Surgical classification using natural language processing of informed consent forms in spine surgery.

OBJECTIVE: In clinical spine surgery research, manually reviewing surgical forms to categorize patients by their surgical characteristics is a crucial yet time-consuming task. Natural language processing (NLP) is a machine learning tool used to adaptively parse and categorize important features from text. These systems function by training on a large, labeled data set in which feature importance is learned prior to encountering a previously unseen data set. The authors aimed to design an NLP classifier for surgical information that can review consent forms and automatically classify patients by the surgical procedure performed. METHODS: Thirteen thousand two hundred sixty-eight patients who underwent 15,227 surgeries from January 1, 2012, to December 31, 2022, at a single institution were initially considered for inclusion. From these surgeries, 12,239 consent forms were classified based on the Current Procedural Terminology (CPT) code, categorizing them into 7 of the most frequently performed spine surgeries at this institution. This labeled data set was split 80%/20% into train and test subsets, respectively. The NLP classifier was then trained and the results demonstrated its performance on the test data set using CPT codes to determine accuracy. RESULTS: This NLP surgical classifier had an overall weighted accuracy rate of 91% for sorting consents into correct surgical categories. Anterior cervical discectomy and fusion had the highest positive predictive value (PPV; 96.8%), whereas lumbar microdiscectomy had the lowest PPV in the testing data (85.0%). Sensitivity was highest for lumbar laminectomy and fusion (96.7%) and lowest for the least common operation, cervical posterior foraminotomy (58.3%). Negative predictive value and specificity were > 95% for all surgical categories. CONCLUSIONS: Utilizing NLP for text classification drastically improves the efficiency of classifying surgical procedures for research purposes. The ability to quickly classify surgical data can be significantly beneficial to institutions without a large database or substantial data review capabilities, as well as for trainees to track surgical experience, or practicing surgeons to evaluate and analyze their surgical volume. Additionally, the capability to quickly and accurately recognize the type of surgery will facilitate the extraction of new insights from the correlations between surgical interventions and patient outcomes. As the database of surgical information grows from this institution and others in spine surgery, the accuracy, usability, and applications of this model will continue to increase.

Descriptive epidemiology of chordomas in the United States.

PURPOSE: Chordomas account for 1% to 4% of all bone malignancies and 0.5% of all primary intracranial central nervous system tumors. Prior epidemiologic literature is based on limited population data. The purpose of this study is to provide the largest and most inclusive population based study of the descriptive epidemiology of chordomas. METHODS: The Centers for Disease Control and Prevention and National Program of Cancer Registries were queried for chordoma in all locations. Age-adjusted incidence per 100,000 persons was calculated by age, sex, race, and ethnicity. Annual percentage change was calculated using Joinpoint. RESULTS: From 2004 to 2014, a total of 3670 chordomas were diagnosed in the US. The most common location was cranial (38.7%), followed by sacral (34.3%) and spinal (27.0%). The average age-adjusted incidence rate was 0.088 per 100,000 persons per year (95% CI 0.086-0.091), with an annual percentage change of 1.29% (95% CI 0.31-2.28%). For all chordomas, the incidence peaks in the 75-84 year age group. The male-to-female incidence rate ratio is 1.54 (p < 0.001). American Indian/Alaskan Native and Black patients had a statistically lower incidence rate than White and Asian/Pacific Islander patients. CONCLUSION: Approximately 0.088 chordomas per 100,000 persons are newly diagnosed in the US each year, with cranial location being the most common, followed by sacral and spinal. Incidence increases with age, and men are at a significantly higher risk than women. This investigation represents the largest population-based epidemiologic study of chordomas in the US.

The epidemiology of central and extraventricular neurocytoma in the United States between 2006 and 2014.

INTRODUCTION: Central neurocytoma (CN) and extraventricular neurocytoma (EVN) are rare intracranial tumors. There is a paucity of studies reporting the population-based incidence of these tumors. We used the Central Brain Tumor Registry of the United States (CBTRUS), which contains the largest aggregation of population-based data on the incidence of primary central nervous system tumors in the United States to describe these tumors. METHODS: The CBTRUS database, provided by CDC representing approximately 100% of the US population, was queried using the following search criteria: diagnosis years 2006-2014, ICD-0-3 histology codes (9506/0: central neurocytoma, benign; 9506/1: central neurocytoma, uncertain). Annual age-adjusted incidence rates are presented per 100,000 population. Incidence was estimated by age, gender, race, and ethnicity. RESULTS: The combined overall annual incidence rate of CN and EVN was 0.032 [0.030-0.034]. The incidence rates were 0.022 [0.021-0.024] and 0.009 [0.008-0.010] for CN and EVN, respectively. The most frequently documented locations for EVN were frontal lobe and cerebellum, followed by temporal lobe. Peak incidence was found in the 20-34 years range for both CN and EVN. The incidence rate was slightly lower in males compared to females for CN and identical for EVN. The overall incidence rate of CN and EVN combined was lower in Blacks 0.026 [0.021-0.032] and Hispanic Whites 0.020 [0.016-0.025] compared to Non-Hispanic Whites 0.035 [0.033-0.038]. CONCLUSION: CN and EVN are rare tumors with a peak incidence in the 20-34 years age group. This study represents the largest population-based epidemiological study on CN and EVN in the US.

Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.

Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase ß. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.

Rapid and complete radiological resolution of an intradural cervical cord lung cancer metastasis treated with spinal stereotactic radiosurgery: case report.

Stereotactic radiosurgery (SRS) has emerged as a treatment option for patients with spinal metastatic disease. Although SRS has been shown to be successful in a multitude of extradural metastatic tumors causing cord compression, very few cases of intradural treatment have been reported. The authors present a rare case of an intradural extramedullary metastatic small cell lung cancer lesion to the cervical spine resulting in cord compression in an area that had also been extensively pretreated with conventional external-beam radiation therapy. The patient underwent successful SRS to this metastatic site, with rapid and complete resolution of his lesion.

Thermal injury to corticospinal tracts and postoperative motor deficits after laser interstitial thermal therapy.

OBJECTIVE Laser interstitial thermal therapy (LITT) has been increasingly used to treat deep-seated tumors. Despite its being minimally invasive, there is a risk of LITT damaging adjacent critical structures, including corticospinal tracts (CSTs). In this study, the authors investigated the predictive value of overlap between the hyperthermic field and CSTs in determining postoperative motor deficit (PMDs). METHODS More than 140 patients underwent an LITT procedure in our institution between April 2011 and June 2015. Because of the tumor's proximity to critical structures, 80 of them underwent preoperative diffusion tensor imaging and were included in this study. Extent of the hyperthermic field was delineated by the software as thermal-damage-threshold (TDT) lines (yellow [43°C for 2 minutes], blue [43°C for 10 minutes], and white [43°C for 60 minutes]). The maximum volume and the surface area of overlaps between motor fibers and the TDT lines were calculated and compared with the PMDs. RESULTS High-grade glioma (n = 46) was the most common indication for LITT. Postoperative motor deficits (partial or complete) were seen in 14 patients (11 with permanent and 3 with temporary PMDs). The median overlap volumes between CSTs with yellow, blue, and white TDT lines in patients with any PMD (temporary or permanent) were 1.15, 0.68, and 0.41 cm3, respectively. The overlap volumes and surface areas revealed significant differences in those with PMDs and those with no deficits (p = 0.0019 and 0.003, 0.012 and 0.0012, and 0.001 and 0.005 for the yellow, blue, and white TDT lines, respectively). The receiver operating characteristic was used to select the optimal cutoff point of the overlapped volumes and areas. Cutoff points for overlap volumes and areas based on optimal sensitivity (92%-100%) and specificity (80%-90%) were 0.103, 0.068, and 0.046 cm3 and 0.15, 0.07, and 0.11 mm2 for the yellow, blue, and white TDT lines, respectively. CONCLUSIONS Even a minimal overlap between the TDT lines and CSTs can cause a PMD after LITT. Precise planning and avoidance of critical structures and important white matter fibers should be considered when treating deep-seated tumors.

Evidence-based interventions to reduce shunt infections: a systematic review.

PURPOSE: Cerebrospinal fluid shunt infection is associated with patient morbidity and high cost. We conducted a systematic review of the current evidence of comprehensive surgical protocols or individual interventions designed to reduce shunt infection incidence. METHODS: A systematic review using PubMed and SCOPUS identified studies evaluating the effect of a particular intervention on shunt infection risk. Systemic prophylactic antibiotic or antibiotic-impregnated shunt efficacy studies were excluded. A total of 7429 articles were screened and 23 articles were included. RESULTS: Eight studies evaluated the effect of comprehensive surgical protocols. Shunt infection was reduced in all studies (absolute risk reduction 2.2-12.3 %). Level of evidence was low (level 4 in seven studies) due to the use of historical controls. Compliance ranged from 24.6 to 74.5 %. Surgical scrub with antiseptic foam and omission of a 5 % chlorhexidine gluconate preoperative hair wash were both associated with increased shunt infection. Twelve studies evaluated the effect of a single intervention. Only antibiotic-impregnated suture, a no-shave policy, and double gloving with glove change prior to shunt handling, were associated with a significant reduction in shunt infection. In a hospital with high methicillin-resistant staphylococcus aureus (MRSA) prevalence, a randomized controlled trial found that perioperative vancomycin rather than cefazolin significantly reduced shunt infection rates. CONCLUSION: Despite wide variation in compliance rates, the implementation of comprehensive surgical protocols reduced shunt infection in all published studies. Antibiotic-impregnated suture, a no-shave policy, double gloving with glove change prior to device manipulation, and 5 % chlorhexidine hair wash were associated with significant reductions in shunt infection.

Neutrophils express oncomodulin and promote optic nerve regeneration.

Although neurons are normally unable to regenerate their axons after injury to the CNS, this situation can be partially reversed by activating the innate immune system. In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve. However, the role of different molecules and cell populations in mediating this phenomenon remains unclear. We show here that neutrophils, the first responders of the innate immune system, play a central role in inflammation-induced regeneration. Numerous neutrophils enter the mouse eye within a few hours of inducing an inflammatory reaction and express high levels of the atypical growth factor oncomodulin (Ocm). Immunodepletion of neutrophils diminished Ocm levels in the eye without altering levels of CNTF, leukemia inhibitory factor, or IL-6, and suppressed the proregenerative effects of inflammation. A peptide antagonist of Ocm suppressed regeneration as effectively as neutrophil depletion. Macrophages enter the eye later in the inflammatory process but appear to be insufficient to stimulate extensive regeneration in the absence of neutrophils. These data provide the first evidence that neutrophils are a major source of Ocm and can promote axon regeneration in the CNS.

Review of mechanisms of expandable spine surgery devices.

INTRODUCTION: Expandable devices such as interbody cages, vertebral body reconstruction cages, and intravertebral body expansion devices are frequently utilized in spine surgery. Since the introduction of expandable implants in the early 2000s, the variety of mechanisms that drive expansion and implant materials have steadily increased. By examining expandable devices that have achieved commercial success and exploring emerging innovations, we aim to offer an in-depth evaluation of the different types of expandable cages used in spine surgery and the underlying mechanisms that drive their functionality. AREAS COVERED: We performed a review of expandable spinal implants and devices by querying the National Library of Medicine MEDLINE database and Google Patents database from 1933 to 2024. Five major types of mechanical jacks that drive expansion were identified: scissor, pneumatic, screw, ratchet, and insertion-expansion. EXPERT OPINION: We identified a trend of screw jack mechanism being the predominant machinery in vertebral body reconstruction cages and scissor jack mechanism predominating in interbody cages. Pneumatic jacks were most commonly found in kyphoplasty devices. Critically reviewing the mechanisms of expansion and identifying trends among effective and successful cages allows both surgeons and medical device companies to properly identify future areas of development.

The Use of Cranial Aneurysm Clips for Repair of Incidental Lumbar Durotomy: Operative Technique and Case Series.

BACKGROUND: Incidental durotomy is a common complication of posterior lumbar spine surgery; however, effective and durable methods for primary repair remain elusive. Multiple existing techniques have previously been reported and extensively described, including sutured repair and the use of nonpenetrating titanium clips. The use of cranial aneurysm clips for primary repair of lumbar durotomy serves as a safe and effective alternative to obtain watertight closure of a dural tear. METHODS: We performed a retrospective review of patients at a single institution who underwent primary repair of an incidental lumbar durotomy with the use of an aneurysm clip during open posterior lumbar surgery between 2012 and 2023. Patient demographics, operative details, and postoperative metrics were collected and examined to evaluate the safety and efficacy of the novel technique. RESULTS: A total of 51 patients were included for analysis. Four patients underwent durotomy repair with an aneurysm clip alone, 27 patients were repaired with an aneurysm clip and fibrin glue, and 20 patients underwent repair with an aneurysm clip, fibrin glue, and a collagen dural substitute. Three patients (5.9%) reported headaches: 2 (3.9%) with pseudomeningocele and 1 (2%) with wound leakage. Two patients (3.9%) had treatment failure with a return to the operating room for repair of a cerebrospinal fluid leak. CONCLUSIONS: To the best of our knowledge, we report the largest series of patients undergoing primary repair of incidental durotomy with the use of an aneurysm clip. Use of an aneurysm clip is noted to be a safe, quick, and effective method of primary repair compared with existing repair techniques such as sutured repair or nonpenetrating titanium clips.

Predicting hypertension control using machine learning.

Hypertension is a widely prevalent disease and uncontrolled hypertension predisposes affected individuals to severe adverse effects. Though the importance of controlling hypertension is clear, the multitude of therapeutic regimens and patient factors that affect the success of blood pressure control makes it difficult to predict the likelihood to predict whether a patient's blood pressure will be controlled. This project endeavors to investigate whether machine learning can accurately predict the control of a patient's hypertension within 12 months of a clinical encounter. To build the machine learning model, a retrospective review of the electronic medical records of 350,008 patients 18 years of age and older between January 1, 2015 and June 1, 2022 was performed to form model training and testing cohorts. The data included in the model included medication combinations, patient laboratory values, vital sign measurements, comorbidities, healthcare encounters, and demographic information. The mean age of the patient population was 65.6 years with 161,283 (46.1%) men and 275,001 (78.6%) white. A sliding time window of data was used to both prohibit data leakage from training sets to test sets and to maximize model performance. This sliding window resulted in using the study data to create 287 predictive models each using 2 years of training data and one week of testing data for a total study duration of five and a half years. Model performance was combined across all models. The primary outcome, prediction of blood pressure control within 12 months demonstrated an area under the curve of 0.76 (95% confidence interval; 0.75-0.76), sensitivity of 61.52% (61.0-62.03%), specificity of 75.69% (75.25-76.13%), positive predictive value of 67.75% (67.51-67.99%), and negative predictive value of 70.49% (70.32-70.66%). An AUC of 0.756 is considered to be moderately good for machine learning models. While the accuracy of this model is promising, it is impossible to state with certainty the clinical relevancy of any clinical support ML model without deploying it in a clinical setting and studying its impact on health outcomes. By also incorporating uncertainty analysis for every prediction, the authors believe that this approach offers the best-known solution to predicting hypertension control and that machine learning may be able to improve the accuracy of hypertension control predictions using patient information already available in the electronic health record. This method can serve as a foundation with further research to strengthen the model accuracy and to help determine clinical relevance.

Exploring tribology and material contact science in spine surgery: implications for implant design.

Tribology, an interdisciplinary field concerned with the science of interactions between surfaces in contact and their relative motion, plays a well-established role in the design of orthopedic implants, such as knee and hip replacements. However, its applications in spine surgery have received comparatively less attention in the literature. Understanding tribology is pivotal in elucidating the intricate interactions between metal, polymer, and ceramic components, as well as their interplay with the native human bone. Numerous studies have demonstrated that optimizing tribological factors is key to enhancing the longevity of joints and implants while simultaneously reducing complications and the need for revision surgeries in both arthroplasty and spinal fusion procedures. With an ever-growing and diverse array of spinal implant devices hitting the market for static and dynamic stabilization of the spine, it is important to consider how each of these devices optimizes these parameters and what factors may be inadequately addressed by currently available technology and methods. In this comprehensive review, the authors' objectives were twofold: 1) delineate the unique challenges encountered in spine surgery that could be addressed through optimization of tribological parameters; and 2) summarize current innovations and products within spine surgery that look to optimize tribological parameters and highlight new avenues for implant design and research.

Real-World Implementation of Artificial Intelligence/Machine Learning for Managing Surgical Spine Patients at 2 Academic Health Care Systems.

Decision-making in spine surgery is complex due to patients' heterogeneity and complexity of spinal pathologies and the various surgical options applied to a given pathology. Artificial intelligence/machine learning algorithms provide an opportunity to improve patient selection, surgical planning, and outcomes. The purpose of this article is to present the experience and applications of in spine surgery at 2 large academic health care systems.

Stratification of spine patients based on self-reported clinical symptom classes: Evaluation of long-term outcomes and subsequent interventions.

Background: Prior work by our group developed a stratification tool based on four PROMIS domains for patients with low back pain (LBP). Our study aimed to evaluate the ability of our previously developed symptom classes to predict long-term outcomes, and determine whether there were differential treatment effects by intervention. Methods: This was a retrospective cohort study of adult patients with LBP seen in spine clinics in a large health system between November 14, 2018 and May 14, 2019 who completed patient-reported outcomes as part of routine care at baseline and again at 12-months follow-up. Latent class analysis identified symptom classes based on PROMIS domain scores (physical function, pain interference, social role satisfaction, and fatigue) that were ≥1 standard deviation worse (meaningfully worse) than the general population. The ability of the profiles to predict long-term outcomes at 12-months was evaluated through multivariable models. Differences in outcomes by subsequent treatments (physical therapy, specialist visits, injections, and surgery) were investigated. Results: There were 3,236 adult patients (average age 61.1 ± 14.2, 55.4% female) included in the study with three distinct classes identified: mild symptoms (n = 986, 30.5%), mixed (n = 798, 24.7%) with poor scores on physical function and pain interference but better scores on other domains, and significant symptoms (n = 1,452, 44.9%). The classes were significantly associated with long-term outcomes, with patients with significant symptoms improving the most across all domains. Utilization differed across classes, with the mixed symptom class receiving more PT and injections and significant symptom class receiving more surgeries and specialist visits. Conclusions: Patients with LBP have distinct clinical symptom classes which could be utilized to stratify patients into groups based on risk of future disability. These symptom classes can also be used to provide estimates of the effectiveness of different interventions, further increasing the clinical utility of these classes in standard care.

Characterizing the Next Generation of Neurosurgeons: A Descriptive Analysis and Publicly Available Web Application of Neurosurgery Residency Programs' Website Data.

OBJECTIVE: Neurosurgery program websites serve as a valuable resource for applicants. However, each website exists in isolation, and it can be difficult to understand the general trends in U.S. neurosurgery resident demographics. In the present study, we collected data from program websites and analyzed the trends in the demographics of the current U.S. neurosurgery residents. METHODS: We used a program list obtained from the American Association of Medical Colleges Electronic Residency Application System to extract data from the current resident complement listed in each program's website, including program, year in program, medical school, sex (male vs. female), graduate and/or PhD degrees, and assessed the trends during 7 years of resident data using linear regression. RESULTS: We identified 116 neurosurgery residency programs in the United States, with 111 providing information on their current resident complement, yielding a dataset of 1599 residents. Of these 1599 residents, 348 (22%) were female, 301 (19%) had a graduate degree in addition to an MD or DO degree, 151 (9.4%) had a PhD degree, 300 (19%) had matched at the program affiliated with their medical school, and 121 (7.6%) had graduated from a foreign medical school. The proportion of matriculating female residents had increased an average of 2.1% annually (95% confidence interval, 0.6%-3.7%) from 2015 to 2021. The other demographic data had not changed significantly during the same period. CONCLUSIONS: In addition to summarizing the current resident demographics, our analysis identified a significant increase in the proportion of female residents between 2015 (15.1%) and 2021 (25.6%). This publicly available dataset should enable additional analyses of the evolution of neurosurgery resident demographics.

A Pilot Remote Curriculum to Enhance Resident and Medical Student Understanding of Machine Learning in Healthcare.

BACKGROUND: Despite the expanding role of machine learning (ML) in health care and patient expectations for clinicians to understand ML-based tools, few for-credit curricula exist specifically for neurosurgical trainees to learn basic principles and implications of ML for medical research and clinical practice. We implemented a novel, remotely delivered curriculum designed to develop literacy in ML for neurosurgical trainees. METHODS: A 4-week pilot medical elective was designed specifically for trainees to build literacy in basic ML concepts. Qualitative feedback from interested and enrolled students was collected to assess students' and trainees' reactions, learning, and future application of course content. RESULTS: Despite 15 interested learners, only 3 medical students and 1 neurosurgical resident completed the course. Enrollment included students and trainees from 3 different institutions. All learners who completed the course found the lectures relevant to their future practice as clinicians and researchers and reported improved confidence in applying and understanding published literature applying ML techniques in health care. Barriers to ample enrollment and retention (e.g., balancing clinical responsibilities) were identified. CONCLUSIONS: This pilot elective demonstrated the interest, value, and feasibility of a remote elective to establish ML literacy; however, feedback to increase accessibility and flexibility of the course encouraged our team to implement changes. Future elective iterations will have a semiannual, 2-week format, splitting lectures more clearly between theory (the method and its value) and application (coding instructions) and will make lectures open-source prerequisites to allow tailoring of student learning to their planned application of these methods in their practice and research.

Comparison of stratification techniques for optimal management of patients with chronic low back pain in spine clinics.

BACKGROUND CONTEXT: Identifying optimal stratification techniques for subgrouping patients with low back pain (LBP) into treatment groups for the purpose of identifying optimal management and improving clinical outcomes is an important area for further research. PURPOSE: Our study aimed to compare performance of the STarT Back Tool (SBT) and 3 stratification techniques involving PROMIS domain scores for use in patients presenting to a spine clinic for chronic LBP. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients with chronic LBP seen in a spine center between November 14, 2018 and May 14, 2019 who completed patient-reported outcomes (PROs) as part of routine care, and were followed up with completed PROs 1 year later. OUTCOME MEASURES: Four stratification techniques, including SBT, and 3 PROMIS-based techniques: the NIH Task Force recommended Impact Stratification Score (ISS), symptom clusters based on latent class analysis (LCA), and SPADE symptom clusters. METHODS: The 4 stratification techniques were compared according to criterion validity, construct validity, and prognostic utility. For criterion validity, overlap in characterization of mild, moderate, and severe subgroups were compared to SBT, which was considered the gold standard, using quadratic weighted kappa statistic. Construct validity compared techniques' ability to differentiate across disability groups defined by modified Oswestry LBP Disability Questionnaire (MDQ), median days in the past month unable to complete activities of daily living (ADLs), and worker's compensation using standardized mean differences (SMD). Prognostic utility was compared based on the techniques' ability to predict long-term improvement in outcomes, defined as improvement in global health and MDQ at 1-year. RESULTS: There were 2,246 adult patients with chronic LBP included in our study (mean age 61.0 [SD 14.0], 55.0% female, 83.4% white). All stratification techniques resulted in roughly a third of patients grouped into mild, moderate, and severe categories, with ISS and LCA demonstrating substantial agreement with SBT, while SPADE had moderate agreement. Construct validity was met for all techniques, with large effects demonstrated between mild and severe categories for differentiating MDQ, ADLs, and worker's compensation disability groups (SMD range 0.57-2.48). All stratification techniques demonstrated ability to detect improvement by 1-year, with severe groups experiencing the greatest improvement in multivariable logistic regression models. CONCLUSIONS: All 4 stratification techniques demonstrated validity and prognostic utility for subgrouping patients with chronic LBP based on risk of long-term disability. ISS and LCA symptom clusters may be the optimal methods given the improved feasibility of including only a few relevant PROMIS domains. Future research should investigate multidisciplinary treatment approaches to target mild, moderate, and severe patients based on these techniques.

Leveraging published randomized controlled trials to inform clinical trial design: a simulation-based study of laminectomy versus laminectomy and fusion.

OBJECTIVE: The US-based Spinal Laminectomy versus Instrumented Pedicle Screw (SLIP) trial reported improvement in disability following laminectomy with fusion versus laminectomy alone for patients with lumbar spondylolisthesis. Despite using similar methods, a concurrent Swedish trial investigating the same question did not reach the same conclusion. The authors performed a simulation-based analysis to elucidate potential causes of these divergent results. METHODS: The mean and standard deviation of the preoperative and 2-year postoperative Oswestry Disability Index (ODI) scores for each study group (laminectomy with fusion and laminectomy alone) were collected from the spondylolisthesis stratum of the Swedish trial and used to create a MATLAB simulator using linear transformations to predict postoperative ODI distributions. Applying this simulator to both varied and published preoperative ODI distributions from the SLIP trial, the authors simulated the results of the US-based trial using treatment effects from the Swedish study and compared simulated US results to those published in the SLIP trial. RESULTS: Simulated US results showed that as preoperative disability increased, the difference in postoperative ODI scores grew between treatment groups and increasingly favored laminectomy alone (p < 0.0001). In 100 simulations of a similarly sized US trial, the average mean change in ODI scores postoperatively was significantly higher than was published for laminectomy alone in the SLIP trial (-21.3 vs -17.9), whereas it was significantly lower than published for fusion (-16.9 vs -26.3). CONCLUSIONS: The expected benefit of surgical treatments for spondylolisthesis varied according to preoperative disability. Adapting Swedish-estimated treatment effects to the US context mildly overapproximated the improvement in postoperative disability scores for laminectomy, but more severely underapproximated the improvement reported for laminectomy and fusion in the SLIP trial. The observed heterogeneity between these studies is influenced more by patient response to fusion than response to laminectomy. This analysis paves the way for future studies on the impact of preoperative treatment group heterogeneity, differences in surgical methods, and empirical design on reported clinical benefits. Although bayesian reanalysis of published randomized controlled trial data is susceptible to biases that typically limit post hoc analyses, the authors' method offers a simple and cost-effective approach to improve the understanding of published clinical trial results and their implications for future studies.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.