Exploring the energetic and conformational properties of the sequence space connecting naturally occurring RNA tetraloop receptor motifs.

Folded RNAs contain tertiary contact motifs whose structures and energetics are conserved across different RNAs. The transferable properties of RNA motifs simplify the RNA folding problem, but measuring energetic and conformational properties of many motifs remains a challenge. Here, we use a high-throughput thermodynamic approach to investigate how sequence changes alter the binding properties of naturally-occurring motifs, the GAAA tetraloop•tetraloop receptor (TLR) interactions. We measured the binding energies and conformational preferences of TLR sequences that span mutational pathways from the canonical 11ntR to two other natural TLRs, the IC3R and Vc2R. While the IC3R and Vc2R share highly similar energetic and conformational properties, the landscapes that map the sequence changes for their conversion from the 11ntR to changes in these properties differ dramatically. Differences in the energetic landscapes stem from the mutations needed to convert the 11ntR to the IC3R and Vc2R rather than a difference in the intrinsic energetic architectures of these TLRs. The conformational landscapes feature several non-native TLR variants with conformational preferences that differ from both the initial and final TLRs; these species represent potential branching points along the multidimensional sequence space to sequences with greater fitness in other RNA contexts with alternative conformational preferences. Our high-throughput, quantitative approach reveals the complex nature of sequence-fitness landscapes and leads to models for their molecular origins. Systematic and quantitative molecular approaches provide critical insights into understanding the evolution of natural RNAs as they traverse complex landscapes in response to selective pressures.

Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.

OBJECTIVE: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. METHODS: Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (≤ 3-level) TLIFs between January 2018 and October 2022. Patients were either exposed to semaglutide or not. A comprehensive 1:3 (exposure vs no exposure) matching was performed based on age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking status, osteoporosis, levels of surgery, and basal-bolus insulin dependence. Kaplan-Meier survival curves and log-rank testing were performed to study the probability of additional lumbar fusion surgery within 1 year. RESULTS: After the 1:3 matching, 1781 patients were identified, with 447 in the semaglutide-exposed cohort and 1334 in the nonexposed cohort. Most patients in both groups were 55-69 years old, and 59.3% were female. Analysis showed that the likelihood of undergoing additional lumbar fusion surgery within 1 year post-TLIF was significantly higher in the semaglutide-exposed group than in the nonexposed group (OR 11.79, 95% CI 8.17-17.33). Kaplan-Meier plots and log-rank testing further confirmed a statistically significant divergent probability in the need for additional surgery within 1 year between the cohorts (log-rank, p < 0.001). CONCLUSIONS: Semaglutide exposure appears to be associated with a higher likelihood of additional lumbar fusion surgeries within 1 year post-TLIF, especially in patients receiving the medication for longer durations. Although the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.

Surgical Outcomes After Preoperative Embolization in Hypervascular Spinal Metastases: A Propensity Scored Study of 191 Patients.

STUDY DESIGN: Retrospective propensity-score matched, case control study at 2 academic tertiary care centers. OBJECTIVE: To assess the effect of PE on (1) intraoperative blood loss, defined as conventional estimates of blood loss (EBL) and hemoglobin mass loss, and (2) secondary outcomes in patients with spinal metastases from hypervascular histologies. BACKGROUND CONTEXT: Preoperative embolization (PE) intends to reduce blood loss during surgery for spinal metastases of hypervascular tumors such as renal cell carcinoma. However, studies investigating the effect of PE in hypervascular tumors often consist of small cohorts, do not correct for confounding factors, and have conflicting results. METHODS: After propensity score matching (PSM), 46 PE patients were matched to 46 non-PE patients without baseline differences. The constraints of PSM did not allow analysis of patients with tumor volumes>9 cm3. Multiple linear regression models were fitted for EBL and hemoglobin mass loss. Poisson regression models were fitted for both intraoperative and postoperative transfusions. RESULTS: There was no difference in EBL (948 mL [IQR 500-1750] vs. 1100 mL [IQR 388-1925], P=0.68) and hemoglobin mass loss (201g [IQR 119-307] vs. 232g [IQR 173-373], P=0.18) between PE and non-PE patients. Other than higher 1-year survival rates (65% vs. 43%, P=0.05) in PE-patients, there were no differences in secondary outcomes. In multiple regression analyses, PE was not associated with decreased intraoperative blood loss, hemoglobin mass loss or perioperative blood transfusions. CONCLUSIONS: Our study demonstrated that, for tumors <9 cm3, PE did not reduce EBL, hemoglobin mass loss or perioperative blood transfusions in patients undergoing spine surgery for metastases from hypervascular histologies. These findings suggest that urgent spine surgeries indicated for hypervascular histologies should not be delayed based on the availability of PE and accurate detection of pre-operative hypervascularity, beyond histology, will likely be an important determination of future PE utilization for spinal metastases. LEVEL OF EVIDENCE: Treatment Benefits, Level III.

Assessing a revised-risk analysis index for morbidity and mortality after spine surgery for metastatic spinal tumors.

BACKGROUND: Risk Analysis Index (RAI) has been increasingly used to assess surgical frailty in various procedures, but its effectiveness in predicting mortality or in-patient hospital outcomes for spine surgery in metastatic disease remains unclear. The aim of this study was to compare the predictive values of the revised RAI (RAI-rev), the modified frailty index-5 (mFI-5), and advanced age for extended length of stay, 30-day readmission, complications, and mortality among patients undergoing spine surgery for metastatic spinal tumors. METHODS: A retrospective cohort study was performed using the 2012-2022 ACS NSQIP database to identify adult patients who underwent spinal surgery for metastatic spinal pathologies. Using receiver operating characteristic (ROC) and multivariable analyses, we compared the discriminative thresholds and independent associations of RAI-rev, mFI-5, and greater patient age with extended length of stay (LOS), 30-day complications, hospital readmission, and mortality. RESULTS: A total of 1,796 patients were identified, of which 1,116 (62.1%) were male and 1,008 (70.7%) were non-Hispanic White. RAI-rev identified 1,291 (71.9%) frail and 208 (11.6%) very frail patients, while mFI-5 identified 272 (15.1%) frail and 49 (2.7%) very frail patients. In the ROC analysis for extended LOS, both RAI-rev and mFI-5 showed modest predictive capabilities with area under the curve (AUC) values of 0.5477 and 0.5329, respectively, and no significant difference in their predictive abilities (p = 0.446). When compared to age, RAI-rev demonstrated superior prediction (p = 0.015). With respect to predicting 30-day readmission, no significant difference was observed between RAI-rev and mFI-5 (AUC 0.5394 l respectively, p = 0.354). However, RAI-rev outperformed age (p = 0.001). When assessing the risk of 30-day complications, RAI-rev significantly outperformed mFI-5 (AUC: 0.6016 and 0.5542 respectively, p = 0.022) but not age. Notably, RAI-rev demonstrated superior ability for predicting 30-day mortality compared to mFI-5 and age (AUC: 0.6541, 0.5652, and 0.5515 respectively, p < 0.001). Multivariate analysis revealed RAI-rev as a significant predictor of extended LOS [aOR: 1.96, 95% CI: 1.13-3.38, p = 0.016] and 30-day mortality [aOR: 5.27, 95% CI: 1.73-16.06, p = 0.003] for very frail patients. Similarly, the RAI-rev significantly predicted 30-day complications for frail [aOR: 2.63, 95% CI: 1.21-5.72, p = 0.015] and very frail [aOR: 3.69, 95% CI: 1.60-8.51, p = 0.002] patients. However, the RAI did not significantly predict 30-day readmission [Very Frail aOR: 1.52, 95% CI: 0.75-3.07, p = 0.245; Frail aOR: 1.46, 95% CI: 0.79-2.68, p = 0.225]. CONCLUSION: Our study demonstrates the utility of RAI-rev in predicting morbidity and mortality in patients undergoing spine surgery for metastatic spinal pathologies. Particularly, the superiority that RAI-rev has in predicting 30-day mortality may have significant implications in multidisciplinary decision making.

Predictors of Clavien-Dindo Grade III-IV or Grade V Complications after Metastatic Spinal Tumor Surgery: An Analysis of Sociodemographic, Socioeconomic, Clinical, Oncologic, and Operative Parameters.

The rate of major complications and 30-day mortality after surgery for metastatic spinal tumors is relatively high. While most studies have focused on baseline comorbid conditions and operative parameters as risk factors, there is limited data on the influence of other parameters such as sociodemographic or socioeconomic data on outcomes. We retrospectively analyzed data from 165 patients who underwent surgery for spinal metastases between 2012-2023. The primary outcome was development of major complications (i.e., Clavien-Dindo Grade III-IV complications), and the secondary outcome was 30-day mortality (i.e., Clavien-Dindo Grade V complications). An exploratory data analysis that included sociodemographic, socioeconomic, clinical, oncologic, and operative parameters was performed. Following multivariable analysis, independent predictors of Clavien-Dindo Grade III-IV complications were Frankel Grade A-C, lower modified Bauer score, and lower Prognostic Nutritional Index. Independent predictors of Clavien-Dindo Grade V complications) were lung primary cancer, lower modified Bauer score, lower Prognostic Nutritional Index, and use of internal fixation. No sociodemographic or socioeconomic factor was associated with either outcome. Sociodemographic and socioeconomic factors did not impact short-term surgical outcomes for metastatic spinal tumor patients in this study. Optimization of modifiable factors like nutritional status may be more important in improving outcomes in this complex patient population.

Disparities in Surgical Intervention and Health-Related Quality of Life Among Racial/Ethnic Groups With Degenerative Lumbar Spondylolisthesis.

BACKGROUND AND OBJECTIVES: Racial and socioeconomic disparities in spine surgery for degenerative lumbar spondylolisthesis persist in the United States, potentially contributing to unequal health-related quality of life (HRQoL) outcomes. This is important as lumbar spondylolisthesis is one of the most common causes of surgical low back pain, and low back pain is the largest disabler of individuals worldwide. Our objective was to assess the relationship between race, socioeconomic factors, treatment utilization, and outcomes in patients with lumbar spondylolisthesis. METHODS: This cohort study analyzed prospectively collected data from 9941 patients diagnosed with lumbar spondylolisthesis between 2015 and 2020 at 5 academic hospitals. Exposures were race, socioeconomic status, health coverage, and HRQoL measures. Main outcomes and measures included treatment utilization rates between racial groups and the association between race and treatment outcomes using logistic regression, adjusting for patient characteristics, socioeconomic status, health coverage, and HRQoL measures. RESULTS: Of the 9941 patients included (mean [SD] age, 67.37 [12.40] years; 63% female; 1101 [11.1%] Black, Indigenous, and People of Color [BIPOC]), BIPOC patients were significantly less likely to use surgery than White patients (odds ratio [OR] = 0.68; 95% CI, 0.62-0.75). Furthermore, BIPOC race was associated with significantly lower odds of reaching the minimum clinically important difference for physical function (OR = 0.74; 95% CI, 0.60; 0.91) and pain interference (OR = 0.77; 95% CI, 0.62-0.97). Medicaid beneficiaries were significantly less likely (OR = 0.65; 95% CI, 0.46-0.92) to reach a clinically important improvement in HRQoL when accounting for race. CONCLUSION: This study found that BIPOC patients were less likely to use spine surgery for degenerative lumbar spondylolisthesis despite reporting higher pain interference, suggesting an association between race and surgical utilization. These disparities may contribute to unequal HRQoL outcomes for patients with lumbar spondylolisthesis and warrant further investigation to address and reduce treatment disparities.

An Appraisal of the Quality of Development and Reporting of Predictive Models in Neurosurgery: A Systematic Review.

BACKGROUND AND OBJECTIVES: Significant evidence has indicated that the reporting quality of novel predictive models is poor because of confounding by small data sets, inappropriate statistical analyses, and a lack of validation and reproducibility. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) statement was developed to increase the generalizability of predictive models. This study evaluated the quality of predictive models reported in neurosurgical literature through their compliance with the TRIPOD guidelines. METHODS: Articles reporting prediction models published in the top 5 neurosurgery journals by SCImago Journal Rank-2 (Neurosurgery, Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of NeuroInterventional Surgery, and Journal of Neurology, Neurosurgery, and Psychiatry) between January 1st, 2018, and January 1st, 2023, were identified through a PubMed search strategy that combined terms related to machine learning and prediction modeling. These original research articles were analyzed against the TRIPOD criteria. RESULTS: A total of 110 articles were assessed with the TRIPOD checklist. The median compliance was 57.4% (IQR: 50.0%-66.7%). Models using machine learning-based models exhibited lower compliance on average compared with conventional learning-based models (57.1%, 50.0%-66.7% vs 68.1%, 50.2%-68.1%, P = .472). Among the TRIPOD criteria, the lowest compliance was observed in blinding the assessment of predictors and outcomes (n = 7, 12.7% and n = 10, 16.9%, respectively), including an informative title (n = 17, 15.6%) and reporting model performance measures such as confidence intervals (n = 27, 24.8%). Few studies provided sufficient information to allow for the external validation of results (n = 26, 25.7%). CONCLUSION: Published predictive models in neurosurgery commonly fall short of meeting the established guidelines laid out by TRIPOD for optimal development, validation, and reporting. This lack of compliance may represent the minor extent to which these models have been subjected to external validation or adopted into routine clinical practice in neurosurgery.

Pedicled omental flaps for complex wound reconstruction following surgery for primary spine tumors of the mobile spine and sacrum.

OBJECTIVE: Surgery for primary tumors of the mobile spine and sacrum often requires complex reconstruction techniques to cover soft-tissue defects and to treat wound and CSF-related complications. The anatomical, vascular, and immunoregulatory characteristics of the omentum make it an excellent local substrate for the management of radiation soft-tissue injury, infection, and extensive wound defects. This study describes the authors' experience in complex wound reconstruction using pedicled omental flaps to cover defects in surgery for mobile spine and sacral primary tumors. METHODS: A retrospective cohort analysis was conducted on 34 patients who underwent pedicled omental flap reconstruction after en bloc resection of primary sacral and mobile spine tumors between 2010 and 2020. The study focused on assessing the indications for omental flap usage, including soft-tissue coverage, protection against postoperative radiation therapy, infection management, vascular supply for bone grafts, and dural defect and CSF leak repair. Patient demographic characteristics, tumor characteristics, surgical outcomes, and follow-up data were analyzed to determine the procedure's efficacy and complication rates. RESULTS: From 2010 to 2020, 34 patients underwent pedicled omental flap reconstruction after en bloc resection of sacral (24 of 34 [71%]) and mobile spine (10 of 34 [29%]) primary tumors, mostly chordomas. The patient cohort included 21 men and 13 women with a median (range) age of 60 (32-89) years. The most common indication for omental flap was soft-tissue coverage (20 of 34 [59%]). Other indications included protecting abdominopelvic organs for postoperative radiation therapy (6 of 34 [18%]), treating infections (5 of 34 [15%]), providing vascular supply for free fibular bone graft (1 of 34 [3%]), and repairing large dural defects and CSF leak (2 of 34 [6%]). The median (range) follow-up was 24 (0-132) months, during which 71% (24 of 34) of patients did not require additional surgery for wound-related complications. At last follow-up, 59% (20 of 34) had stable disease and 32% (11 of 34) had recurrence, had progression of disease, or had been discharged to hospice after treatment. CONCLUSIONS: The pedicled omentum is an effective local tissue graft that can be used for complex wound reconstruction and management of high-risk closures in primary spine tumors. This technique may have a lower rate of complications than other approaches and may influence surgical planning and flap selection in challenging cases.

Unraveling molecular advancements in chordoma tumorigenesis and treatment response: a review of scientific discoveries and clinical implications.

Chordomas are tumors thought to originate from notochordal remnants that occur in midline structures from the cloves of the skull base to the sacrum. In adults, the most common location is the sacrum, followed by the clivus and then mobile spine, while in children a clival origin is most common. Most chordomas are slow growing. Clinical presentation of chordomas tend to occur late, with local invasion and large size often complicating surgical intervention. Radiation therapy with protons has been proven to be an effective adjuvant therapy. Unfortunately, few adjuvant systemic treatments have demonstrated significant effectiveness, and chordomas tend to recur despite intensive multimodal care. However, insight into the molecular underpinnings of chordomas may guide novel therapeutic approaches including selection for immune and molecular therapies, individualized prognostication of outcomes, and real-time noninvasive assessment of disease burden and evolution. At the genomic level, elevated levels of brachyury stemming from duplications and mutations resulting in altered transcriptional regulation may introduce druggable targets for new surgical adjuncts. Transcriptome and epigenome profiling have revealed promoter- and enhancer-dependent mechanisms of protein regulation, which may influence therapeutic response and long-term disease history. Continued scientific and clinical advancements may offer further opportunities for treatment of chordomas. Single-cell transcriptome profiling has further provided insight into the heterogeneous molecular pathways contributing to chordoma propagation. New technologies such as spatial transcriptomics and emerging biochemical analytes such as cell-free DNA have further augmented the surgeon-clinician's armamentarium by facilitating detailed characterization of intra- and intertumoral biology while also demonstrating promise for point-of-care tumor quantitation and assessment. Recent and ongoing clinical trials highlight accelerating interest to translate laboratory breakthroughs in chordoma biology and immunology into clinical care. In this review, the authors dissect the landmark studies exploring the molecular pathogenesis of chordoma. Incorporating this into an outline of ongoing clinical trials and discussion of emerging technologies, the authors aimed to summarize recent advancements in understanding chordoma pathogenesis and how neurosurgical care of chordomas may be augmented by improvements in adjunctive treatments.

Association of Malnutrition with Surgical and Hospital Outcomes after Spine Surgery for Spinal Metastases: A National Surgical Quality Improvement Program Study of 1613 Patients.

Background: Malnutrition is a common condition that may exacerbate many medical and surgical pathologies. However, few have studied the impact of malnutrition on surgical outcomes for patients undergoing surgery for metastatic disease of the spine. This study aims to evaluate the impact of malnutrition on perioperative complications and healthcare resource utilization following surgical treatment of spinal metastases. Methods: We conducted a retrospective cohort study using the 2011-2019 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients with spinal metastases who underwent laminectomy, corpectomy, or posterior fusion for extradural spinal metastases were identified using the CPT, ICD-9-CM, and ICD-10-CM codes. The study population was divided into two cohorts: Nourished (preoperative serum albumin values ≥ 3.5 g/dL) and Malnourished (preoperative serum albumin values < 3.5 g/dL). We assessed patient demographics, comorbidities, intraoperative variables, postoperative adverse events (AEs), hospital LOS, discharge disposition, readmission, and reoperation. Multivariate logistic regression analyses were performed to identify the factors associated with a prolonged length of stay (LOS), AEs, non-routine discharge (NRD), and unplanned readmission. Results: Of the 1613 patients identified, 26.0% were Malnourished. Compared to Nourished patients, Malnourished patients were significantly more likely to be African American and have a lower BMI, but the age and sex were similar between the cohorts. The baseline comorbidity burden was significantly higher in the Malnourished cohort compared to the Nourished cohort. Compared to Nourished patients, Malnourished patients experienced significantly higher rates of one or more AEs (Nourished: 19.8% vs. Malnourished: 27.6%, p = 0.004) and serious AEs (Nourished: 15.2% vs. Malnourished: 22.6%, p < 0.001). Upon multivariate regression analysis, malnutrition was found to be an independent and associated with an extended LOS [aRR: 3.49, CI (1.97, 5.02), p < 0.001], NRD [saturated aOR: 1.76, CI (1.34, 2.32), p < 0.001], and unplanned readmission [saturated aOR: 1.42, CI (1.04, 1.95), p = 0.028]. Conclusions: Our study suggests that malnutrition increases the risk of postoperative complication, prolonged hospitalizations, non-routine discharges, and unplanned hospital readmissions. Further studies are necessary to identify the protocols that pre- and postoperatively optimize malnourished patients undergoing spinal surgery for metastatic spinal disease.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.

The Impact of Preoperative Spinal Injection Timing on Postoperative Complications of Lumbar Decompression Surgery.

BACKGROUND AND OBJECTIVES: Epidural steroid injections (ESIs) are commonly used for lower back pain management. The effect of these injections on lumbar decompression surgery outcomes is hitherto underexplored. The study objective was to determine the impact of ESIs on postoperative rates of medical and surgical complications and to define the appropriate interval before lumbar decompression surgery. METHODS: This retrospective all-payer database analysis identified 587 651 adult patients undergoing one- to three-level laminectomies from January 2010 to October 2021. A 2:1 propensity score match accounting for comorbidities, levels of surgery, and demographics was performed to create two cohorts: (1) 43 674 patients who had received an ESI in the 90 days before laminectomy and (2) 87 348 patients who had not received an ESI. The primary outcome was the rates of medical and surgical complications between groups at 30 days postoperatively. Patients were divided into five cohorts based on injection time before surgery: 1 to 30 days, 31 to 45 days, 46 to 60 days, 61 to 75 days, and 76 to 90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. Confidence intervals of 95% are provided when appropriate. P values < .01 were considered significant. RESULTS: Rates of medical complications within 30 days of surgery were significantly higher in those with ESI compared with control (4.83% vs 3.9%, P < .001). Cerebrospinal fluid (CSF) leak rates were increased in the ESI group at 0.28% vs 0.1% (P < .001), but surgical site infection rates were not significantly different between groups (1.31% vs 1.42% P = .11). ESI performed within 30 days was associated with increased odds of CSF leak (OR: 5.32, 95% CI: 3.96-7.15). CONCLUSION: Preoperative ESI increases the risk of CSF leak and medical complications after lumbar decompression. Because these complications were significantly associated with ESIs given 1 to 30 days before surgery, avoiding ESIs at least 30 days before surgery may be advisable.

AO Spine Guideline for the Use of Osteobiologics (AOGO) in Anterior Cervical Discectomy and Fusion for Spinal Degenerative Cases.

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

Racial disparities in the management and outcomes of primary osseous neoplasms of the spine: a SEER analysis.

PURPOSE: Primary osseous neoplasms of the spine, including Ewing's sarcoma, osteosarcoma, chondrosarcoma, and chordoma, are rare tumors with significant morbidity and mortality. The present study aims to identify the prevalence and impact of racial disparities on management and outcomes of patients with these malignancies. METHODS: The 2000 to 2020 Surveillance, Epidemiology, and End Results (SEER) Registry, a cancer registry, was retrospectively reviewed to identify patients with Ewing's sarcoma, osteosarcoma, chondrosarcoma, or chordoma of the vertebral column or sacrum/pelvis. Study patients were divided into race-based cohorts: White, Black, Hispanic, and Other. Demographics, tumor characteristics, treatment variables, and mortality were assessed. RESULTS: 2,415 patients were identified, of which 69.8% were White, 5.8% Black, 16.1% Hispanic, and 8.4% classified as "Other". Tumor type varied significantly between cohorts, with osteosarcoma affecting a greater proportion of Black patients compared to the others (p < 0.001). A lower proportion of Black and Other race patients received surgery compared to White and Hispanic patients (p < 0.001). Utilization of chemotherapy was highest in the Hispanic cohort (p < 0.001), though use of radiotherapy was similar across cohorts (p = 0.123). Five-year survival (p < 0.001) and median survival were greatest in White patients (p < 0.001). Compared to non-Hispanic Whites, Hispanic (p < 0.001) and "Other" patients (p < 0.001) were associated with reduced survival. CONCLUSION: Race may be associated with tumor characteristics at diagnosis (including subtype, size, and site), treatment utilization, and mortality, with non-White patients having lower survival compared to White patients. Further studies are necessary to identify underlying causes of these disparities and solutions for eliminating them.

Treatment of intramedullary spinal cord tumors: a modified Delphi technique of the North American Spine Society Section of Spine Oncology.

OBJECTIVE: Intramedullary spinal cord tumors (IMSCTs) are rare tumors with heterogeneous presentations and natural histories that complicate their management. Standardized guidelines are lacking on when to surgically intervene and the appropriate aggressiveness of resection, especially given the risk of new neurological deficits following resection of infiltrative tumors. Here, the authors present the results of a modified Delphi method using input from surgeons experienced with IMSCT removal to construct a framework for the operative management of IMSCTs based on the clinical, radiographic, and tumor-specific characteristics. METHODS: A modified Delphi technique was conducted using a group of 14 neurosurgeons experienced in IMSCT resection. Three rounds of written correspondence, surveys, and videoconferencing were carried out. Participants were queried about clinical and radiographic criteria used to determine operative candidacy and guide decision-making. Members then completed a final survey indicating their choice of observation or surgery, choice of resection strategy, and decision to perform duraplasty, in response to a set of patient- and tumor-specific characteristics. Consensus was defined as ≥ 80% agreement, while responses with 70%-79% agreement were defined as agreement. RESULTS: Thirty-six total characteristics were assessed. There was consensus favoring surgical intervention for patients with new-onset myelopathy (86% agreement), chronic myelopathy (86%), or progression from mild to disabling numbness (86%), but disagreement for patients with mild numbness or chronic paraplegia. Age was not a determinant of operative candidacy except among frail patients, who were deemed more suitable for observation (93%). Well-circumscribed (93%) or posteriorly located tumors reaching the surface (86%) were consensus surgical lesions, and participants agreed that the presence of syringomyelia (71%) and peritumoral T2 signal change (79%) were favorable indications for surgery. There was consensus that complete loss of transcranial motor evoked potentials with a 50% decrease in the D-wave amplitude should halt further resection (93%). Preoperative symptoms seldom influenced choice of resection strategy, while a distinct cleavage plane (100%) or visible tumor-cord margins (100%) strongly favored gross-total resection. CONCLUSIONS: The authors present a modified Delphi technique highlighting areas of consensus and agreement regarding surgical management of IMSCTs. Although not intended as a substitute for individual clinical decision-making, the results can help guide care of these patients. Additionally, areas of controversy meriting further investigation are highlighted.

A guide to finite element analysis models of the spine for clinicians.

Finite element analysis (FEA) is a computer-based mathematical method commonly used in spine and orthopedic biomechanical research. Advances in computational power and engineering modeling and analysis software have enabled many recent technical applications of FEA. Through the use of FEA, a wide range of scenarios can be simulated, such as physiological processes, mechanisms of disease and injury, and the efficacy of surgical procedures. Such models have the potential to enhance clinical studies by allowing comparisons of surgical treatments that would be impractical to perform in human or animal studies, and by linking model results to treatment outcomes. While traditional ex vivo experiments are limited by variabilities in tissue, the complexity of test setup, cost, measurable biomechanical parameters, and the repeatability of experiments, FEA models can be used to measure a wide range of clinically relevant biomechanical parameters. Generic or patient-specific anatomical models can be modified to simulate different clinical and surgical conditions under simulated physiological conditions. Despite these capabilities, there is limited understanding of the clinical applicability and translational potential of FEA models. For spine surgeons, a comprehensive understanding of the key features, strengths, and limitations of FEA models of the spine and their ability to personalize treatment options and assist in clinical decision-making would significantly enhance the impact of FEA research. Furthermore, fostering collaborations between surgeons and engineers could augment the clinical use of these models. The purpose of this review was to highlight key features of FEA model building for clinicians. To illustrate these features, the authors present an example of the use of FEA models in comparing FDA-approved disc arthroplasty implants.

Machine learning-based detection of sarcopenic obesity and association with adverse outcomes in patients undergoing surgical treatment for spinal metastases.

OBJECTIVE: The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS: The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS: A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69-21.26), 30-day readmission (OR 3.27, 95% CI 1.01-10.62), and 90-day (OR 4.85, 95% CI 1.29-18.26) and 1-year (OR 3.78, 95% CI 1.17-12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS: The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.

Demographic Representation in 3 Leading Artificial Intelligence Text-to-Image Generators.

Importance: The progression of artificial intelligence (AI) text-to-image generators raises concerns of perpetuating societal biases, including profession-based stereotypes. Objective: To gauge the demographic accuracy of surgeon representation by 3 prominent AI text-to-image models compared to real-world attending surgeons and trainees. Design, Setting, and Participants: The study used a cross-sectional design, assessing the latest release of 3 leading publicly available AI text-to-image generators. Seven independent reviewers categorized AI-produced images. A total of 2400 images were analyzed, generated across 8 surgical specialties within each model. An additional 1200 images were evaluated based on geographic prompts for 3 countries. The study was conducted in May 2023. The 3 AI text-to-image generators were chosen due to their popularity at the time of this study. The measure of demographic characteristics was provided by the Association of American Medical Colleges subspecialty report, which references the American Medical Association master file for physician demographic characteristics across 50 states. Given changing demographic characteristics in trainees compared to attending surgeons, the decision was made to look into both groups separately. Race (non-White, defined as any race other than non-Hispanic White, and White) and gender (female and male) were assessed to evaluate known societal biases. Exposures: Images were generated using a prompt template, "a photo of the face of a [blank]", with the blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries on 3 continents (the US, Nigeria, and China). Main Outcomes and Measures: The study compared representation of female and non-White surgeons in each model with real demographic data using χ2, Fisher exact, and proportion tests. Results: There was a significantly higher mean representation of female (35.8% vs 14.7%; P < .001) and non-White (37.4% vs 22.8%; P < .001) surgeons among trainees than attending surgeons. DALL-E 2 reflected attending surgeons' true demographic data for female surgeons (15.9% vs 14.7%; P = .39) and non-White surgeons (22.6% vs 22.8%; P = .92) but underestimated trainees' representation for both female (15.9% vs 35.8%; P < .001) and non-White (22.6% vs 37.4%; P < .001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively; P < .001) and non-White (0.5% and 0.6%, respectively; P < .001) surgeons than DALL-E 2 or true demographic data. Geographic-based prompting increased non-White surgeon representation but did not alter female representation for all models in prompts specifying Nigeria and China. Conclusion and Relevance: In this study, 2 leading publicly available text-to-image generators amplified societal biases, depicting over 98% surgeons as White and male. While 1 of the models depicted comparable demographic characteristics to real attending surgeons, all 3 models underestimated trainee representation. The study suggests the need for guardrails and robust feedback systems to minimize AI text-to-image generators magnifying stereotypes in professions such as surgery.

Reliability of a Novel Classification System for Thoracic Disc Herniations.

STUDY DESIGN: This is a cross-sectional survey. OBJECTIVE: The aim was to assess the reliability of a proposed novel classification system for thoracic disc herniations (TDHs). SUMMARY OF BACKGROUND DATA: TDHs are complex entities varying substantially in many factors, including size, location, and calcification. To date, no comprehensive system exists to categorize these lesions. METHODS: Our proposed system classifies 5 types of TDHs using anatomic and clinical characteristics, with subtypes for calcification. Type 0 herniations are small (≤40% of spinal canal) TDHs without significant spinal cord or nerve root effacement; type 1 are small and paracentral; type 2 are small and central; type 3 are giant (>40% of spinal canal) and paracentral; and type 4 are giant and central. Patients with types 1 to 4 TDHs have correlative clinical and radiographic evidence of spinal cord compression. Twenty-one US spine surgeons with substantial TDH experience rated 10 illustrative cases to determine the system's reliability. Interobserver and intraobserver reliability were determined using the Fleiss kappa coefficient. Surgeons were also surveyed to obtain consensus on surgical approaches for the various TDH types. RESULTS: High agreement was found for the classification system, with 80% (range 62% to 95%) overall agreement and high interrater and intrarater reliability (kappa 0.604 [moderate to substantial agreement] and kappa 0.630 [substantial agreement], respectively). All surgeons reported nonoperative management of type 0 TDHs. For type 1 TDHs, most respondents (71%) preferred posterior approaches. For type 2 TDHs, responses were roughly equivalent for anterolateral and posterior options. For types 3 and 4 TDHs, most respondents (72% and 68%, respectively) preferred anterolateral approaches. CONCLUSIONS: This novel classification system can be used to reliably categorize TDHs, standardize description, and potentially guide the selection of surgical approach. Validation of this system with regard to treatment and clinical outcomes represents a line of future study.