperative complications, and hospital stay. RESULTS: A total of 365 patients were included in the study. Among these patients, 2.2% had ALL rupture, 0.3% had cage subsidence, 0.3% had a vascular injury, 0.3% had a ureteric injury, and no other visceral injuries were reported. Mean operative time was 226.2 ± 147.9 minutes. Mean EBL was 138.4 ± 215.6 mL. Mean hospital stay was 2.7 ± 2.2 days. Postoperative complications included new sensory symptoms-8.2%, new lower extremity weakness-5.8%, wound infection-1.4%, cage subsidence-0.8%, psoas hematoma-0.5%, small bowel obstruction and ischemia-0.3%, and 90-day readmission-1.9%. CONCLUSION: In this multicenter case series, the PTP approach was well tolerated and associated with a satisfactory safety profile.

Current Trends in Recombinant Human Bone Morphogenetic Protein 2 (rhBMP2) Usage for Spinal Fusion Surgery.

(1) Background: Since first approved by the FDA, on-label and off-label usage of recombinant human bone morphogenetic protein 2 (rhBMP2) for spinal fusion surgeries has become widespread. While many studies have investigated the safety and efficacy of its use, as well as its economic impact, few have looked at the current trends in its on- and off-label use. The goal of this study is to evaluate the current trends of on- and off-label rhBMP2 use for spinal fusion surgery. (2) Methods: A deidentified survey was created and electronically distributed to members of two international spine societies. Surgeons were asked to report their demographic information, surgical experience, and current usage of rhBMP2. They were then presented with five spinal fusion procedures and asked to report if they use rhBMP2 for these indications in their current practice. Responses were stratified between rhBMP2 users vs. non-users and on-label vs. off-label use. Data were analyzed using chi-square with Fisher's exact test for categorical data. (3) Results: A total of 146 respondents completed the survey with a response rate of 20.5%. There was no difference in overall rhBMP2 usage based on specialty, experience, or number of cases per year. Fellowship-trained surgeons and those who practice in the United States were more likely to use rhBMP2. Surgeons who were trained in the Southeast and Midwest regions reported the highest usage rates. rhBMP2 use was more common among fellowship-trained and US surgeons for ALIFs; non-US surgeons for multilevel anterior cervical discectomy and fusions; and fellowship-trained and orthopedic spine surgeons for lateral lumbar interbody fusions. Non-US surgeons were more likely to use rhBMP2 for off-label indications compared to surgeons from the US. (4) Conclusions: While various demographics of surgeons report different rates of rhBMP2 use, off-label use remains relatively commonplace amongst practicing spine surgeons.

The Prone Lateral Approach for Lumbar Fusion-A Review of the Literature and Case Series.

Lateral lumbar interbody fusion is an evolving procedure in spine surgery allowing for the placement of large interbody devices to achieve indirect decompression of segmental stenosis, deformity correction and high fusion rates through a minimally invasive approach. Traditionally, this technique has been performed in the lateral decubitus position. Many surgeons have adopted simultaneous posterior instrumentation in the lateral position to avoid patient repositioning; however, this technique presents several challenges and limitations. Recently, lateral interbody fusion in the prone position has been gaining in popularity due to the surgeon's ability to perform simultaneous posterior instrumentation as well as decompression procedures and corrective osteotomies. Furthermore, the prone position allows improved correction of sagittal plane imbalance due to increased lumbar lordosis when prone on most operative tables used for spinal surgery. In this paper, we describe the evolution of the prone lateral approach for interbody fusion and present our experience with this technique. Case examples are included for illustration.

Novel Injectable Fluorescent Polymeric Nanocarriers for Intervertebral Disc Application.

Damage to intervertebral discs (IVD) can lead to chronic pain and disability, and no current treatments can fully restore their function. Some non-surgical treatments have shown promise; however, these approaches are generally limited by burst release and poor localization of diverse molecules. In this proof-of-concept study, we developed a nanoparticle (NP) delivery system to efficiently deliver high- and low-solubility drug molecules. Nanoparticles of cellulose acetate and polycaprolactone-polyethylene glycol conjugated with 1-oxo-1H-pyrido [2,1-b][1,3]benzoxazole-3-carboxylic acid (PBC), a novel fluorescent dye, were prepared by the oil-in-water emulsion. Two drugs, a water insoluble indomethacin (IND) and a water soluble 4-aminopyridine (4-AP), were used to study their release patterns. Electron microscopy confirmed the spherical nature and rough surface of nanoparticles. The particle size analysis revealed a hydrodynamic radius ranging ~150-162 nm based on dynamic light scattering. Zeta potential increased with PBC conjugation implying their enhanced stability. IND encapsulation efficiency was almost 3-fold higher than 4-AP, with release lasting up to 4 days, signifying enhanced solubility, while the release of 4-AP continued for up to 7 days. Nanoparticles and their drug formulations did not show any apparent cytotoxicity and were taken up by human IVD nucleus pulposus cells. When injected into coccygeal mouse IVDs in vivo, the nanoparticles remained within the nucleus pulposus cells and the injection site of the nucleus pulposus and annulus fibrosus of the IVD. These fluorescent nano-formulations may serve as a platform technology to deliver therapeutic agents to IVDs and other tissues that require localized drug injections.

Early Clinical Outcomes of the Prone Transpsoas Lumbar Interbody Fusion Technique.

BACKGROUND: The prone transpsoas (PTP) approach for lateral lumbar interbody fusion (LLIF) is a relatively novel technique. Currently, little is known about its associated complications and early patient-reported outcomes. The aim of this study was to investigate the effect of LLIF performed via the PTP approach on sagittal radiographic parameters, patient-reported outcome measures (PROMs), and rates of complications. METHODS: A retrospective review was performed of 82 consecutive patients who underwent LLIF via a PTP technique. Lumbar lordosis (LL), segmental lordosis (SL), anterior disc height (ADH), and posterior disc height (PDH) were measured on preoperative, initial postoperative, and 3-month postoperative radiographs. PROMs including the Oswestry Disability Index (ODI); the visual analog scale (VAS); and pain portions of the EQ5D, VAS back, and VAS leg ratings were collected at the preoperative and subsequent postoperative visits. Length of hospital stay and postoperative complications related to the procedure were recorded. RESULTS: Significant improvements were seen at the initial (4.5° ± 8.6°, P < 0.001) and 3-month (4.4° ± 7.2°, P < 0.001) postoperative periods for LL, as well as SL (6.8° ± 4.8°, P < 0.001; 6.7° ± 4.4°, P < 0.001), ADH (8.0 mm ± 3.6, P < 0.001; 7.4 mm ± 3.6, P < 0.001), and PDH (3.3 mm ± 2.4, P < 0.001; 3.1 mm ± 2.5, P < 0.001). Significant improvements were seen at 3 months postoperatively for ODI (P < 0.001), EQ5D pain (P = 0.016), VAS leg (P < 0.001), and VAS back (P < 0.001). The average length of stay was 2.7 ± 4.5 days. The most common complications were ipsilateral thigh pain/numbness (45.1%), ipsilateral hip flexor weakness (39.0%), and contralateral thigh pain/numbness (14.6%). CONCLUSIONS: While early PROMs and correction of sagittal radiographic parameters show promising results for the PTP approach for LLIF, it is not without risks. CLINICAL RELEVANCE: PTP interbody fusion is an emerging technique that allows for simultaneous access to the anterior and posterior columns of the lumbar spine. This early case series demonstrates significant improvement in functional outcomes and lumbar lordosis with a safety profile comparable to other well-established techniques.

Pilocytic Astrocytoma Arising from the Conus Medullaris in an Adult: A Case Report.

Low-grade, sporadic, pilocytic astrocytomas (PAs) are rare spinal cord tumors diagnosed in adult patients. Their localization to the conus medullaris is exceedingly rare, having only been described in a limited number of case reports. Here, we describe a case of a 22-year-old female presenting with back pain, lower extremity weakness, hypoesthesia, and urinary incontinence. Imaging studies demonstrated a cystic lesion of the conus medullaris that was treated with subtotal resection and cyst-subarachnoid shunt placement. Final pathology report confirmed PA from the histology of surgical specimens. We discuss the current literature of conus medullaris lesions and their differential diagnosis.

Determination of a neurologic safe zone for bicortical S1 pedicle screw placement.

BACKGROUND CONTEXT: Lumbosacral fixation is commonly used for the management of lumbosacral instability. As the sacrum mainly consists of cancellous bone, bicortical fixation, in which the pedicle screw penetrates the anterior sacral cortex, can help increase the strength of fixation. However, this method carries a risk to the L5 nerves which lie anterior to the sacrum at this level. PURPOSE: The goal of this study is to determine a safe zone for the placement of S1 pedicle screws to decrease the likelihood of L5 nerve injury. STUDY DESIGN: Retrospective imaging review. PATIENT SAMPLE: This study evaluated imaging data of patients who underwent lumbar spine magnetic resonance imaging (MRI) at our institute between September 1, 2020 and September 1, 2021. OUTCOME MEASURES: T1-weighted axial MRIs were measured at the level of S1 pedicle screw placement. The space medial and lateral to the L5 nerve root on the anterior sacrum were measured and defined as safe zones. Additionally, the nerve width and sacral lengths were measured at this level. METHODS: The distribution of the measurements were evaluated to determine a medial and lateral safe zone, as well as the average nerve width at the level of S1 pedicle screw placement. Correlation analysis was performed to determine a relationship between safe zone sizes and sacral size. RESULTS: A total of 400 MRIs were analyzed. The average medial safe zone measured was 32.8 mm (95% CI: 32.2-33.4) with no nerves lying within 22.3 mm of the midline sacrum. The average lateral safe zone measured was 17.7 mm (95% CI: 17.1-18.2), with no nerves within 5.3 mm of the lateral border of the sacrum. The average nerve root width was 6.2 mm (95% CI: 6.13-6.34). An increased sacral length was associated with a larger medial (p<.001) and lateral (p<.001) safe zone. CONCLUSIONS: Our study revealed lateral and medial safe zones for the placement of S1 pedicle screws to avoid iatrogenic nerve injury in a retrospective cohort of 400 patients. There were no L5 nerve roots found within 22.3 mm of the sacrum's mid-axis or within 5.3 mm of the sacrum's anterolateral border. These defined safe zones can be used during pedicle screw planning and placement to decrease the risk of injury to the L5 nerve root.

Notch signaling enhances bone regeneration in the zebrafish mandible.

Loss or damage to the mandible caused by trauma, treatment of oral malignancies, and other diseases is treated using bone-grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling during the initial post-operative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone, resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone, improving bone healing. Given the conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.

Correction: Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Correction for 'Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions' by Matthew D. Harmon et al., Biomater. Sci., 2020, 8, 1216-1239, DOI: .

Atomic force microscopy imaging for nanoscale and microscale assessments of extracellular matrix in intervertebral disc and degeneration.

Degeneration of the intervertebral disc (IVD) is a condition that is often associated with debilitating back pain. There are no disease-modifying treatments available to halt the progression of this ubiquitous disorder. This is partly due to a lack of understanding of extracellular matrix (ECM) changes that occur at the micro- and nanometer size scales as the disease progresses. Over the past decade, atomic force microscopy (AFM) has been utilized as a tool to investigate the impact of disease on nanoscale structure of ECM in bone, skin, tendon, and dentin. We have expanded this methodology to include the IVD and report the first quantitative analysis of ECM structure at submicron size scales in a murine model for progressive IVD degeneration. Collagen D-spacing, a metric of nanoscale structure at the fibril level, was observed as a distribution of values with an overall average value of 62.5 ± 2.5 nm. In degenerative discs, the fibril D-spacing distribution shifted towards higher values in both the annulus fibrosus and nucleus pulposus (NP) (P < .05). A novel microstructural feature, collagen toroids, defined by a topographical pit enclosed by fibril-forming matrix was observed in the NP. With degeneration, these microstructures became more numerous and the morphology was altered from circular (aspect ratio 1.0 ± 0.1) to oval (aspect ratio 1.5 ± 0.4), P < .005. These analyses provide ECM structural details of the IVD at size scales that have historically been missing in studies of disc degeneration. Knowledge gained from these insights may aid the development of novel disease-modifying therapeutics.

Lumbar Laminectomy in the Outpatient Setting Is Associated With Lower 30-Day Complication Rates.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To compare the incidence of complications in patients undergoing single-level and 2-level lumbar laminectomy in either the inpatient or outpatient settings. METHODS: Patients who underwent single-level and 2-level lumbar laminectomy were identified in the ACS NSQIP database from the years 2006 to 2015. Independent patient variables were recorded, including demographics and preoperative health characteristics. Logistic regression was used to determine the risk of postoperative complications for both a 1- and 2-level lumbar laminectomy as well as to identify independent risk factors for a complication. Comparisons were made between 2 groups: (1) inpatient and (2) outpatient as determined by billing data. RESULTS: A total of 18 076 single- and 2-level lumbar laminectomy cases were identified with 10 743 (59.4%) inpatient procedures and 7333 (40.6%) outpatient procedures. The incidence of any postoperative complication was significantly lower in the outpatient group than in the inpatient group among all cohorts including 1-level lumbar laminectomy (1.9% vs 6.7%), 2-level lumbar laminectomy (3.17% vs 7.38%), as well as in the combined cohort of 1- and 2-level laminectomies (2.47% vs 7.01%). Significant independent risk factors for complications after lumbar laminectomy were identified, including body mass index (BMI) >30 kg/m2, age ≥55 years, a functional status of partially dependent, chronic obstructive pulmonary disease (COPD), chronic steroid use, American Society of Anesthesiologists (ASA) class 3 or 4, and operative time >90 minutes. CONCLUSIONS: This study reports a lower overall complication rate in the 30-day postoperative period following 1- and 2-level lumbar laminectomy performed in an outpatient versus inpatient setting. Significant risk factors for complications included BMI >30 kg/m2, age ≥55 years, a functional status of partially dependent, COPD, chronic steroid use, ASA class 3 or 4, and operative time >90 minutes.

Growing a backbone - functional biomaterials and structures for intervertebral disc (IVD) repair and regeneration: challenges, innovations, and future directions.

Back pain and associated maladies can account for an immense amount of healthcare cost and loss of productivity in the workplace. In particular, spine related injuries in the US affect upwards of 5.7 million people each year. The degenerative disc disease treatment almost always arises due to a clinical presentation of pain and/or discomfort. Preferred conservative treatment modalities include the use of non-steroidal anti-inflammatory medications, physical therapy, massage, acupuncture, chiropractic work, and dietary supplements like glucosamine and chondroitin. Artificial disc replacement, also known as total disc replacement, is a treatment alternative to spinal fusion. The goal of artificial disc prostheses is to replicate the normal biomechanics of the spine segment, thereby preventing further damage to neighboring sections. Artificial functional disc replacement through permanent metal and polymer-based components continues to evolve, but is far from recapitulating native disc structure and function, and suffers from the risk of unsuccessful tissue integration and device failure. Tissue engineering and regenerative medicine strategies combine novel material structures, bioactive factors and stem cells alone or in combination to repair and regenerate the IVD. These efforts are at very early stages and a more in-depth understanding of IVD metabolism and cellular environment will also lead to a clearer understanding of the native environment which the tissue engineering scaffold should mimic. The current review focusses on the strategies for a successful regenerative scaffold for IVD regeneration and the need for defining new materials, environments, and factors that are so finely tuned in the healthy human intervertebral disc in hopes of treating such a prevalent degenerative process.

Comparative and Predictor Analysis of 30-day Readmission, Reoperation, and Morbidity in Patients Undergoing Multilevel ACDF Versus Single and Multilevel ACCF Using the ACS-NSQIP Dataset.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim of this study was to determine the differences in 30-day readmission, reoperation, and morbidity for patients undergoing multilevel anterior cervical discectomy and fusion (ACDF) or single and multilevel anterior cervical corpectomy and fusion (ACCF). SUMMARY OF BACKGROUND DATA: Despite increasing rates of surgical treatment of cervical spine disease, few studies have compared outcomes by surgical technique. To the best of our knowledge, this is the only large-scale administrative database study that directly evaluates early outcomes between multilevel ACDF and single and multilevel ACCF. METHODS: Patients who underwent ACDF and ACCF were identified using the NSQIP database. Multivariate regression was utilized to compare rates of readmission, reoperation, morbidity, and specific complications between surgical techniques, and to evaluate for predictors of primary outcomes. RESULTS: We identified 15,600 patients. ACCF independently predicted (P < 0.001) greater reoperation (odds ratio [OR] = 1.876) and morbidity (OR = 1.700), but not readmission, on multivariate analysis. ACCF was also associated with greater rates of transfusion (OR = 3.273, P < 0.001) and DVT/thrombophlebitis (OR = 2.852, P = 0.001). ACCF had significantly (P < 0.001) greater operative time and length of stay. In the cohort, increasing age (P < 0.001), diabetes (P = 0.025), chronic obstructive pulmonary disease (P = 0.027), disseminated cancer (P = 0.009), and American Society of Anesthesiologists (ASA) class ≥3 (P < 0.001) predicted readmission. Age (P = 0.011), female sex (P = 0.001), heart failure (P = 0.002), ASA class ≥3 (P < 0.001), and increased creatinine (P = 0.044), white cell count (P = 0.033), and length of stay (P < 0.001) predicted reoperation. Age (P < 0.001), female sex (P = 0.002), disseminated cancer (P = 0.010), ASA class ≥3 (P < 0.001), increased white cell count (P = 0.036) and length of stay (P < 0.001), and decreased hematocrit (P < 0.001) predicted morbidity. Within ACDF, three or more levels treated compared to two levels did not predict poorer 30-day outcomes. CONCLUSION: Compared to multilevel ACDF, ACCF was associated with an 88% increased odds of reoperation and 70% increased odds of morbidity; readmission was similar between techniques. Older age, higher ASA class, and specific comorbidities predicted poorer 30-day outcomes. These findings can guide surgical solution given specific factors. LEVEL OF EVIDENCE: 3.

Clinical and Radiographic Evaluation of Multilevel Lateral Lumbar Interbody Fusion in Adult Degenerative Scoliosis.

STUDY DESIGN: Retrospective review of prospective data. OBJECTIVE: The objective of this study was to describe the clinical, radiographic, and complication-related outcomes through ≥1-year of 27 patients who underwent lateral lumbar interbody fusion (LLIF) with posterior instrumentation to treat ≥3 contiguous levels of degenerative lumbar scoliosis. SUMMARY OF BACKGROUND DATA: Multilevel disease has traditionally been treated with open posterior fusion. Literature on multilevel LLIF is limited. We present our experience with utilizing LLIF to treat multilevel degenerative scoliosis. METHODS: Clinical outcomes were evaluated using VAS, SF-12, and ODI. Radiographic outcomes included pelvic tilt, pelvic incidence, lumbar lordosis, pelvic incidence-lumbar lordosis mismatch, Cobb angle, and cage subsidence. Perioperative and long-term complications through the ≥1-year final-postoperative visit were reviewed; transient neurological disturbances were assessed independently. Demographic, comorbidity, operative, and recovery variables, including opioid use, were explored for association with primary outcomes. RESULTS: Mean time to final-postoperative visit was 22.5 months; levels treated with LLIF per patient, 3.7; age, 66 years; and lateral operative time, 203 minutes. EBL was ≤100 mL in 74% of cases. Clinical outcomes remained significantly improved at ≥1-year. Cobb angle was corrected from 21.1 to 7.9 degrees (P<0.001), lordosis from 47.3 to 52.6 degrees (P<0.001), and mismatch from 11.4 to 6.4 degrees (P=0.003). High-grade subsidence occurred in 3 patients. Subsidence did not significantly impact primary outcomes. In total, 11.1% returned to the operating room for complication-related intervention over nearly 2-years; 37% experienced complications. Experiencing a complication was associated with having an open-posterior portion (P=0.048), but not with number of LLIF levels treated, or with clinical or radiographic outcomes. No patients experienced protracted neurological deficits; psoas weakness was associated with increased lateral operative time (P=0.049) and decreased surgeon experience (P=0.028). CONCLUSIONS: Patients who underwent multilevel LLIF with adjunctive posterior surgery had significant clinical and radiographic improvements. Complication rates were similar compared to literature on single-level LLIF. LLIF is a viable treatment for multilevel degenerative scoliosis.

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes.

Traumatic spinal cord injury (SCI) has devastating implications for patients, including a high predisposition for developing chronic pain distal to the site of injury. Chronic pain develops weeks to months after injury, consequently, patients are treated after irreparable changes have occurred. Nociceptors are central to chronic pain; however, the diversity of this cellular population presents challenges to understanding mechanisms and attributing pain modalities to specific cell types. To begin to address how peripheral sensory neurons below the injury level may contribute to the below-level pain reported by SCI patients, we examined SCI-induced changes in gene expression in lumbar dorsal root ganglia (DRG) below the site of injury. SCI was performed at the T10 vertebral level, with injury produced by a vessel clip with a closing pressure of 15 g for 1 min. Alterations in gene expression produce long-term sensory changes, therefore, we were interested in studying SCI-induced transcripts before the onset of chronic pain, which may trigger changes in downstream signaling pathways and ultimately facilitate the transmission of pain. To examine changes in the nociceptor subpopulation in DRG distal to the site of injury, we retrograde labeled sensory neurons projecting to the hairy hindpaw skin with fluorescent dye and collected the corresponding lumbar (L2-L6) DRG 4 days post-injury. Following dissociation, labeled neurons were purified by fluorescence-activated cell sorting (FACS). RNA was extracted from sorted sensory neurons of naïve, sham, or SCI mice and sequenced. Transcript abundances validated that the desired population of nociceptors were isolated. Cross-comparisons to data sets from similar studies confirmed, we were able to isolate our cells of interest and identify a unique pattern of gene expression within a subpopulation of neurons projecting to the hairy hindpaw skin. Differential gene expression analysis showed high expression levels and significant transcript changes 4 days post-injury in SCI cell populations relevant to the onset of chronic pain. Regulatory interrelationships predicted by pathway analysis implicated changes within the synaptogenesis signaling pathway as well as networks related to inflammatory signaling mechanisms, suggesting a role for synaptic plasticity and a correlation with pro-inflammatory signaling in the transition from acute to chronic pain.

Approach-based Comparative and Predictor Analysis of 30-day Readmission, Reoperation, and Morbidity in Patients Undergoing Lumbar Interbody Fusion Using the ACS-NSQIP Dataset.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study was to determine the difference in 30-day readmission, reoperation, and morbidity for patients undergoing either posterior or anterior lumbar interbody fusion. SUMMARY OF BACKGROUND DATA: Despite increasing utilization of lumbar interbody fusion to treat spinal pathology, few studies compare outcomes by surgical approach, particularly using large nationally represented cohorts. METHODS: Patients who underwent lumbar interbody fusion were identified using the NSQIP database. Rates of readmission, reoperation, morbidity, and associated predictors were compared between posterior/transforaminal (PLIF/TLIF) and anterior/lateral (ALIF/LLIF) lumbar interbody fusion using multivariate regression. Bonferroni-adjusted alpha-levels were utilized whereby variables were significant if their P values were less than the alpha-level or trending if their P values were between 0.05 and the alpha-level. RESULTS: We identified 26,336 patients. PLIF/TLIF had greater operative time (P = 0.015), transfusion (P < 0.001), UTI (P = 0.008), and stroke/CVA (P = 0.026), but lower prolonged ventilation (P < 0.001) and DVT (P = 0.002) rates than ALIF/LLIF. PLIF/TLIF independently predicted greater morbidity on multivariate analysis (odds ratio: 1.155, P = 0.0019).In both groups, experiencing a complication and, in PLIF/TLIF, ASA-class ≥3 predicted readmission (P < 0.001). Increased age trended toward readmission in ALIF/LLIF (P = 0.003); increased white cell count (P = 0.003), dyspnea (P = 0.030), and COPD (P = 0.005) trended in PLIF/TLIF. In both groups, increased hospital stay and wound/site-related complication predicted reoperation (P < 0.001). Adjunctive posterolateral fusion predicted reduced reoperation in ALIF/LLIF (P = 0.0018). ASA-class ≥3 (P = 0.016) and age (P = 0.021) trended toward reoperation in PLIF/TLIF and ALIF/LLIF, respectively. In both groups, age, hospital stay, reduced hematocrit, dyspnea, ASA-class ≥3, posterolateral fusion, and revision surgery and, in PLIF/TLIF, bleeding disorder predicted morbidity (P < 0.001). Female sex (P = 0.010), diabetes (P = 0.042), COPD (P = 0.011), and disseminated cancer (P = 0.032) trended toward morbidity in PLIF/TLIF; obesity trended in PLIF/TLIF (P = 0.0022) and ALIF/LLIF (P = 0.020). CONCLUSION: PLIF/TLIF was associated with a 15.5% increased odds of morbidity; readmission and reoperation were similar between approaches. Older age, higher ASA-class, and specific comorbidities predicted poorer 30-day outcomes, while procedural-related factors predicted only morbidity. These findings can guide surgical approach given specific factors. LEVEL OF EVIDENCE: 3.