Emerging roles for stromal cells in bone metastasis.

The skeleton is a common site of cancer metastasis and malignancy with the resultant lesions often being incurable. Interactions between metastatic cancer cells and the bone microenvironment are critical for cancer cell survival, outgrowth, and progression. Mesenchymal Stem Cells (MSCs) are an essential stromal cell type in bone that are appreciated for their impacts on cancer-induced bone disease, however, newer evidence suggests that MSCs possess extensive roles in cancer-bone crosstalk, including cancer cell dormancy, metabolic demands, and immune-oncology. Emerging evidence has also identified the importance of MSC tissue source and the influence of ageing when studying MSC biology. Combining these considerations together with developing technologies such as spatial transcriptomics will contribute to defining the molecular mechanisms underlying complex stroma-cancer interactions in bone and assist with identification of therapeutically tractable targets.

The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease.

Multiple myeloma (MM) is an osteolytic malignancy that is incurable due to the emergence of treatment resistant disease. Defining how, when and where myeloma cell intrinsic and extrinsic bone microenvironmental mechanisms cause relapse is challenging with current biological approaches. Here, we report a biology-driven spatiotemporal hybrid agent-based model of the MM-bone microenvironment. Results indicate MM intrinsic mechanisms drive the evolution of treatment resistant disease but that the protective effects of bone microenvironment mediated drug resistance (EMDR) significantly enhances the probability and heterogeneity of resistant clones arising under treatment. Further, the model predicts that targeting of EMDR deepens therapy response by eliminating sensitive clones proximal to stroma and bone, a finding supported by in vivo studies. Altogether, our model allows for the study of MM clonal evolution over time in the bone microenvironment and will be beneficial for optimizing treatment efficacy so as to significantly delay disease relapse.

The Risk of Early Postoperative Complications Associated With Preoperative Immunosuppression in Patients Undergoing Total Elbow Arthroplasty.

PURPOSE: Patients considering total elbow arthroplasty (TEA) may be receiving immunosuppressive therapy; however, the relationship between immunosuppressive medications and postoperative complications is not well defined. Our purpose was to assess the relationship between preoperative immunosuppression and short-term complications following TEA. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2005 to 2020 to identify patients undergoing TEA. Procedures indicated for malignancy or infection were excluded. Patients were grouped according to preoperative chronic immunosuppressive status. Demographic and operative characteristics were compared between groups. The 30-day incidence of complications and reoperations were compared between groups. Multiple logistic regression models, inverse-weighted by propensity scores, were used to calculate odds ratio (OR) of experiencing any complication or return to the operating room based on immunosuppression status and other demographic characteristics. RESULTS: A total of 769 patients undergoing TEA were included, of whom 142 (18.5%) received chronic immunosuppression. Distribution of age, sex, race, body mass index, diabetes, and American Society of Anesthesiologists classification differed significantly between groups. Most procedures were performed on an inpatient basis, and the median operative duration was 148 minutes. Most procedures were indicated for fracture in the nonimmunosuppressed group and rheumatoid arthritis in the immunosuppressed group. Overall complication rates were 7.0% for immunosuppressed patients and 10.2% for nonimmunosuppressed patients. The incidence of complications and reoperations did not significantly differ between groups. After controlling for confounding and adjusting for patient characteristics, immunosuppressed patients were 0.52 times less likely to experience a complication. Additionally, there was no association between immunosuppression status and odds of return to the operating room. CONCLUSION: Similar rates of complications were observed following TEA, regardless of preoperative immunosuppression status. Chronic immunosuppression does not appear to increase the rates of postoperative complications for patients undergoing TEA. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The Current Status of Awake Endoscopic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine the use of local anesthesia and/or conscious sedation in endoscopic spine procedures within the past decade. METHODS: This systematic review abided by PRISMA guidelines. Embase, PubMed, Google Scholar, and Cochrane databases were searched for post-2011 articles with patients >18 years old, lumbar/cervical percutaneous endoscopic spine procedures using local/awake anesthesia, and patient/surgical outcomes. Reviews, book chapters, single case reports, or small case series (n ≤15 patients) were excluded. Scoring systems of the National Institutes of Health quality assessment tool, Newcastle-Ottawa Scale, and Cochrane Risk of Bias evaluated interventional case series, comparative studies, and randomized control trials, respectively. RESULTS: Twenty-six articles were included, with 4 studies comparing general and local anesthesia. Of 2113 total patients, 1873 patients received local anesthesia. Significant improvements were seen in pain and disability scores. Studies that included MacNab scores showed that 96% of patients rated their postoperative satisfaction as excellent to good. Subanalysis of comparative studies showed a reduced risk of surgical/major medical complications and a slight increased risk for minor medical complications among awake spine patients. Length of stay was shorter for patients receiving local anesthesia. CONCLUSIONS: The current systematic review and meta-analysis shows that use of local anesthesia is a safe and effective alternative to general anesthesia among different endoscopic spinal procedures. Although awake spine surgery is associated with a decreased risk of severe complications, lower revision rates, and higher postoperative satisfaction, more robust studies involving larger cohorts of patients are needed to evaluate the true impact of awake spine surgery on outcomes.

How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy.

Circulating tumor cells (CTCs) are known to be prognostic for metastatic relapse and are detected in patients as solitary cells or cell clusters. Circulating tumor cell clusters (CTC clusters) have been observed clinically for decades and are of significantly higher metastatic potential compared to solitary CTCs. Recent studies suggest distinct differences in CTC cluster biology regarding invasion and survival in circulation. However, differences regarding dissemination, dormancy, and reawakening require more investigations compared to solitary CTCs. Here, we review the current state of CTC cluster research and consider their clinical significance. In addition, we discuss the concept of collective invasion by CTC clusters and molecular evidence as to how cluster survival in circulation compares to that of solitary CTCs. Molecular differences between solitary and clustered CTCs during dormancy and reawakening programs will also be discussed. We also highlight future directions to advance our current understanding of CTC cluster biology.

γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer.

Immune checkpoint blockade has been largely unsuccessful for the treatment of bone metastatic castrate-resistant prostate cancer (mCRPC). Here, we report a combinatorial strategy to treat mCRPC using γδ-enriched chimeric antigen receptor (CAR) T cells and zoledronate (ZOL). In a preclinical murine model of bone mCRPC, γδ CAR-T cells targeting prostate stem cell antigen (PSCA) induced a rapid and significant regression of established tumors, combined with increased survival and reduced cancer-associated bone disease. Pretreatment with ZOL, a U.S. Food and Drug Administration-approved bisphosphonate prescribed to mitigate pathological fracture in mCRPC patients, resulted in CAR-independent activation of γδ CAR-T cells, increased cytokine secretion, and enhanced antitumor efficacy. These data show that the activity of the endogenous Vγ9Vδ2 T cell receptor is preserved in CAR-T cells, allowing for dual-receptor recognition of tumor cells. Collectively, our findings support the use of γδ CAR-T cell therapy for mCRPC treatment.

Validation of Neck Disability Index Severity among Patients Receiving One or Two-Level Anterior Cervical Surgery.

STUDY DESIGN: Retrospective cohort. PURPOSE: To evaluate the validity of established severity thresholds for Neck Disability Index (NDI) among patients undergoing anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA). OVERVIEW OF LITERATURE: Few studies have examined the validity of established NDI threshold values among patients undergoing ACDF or CDA. METHODS: A surgical database was reviewed to identify patients undergoing cervical spine procedures. Demographics, operative characteristics, comorbidities, NDI, Visual Analog Scale (VAS), and 12-item Short Form (SF-12) physical and mental composite scores (PCS and MCS) were recorded. NDI severity was categorized using previously established threshold values. Improvement from preoperative scores at each postoperative timepoint and convergent validity of NDI was evaluated. Discriminant validity of NDI was evaluated against VAS neck and arm and SF-12 PCS and MCS. RESULTS: All 290 patients included in the study demonstrated significant improvements from baseline values for all patient-reported outcome measures (PROMs) at all postoperative timepoints (p<0.001) except SF-12 MCS at 2 years (p =0.393). NDI showed a moderate- to-strong correlation (r≥0.419) at most timepoints for VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS (p<0.001, all). NDI severity categories demonstrated significant differences in mean VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS at all timepoints (p<0.001, all). Differences between NDI severity groups were not uniform for all PROMs. VAS neck values demonstrated significant intergroup differences at most timepoints, whereas SF-12 MCS showed significantly different values between most severity groups. CONCLUSIONS: Neck disability is strongly correlated with neck and arm pain, physical function, and mental health and demonstrates worse outcomes with increasing severity. Previously established severity categories may be more applicable to pain than physical function or mental health and may be more uniformly applied preoperatively for cervical spine patients.

Dysphagia May Attenuate Improvements in Postoperative Outcomes Following Anterior Cervical Discectomy and Fusion.

BACKGROUND: Past studies outline potential risk factors for dysphagia following anterior cervical discectomy and fusion (ACDF). Few studies explored the impact of dysphagia, as measured by the swallowing quality of life (SWAL-QOL), on postoperative patient-reported outcome measure (PROM) improvement. This study aimed to determine the relationship between dysphagia and improvement in pain, disability, physical function, and mental health following ACDF. METHODS: A retrospective review of patients undergoing primary 1- or 2-level ACDF was performed. Individuals without a completed preoperative SWAL-QOL were excluded. Outcomes were collected for visual analog scale (VAS) neck and arm pain, Neck Disability Index (NDI), Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF), 12-Item Short Form Physical Component Score (SF-12 PCS), 9-Item Patient Health Questionnaire (PHQ-9), and SWAL-QOL. Postoperative improvement from preoperative values was evaluated using a paired t test. The impact of SWAL-QOL on each PROM was assessed using linear regression. RESULTS: A total of 91 patients were included. Mean preoperative SWAL-QoL was 90.4, which worsened at 6 weeks and resolved by 6 months (P ≤ 0.007, both). VAS neck and arm scores significantly improved postoperatively (P < 0.001), as did the NDI score (P < 0.001). Physical function significantly improved at 12 weeks and 6 months (P ≤ 0.021, both). Depressive symptoms improved at 6 weeks and 12 weeks (P ≤ 0.007, both). Preoperatively, SWAL-QOL demonstrated significant relationships with all PROMs (P ≤ 0.005, all). At 6 weeks, 12 weeks, and 6 months (P ≤ 0.048, all), SWAL-QoL again demonstrated a similar significant association with all PROMs. Multiple regression did not demonstrate common demographic or operative variables that were significant predictors of PROMs. CONCLUSION: Following ACDF, patients experienced a worsening of dysphagia but resolved by 12 weeks. All PROMs demonstrated significant improvements by the 6-month timepoint, except for PHQ-9. SWAL-QoL demonstrated a significant effect on all postoperative outcomes, which may suggest that this questionnaire could effectively evaluate dysphagia and predict positive or negative outcomes following ACDF. LEVEL OF EVIDENCE: 3 CLINICAL RELEVANCE: The severity of dysphagia has a significant association with pain, disability, mental health, and physical function patient-reported outcome measures in patients undergoing ACDF.

Predicting Acute Changes in Depressive Symptoms Following Lumbar Decompression.

BACKGROUND: While depressive symptoms improve for most patients following minimally invasive lumbar decompression (MIS LD), for some, symptoms may worsen. This study aimed to investigate predictors of change in depressive symptoms in the short-term postoperative period following MIS LD. METHODS: We retrospectively analyzed a prospective surgical database for patients undergoing primary MIS LD procedures from 2016 to 2020. Preoperative pain (visual analog scale back and leg) scores were recorded, and the 9-Item Patient Health Questionnaire (PHQ-9) was administered at the preoperative and postoperative (6 weeks, 12 weeks, 6 months, and 1 year) timepoints. Patients were grouped into 1 of 3 categories of depression severity based on preoperative PHQ-9 scores: minimal (0-4), mild (5-9), and moderate to severe (10-27). Postoperative change in depressive symptoms was calculated by determining differences from baseline scores to scores at 6 weeks, 12 weeks, and 6 months. Analysis of demographics, perioperative characteristics, and spinal pathologies was conducted using χ 2 test. Significant factors contributing to postoperative changes in depression were analyzed using multiple linear regression analysis. Significance was set at P = 0.05. RESULTS: The 216 patients included had a mean age of 48 years, and a majority were men (70.4%). Most patients had a preoperative diagnosis of spinal stenosis (90.3%) or herniated nucleus pulposus (69.9%). Univariate analysis identified age, ethnicity, insurance, and diabetes as significant variables among depression severity groups. Patients demonstrated significant improvements in depressive symptoms at all postoperative timepoints (P < 0.001). Multivariate analysis identified several significant predictors of postoperative change in PHQ-9, which included moderate to severe preoperative depression for all postoperative timepoints (all P ≤ 0.038), mild preoperative depression for 6 weeks and 12 weeks (both P ≤ 0.029), and private insurance (P = 0.002) and smoking status (P = 0.047) at 12 weeks. CONCLUSION: Depression improved at all postoperative timepoints following LD. Insurance type, smoking status, and preoperative depression severity were all identified as significant predictors of postoperative changes in depressive symptoms. CLINICAL RELEVANCE: This study explores predictors of changes in depressive symptoms following LD.

Impact of Lower Extremity Arthroplasty on Improvement of Quality-of-Life Outcomes Following Lumbar Fusion.

BACKGROUND: Both hip-spine and knee-spine syndromes can significantly impact a patient's quality of life; however, few studies have investigated their effect on postoperative outcomes following lumbar fusion. OBJECTIVE: Our study aimed to evaluate the impact of a prior lower extremity arthroplasty on the improvement of patient-reported outcome measures (PROMs) following lumbar fusion surgery. METHODS: Patients undergoing primary, single, or multilevel lumbar interbody fusion were retrospectively reviewed. Patients missing preoperative PROMs were excluded. PROMs were collected preoperatively and postoperatively and included the Oswestry Disability Index (ODI), 12-Item Short Form Physical Component Summary, Patient-Reported Outcomes Measurement Information System Physical Function, and visual analog scale (VAS). A minimum clinically important difference (MCID) was calculated. Patients were categorized based on a history of hip/knee arthroplasty and propensity score matched. Intragroup improvement of PROM scores and intergroup differences in mean scores were evaluated using a paired t test and linear regression. MCID achievement differences were evaluated using logistic regression. RESULTS: A total of 335 patients were included, with 25 having a history of hip/knee arthroplasty. Arthroplasty patients were significantly older (P = 0.001) and typically had a higher Charlson Comorbidity Index (P ≤ 0.003, both). Patients differed in spinal pathology of degenerative spondylolisthesis (P = 0.049). Nonarthroplasty patients demonstrated significant improvements in all PROMs by 2 years (P < 0.001, all). The arthroplasty group demonstrated significant improvements in all PROMs by 1 year (P < 0.031, all). Preoperative VAS back was significantly worse for nonarthroplasty patients (P = 0.035). MCID achievement did not significantly differ between groups except at 6 months for ODI (P = 0.035). CONCLUSION: Following lumbar fusion, patients with a past surgical history did not demonstrate differences in outcome measures or MCID from those without. These results suggest that comorbid orthopedic conditions requiring surgery do not negatively impact the ability of patients to improve following lumbar fusion. CLINICAL RELEVANCE: Prior surgical history of lower extremity arthroplasty should not discourage the use of lumbar fusion when properly indicated, as patients reported clinical improvement regardless of history of hip or knee arthroplasty.

Anterior Cervical Discectomy and Fusion Results in Clinically Significant Improvements in Patients With Preoperative Sleep Difficulties.

BACKGROUND: Individual items within the Patient Health Questionnaire-9 (PHQ-9) have not been assessed as predictors of postoperative outcomes. Our objective is to study the relationship between responses to individual PHQ-9 items and achievement of a minimum clinically important difference (MCID) following anterior cervical discectomy and fusion (ACDF). METHODS: A prospective surgical database was reviewed for primary, single-level ACDF procedures performed for degenerative spinal pathology. Patient demographics, preoperative spinal pathology, and perioperative characteristics were recorded. Patient-reported outcome measures (PROMs) including PHQ-9, visual analog scale (VAS) neck and arm, Neck Disability Index, 12-item Short Form physical component score (SF-12 PCS), and Patient-Reported Outcomes Measurement Information System Physical Function were administered at preoperative and 6-week, 12-week, 6-month, 1-year, and 2-year postoperative timepoints. MCID achievement was determined by comparing postoperative PROM improvement from baseline to previously established values. Logistic regression assessed responses to each individual question of the preoperative PHQ-9 as predictors of MCID achievement in each other PROMs. RESULTS: Sixty-six ACDF patients were included with a mean age of 47.2 years. Herniated nucleus pulposus was the most common preoperative spinal diagnosis (95.6%). The mean operative duration was 50.3 minutes, the mean estimated blood loss was 27.5 mL, and most patients were discharged on postoperative day 0 (81.8%). A majority of patients achieved MCID for all measures except SF-12 PCS. PHQ-9 question 3 significantly predicted MCID achievement for VAS neck (P = 0.045), VAS arm (P = 0.049), and SF-12 PCS (P = 0.037). No other PHQ-9 items or overall PHQ-9 scores significantly predicted MCID achievement. CONCLUSION: Question 3 of the PHQ-9 regarding "trouble falling asleep, staying asleep, or sleeping too much" significantly predicted clinically meaningful improvement in neck pain, arm pain, and physical function following ACDF, although overall PHQ-9 scores did not. Providers should inform patients experiencing significant sleep-related difficulties that they may be especially likely to benefit from ACDF surgery. CLINICAL RELEVANCE: Evaluation of sleep from the PHQ-9 predicts clinically relevant improvement in neck pain, arm pain, and physical function in patients undergoing ACDF.

History of Prior Lumbar Surgery Does Not Impact Mental Health Outcomes Following Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to evaluate the impact of undergoing a prior lumbar procedure on mental health outcomes following anterior cervical discectomy and fusion. SUMMARY OF BACKGROUND DATA: Revision and reoperations are perceived as risk factors for worse mental health outcomes. METHODS: A retrospective review of a surgical database was performed for cervical and lumbar procedures. The mental health measures used were: Short Form 12-Item Mental Composite Score (SF-12 MCS) and Patient Health Questionnaire 9 (PHQ-9). Secondary outcomes of interest were Visual Analogue Scale for neck and arm pain, Neck Disability Index, and Short Form 12-Item Physical Composite Score (SF-12 PCS). All outcomes were collected preoperatively and at 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Minimum clinically important difference (MCID) was calculated using established values. Patients were grouped based on the surgical history of an elective lumbar spine procedure and propensity-matched. Differences in postoperative outcome scores and MCID achievement were evaluated using linear and logistic regression respectively. RESULTS: A total of 74 patients were included in this study. Mental health outcomes did not demonstrate significant differences between groups for SF-12 MCS and PHQ-9 for all time points except at 6 weeks for PHQ-9 ( P =0.038). MCID achievement was not significantly impacted by surgical history for all outcome measures at all postoperative time points (all P >0.050). The majority of patients achieved an MCID by the 1-year time point for all outcomes for patients without a prior lumbar surgery except for Visual Analogue Scale arm and SF-12 PCS, while those with a surgical history achieved an MCID for all outcomes except SF-12 PCS and PHQ-9. CONCLUSIONS: Anterior cervical discectomy and fusion patients with a past history of lumbar surgery demonstrated significant improvements in depression, neck and arm pain, disability, and physical function as those without a past lumbar surgical history. Prior surgery also did not impact MCID achievement for all outcomes.

Validation of Veterans RAND 12-Item Physical Function Survey in Minimally Invasive Transforaminal Lumbar Interbody Fusion.

BACKGROUND: Veterans RAND 12-item (VR-12) physical component score (PCS) has been validated in both veteran and US citizen populations; however, its use for spine surgery populations has not been evaluated. This study aims to correlate the VR-12 PCS survey with legacy patient-reported outcome measures (PROMs) in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). METHODS: A prospective surgical database was retrospectively assessed for MIS TLIFs performed at 1 level from March 2015 to June 2019. Inclusion criteria were elective procedures for degenerative spinal pathology. Patients were excluded if they had surgery for metastatic, traumatic, or infectious etiologies or had incomplete preoperative 12-item Short Form (SF-12) PCS or Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF) survey. Additionally, patients with any incomplete VR-12 PCS surveys through 1 year were excluded. Demographics and perioperative characteristics were recorded. Mean postoperative PROM scores and score difference from preoperative baseline were calculated at each postoperative timepoint through 1 year. The relationship of VR-12-PCS with SF-12-PCS and PROMIS PF was evaluated with a Pearson's correlation coefficient and time-independent partial correlation. RESULTS: A total of 59 patients underwent single-level MIS TLIFs. The cohort was 44.1% women with an average age of 53.8 years, and 52.5% were obese (body mass index ≥30 kg/m2). The VR-12 PCS, SF-12 PCS, and PROMIS PF surveys had significant improvements from baseline to the 6 month through 1 year postoperative timepoints (P ≤ 0.001, all). All timepoints revealed strong VR-12-PCS correlations with SF-12-PCS and PROMIS PF (all P ≤ 0.001). CONCLUSION: VR-12 PCS, SF-12 PCS, and PROMIS PF scores all indicate statistically significant improvements in physical function for patients following MIS TLIF. VR-12 PCS was strongly correlated with the historically validated SF-12 PCS system as well as with the more recent PROMIS PF survey. Our observations give weight to utilizing the VR-12 PCS survey as a valid measure of physical function among patients undergoing MIS TLIF. CLINICAL RELEVANCE: This study validates VR-12 PCS to measure physical function for TLIF patients.

Patient Satisfaction Following Lumbar Decompression: What is the Role of Mental Health?

OBJECTIVE: To determine the association between patient-reported depressive symptoms and patient satisfaction following minimally invasive lumbar decompression. METHODS: Primary, single-level/multilevel minimally invasive lumbar decompression was identified. Patient-reported outcome measures (PROMs) collected preoperatively/postoperatively included visual analog scale back/leg, Oswestry Disability Index, 9-Item Patient Health Questionnaire (PHQ-9), and 12-Item Short Form Mental Composite Score (SF-12 MCS). Patients rated current satisfaction level (0-10) with back/leg pain and disability. A paired Student's t-test compared each postoperative PROM score to its preoperative baseline. At each timepoint, patients were categorized by PHQ-9 and SF-12 MCS scores. One-way analysis of variance compared patient satisfaction with back/leg pain and disability among PHQ-9 subgroups. The Student's t-test for independent samples compared patient satisfaction between SF-12 MCS subgroups. Analysis of covariance (ANCOVA) assessed differences in satisfaction between depression subgroups while controlling for preoperative/postoperative values in corresponding PROMs. RESULTS: 193 patients were included. All PROMs demonstrated significant postoperative improvement from 6-weeks through 2-years (P < 0.001, all), except PHQ at 9 2-years (P = 0.874). Mean satisfaction scores ranged from 6.9-7.9 (back pain), 7.3-8.0 (leg pain), and 7.6-8.0 (disability). Satisfaction with back/leg pain and disability significantly differed among PHQ-9 subgroups at all postoperative timepoints (P < 0.001, all). Accounting for baseline and current pain/disability values, ANCOVA revealed differences between PHQ-9 subgroups only in satisfaction with back pain at 2 years (P < 0.001), leg pain at 12 weeks/1 year/2 years (P ≤ 0.047, all), and disability at 6 months/2 years (P ≤ 0.049, both). Satisfaction differed between SF-12 MCS subgroups at all timepoints (P ≤ 0.047), except back pain 6 months (P = 0.263). Accounting for baseline and postoperative pain/disability, ANCOVA revealed differences in satisfaction between SF-12 MCS groups only for back/leg pain at 2 years (P ≤ 0.001, both). CONCLUSIONS: Independent effect of depression at long-term follow-up was significant. This highlights the importance of understanding the interaction between physical and mental health outcomes to optimize patients' perceptions of surgical outcomes.

Influence of Preoperative Depressive Burden on Achieving a Minimal Clinically Important Difference Following Lumbar Decompression.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: This study evaluates the association of preoperative mental health with the rate of achieving minimal clinically important difference (MCID) in patient-reported outcomes following lumbar decompression (LD). SUMMARY OF BACKGROUND DATA: Research is scarce regarding the influence of preoperative depression on the rate of achieving MCID for mental health, physical function, and pain among LD patients. METHODS: A surgical registry was retrospectively reviewed for primary LD surgeries. Patients were grouped by depressive symptom severity according to the preoperative Patient Health Questionnaire 9 score. The association of Patient Health Questionnaire 9 subgroups with demographic and surgical variables was analyzed, and differences among subgroups were assessed. Achievement rates of MCID for physical function, pain, disability, and mental health were compared among groups at each time point using previously established MCID thresholds. RESULTS: Of the 321 subjects, 69.8% were male, and 170 subjects had minimal preoperative depressive symptoms, 86 had moderate, and 65 had severe. Patients in moderate and severe groups demonstrated a significantly greater rate of MCID achievement for disability at 6 weeks and 3 months postoperatively. The severe group demonstrated a significantly higher rate of achieving MCID for mental health at the 1-year time point. CONCLUSIONS: Patients with any range of preoperative depressive symptom severity had a similar rate of achieving MCID for pain and physical function throughout 1 year following LD. The severe depressive symptom group had a higher rate of MCID achievement with disability at 6 weeks and with mental health at 1 year. This study demonstrates that patients with any preoperative depressive symptom severity have an indistinguishable ability to attain MCID by 1 year following LD. LEVEL OF EVIDENCE: Level III.

Integrated computational and in vivo models reveal Key Insights into macrophage behavior during bone healing.

Myeloid-derived monocyte and macrophages are key cells in the bone that contribute to remodeling and injury repair. However, their temporal polarization status and control of bone-resorbing osteoclasts and bone-forming osteoblasts responses is largely unknown. In this study, we focused on two aspects of monocyte/macrophage dynamics and polarization states over time: 1) the injury-triggered pro- and anti-inflammatory monocytes/macrophages temporal profiles, 2) the contributions of pro- versus anti-inflammatory monocytes/macrophages in coordinating healing response. Bone healing is a complex multicellular dynamic process. While traditional in vitro and in vivo experimentation may capture the behavior of select populations with high resolution, they cannot simultaneously track the behavior of multiple populations. To address this, we have used an integrated coupled ordinary differential equations (ODEs)-based framework describing multiple cellular species to in vivo bone injury data in order to identify and test various hypotheses regarding bone cell populations dynamics. Our approach allowed us to infer several biological insights including, but not limited to,: 1) anti-inflammatory macrophages are key for early osteoclast inhibition and pro-inflammatory macrophage suppression, 2) pro-inflammatory macrophages are involved in osteoclast bone resorptive activity, whereas osteoblasts promote osteoclast differentiation, 3) Pro-inflammatory monocytes/macrophages rise during two expansion waves, which can be explained by the anti-inflammatory macrophages-mediated inhibition phase between the two waves. In addition, we further tested the robustness of the mathematical model by comparing simulation results to an independent experimental dataset. Taken together, this novel comprehensive mathematical framework allowed us to identify biological mechanisms that best recapitulate bone injury data and that explain the coupled cellular population dynamics involved in the process. Furthermore, our hypothesis testing methodology could be used in other contexts to decipher mechanisms in complex multicellular processes.

The Worldwide Influence of Social Media on Cervical Spine Literature.

BACKGROUND: The Altmetric (Digital Science, Holtzbrinck Publishing) Attention Score (AAS) is an automatically calculated score that accounts for other literary influences, which include academic sources as well as nonacademically focused social media outlets such as Twitter, Facebook, and news articles. This study compares the most popular cervical surgery articles on social media to the most cited articles within peer-reviewed literature and identifies journals that contribute the most articles and geographic trends. METHODS: We searched the Altmetric database for cervical spine surgery articles since inception using the search phrase "cervical" and "spine." We ranked journals that contributed the most articles and calculated their AAS, contributing social media outlets (eg, Twitter, Facebook, News, etc) and citation counts. We also ranked the top 100 most popular cervical spine articles on social media and compared them to the most cited articles. Countries were assessed based on their mentions through the most contributing social media platform. RESULTS: Of the 527 total journals identified in our search, the top 10 journals were responsible for contributing 60.2% of the total articles. The 3 journals that contributed the most articles were Spine (18.9%), European Spine Journal (11.8%), and The Spine Journal (10.3%). The journals with the highest AAS scores included Journal of Neurosurgery: Spine (11.3), Spine (8.8), and Journal of Manipulative & Physiological Therapeutics (5.8). Social media outlets that contributed the most mentions per article were Twitter (4.4), Facebook (0.5), and news sources (0.3). Among all countries contributing Twitter mentions, the 3 countries with the most cervical spine posts included the United States (23.3%), the United Kingdom (10.3%), and Spain (5.5%). CONCLUSION: Our evaluation of cervical spine literature revealed Twitter, Facebook, and news sources are the most common social media outlets influencing title dissemination. Journals contributing the most articles did not necessarily have the highest average AAS. CLINICAL RELEVANCE: Spinal surgeons should consider utilization of social media outlets, such as Twitter, Facebook, and news sources, to potentially increase the dissemination of their articles.

Supplemental Essays for Residency Applications: The Modern Day Typewriter.

OBJECTIVE: The purpose of this study is to evaluate one institution's use of a supplemental essay and its effect on the total number and demographics of applicants as compared to previous years. DESIGN: A retrospective cohort review of candidates applying to our institution's Orthopedic Surgery residency program in the 2020 to 2021 cycle was performed. All applicants were presented a prompt for a short supplemental essay. Only candidates who completed the essay were considered for an invitation to interview. Differences in proportions of female and under-represented minority (URM) applicants associated with the year of application and with essay completion were evaluated. A similar analysis was also performed to assess differences in demographics of interviewees between years. SETTING: A single academic medical center providing tertiary care. PARTICIPANTS: All orthopedic residency applicants from the 2019 to 2020 and 2020 to 2021 cycles. RESULTS: Of 863 applicants in 2021, 506 (59%) completed the supplemental essay. URM status was significantly associated with application year and essay completion. However, demographics of eligible applicants and interviewees were not significantly associated with the application year, nor were the proportion of female or URM candidates offered an interview. CONCLUSIONS: Our analysis based on use of the supplemental essay in one application cycle demonstrated that it was effective in reducing the application review burden by approximately 41.4% without adversely affecting the demographics of the interviewee pool.

How Does Open Access Publication Impact Readership and Citation Rates of Lumbar Spine Literature?

STUDY DESIGN: This was a retrospective review. OBJECTIVE: The objective of this study was to assess the impact of open access (OA) publication on citation rates and attention scores of literature related to lumbar spine surgery. SUMMARY OF BACKGROUND DATA: OA literature allows readers to view full-text manuscripts of research publications free of charge, however, OA publication is often associated with substantial fees for authors. METHODS: The Altmetric database was searched for articles related to lumbar spine surgery. Title, journal, publication date, Dimensions Citations, Mendeley Readers, Altmetric Attention Score (AAS), number of public mentions, and OA status were collected for each included article. The influence of OA status on Dimensions Citations, Mendeley Readers, and each individual component of the AAS was assessed. To control for journal influence, impact of OA on Dimensions Citations and AAS was separately assessed for each of the top 10 journals contributing the most mentioned articles. The top 25 most cited articles and top 25 articles by AAS were also characterized. RESULTS: A total of 5245 articles were included, of which 2063 were published with OA and 3182 were not. OA status was a significant, independent predictor of AAS and Mendeley Readers (both P <0.001), but not Dimensions Citations ( P =0.422). OA status significantly predicted mentions in news stories ( P =0.003), Twitter posts ( P <0.001), Facebook posts ( P <0.001), and Wikipedia citations ( P =0.011). Of the top 10 contributing journals, OA status significantly predicted Dimensions Citations for European Spine Journal , Journal of Neurosurgery: Spine , and Neurosurgery ( P ≤0.005) and predicted AAS for Spine , European Spine Journal , The Spine Journal , Journal of Neurosurgery: Spine , and Neurosurgery ( P ≤0.017, all). DISCUSSION: OA status appeared to significantly impact public attention scores, but not citation rates, although these effects did vary based on the journal in which articles were published. Authors may want to consider OA publication based on their target audience and the goal of their research.