Outcomes from 871,441 Consecutive Surgical Procedures without Overlap or with Maximally Permissible Non-Concurrent Overlap.

OBJECTIVE: To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes. SUMMARY BACKGROUND DATA: The American College of Surgeons recently recommended the elimination of "concurrent surgery" with overlap during a procedure's critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined. METHODS: All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations. RESULTS: Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon. CONCLUSIONS: Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.

The effects of Facebook and Instagram on the 2020 election: A deactivation experiment.

We study the effect of Facebook and Instagram access on political beliefs, attitudes, and behavior by randomizing a subset of 19,857 Facebook users and 15,585 Instagram users to deactivate their accounts for 6 wk before the 2020 U.S. election. We report four key findings. First, both Facebook and Instagram deactivation reduced an index of political participation (driven mainly by reduced participation online). Second, Facebook deactivation had no significant effect on an index of knowledge, but secondary analyses suggest that it reduced knowledge of general news while possibly also decreasing belief in misinformation circulating online. Third, Facebook deactivation may have reduced self-reported net votes for Trump, though this effect does not meet our preregistered significance threshold. Finally, the effects of both Facebook and Instagram deactivation on affective and issue polarization, perceived legitimacy of the election, candidate favorability, and voter turnout were all precisely estimated and close to zero.

Low Household Income Increases Hospital Length of Stay and Decreases Home Discharge Rates in Lumbar Fusion.

STUDY DESIGN: Retrospective Matched Cohort Study. OBJECTIVES: Low median household income (MHI) has been correlated with worsened surgical outcomes, but few studies have rigorously controlled for demographic and medical factors at the patient level. This study isolates the relationship between MHI and surgical outcomes in a lumbar fusion cohort using coarsened exact matching. METHODS: Patients undergoing single-level, posterior lumbar fusion at a single institution were consecutively enrolled and retrospectively analyzed (n = 4263). Zip code was cross-referenced to census data to derive MHI. Univariate regression correlated MHI to outcomes. Patients with low MHI were matched to those with high MHI based on demographic and medical factors. Outcomes evaluated included complications, length of stay, discharge disposition, 30- and 90 day readmissions, emergency department (ED) visits, reoperations, and mortality. RESULTS: By univariate analysis, MHI was significantly associated with 30- and 90 day readmission, ED visits, reoperation, and non-home discharge, but not mortality. After exact matching (n = 270), low-income patients had higher odds of non-home discharge (OR = 2.5, P = .016) and higher length of stay (mean 100.2 vs 92.6, P = .02). There were no differences in surgical complications, ED visits, readmissions, or reoperations between matched groups. CONCLUSIONS: Low MHI was significantly associated with adverse short-term outcomes from lumbar fusion. A matched analysis controlling for confounding variables uncovered longer lengths of stay and higher rates of discharge to post-acute care (vs home) in lower MHI patients. Socioeconomic disparities affect health beyond access to care, worsen surgical outcomes, and impose costs on healthcare systems. Targeted interventions must be implemented to mitigate these disparities.

Racial disparities in short-term spinal fusion outcomes across 4263 consecutive patients.

OBJECTIVE: Race plays a salient role in access to surgical care. However, few investigations have assessed the impact of race within surgical populations after care has been delivered. The objective of this study was to employ an exact matching protocol to a homogenous population of spine surgery patients in order to isolate the relationships between race and short-term postoperative outcomes. METHODS: In total, 4263 consecutive patients who underwent single-level, posterior-only lumbar fusion at a single multihospital academic medical center were retrospectively enrolled. Of these patients, 3406 patients self-identified as White and 857 patients self-identified as non-White. Outcomes were initially compared across all patients via logistic regression. Subsequently, White patients and non-White patients were exactly matched on the basis of key demographic and health characteristics (1520 matched patients). Outcome disparities were evaluated between the exact-matched cohorts. Primary outcomes were readmissions, emergency department (ED) visits, reoperations, mortality, intraoperative complications, and discharge disposition. RESULTS: Before matching, non-White patients were less likely to be discharged home and more likely to be readmitted, evaluated in the ED, and undergo reoperation. After matching, non-White patients experienced higher rates of nonhome discharge, readmissions, and ED visits. Non-White patients did not have more surgical complications either before or after matching. CONCLUSIONS: Between otherwise similar cohorts of spinal fusion cases, non-White patients experienced unfavorable discharge disposition and higher risk of multiple adverse postoperative outcomes. However, these findings were not accounted for by differences in surgical complications, suggesting that structural factors underlie the observed disparities.

Association Between Race and Short-Term Outcomes Across 3988 Consecutive Single-Level Spinal Fusions.

BACKGROUND AND OBJECTIVES: Race has implications for access to medical care. However, the impact of race, after access to care has been attained, remains poorly understood. The objective of this study was to isolate the relationship between race and short-term outcomes across patients undergoing a single, common neurosurgical procedure. METHODS: In this retrospective cohort study, 3988 consecutive patients undergoing single-level, posterior-only open lumbar fusion at a single, multihospital, academic medical center were enrolled over a 6-year period. Among them, 3406 patients self-identified as White, and 582 patients self-identified as Black. Outcome disparities between all White patients vs all Black patients were estimated using logistic regression. Subsequently, coarsened exact matching controlled for outcome-mitigating factors; White and Black patients were exact-matched 1:1 on key demographic and health characteristics (matched n = 1018). Primary outcomes included 30-day and 90-day hospital readmissions, emergency department (ED) visits, reoperations, mortality, discharge disposition, and intraoperative complication. RESULTS: Before matching, Black patients experienced increased rate of nonhome discharge, readmissions, ED visits, and reoperations (all P < .001). After exact matching, Black patients were less likely to be discharged to home (odds ratio [OR] 2.68, P < .001) and had higher risk of 30-day and 90-day readmissions (OR 2.24, P < .001; OR 1.91, P < .001; respectively) and ED visits (OR 1.79, P = .017; OR 2.09, P < .001). Black patients did not experience greater risk of intraoperative complication (unintentional durotomy). CONCLUSION: Between otherwise homogenous spinal fusion cohorts, Black patients experienced unfavorable short-term outcomes. These disparities were not explained by differences in intraoperative complications. Further investigation must characterize and mitigate institutional and societal factors that contribute to outcome disparities.

Quantifying a novel three-dimensional marker of scoliosis.

BACKGROUND: Scoliosis causes abnormal spinal curvature and torsional rotation of the vertebrae and has implications for human suffering and societal cost. In differential geometry, Writhe describes three-dimensional curvature. Differential geometric quantities can inform better diagnostic metrics of scoliotic deformity. This evaluation could help physicians and researchers study scoliosis and determine treatments. METHODS: Eight adult lumbar spine CT scans were analyzed in custom MATLAB programs to estimate Writhe and Cobb angle. Five patients exhibited scoliotic curvature, and three controls were asymptomatic. Vertebral centroids in three-dimensional space were determined, and Writhe was approximated. A T-test determined whether the affected spines had greater Writhe than the controls. Cohen's D test was used to determine effect size. RESULTS: Writhe of scoliotic spines (5.4E-4 ± 2.7E-4) was significantly higher than non-scoliotic spines (8.2E-5 ± 1.1E-4; p = 0.008). CONCLUSION: Writhe, a measure of curvature derived from 3D imaging, is significantly greater in scoliotic than in non-scoliotic spines. Future directions must include more subjects and examine writhe as a marker of scoliosis severity, progression, and response to treatment.

Effects of a US Supreme Court ruling to restrict abortion rights.

Previous research focused on popular US Supreme Court rulings expanding rights; however, less is known about rulings running against prevailing public opinion and restricting rights. We examine the impact of the Dobbs v. Jackson Women's Health Organization opinion, which overturned Roe v. Wade's (1973) constitutional protection of abortion rights. A three-wave survey panel (5,489 interviews) conducted before the leak of the drafted Dobbs opinion, after the leak, and after the official opinion release, and cross-sectional data from these three time points (10,107 interviews) show that the ruling directly influenced views about the constitutional legality of abortion and fetal viability. However, personal opinions were not directly influenced and perceived social norms shifted away from the ruling, meaning that individuals perceived greater public support for abortion. We argue that extensive coverage of opposition to overturning Roe v. Wade supported this shift. Dobbs v. Jackson Women's Health Organization also caused large changes, polarized by party identification, in opinions about the Supreme Court.

Single cell RNA sequencing reveals emergent notochord-derived cell subpopulations in the postnatal nucleus pulposus.

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus (NP) hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native NP cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study, we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived NP cells in the postnatal mouse disc. Specifically, we established the existence of progenitor and mature NP cells, corresponding to notochordal and chondrocyte-like cells, respectively. Mature NP cells exhibited significantly higher expression levels of extracellular matrix (ECM) genes including aggrecan, and collagens II and VI, along with elevated transforming growth factor-beta and phosphoinositide 3 kinase-protein kinase B signaling. Additionally, we identified Cd9 as a novel surface marker of mature NP cells, and demonstrated that these cells were localized to the NP periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show that Cd9+ NP cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy NP ECM. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.

Comparison of Staged vs Same-Day Circumferential Spinal Fusions for Adult Spinal Deformity.

BACKGROUND: Patients often undergo circumferential (anterior and posterior) spinal fusions to maximize adult spinal deformity (ASD) correction and achieve adequate fusion. Currently, such procedures are performed in staged (ST) or same-day (SD) procedures with limited evidence to support either strategy. This study aims to compare perioperative outcomes and costs of ST vs SD circumferential ASD corrective surgeries. METHODS: This is a retrospective review of patients undergoing circumferential ASD surgeries between 2013 and 2018 in a single institution. Patient characteristics, preoperative comorbidities, surgical details, perioperative complications, readmissions, total hospital admission costs, and 90-day postoperative care costs were identified. All variables were tested for differences between ST and SD groups unadjusted and after applying inverse probability weighting (IPW), and the results before and after IPW were compared. RESULTS: The entire cohort included a total of 211 (ST = 50, SD = 161) patients, 100 of whom (ST = 44, SD = 56) underwent more than 4 levels fused posteriorly and anterior lumbar interbody fusion (ALIF). Although patient characteristics and comorbidities were not dissimilar between the ST and SD groups, both the number of levels fused in ALIF and posterior spinal fusion (PSF) were significantly different. Thus, using IPW, we were able to minimize the cohort incongruities in the number of levels fused in ALIF and PSF while maintaining comparable patient characteristics. In both the whole cohort and the long segment fusions, postoperative pulmonary embolism was more common in ST procedures. After adjustment utilizing IPW, both groups were not significantly different in disposition, 30-day readmissions, and reoperations. However, within the whole cohort and the long segment fusion cohort, the ST group continued to show significantly increased rates of pulmonary embolism, longer length of stay, and higher hospital admission costs compared with the SD group. CONCLUSIONS: Adjusted comparisons between ST and SD groups showed staging associated with significantly increased length of stay, risk of pulmonary embolism, and admission costs.

Large Language Model-Based Neurosurgical Evaluation Matrix: A Novel Scoring Criteria to Assess the Efficacy of ChatGPT as an Educational Tool for Neurosurgery Board Preparation.

INTRODUCTION: Technological advancements are reshaping medical education, with digital tools becoming essential in all levels of training. Amidst this transformation, the study explores the potential of ChatGPT, an artificial intelligence model by OpenAI, in enhancing neurosurgical board education. The focus extends beyond technology adoption to its effective utilization, with ChatGPT's proficiency evaluated against practice questions from the Primary Neurosurgery Written Board Exam. METHODS: Using the Congress of Neurologic Surgeons (CNS) Self-Assessment Neurosurgery (SANS) Exam Board Review Prep questions, we conducted 3 rounds of analysis with ChatGPT. We developed a novel ChatGPT Neurosurgical Evaluation Matrix (CNEM) to assess the output quality, accuracy, concordance, and clarity of ChatGPT's answers. RESULTS: ChatGPT achieved spot-on accuracy for 66.7% of prompted questions, 59.4% of unprompted questions, and 63.9% of unprompted questions with a leading phrase. Stratified by topic, accuracy ranged from 50.0% (Vascular) to 78.8% (Neuropathology). In comparison to SANS explanations, ChatGPT output was considered better in 19.1% of questions, equal in 51.6%, and worse in 29.3%. Concordance analysis showed that 95.5% of unprompted ChatGPT outputs and 97.4% of unprompted outputs with a leading phrase were aligned. CONCLUSIONS: Our study evaluated the performance of ChatGPT in neurosurgical board education by assessing its accuracy, clarity, and concordance. The findings highlight the potential and challenges of integrating AI technologies like ChatGPT into medical and neurosurgical board education. Further research is needed to refine these tools and optimize their performance for enhanced medical education and patient care.

The Impact of Neighborhood Socioeconomic Disadvantage on Operative Outcomes after Single-Level Lumbar Fusion.

INTRODUCTION: The relationship between socioeconomic status and neurosurgical outcomes has been investigated with respect to insurance status or median household income, but few studies have considered more comprehensive measures of socioeconomic status. This study examines the relationship between Area Deprivation Index (ADI), a comprehensive measure of neighborhood socioeconomic disadvantage, and short-term postoperative outcomes after lumbar fusion surgery. METHODS: 1861 adult patients undergoing single-level, posterior-only lumbar fusion at a single, multihospital academic medical center were retrospectively enrolled. An ADI matching protocol was used to identify each patient's 9-digit zip code and the zip code-associated ADI data. Primary outcomes included 30- and 90-day readmission, emergency department visits, reoperation, and surgical complication. Coarsened exact matching was used to match patients on key demographic and baseline characteristics known to independently affect neurosurgical outcomes. Odds ratios (ORs) were computed to compare patients in the top 10% of ADI versus lowest 40% of ADI. RESULTS: After matching (n = 212), patients in the highest 10% of ADI (compared to the lowest 40% of ADI) had significantly increased odds of 30- and 90-day readmission (OR = 5.00, P < 0.001 and OR = 4.50, P < 0.001), ED visits (OR = 3.00, P = 0.027 and OR = 2.88, P = 0.007), and reoperation (OR = 4.50, P = 0.039 and OR = 5.50, P = 0.013). There was no significant association with surgical complication (OR = 0.50, P = 0.63). CONCLUSIONS: Among otherwise similar patients, neighborhood socioeconomic disadvantage (measured by ADI) was associated with worse short-term outcomes after single-level, posterior-only lumbar fusion. There was no significant association between ADI and surgical complications, suggesting that perioperative complications do not explain the socioeconomic disparities in outcomes.

Relationship Between Comorbidity Burden and Short-Term Outcomes Across 4680 Consecutive Spinal Fusions.

OBJECTIVE: Preoperative management requires the identification and optimization of modifiable medical comorbidities, though few studies isolate comorbid status from related patient-level variables. This study evaluates Charlson Comorbidity Index (CCI)-an easily derived measure of aggregate medical comorbidity-to predict outcomes from spinal fusion surgery. Coarsened exact matching is employed to control for key patient characteristics and isolate CCI. METHODS: We retrospectively assessed 4680 consecutive patients undergoing single-level, posterior-only lumbar fusion at a single academic center. Logistic regression evaluated the univariate relationship between CCI and patient outcomes. Coarsened exact matching generated exact demographic matches between patients with high comorbid status (CCI >6) or no medical comorbidities (matched n = 524). Patients were matched 1:1 on factors associated with surgical outcomes, and outcomes were compared between matched cohorts. Primary outcomes included surgical complications, discharge status, 30- and 90-day risk of readmission, emergency department (ED) visits, reoperation, and mortality. RESULTS: Univariate regression of increasing CCI was significantly associated with non-home discharge, as well as 30- and 90-day readmission, ED visits, and mortality (all P < 0.05). Subsequent isolation of comorbidity between otherwise exact-matched cohorts found comorbid status did not affect readmissions, reoperations, or mortality; high CCI score was significantly associated with non-home discharge (OR = 2.50, P < 0.001) and 30-day (OR = 2.44, P = 0.02) and 90-day (OR = 2.29, P = 0.008) ED evaluation. CONCLUSIONS: Comorbidity, measured by CCI, did not increase the risk of readmission, reoperation, or mortality. Single-level, posterior lumbar fusions may be safe in appropriately selected patients regardless of comorbid status. Future studies should determine whether CCI can guide discharge planning and postoperative optimization.

Varying Degree of Overlap Following the Critical Steps of Lumbar Fusion and Short-term Outcomes.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The present study analyzes the impact of end-overlap on short-term outcomes after single-level, posterior lumbar fusions. SUMMARY OF BACKGROUND DATA: Few studies have evaluated how "end-overlap" (i.e., surgical overlap after the critical elements of spinal procedures, such as during wound closure) influences surgical outcomes. METHODS: Retrospective analysis was performed on 3563 consecutive adult patients undergoing single-level, posterior-only lumbar fusion over a 6-year period at a multi-hospital university health system. Exclusion criteria included revision surgery, missing key health information, significantly elevated body mass index (>70), non-elective operations, non-general anesthesia, and unclean wounds. Outcomes included 30-day emergency department visit, readmission, reoperation, morbidity, and mortality. Univariate analysis was carried out on the sample population, then limited to patients with end-overlap. Subsequently, patients with the least end-overlap were exact-matched to patients with the most. Matching was performed based on key demographic variables-including sex and comorbid status-and attending surgeon, and then outcomes were compared between exact-matched cohorts. RESULTS: Among the entire sample population, no significant associations were found between the degree of end-overlap and short-term adverse events. Limited to cases with any end-overlap, increasing overlap was associated with increased 30-day emergency department visits ( P =0.049) but no other adverse outcomes. After controlling for confounding variables in the demographic-matched and demographic/surgeon-matched analyses, no differences in outcomes were observed between exact-matched cohorts. CONCLUSIONS: The degree of overlap after the critical steps of single-level lumbar fusion did not predict adverse short-term outcomes. This suggests that end-overlap is a safe practice within this surgical population.

Like-minded sources on Facebook are prevalent but not polarizing.

Many critics raise concerns about the prevalence of 'echo chambers' on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from 'like-minded' sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes.

How do social media feed algorithms affect attitudes and behavior in an election campaign?

We investigated the effects of Facebook's and Instagram's feed algorithms during the 2020 US election. We assigned a sample of consenting users to reverse-chronologically-ordered feeds instead of the default algorithms. Moving users out of algorithmic feeds substantially decreased the time they spent on the platforms and their activity. The chronological feed also affected exposure to content: The amount of political and untrustworthy content they saw increased on both platforms, the amount of content classified as uncivil or containing slur words they saw decreased on Facebook, and the amount of content from moderate friends and sources with ideologically mixed audiences they saw increased on Facebook. Despite these substantial changes in users' on-platform experience, the chronological feed did not significantly alter levels of issue polarization, affective polarization, political knowledge, or other key attitudes during the 3-month study period.

Asymmetric ideological segregation in exposure to political news on Facebook.

Does Facebook enable ideological segregation in political news consumption? We analyzed exposure to news during the US 2020 election using aggregated data for 208 million US Facebook users. We compared the inventory of all political news that users could have seen in their feeds with the information that they saw (after algorithmic curation) and the information with which they engaged. We show that (i) ideological segregation is high and increases as we shift from potential exposure to actual exposure to engagement; (ii) there is an asymmetry between conservative and liberal audiences, with a substantial corner of the news ecosystem consumed exclusively by conservatives; and (iii) most misinformation, as identified by Meta's Third-Party Fact-Checking Program, exists within this homogeneously conservative corner, which has no equivalent on the liberal side. Sources favored by conservative audiences were more prevalent on Facebook's news ecosystem than those favored by liberals.

Reshares on social media amplify political news but do not detectably affect beliefs or opinions.

We studied the effects of exposure to reshared content on Facebook during the 2020 US election by assigning a random set of consenting, US-based users to feeds that did not contain any reshares over a 3-month period. We find that removing reshared content substantially decreases the amount of political news, including content from untrustworthy sources, to which users are exposed; decreases overall clicks and reactions; and reduces partisan news clicks. Further, we observe that removing reshared content produces clear decreases in news knowledge within the sample, although there is some uncertainty about how this would generalize to all users. Contrary to expectations, the treatment does not significantly affect political polarization or any measure of individual-level political attitudes.

A Randomized Controlled Trial to Assess the Impact of Enhanced Recovery After Surgery on Patients Undergoing Elective Spine Surgery.

OBJECTIVE: To conduct a prospective, randomized controlled trial (RCT) of an enhanced recovery after surgery (ERAS) protocol in an elective spine surgery population. BACKGROUND: Surgical outcomes such as length of stay (LOS), discharge disposition, and opioid utilization greatly contribute to patient satisfaction and societal healthcare costs. ERAS protocols are multimodal, patient-centered care pathways shown to reduce postoperative opioid use, reduced LOS, and improved ambulation; however, prospective ERAS data are limited in spine surgery. METHODS: This single-center, institutional review board-approved, prospective RCT-enrolled adult patients undergoing elective spine surgery between March 2019 and October 2020. Primary outcomes were perioperative and 1-month postoperative opioid use. Patients were randomized to ERAS (n=142) or standard-of-care (SOC; n=142) based on power analyses to detect a difference in postoperative opioid use. RESULTS: Opioid use during hospitalization and the first postoperative month was not significantly different between groups (ERAS 112.2 vs SOC 117.6 morphine milligram equivalent, P =0.76; ERAS 38.7% vs SOC 39.4%, P =1.00, respectively). However, patients randomized to ERAS were less likely to use opioids at 6 months postoperatively (ERAS 11.4% vs SOC 20.6%, P =0.046) and more likely to be discharged to home after surgery (ERAS 91.5% vs SOC 81.0%, P =0.015). CONCLUSION: Here, we present a novel ERAS prospective RCT in the elective spine surgery population. Although we do not detect a difference in the primary outcome of short-term opioid use, we observe significantly reduced opioid use at 6-month follow-up as well as an increased likelihood of home disposition after surgery in the ERAS group.

Single Cell RNA Sequencing Reveals Emergent Notochord-Derived Cell Subpopulations in the Postnatal Nucleus Pulposus.

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived nucleus pulposus cells in the postnatal mouse disc. Specifically, we established the existence of early and late stage nucleus pulposus cells, corresponding to notochordal progenitor and mature cells, respectively. Late stage cells exhibited significantly higher expression levels of extracellular matrix genes including aggrecan, and collagens II and VI, along with elevated TGF-ß and PI3K-Akt signaling. Additionally, we identified Cd9 as a novel surface marker of late stage nucleus pulposus cells, and demonstrated that these cells were localized to the nucleus pulposus periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show the Cd9+ nucleus pulposus cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy nucleus pulposus extracellular matrix. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.