Racial and Socioeconomic Disparities in Laminoplasty Versus Laminectomy With Fusion in Patients With Cervical Spondylosis.

STUDY DESIGN: A retrospective cohort study using prospectively collected data. OBJECTIVE: The aim of this study was to investigate preoperative differences in racial and socioeconomic factors in patients undergoing laminoplasty (LP) versus laminectomy and fusion (LF) for degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: DCM is prevalent in the United States, requiring surgical intervention to prevent neurological degeneration. While LF is utilized more frequently, LP is an emerging alternative. Previous studies have demonstrated similar neurological outcomes for both procedures. However, treatment selection is primarily at the discretion of the surgeon and may be influenced by social determinants of health that impact surgical outcomes. MATERIALS AND METHODS: The Quality Outcome Database (QOD), a national spine registry, was queried for adult patients who underwent either LP or LF for the management of DCM. Covariates associated with socioeconomic status, pain and disability, and demographic and medical history were collected. Multivariate logistic regression was performed to assess patient factors associated with undergoing LP versus LF. RESULTS: Of 1673 DCM patients, 157 (9.4%) underwent LP and 1516 (90.6%) underwent LF. A significantly greater proportion of LP patients had private insurance (P<0.001), a greater than high school level education (P<0.001), were employed (P<0.001), and underwent primary surgery (P<0.001). LP patients reported significantly lower baseline neck/arm pain and Neck Disability Index (P<0.001). In the multivariate regression model, lower baseline neck pain [odds ratio (OR)=0.915, P=0.001], identifying as non-Caucasian (OR=2.082, P<0.032), being employed (OR=1.592, P=0.023), and having a greater than high school level education (OR=1.845, P<0.001) were associated with undergoing LP rather than LF. CONCLUSIONS: In DCM patients undergoing surgery, factors associated with patients undergoing LP versus LF included lower baseline neck pain, non-Caucasian race, higher education, and employment. While symptomatology may influence the decision to choose LP over LF, there may also be socioeconomic factors at play. The trend of more educated and employed patients undergoing LP warrants further investigation.

Impact of occupational characteristics on return to work for employed patients after elective cervical spine surgery.

OBJECTIVE: In a cohort of employed patients undergoing elective cervical spine surgery with an uncomplicated postoperative course, the authors sought to determine the demographic, functional, and occupational characteristics associated with return to work (RTW) following surgery. METHODS: A retrospective cohort study of prospectively collected data was undertaken of patients undergoing elective cervical spine surgery for degenerative disease in the Quality Outcomes Database. Study inclusion criteria were: 1) employed prior to surgery and planned to RTW, 2) no unplanned readmissions, 3) achieved 30% improvement on the Neck Disability Index (NDI), and 4) were satisfied with the surgical outcome at 3 or 12 months postoperatively. A multivariable Cox regression model was built using demographic, functional, operative, and occupational characteristic to predict time to RTW. RESULTS: Of 5110 included patients, 4788 (93.7%) returned to work within 12 months, with a median time of 35 (IQR 19-60) days. Patients who did RTW were significantly younger (51.3 ± 9.4 vs 55.8 ± 9.6 years, p < 0.001), more often underwent an anterior approach (85.8% vs 80.7%, p = 0.009), were significantly more privately insured (82.1% vs 64.0%, p < 0.001), and were less likely to have workers' disability insurance (6.7% vs 14.6%, p < 0.001) compared with patients who did not RTW. On multivariable Cox regression, demographic factors associated with a longer RTW were older age (hazard ratio [HR] 0.99, 95% CI 0.99-1.00, p < 0.001) and Black race (HR 0.71, 95% CI 0.62-0.81, p < 0.001). Male sex was associated with a shorter RTW time (HR 1.19, 95% CI 1.11-1.26, p < 0.001). Regarding baseline functional status, worse preoperative NDI (HR 0.99, 95% CI 0.99-0.99, p < 0.001) was associated with a longer RTW, whereas the absence of myelopathy was associated with a shorter RTW (HR 1.17, 95% CI 1.09-1.25, p < 0.001). Having a sedentary (HR 1.81, 95% CI 1.65-1.99, p < 0.001), light-intensity (HR 1.60, 95% CI 1.45-1.76, p < 0.001), and medium-intensity (HR 1.11, 95% CI 1.01-1.22, p = 0.037) occupation was associated with a shorter RTW time compared with a heavy-intensity occupation at any time point. Heavy-intensity occupations were independently the strongest predictor of longer RTW. Similar predictors of shorter RTW were found in a subanalysis of occupation intensity and among operative approaches used. CONCLUSIONS: Among patients undergoing elective degenerative cervical spine surgery who had favorable surgical outcomes and planned to RTW before surgery, 94% had a successful RTW. Age was the strongest predictor of lower odds of RTW. Regarding time to RTW, having a sedentary, light-intensity, or medium-intensity occupation was associated with a shorter RTW time compared with a heavy-intensity occupation. These findings highlight the importance of considering the demographic and occupational characteristics when predicting postoperative RTW in patients with satisfactory surgical outcomes.

Impact of Unplanned Readmission on Patient-Reported Outcomes After Cervical Spine Surgery: A National Study of 13 355 Patients.

BACKGROUND AND OBJECTIVES: Although risk factors for unplanned readmission after cervical spine surgery have been widely reported, less is known about how readmission itself affects patient-reported outcome measures (PROMs). Using the Quality Outcomes Database registry of patients undergoing elective cervical spine surgery, we sought to (1) determine the impact of unplanned readmission on PROMs and (2) compare the effect of specific readmission reasons on PROMs. METHODS: An observational study was performed using a multi-institution, retrospective registry for patients undergoing cervical spine surgery. The occurrence of 90-day unplanned readmission classified into medical, surgical, pain only, and no readmissions was the exposure variable. Outcome variables included 12-month PROMs of Neck Disability Index (NDI), Numeric Rating Scale (NRS)-neck/arm pain, EuroQol-5D (EQ-5D), and patient dissatisfaction. Multivariable models predicting each PROM were built using readmission reasons controlling for demographics, clinical characteristics, and preoperative PROMs. RESULTS: Data from 13 355 patients undergoing elective cervical spine surgery (82% anterior approach and 18% posterior approach) were analyzed. Unplanned readmission within 90 days of surgery occurred in 3.8% patients, including medical (1.6%), surgical (1.8%), and pain (0.3%). Besides medical reasons, wound infection/dehiscence was the most common reason for unplanned readmission for the total cohort (0.5%), dysphagia in the anterior approach (0.6%), and wound infection/dehiscence in the posterior approach (1.5%). Based on multivariable regression, surgical readmission was significantly associated with worse 12-month NDI, NRS-neck pain, NRS-arm pain, EQ-5D, and higher odds of dissatisfaction. Pain readmissions were associated with worse 12-month NDI and NRS-neck pain scores, and worse dissatisfaction. For specific readmission reasons, pain, surgical site infection/wound dehiscence, hematoma/seroma, revision surgery, deep vein thrombosis, and pulmonary embolism were significantly associated with worsened 12-month PROMs. CONCLUSION: In patients undergoing elective cervical spine surgery, 90-day unplanned surgical and pain readmissions were associated with worse 12-month PROMs compared with patients with medical readmissions and no readmissions.

Determining the Effect of Intraoperative TXA on Postoperative Blood Loss in ACDF.

STUDY DESIGN: Retrospective cohort study using prospectively collected data. OBJECTIVE: To determine the effectiveness of intraoperative tranexamic acid (TXA) in anterior cervical discectomy and fusion (ACDF) on postoperative blood loss. SUMMARY OF BACKGROUND DATA: TXA has been proven to be a safe and effective agent in reducing blood loss after cervical surgery; however, its efficacy when used intraoperatively for ACDF surgeries had yet to be researched. Currently, there are few studies examining the effects of intraoperative TXA in cervical spinal fusion, and none specifically examining TXA use in ACDF. METHODS: A tertiary medical center's prospectively collected spine registry was queried between 1/1/18 and 12/1/21 for all patients who underwent elective ACDF surgery and received a drain postoperatively. Patients were separated into 2 groups; those who had received intraoperative TXA and those who did not. Baseline demographic and operative variables were collected from the registry. The primary outcome was postoperative blood loss over a 24-hour period. Secondary outcomes included total drain output, intraoperative estimated blood loss, operative duration, drain duration, changes in preoperative to postoperative hemoglobin and hematocrit levels, and rate of transfusions, complications, revisions, and reoperations. Univariate and multivariate regression analyses were performed. RESULTS: Two hundred eighty-six patients were included. One hundred ninety patients underwent ACDF and did not receive intraoperative TXA, whereas 96 patients underwent ACDF and did receive TXA. There were no differences in any demographic or baseline variables. Multivariate analysis showed intraoperative TXA was associated with shorter drain duration (ß=-5.74, 95% CI: -10.9 to -0.53, P =0.031) and reduction in 24-hour drain output (ß=-12.2, 95% CI: -19.4 to -4.89, P =0.001) and total drain output (ß=-14.0, 95% CI: -22.9 to -5.05, P =0.002). CONCLUSIONS: TXA use during ACDF procedures leads to a decrease in perioperative blood loss and faster drain removal. TXA is an effective and safe agent for reducing perioperative blood loss in ACDF surgery. LEVEL OF EVIDENCE: III.

Comparing Patient-Reported Outcomes, Complications, Readmissions, and Revisions in Posterior Lumbar Fusion With, Versus Without, an Interbody Device.

STUDY DESIGN: Retrospective analysis on prospectively collected data. OBJECTIVES: To compare posterior lumbar fusions with versus without an interbody in: (1) Patient-reported outcomes (PROs) at 1 year and (2) postoperative complications, readmission, and reoperations. SUMMARY OF BACKGROUND DATA: Elective lumbar fusion is commonly used to treat various lumbar pathologies. Two common approaches for open posterior lumbar fusion include posterolateral fusion (PLF) alone without an interbody and with an interbody through techniques, like transforaminal lumbar interbody fusion. Whether fusion with or without an interbody leads to better outcomes remains an area of active research. PATIENTS AND METHODS: The Lumbar Module of the Quality Outcomes Database was queried for adults undergoing elective primary posterior lumbar fusion with or without an interbody. Covariates included demographic variables, comorbidities, primary spine diagnosis, operative variables, and baseline PROs, including Oswestry Disability Index, North American Spine Society satisfaction index, numeric rating scale-back/leg pain, and Euroqol 5-dimension. Outcomes included complications, reoperations, readmissions, return to work/activities, and PROs. Propensity score matching and linear regression modeling were used to estimate the average treatment effect on the treated to assess the impact of interbody use on patient outcomes. RESULTS: After propensity matching, there were 1044 patients with interbody and 215 patients undergoing PLF. The average treatment effect on the treated analysis showed that having an interbody or not had no significant impact on any outcome of interest, including 30-day complications and reoperations, 3-month readmissions, 12-month return to work, and 12-month PROs. CONCLUSION: There were no discernible differences in outcomes between patients undergoing PLF alone versus with an interbody in elective posterior lumbar fusion. These results add to the growing body of evidence that posterior lumbar fusions with and without an interbody seem to have similar outcomes up to 1 year postoperatively when treating degenerative lumbar spine conditions.

Impact of unplanned readmissions on lumbar surgery outcomes: a national study of 33,447 patients.

BACKGROUND CONTEXT: Unplanned readmissions following lumbar spine surgery have immense clinical and financial implications. However, little is known regarding the impact of unplanned readmissions on patient-reported outcomes (PROs) following lumbar spine surgery. PURPOSE: To evaluate the impact of unplanned readmissions, including specific readmission reasons, on patient reported outcomes 12 months after lumbar spine surgery. STUDY DESIGN/SETTING: A retrospective cohort study of prospectively collected data was conducted using patients included in the lumbar module of the Quality and Outcomes Database (QOD), a national, multicenter spine registry. PATIENT SAMPLE: A total of 33,447 patients who underwent elective lumbar spine surgery for degenerative diseases were included. Mean age was 59.8 (SD=14.04), 53.6% were male, 89.5% were white, 45.9% were employed, and 47.5% had private insurance. OUTCOME MEASURES: Unplanned 90-day readmissions and 12-month patient-reported outcomes (PROs) including numeric rating scale (NRS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, EuroQol-5 Dimension (EQ-5D) scores, and North American Spine Society (NASS) patient-satisfaction scores. METHODS: The lumbar module of the QOD was queried for adults undergoing elective lumbar spine surgery for degenerative disease. Unplanned 90-day readmissions were classified into 4 groups: medical, surgical, pain-only, and no readmissions. Medical and surgical readmissions were further categorized into primary reason for readmission. 12-month PROs assessing patient back and leg pain (NRS), disability (ODI), quality of life (EQ-5D), and patient satisfaction were collected. Multivariable models predicting 12-month PROs were built controlling for covariates. RESULTS: A total of 31,430 patients (94%) had no unplanned readmission while 2,017 patients (6%) had an unplanned readmission within 90 days following lumbar surgery. Patients with readmissions had significantly worse 12-month PROs compared with those with no unplanned readmissions in covariate-adjusted models. Using Wald-df as a measure of predictor importance, surgical readmissions were associated with the worst 12-month outcomes, followed by pain-only, then medical readmissions. In separate covariate adjusted models, we found that readmissions for pain, SSI/wound dehiscence, and revisions were among the most important predictors of worse outcomes at 12-months. CONCLUSIONS: Unplanned 90-day readmissions were associated with worse pain, disability, quality of life, and greater dissatisfaction at 12-months, with surgical readmissions having the greatest impact, followed by pain-only readmissions, then medical readmissions. Readmissions for pain, SSI/wound dehiscence, and revisions were the most important predictors of worse outcomes. These results may help providers better understand the factors that impact outcomes following lumbar spine surgery and promote improved patient counseling and perioperative management.

Implant Surface Technologies to Promote Spinal Fusion: A Narrative Review.

The technology surrounding spinal fusion surgery has continuously evolved in tandem with advancements made in bioengineering. Over the past several decades, developments in biomechanics, surgical techniques, and materials science have expanded innovation in the spinal implant industry. This narrative review explores the current state of implant surface technologies utilized in spinal fusion surgery. This review covers various types of implant surface materials, focusing on interbody spacers composed of modified titanium, polyetheretherketone, hydroxyapatite, and other materials, as well as pedicle screw surface modifications. Advantages and disadvantages of the different surface materials are discussed, including their biocompatibility, mechanical properties, and radiographic visibility. In addition, this review examines the role of surface modifications in enhancing osseointegration and reducing implant-related complications and, hopefully, improving patient outcomes. The findings suggest that while each material has its potential advantages, further research is needed to determine the optimal surface properties for enhancing spinal fusion outcomes.

L1-pelvic angle: a convenient measurement to attain optimal deformity correction.

PURPOSE: (1) Evaluate the associations between L1-pelvic angle (L1PA) and both sagittal vertical axis (SVA) and T1-pelvic angle (T1PA), and (2) assess the clinical impact of L1PA. METHODS: A single-institution retrospective cohort study was undertaken for patients undergoing adult spinal deformity (ASD) surgery from 2013 to 2017. Ideal L1PA was defined as (0.5xPelvic Incidence)-21. Pearson correlation was performed to compare L1PA, SVA, and T1PA. Univariate/multivariate regression was performed to assess the effect of L1PA on mechanical complications, controlling for age, BMI, and postoperative pelvic incidence-lumbar lordosis mismatch (PI/LL). Due to the overlapping nature of patients with pseudarthrosis and rod fracture, these patients were analyzed together. RESULTS: A total of 145 patients were included. Mean preoperative L1PA, SVA, and T1PA were 15.5 ± 8.9°, 90.7 ± 66.8 mm, and 27.1 ± 13.0°, respectively. Mean postoperative L1PA, SVA, and T1PA were 15.0 ± 8.9°, 66.7 ± 52.8 mm, and 22.3 ± 11.1°, respectively. Thirty-six (24.8%) patients achieved ideal L1PA. Though the correlation was modest, preoperative L1PA was linearly correlated with preoperative SVA (r2 = 0.16, r = 0.40, 95%CI = 0.22-0.60, p < 0.001) and T1PA (r2 = 0.41, r = 0.62, 95%CI = 0.46-0.76, p < 0.001). Postoperative L1PA was linearly correlated with postoperative SVA (r2 = 0.12, r = 0.37, 95%CI = 0.18-0.56, p < 0.001) and T1PA (r2 = 0.40, r = 0.62, 95%CI = 0.45-0.74, p < 0.001). Achieving ideal L1PA ± 5° was associated with a decreased risk of rod fracture/pseudarthrosis on univariate and multivariate regression (OR = 0.33, 95%CI = 0.12-0.86, p = 0.024). No association between achieving ideal L1PA and patient-reported outcomes was observed. CONCLUSION: L1PA was modestly correlated with SVA and T1PA, and achieving ideal L1PA was associated with lower rates of rod fracture/pseudarthrosis. Future studies are warranted to better define the clinical implications of achieving a normal L1PA. LEVEL OF EVIDENCE: III.

Clinical and radiographic outcomes following correction of idiopathic scoliosis in adolescence vs young adulthood.

PURPOSE: The natural history of adolescent idiopathic scoliosis (AIS) has been well documented, but the impact of age at the time of surgical correction is relatively understudied. In this study, we matched patients undergoing surgical correction of adult idiopathic scoliosis (AdIS) with a cohort of AIS patients to compare: (1) coronal and sagittal radiographic correction, (2) operative variables, and (3) postoperative complications. METHODS: A single-institution scoliosis registry was queried for patients undergoing idiopathic scoliosis surgery from 2000-2017. INCLUSION CRITERIA: patients with idiopathic scoliosis, no previous spine surgery, and 2-year follow-up. AdIS patients were matched 1:2 with AIS patients based on Lenke classification and curve characteristics. Independent sample t-test and Chi-square test was used to analyze the data. RESULTS: 31 adults underwent surgical correction of idiopathic scoliosis and were matched with 62 adolescents. Mean age of adults was 26.2 ± 11.05, mean BMI was 25.6 ± 6.0, and 22 (71.0%) were female. Mean age of adolescents was 14.2 ± 1.8, mean BMI was 22.7 ± 5.7, and 41(66.7%) were female. AdIS had significantly less postoperative major Cobb correction (63.9% vs 71.3%, p = 0.006) and final major Cobb correction (60.6% vs 67.9%, p = 0.025). AdIS also had significantly greater postoperative T1PA (11.8 vs 5.8, p = 0.002). AdIS had longer operative times (p = 0.003), higher amounts of pRBCs transfused (p = 0.005), longer LOS (p = 0.016), more ICU requirement (p = 0.013), higher overall complications (p < 0.001), higher rate of pseudarthrosis (p = 0.026), and more neurologic complications (p = 0.013). CONCLUSION: Adult patients undergoing surgical correction of idiopathic scoliosis had significantly worse postoperative coronal and sagittal alignment when compared with adolescent patients. Adult patients also had higher rates of complications, longer operative times, and longer hospital stays. LEVEL OF EVIDENCE: III.

Efficacy and Safety of the Ultrasonic Bone Scalpel in Lumbar Laminectomies.

Introduction: Despite recent advances in applied instruments and surgical techniques, the incidence of iatrogenic durotomies caused by traditional techniques remains significant. The ultrasonic bone scalpel (UBS) has been shown to improve speed and reduce complications in laminectomies in the cervical and thoracic spine when compared to traditional methods utilizing high-speed burr, punch forceps, or rongeurs. Thus, in this study, we aim to evaluate whether the use of the UBS in the lumbar spine would result in equivalent safety, efficacy, and patient-reported outcomes (PROs) improvement when compared to traditional methods of laminectomy. Methods: Data from a prospectively collected, single-institution registry was queried between January 1, 2019 and September 1, 2021 for patients with a primary diagnosis of lumbar stenosis who received a laminectomy (with or without fusion) using traditional methods or UBS method. Outcomes included 3-month and 12-month values for all PROs Measurement Information System (PROMIS) subdomains, Numerical Rating Scale (NRS) pain score, Oswestry Disability Index (ODI) percentage, Patient Health Questionnaire 9 (PHQ-9) score, operative complications, reoperations, and readmissions. Covariates selected for matching included age, operation type, and number of levels. A variety of statistical tests were utilized. Results: As per our findings, 2:1 propensity matching resulted in 64 "traditional group" patients and 32 "UBS group" patients. Post-match analysis found no differences between the traditional and UBS groups for demographic and baseline measures except for race and ethnicity. For the matched sample, no differences were noted in PROs, reoperations, or readmissions. There was a significant difference in rates of durotomies between the traditional and UBS groups (12.5% vs. 0.0%, p=0.049). Conclusions: Results showed the high-frequency oscillation technology implemented by the UBS helps to decrease the rate of injury to the dura, thus reducing the overall incidence of iatrogenic durotomies. We believe these data provide valuable information to surgeons and patients about the safety and efficacy of the UBS in performing lumbar laminectomies.

Case Report-Traumatic L5-S1 Instability: Are Upright Radiographs Potentially Dangerous?

BACKGROUND: Traumatic lumbosacral instability is a rare but potentially devastating injury. These injuries are frequently associated with neurologic injury and often result in long-term disability. Despite their severity, radiographic findings can be subtle, and multiple reports exist in which these injuries were not recognized on initial imaging. Transverse process fractures, high-energy mechanisms, and other injury features have been suggested as indications for advanced imaging, which has a high degree of sensitivity in detecting unstable injuries. CASE PRESENTATION: A 21-year-old man presented to our level I trauma center after being ejected in a rollover motor vehicle collision. He sustained multiple injuries, including multiple lumbar transverse process fractures and a unilateral superior articular facet fracture of S1. PRIMARY OUTCOMES: Initial supine computed tomography (CT) images showed no displacement of the fracture and no listhesis or instability. Subsequent upright imaging in a brace, however, demonstrated significant displacement of the fracture with dislocation of the contralateral L5-S1 facet joint and significant anterolisthesis. The patient underwent open posterior reduction and stabilization of L4-S1 followed by L5-S1 anterior lumbar interbody fusion. The patient demonstrated excellent alignment on postoperative imaging. At 3 months postoperatively, he had returned to work, was ambulating without assistance, and reported minimal back discomfort and no lower extremity pain, numbness, or weakness. CONCLUSION: This case serves as a warning that supine CT imaging alone may not be sufficient to rule out unstable lumbar spine injuries, such as traumatic L5-S1 instability, and that upright radiographs in these potentially unstable injuries may represent a hazard to patients. Fractures involving the pedicle, pars, or facet joints as well as multiple transverse process fractures and/or a high-energy mechanism of injury should all raise suspicion of instability and warrant additional imaging. CLINICAL RELEVANCE: This article provides guidance on approaching treatment for patients with potential traumatic lumbosacral instability.

Assessing the Insurance Deductible Effect on Outcomes After Elective Spinal Surgery.

BACKGROUND: Private insurers use the calendar deductible system, placing pressure on patients and medical personnel to perform medical services before the end of the year to maximize patient savings. The impact of the deductible calendar on patient-reported outcomes (PROs) after spine surgery is poorly understood. The objective of our study was to investigate if patients undergoing surgery in December had different PROs and demographics compared with all other months. METHODS: The Quality Outcome Database, a national spine registry, was queried for patients who underwent elective spine surgery between January 2012 and January 2021 for degenerative spine conditions. PROs and demographics were compared between the December and non-December groups using various statistical tests. RESULTS: A total of 978 patients (9.3%) underwent anterior cervical discectomy and fusion in December versus 9548 (90.7%) in other months. There was a significantly higher percentage of patients in December who had private insurance and were employed. A total of 1104 patients (8.5%) underwent lumbar fusion in December versus 11,826 (91.5%) in other months. There was a significantly greater chance of undergoing surgery in December if patients had private insurance and were employed. Although some PROs were statistically significant for the lumbar and cervical cohorts between December and non-December patients, none were clinically significant. CONCLUSIONS: Patients undergoing elective spine surgery in December were more likely to have private insurance and be employed. PROs for ACDF and lumbar fusions were not affected by surgical timing (December yes/no). Other spinal procedures directed at more chronic diseases might be more susceptible to external influence of insurance deductibles.

Interleukin-34 permits Porphyromonas gingivalis survival and NF-κB p65 inhibition in macrophages.

Interleukin-34 (IL-34) is a cytokine that supports the viability and differentiation of macrophages. An important cytokine for the development of epidermal immunity, IL-34, is present and plays a role in the immunity of the oral environment. IL-34 has been linked to inflammatory periodontal diseases, which involve innate phagocytes, including macrophages. Whether IL-34 can alter the ability of macrophages to effectively interact with oral microbes is currently unclear. Using macrophages derived from human blood monocytes with either the canonical cytokine colony-stimulating factor (CSF)1 or IL-34, we compared the ability of the macrophages to phagocytose, kill, and respond through the production of cytokines to the periodontal keystone pathogen Porphyromonas gingivalis. While macrophages derived from both cytokines were able to engulf the bacterium equally, IL-34-derived macrophages were much less capable of killing internalized P. gingivalis. Of the macrophage cell surface receptors known to interact with P. gingivalis, dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin was found to have the largest variation between IL-34- and CSF1-derived macrophages. We also found that upon interaction with P. gingivalis, IL-34-derived macrophages produced significantly less of the neutrophil chemotactic factor IL-8 than macrophages derived in the presence of CSF1. Mechanistically, we identified that the levels of IL-8 corresponded with P. gingivalis survival and dephosphorylation of the major transcription factor NF-κB p65. Overall, we found that macrophages differentiated in the presence of IL-34, a dominant cytokine in the oral gingiva, have a reduced ability to kill the keystone pathogen P. gingivalis and may be susceptible to specific bacteria-mediated cytokine modification.

Macrophage Polarization Alters Postphagocytosis Survivability of the Commensal Streptococcus gordonii.

Oral streptococci are generally considered commensal organisms; however, they are becoming recognized as important associate pathogens during the development of periodontal disease as well as being associated with several systemic diseases, including as a causative agent of infective endocarditis. An important virulence determinant of these bacteria is an ability to evade destruction by phagocytic cells, yet how this subversion occurs is mostly unknown. Using Streptococcus gordonii as a model commensal oral streptococcus that is also associated with disease, we find that resistance to reactive oxygen species (ROS) with an active ability to damage phagosomes allows the bacterium to avoid destruction within macrophages. This ability to survive relies not only on the ROS resistance capabilities of the bacterium but also on ROS production by macrophages, with both being required for maximal survival of internalized bacteria. Importantly, we also show that this dependence on ROS production by macrophages for resistance has functional significance: S. gordonii intracellular survival increases when macrophages are polarized toward an activated (M1) profile, which is known to result in prolonged phagosomal ROS production compared to that of alternatively (M2) polarized macrophages. We additionally find evidence of the bacterium being capable of both delaying the maturation of and damaging phagosomes. Taken together, these results provide essential insights regarding the mechanisms through which normally commensal oral bacteria can contribute to both local and systemic inflammatory disease.