Prone Transpsoas Lateral Interbody Fusion (PTP LIF) with Anterior Docking: Preliminary functional and radiographic outcomes.

Background: Disadvantages of lateral interbody fusion (LIF) through a direct, transpsoas approach include difficulties associated with lateral decubitus positioning and limited sagittal correction without anterior longitudinal ligament release or posterior osteotomy. Prior technical descriptions advocate anchoring or docking the retractor into the posterior to middle aspect of the disc space. Methods: 72 patients who underwent 116 total levels of Prone Transpsoas (PTP) LIF with anterior docking with a single surgeon between December 2021 and May 2023 were included. Patient characteristics, perioperative data, as well as postoperative functional and radiographic outcomes were recorded. Subgroup analysis was performed for patients who underwent single-level PTP LIF with single-level percutaneous fixation (SLP). Patients in the SLP subgroup did not undergo direct decompression, release, or osteotomy. Results: N=41 (56.9%) of cases included the L4-5 level. No vascular, bowel, or other visceral complications occurred. No patients developed a permanent motor deficit. Both the total cohort and the SLP group demonstrated statistically significant improvements in functional outcomes including Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) as well as all radiographic parameters measured. Mean total operative time (incision to completion of closure for lateral and posterior fusion) in the SLP group was 104.3 minutes with a significant downward trend with increasing surgeon experience. The SLP group demonstrated a 9.9° increase in segmental lordosis (SL), a 7.5° increase in lumbar lordosis (LL), 5.3° reduction in pelvic tilt (PT), and a decrease in pelvic incidence - lumbar lordosis mismatch (PI-LL) from 11.0° preoperatively to 3.9°, postoperatively (p<.01). Conclusions: PTP LIF with anterior docking may address shortcomings associated with traditional lateral interbody fusion by producing safe and reproducible access with improved restoration of segmental lordosis and optimization of spinopelvic parameters.

Optimization of a rat lumbar IVD degeneration model for low back pain.

INTRODUCTION: Intervertebral disc (IVD) degeneration is often associated with low back pain and radiating leg pain. The purpose of this study is to develop a reproducible and standardized preclinical model of painful lumbar IVD degeneration by evaluation of structural and behavioral changes in response to IVD injury with increasing needle sizes. This model can be used to develop new therapies for IVD degeneration. METHODS: Forty-five female Sprague Dawley rats underwent anterior lumbar disc needle puncture at levels L4-5 and L5-6 under fluoroscopic guidance. Animals were randomly assigned to four different experimental groups: needle sizes of 18 Gauge (G), 21G, 23G, and sham control. To monitor the progression of IVD degeneration and pain, the following methods were employed: µMRI, qRT-PCR, histology, and biobehavioral analysis. RESULTS: T1- and T2-weighted µMRI analysis showed a correlation between the degree of IVD degeneration and needle diameter, with the most severe degeneration in the 18G group. mRNA expression of markers for IVD degeneration markers were dysregulated in the 18G and 21G groups, while pro-nociceptive markers were increased in the 18G group only. Hematoxylin and Eosin (H&E) and Alcian Blue/Picrosirius Red staining confirmed the most pronounced IVD degeneration in the 18G group. Randall-Selitto and von Frey tests showed increased hindpaw sensitivity in the 18G group. CONCLUSION: Our findings demonstrate that anterior disc injury with an 18G needle creates severe IVD degeneration and mechanical hypersensitivity, while the 21G needle results in moderate degeneration with no increased pain sensitivity. Therefore, needle sizes should be selected depending on the desired phenotype for the pre-clinical model.

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.

The effects of varenicline on lumbar spinal fusion in a rat model.

BACKGROUND CONTEXT: Smoking is detrimental to obtaining a solid spinal fusion mass with previous studies demonstrating its association with pseudoarthrosis in patients undergoing spinal fusion. Varenicline is a pharmacologic adjunct used in smoking cessation which acts as a partial agonist of the same nicotinic receptors activated during tobacco use. However, no clinical or basic science studies to date have characterized if varenicline has negative effects on spinal fusion and bone healing by itself. PURPOSE: Our study's aim was to elucidate whether varenicline affects the frequency or quality of posterolateral spinal fusion in a rodent model at an endpoint of 12 weeks. STUDY DESIGN: Randomized control trial. PATIENT SAMPLE: Fourteen male Lewis rats randomly separated into two experimental groups. OUTCOME MEASURES: Manual palpation of fusion segment, radiography, µCT imaging, and four-point bend. METHODS: Fourteen male Lewis rats were randomly separated into two experimental groups undergoing L4-L5 posterior spinal fusion procedure followed by daily subcutaneous injections of human dose varenicline or saline (control) for 12 weeks postsurgery. Spine samples were explanted, and fusion was determined via manual palpation of segments by two independent observers. High-resolution radiographs were obtained to evaluate bridging fusion mass. µCT imaging was performed to characterize fusion mass and consolidation. Lumbar spinal fusion units were tested in four-point bending to evaluate stiffness and peak load. Study funding sources include $5000 OREF Grant. There were no applicable financial relationships or conflicts of interest. RESULTS: At 3 months postsurgery, 12 out of 14 rats demonstrated lumbar spine fusion (86% fused) with no difference in fusion frequency between the varenicline and control groups as detected by manual palpation. High-resolution radiography revealed six out of seven rats (86%) having complete fusion in both groups. µCT showed no significant difference in bone mineral density or bone fraction volume between groups in the region of interest. Biomechanical testing demonstrated no significant different in the average stiffness or peak loads at the fusion site of the varenicline and control groups. CONCLUSION: Based on the results of our rat study, there is no indication that varenicline itself has a detrimental effect on the frequency and quality of spinal fusion.

The effect of insulin dependent diabetes on bone metabolism and growth after spinal fusion.

STUDY DESIGN: Experimental animal model. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that insulin dependent diabetes mellitus (IDDM) will inhibit the formation of a solid bony union after spinal fusion surgery via an alteration of the microenvironment at the fusion site in a rat model. SUMMARY OF BACKGROUND DATA: Previous studies report diabetes mellitus (DM) and specifically IDDM as a risk factor for complications and poor surgical outcomes following spinal fusion. METHODS: Twenty control and 22 diabetic rats were obtained at 5 weeks of age. At 20 weeks of age, all animals underwent posterolateral lumbar fusion surgery using a tailbone autograft with diabetic rats receiving an implantable time release insulin pellet. A subset of rats was sacrificed 1-week postsurgery for growth factor (PDGF, IGF-I, TGF-ß, and VEGF) and proinflammatory cytokine ELISA analysis. All other rats were sacrificed 3-months postsurgery for fusion evaluation via manual palpation and micro CT. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. RESULTS: Compared with healthy rats undergoing spinal fusion, rats with IDDM demonstrated a significant reduction in manual palpation fusion rates (16.7% vs. 43%, p<.05). Average bone mineral density, bone volume, and bone volume fraction were also significantly reduced and negatively correlated to blood glucose levels. IL-1B, IL-5, IL-10, TNF-α, and KC/GRO were significantly elevated in fusion beds of IDDM rats. CONCLUSIONS: This study demonstrates that rats with IDDM demonstrate a reduced rate and quality of spinal fusion with increased local levels of inflammatory cytokines. Targeted modalities are required to improve bone healing in this growing, high-risk population. CLINICAL SIGNIFICANCE: This is the first translational animal model of IDDM to evaluate the rate and quality of spinal fusion while controlling for other surgical and patient-related risk factors. Our findings demonstrate the complex nature by which IDDM impairs bone healing and highlight the need for additional basic science research to further elucidate this mechanism in order to develop more effective therapeutic interventions.

Omega-3 Fatty Acid Supplementation Reduces Intervertebral Disc Degeneration.

BACKGROUND Intervertebral disc (IVD) degeneration is a common cause of lower back pain, which carries substantial morbidity and economic cost. Omega-3 fatty acids (n-3 FA) are known to reduce inflammatory processes with a relatively benign side effect profile. This study aimed to investigate the effect of n-3 FA supplementation on IVD degeneration. MATERIAL AND METHODS Two non-contiguous lumbar discs of 12 Sprague Dawley rats were needle-punctured to induce disc degeneration. Post-surgery, rats were randomly assigned to either a daily n-3 FA diet (530 mg/kg/day of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in a 2: 1 ratio, administered in sucrose solution) or control diet (sucrose solution only), which was given for the duration of the study. After 1 month, blood serum arachidonic acid/eicosapentaenoic acid (AA/EPA) ratios were analyzed. After 2 months, micro-MRI (magnetic resonance imaging) analysis and histological staining of disc explants were performed to analyze the IVD. RESULTS A reduction of blood AA/EPA ratios from 40 to 20 was demonstrated after 1 month of daily supplementation with n-3 FA. Micro-MRI analysis showed an injury-induced reduction of IVD hydration, which was attenuated in rats receiving n-3 FA. Histological evaluation demonstrated the destruction of nucleus pulposus tissue in response to needle puncture injury, which was less severe in the n-3 FA diet group. CONCLUSIONS The results of this study suggest that n-3 FA dietary supplementation reduces systemic inflammation by lowering AA/EPA ratios in blood serum and has potential protective effects on the progression of spinal disc degeneration, as demonstrated by reduced needle injury-induced dehydration of intervertebral discs and reduced histological signs of IVD degeneration.

Anti-Inflammatory Peptide Attenuates Edema and Promotes BMP-2-Induced Bone Formation in Spine Fusion.

Recombinant human bone morphogenic protein-2 (BMP-2)-loaded absorbable collagen sponges (ACS) have been successfully used to enhance bone formation and to induce spinal fusion in humans. However, side effects, such as soft tissue edema and inflammation, have been reported. NEMO binding domain peptide (NBD) inhibits activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a central regulator of immune response. In this study, we investigated NBD's potential to reduce BMP-2-induced soft tissue inflammation without affecting BMP-2-mediated spinal fusion in rat. For evaluation of soft tissue inflammation, ACS containing BMP-2, BMP-2+NBD, NBD, or ACS only were implanted into intramuscular paraspinal sites of 32 rats. At day 2 postsurgery, edema formation at the implant sites was assessed using magnetic resonance imaging. T2-weighted relaxation time (T2-RT) values were increased in the BMP-2 group compared with BMP-2+NBD, NBD, and ACS groups. No difference in T2-RT values was detected between BMP-2+NBD versus NBD and ACS controls. Postsacrifice, histological analysis of the implant-surrounding zones showed increased mononuclear cell infiltration in the BMP-2 group compared with BMP-2+NBD and controls. The presence of BMP-2 increased relative NF-κB binding and gene expression of inflammatory markers, interleukin (IL)1ß, IL6, IL18, and chemokine ligand (CCL)2 and CCL3 compared with controls. In the BMP-2+NBD group, cytokine expression was blocked. No differences were found between BMP-2+NBD and control groups. For evaluation of spinal fusion, posterolateral intertransverse lumbar fusion procedures were performed on 16 rats. ACS were loaded with BMP-2 or BMP-2+NBD. After sacrifice at week 12, microcomputed tomographic assessment of the fusion site detected a higher bone volume and reduced trabecular spacing in the BMP-2+NBD group compared with BMP-2. Histological analysis did not show any differences in newly formed bone microarchitecture. In summary, addition of NBD to BMP-2-loaded ACS reduces BMP-2-induced soft tissue edema formation and mononuclear cell infiltration, diminishes NF-κB binding, and thus blocks transcription of NF-κB-regulated cytokines in rat. Furthermore, NBD stimulates bone formation in BMP-2-mediated spinal fusion, possibly through crosstalk of the NF-κB pathway with other pathways. The results of this study might provide the basis to develop new therapeutic bone grafting approaches with combinatory administration of BMP-2 and NBD for spinal fusion.

Step-based cognitive virtual surgery simulation: an innovative approach to surgical education.

BioDigital Systems, LLC in collaboration with New York University Langone Medical Center Department of Reconstructive Plastic Surgery has created a complex, real-time, step-based simulation platform for plastic surgery education. These simulators combine live surgical footage, interactive 3D visualization, text labels, and voiceover as well as a high-yield, expert-approved testing mode to create a comprehensive virtual educational environment for the plastic surgery resident or physician.

The biodigital human: a web-based 3D platform for medical visualization and education.

NYU School of Medicine's Division of Educational Informatics in collaboration with BioDigital Systems LLC (New York, NY) has created a virtual human body dataset that is being used for visualization, education and training and is accessible over modern web browsers.

Integration of surgical simulation in plastic surgery residency training.

BioDigital Systems, LLC in collaboration with New York University Langone Medical Center Department of Reconstructive Plastic Surgery has created an interactive, step-based latissimus musculocutaneous flap simulator. Preliminary testing of fourteen residents (PGY1-6) demonstrates that simulator training results in significant improvement in an objective assessment of surgical knowledge (p < 0.0006, pre-training score: 81.0%, post-training score 92.7%). This study is the first in the field of plastic and reconstructive surgery to demonstrate objective improvement in surgical knowledge as a result of simulator training, suggesting the potential effectiveness of simulators for a panopoly of breast reconstruction options.