Engineered T cell therapy for central nervous system injury.

Traumatic injuries to the central nervous system (CNS) afflict millions of individuals worldwide1, yet an effective treatment remains elusive. Following such injuries, the site is populated by a multitude of peripheral immune cells, including T cells, but a comprehensive understanding of the roles and antigen specificity of these endogenous T cells at the injury site has been lacking. This gap has impeded the development of immune-mediated cellular therapies for CNS injuries. Here, using single-cell RNA sequencing, we demonstrated the clonal expansion of mouse and human spinal cord injury-associated T cells and identified that CD4+ T cell clones in mice exhibit antigen specificity towards self-peptides of myelin and neuronal proteins. Leveraging mRNA-based T cell receptor (TCR) reconstitution, a strategy aimed to minimize potential adverse effects from prolonged activation of self-reactive T cells, we generated engineered transiently autoimmune T cells. These cells demonstrated notable neuroprotective efficacy in CNS injury models, in part by modulating myeloid cells via IFNγ. Our findings elucidate mechanistic insight underlying the neuroprotective function of injury-responsive T cells and pave the way for the future development of T cell therapies for CNS injuries.

Invasive devices to monitor the intraspinal perfusion pressure in the hemodynamic management of acute spinal cord injury: A systematic scoping review.

BACKGROUND: Various methods for measuring intrathecal pressure (ITP) after spinal cord injury (SCI) to guide hemodynamic management have been investigated. To synthesize the current literature, this current study conducted a scoping review of the use of intrathecal devices to monitor ITP during acute management of SCI with the aim of understanding the association between ITP monitoring with physiological and clinical outcomes. METHODS: A systematic review of literature following the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. All eligible studies were screened for inclusion and exclusion criteria. Data extracted included number of patients included, severity of injury, characteristics of the intervention-intrathecal device used to record the ITP, outcomes -hemodynamic parameters observed, changes in the American Spinal Injury Association (ASIA) Impairment Scale (AIS), total motor scores, association of ITP with other physiological variables. RESULTS: The search yielded a total of 1,698 articles, of which 30 observational studies and 2 randomized clinical trials were deemed eligible based on their use of an intrathecal invasive device to monitor spinal cord perfusion pressure (SCPP) in patients with SCI. Of these, 9 studies used a lumbar drain, 23 a Codman pressure probe and 1 study that used both. These studies underscore the crucial interplay between ITP, the SCPP and physiological variables, with neurological outcome. It is still unclear whether monitoring from a lumbar drain is accurate enough to highlight what is occurring at the site of SCI, which is the main advantage of Codman Probe, however, the latter requires specialized personnel that may not be available in most settings. Minor adverse effects were associated with lumbar drain catheters, while cerebrospinal fluid leak requiring repair (~ 7%) is the main concern with Codman Probes. CONCLUSION: Future investigation of SCPP protocols via lumbar drains and Codman probes ought to involve multi-centered randomized controlled trials and continued translational investigation with animal models.

Virtual, Augmented, and Mixed Reality Applications for Surgical Rehearsal, Operative Execution, and Patient Education in Spine Surgery: A Scoping Review.

Background and Objectives: Advances in virtual reality (VR), augmented reality (AR), and mixed reality (MR) technologies have resulted in their increased application across many medical specialties. VR's main application has been for teaching and preparatory roles, while AR has been mostly used as a surgical adjunct. The objective of this study is to discuss the various applications and prospects for VR, AR, and MR specifically as they relate to spine surgery. Materials and Methods: A systematic review was conducted to examine the current applications of VR, AR, and MR with a focus on spine surgery. A literature search of two electronic databases (PubMed and Scopus) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The study quality was assessed using the MERSQI score for educational research studies, QUACS for cadaveric studies, and the JBI critical appraisal tools for clinical studies. Results: A total of 228 articles were identified in the primary literature review. Following title/abstract screening and full-text review, 46 articles were included in the review. These articles comprised nine studies performed in artificial models, nine cadaveric studies, four clinical case studies, nineteen clinical case series, one clinical case-control study, and four clinical parallel control studies. Teaching applications utilizing holographic overlays are the most intensively studied aspect of AR/VR; the most simulated surgical procedure is pedicle screw placement. Conclusions: VR provides a reproducible and robust medium for surgical training through surgical simulations and for patient education through various platforms. Existing AR/MR platforms enhance the accuracy and precision of spine surgeries and show promise as a surgical adjunct.

Utilization of Augmented Reality Head-Mounted Display for the Surgical Management of Thoracolumbar Spinal Trauma.

Background and Objectives: Augmented reality head-mounted display (AR-HMD) is a novel technology that provides surgeons with a real-time CT-guided 3-dimensional recapitulation of a patient's spinal anatomy. In this case series, we explore the use of AR-HMD alongside more traditional robotic assistance in surgical spine trauma cases to determine their effect on operative costs and perioperative outcomes. Materials and Methods: We retrospectively reviewed trauma patients who underwent pedicle screw placement surgery guided by AR-HMD or robotic-assisted platforms at an academic tertiary care center between 1 January 2021 and 31 December 2022. Outcome distributions were compared using the Mann-Whitney U test. Results: The AR cohort (n = 9) had a mean age of 66 years, BMI of 29.4 kg/m2, Charlson Comorbidity Index (CCI) of 4.1, and Surgical Invasiveness Index (SII) of 8.8. In total, 77 pedicle screws were placed in this cohort. Intra-operatively, there was a mean blood loss of 378 mL, 0.78 units transfused, 398 min spent in the operating room, and a 20-day LOS. The robotic cohort (n = 13) had a mean age of 56 years, BMI of 27.1 kg/m2, CCI of 3.8, and SII of 14.2. In total, 128 pedicle screws were placed in this cohort. Intra-operatively, there was a mean blood loss of 432 mL, 0.46 units transfused units used, 331 min spent in the operating room, and a 10.4-day LOS. No significant difference was found between the two cohorts in any outcome metrics. Conclusions: Although the need to address urgent spinal conditions poses a significant challenge to the implementation of innovative technologies in spine surgery, this study represents an initial effort to show that AR-HMD can yield comparable outcomes to traditional robotic surgical techniques. Moreover, it highlights the potential for AR-HMD to be readily integrated into Level 1 trauma centers without requiring extensive modifications or adjustments.

Buried filet of limb flaps for the reconstruction of forequarter and hindquarter amputations.

BACKGROUND AND OBJECTIVES: Forequarter and hindquarter amputations have traditionally been closed with local tissues, but the technique is plagued by a high rate of complication such as marginal necrosis, seroma, infection, and dehiscence. Filet of limb flaps have been used when local tissues are insufficient for closure, and despite their use in more extensive and complex wounds, outcomes seem to be better in these cases. Recognizing that filet of limb flaps not only serve to cover the wound, but also eliminate dead space, supplement at-risk and/or radiated tissue, pad underlying hard structures, and facilitate neuroma prevention with target muscle reinnervation, we have change our practice to utilize buried filet of limb flaps even when local tissues are technically "sufficient" to close the wound. The purpose of this article to organize and describe the ways in which buried filet-of-limb flaps can be used to achieve important and discrete surgical objectives in forequarter and hindquarter amputation, and to facilitate increased recognition of collaborative interdisciplinary opportunities for spare-part reconstruction. METHODS: Retrospective data from the medical records of seven patients, collected between 2010 to 2023 at our single tertiary referral center, were reviewed. This included all patients for whom a buried (or partially buried) filet of limb flap was attempted for forequarter or hindquarter amputation reconstruction. RESULTS: Five males and two females ranging 55 to 75 years of age, met the inclusion criteria. Three cases of forequarter amputation and four cases of hindquarter amputation were included. Six flaps were successfully transferred without major flap-related complications. The mean follow-up period was eight and a half months. CONCLUSION: Even when local tissues are technically "sufficient" to close forequarter and hindquarter amputation wounds, we have found buried filet of limb flaps to be useful in several ways. These include occupying dead space, providing double-layer coverage, padding hard structures, preventing neuromas, and reconstructing sacro- and spino-pelvic continuity. Our approach emphasizes interdisciplinary collaboration and highlights the potential advantages of buried filet of limb flaps in optimizing patient outcomes for complex limb amputations.

Resveratrol glucosylation by GTF-SI from Streptococcus mutans: computational insights into a GH70 family enzyme.

Resveratrol, a polyphenolic compound known for its health benefits but limited by poor water solubility and low bioavailability, represents a valuable substrate for glucosylation by carbohydrate-active enzymes such as glucosyltransferase-SI (GTF-SI). Using quantum mechanics/molecular mechanics (QM/MM) calculations and molecular dynamics simulations, this study reveals the atomic scale dynamics of resveratrol glucosylation by wild-type GTF-SI. This enzyme exhibited an energy barrier of 8.8 kcal mol-1 and an exothermic process, both consistent with experimental data of similar enzymes. We report a concerted and synchronous reaction mechanism for the catalytic step, characterized by an oxocarbenium ion-like transition state, and elucidate a conformational itinerary of the glucosyl moiety (4H3/E3) → [E3]‡ → 4C1, which aligns with the consistent patterns observed across enzymes of the GH13 and GH70 families. A key interaction was observed between Asp477 and the OH group on carbon 6 of the glucosyl moiety, together with a 2.0 kcal mol-1 transition state stabilization by three water molecules within the active site. Comparative insights with the previously studied Q345F SP enzyme system shed light on the unique and common features that govern transglucosylation reactions. Importantly, the calculated activation barriers strongly support the capability of GTF-SI to facilitate resveratrol glucosylation. This study advances our understanding of the transglucosylation reaction and opens up new ways for the glycodiversification of organic compounds such as polyphenols, thus expanding their potential applications in the food, cosmetic, and pharmaceutical industries.

Elucidation of the Reaction Mechanism of Cavia porcellus l-Asparaginase: A QM/MM Study.

The l-asparaginase (l-ASNase) enzyme catalyzes the conversion of the non-essential amino acid l-asparagine into l-aspartic acid and ammonia. Importantly, the l-ASNases are used as a key part of the treatment of acute lymphoblastic leukemia (ALL); however, despite their benefits, they trigger severe side effects because they have their origin in bacterial species (Escherichia coli and Erwinia chrysanthemi). Therefore, one way to solve these side effects is the use of l-ASNases with characteristics similar to those of bacterial types, but from different sources. In this sense, Cavia porcellus l-ASNase (CpA) of mammalian origin is a promising enzyme because it possesses similarities with bacterial species. In this work, the hydrolysis reaction for C. porcellus l-asparaginase was studied from an atomistic point of view. The QM/MM methodology was employed to describe the reaction, from which it was found that the conversion mechanism of l-asparagine into l-aspartic acid occurs in four steps. It was identified that the nucleophilic attack and release of the ammonia group is the rate-limiting step of the reaction. In this step, the nucleophile (Thr19) attacks the substrate (ASN) leading to the formation of a covalent intermediate and release of the leaving group (ammonia). The calculated energy barrier is 18.9 kcal mol-1, at the M06-2X+D3(0)/6-311+G(2d,2p)//CHARMM36 level of theory, which is in agreement with the kinetic data available in the literature, 15.9 kcal mol-1 (derived from the kcat value of 38.6 s-1). These catalytic aspects will hopefully pave the way toward enhanced forms of CpA. Finally, our work emphasizes that computational calculations may enhance the rational design of mutations to improve the catalytic properties of the CpA enzyme.

Insight into the Role of Active Site Protonation States and Water Molecules in the Catalytic Inhibition of DPP4 by Vildagliptin.

Vildagliptin (VIL) is an antidiabetic drug that inhibits dipeptidyl peptidase-4 (DPP4) through a covalent mechanism. The molecular bases for this inhibitory process have been addressed experimentally and computationally. Nevertheless, relevant issues remain unknown such as the roles of active site protonation states and conserved water molecules nearby the catalytic center. In this work, molecular dynamics simulations were applied to examine the structures of 12 noncovalent VIL-DPP4 complexes encompassing all possible protonation states of three noncatalytic residues (His126, Asp663, Asp709) that were inconclusively predicted by different computational tools. A catalytically competent complex structure was only achieved in the system with His126 in its ε-form and nonconventional neutral states for Asp663/Asp709. This complex suggested the involvement of one water molecule in the catalytic process of His740/Ser630 activation, which was confirmed by QM/MM simulations. Our findings support the suitability of a novel water-mediated mechanism in which His740/Ser630 activation occurs concertedly with the nucleophilic attack on VIL and the imidate protonation by Tyr547. Then, the restoration of His740/ Tyr547 protonation states occurs via a two-water hydrogen bonding network in a low-barrier process, thus describing the final step of the catalytic cycle for the first time. Additionally, two hydrolytic mechanisms were proposed based on the hydrogen bonding networks formed by water molecules and the catalytic residues along the inhibitory mechanism. These findings are valuable to unveil the molecular features of the covalent inhibition of DPP4 by VIL and support the future development of novel derivatives with improved structural or mechanistic profiles.

Glucosylation mechanism of resveratrol through the mutant Q345F sucrose phosphorylase from the organism Bifidobacterium adolescentis: a computational study.

Mainly due to their great antioxidant, anti-inflammatory and anticancer capacities, natural polyphenolic compounds have many properties with important applications in the food, cosmetic and pharmaceutical industries. Unfortunately, these molecules have very low water solubility and bioavailability. Glucosylation of polyphenols is an excellent alternative to overcome these drawbacks. Specifically, for the natural polyphenol resveratrol this process is very inefficiently performed by the native enzyme sucrose phosphorylase (BaSP) from the organism Bifidobacterium adolescentis (4%). However, the Q345F point mutation of the sucrose phosphorylase (BaSP Q345F) has been shown to achieve 97% monoglucosylation for the same substrate and the mechanism is still unknown. This report presents an analysis of MD simulations performed with the BaSP Q345F and BaSP systems in complex with resveratrol monoglucoside, followed by a study of the transglucosylation reaction of the mutant enzyme BaSP Q345F with resveratrol through the QM/MM hybrid method. With respect to the MD simulations, both protein structures showed greater similarity to the phosphate-binding conformation, and a larger active site and conformational changes in certain structures were found for the mutant system compared with the native enzyme; all this is in agreement with experimental data. With regard to the QM/MM calculations, the structure of an oxocarbenium ion-like transition state and the minimum energy adiabatic path (MEP) that connects the reactants with the products were obtained with a 20.3 kcal mol-1 energy barrier, which fits within the known experimental range for this type of enzyme. Finally, the analyses performed along the MEP suggest a concerted but asynchronous mechanism. In particular, they show that the interactions involving the residues of the catalytic triad (Asp192, Glu232, and Asp290) together with two water molecules at the active site strongly contribute to the stabilization of the transition state. The understanding of this glucosylation mechanism of the polyphenol resveratrol carried out by the mutant sucrose phosphorylase enzyme presented in this work could serve as the basis for subsequent studies on related carbohydrate-active enzymes.

First in-human report of the clinical accuracy of thoracolumbar percutaneous pedicle screw placement using augmented reality guidance.

OBJECTIVE: Augmented reality (AR) is an emerging technology that has great potential for guiding the safe and accurate placement of spinal hardware, including percutaneous pedicle screws. The goal of this study was to assess the accuracy of 63 percutaneous pedicle screws placed at a single institution using an AR head-mounted display (ARHMD) system. METHODS: Retrospective analyses were performed for 9 patients who underwent thoracic and/or lumbar percutaneous pedicle screw placement guided by ARHMD technology. Clinical accuracy was assessed via the Gertzbein-Robbins scale by the authors and by an independent musculoskeletal radiologist. Thoracic pedicle subanalysis was also performed to assess screw accuracy based on pedicle morphology. RESULTS: Nine patients received thoracic or lumbar AR-guided percutaneous pedicle screws. The mean age at the time of surgery was 71.9 ± 11.5 years and the mean number of screws per patient was 7. Indications for surgery were spinal tumors (n = 4, 44.4%), degenerative disease (n = 3, 33.3%), spinal deformity (n = 1, 11.1%), and a combination of deformity and infection (n = 1, 11.1%). Presenting symptoms were most commonly low-back pain (n = 7, 77.8%) and lower-extremity weakness (n = 5, 55.6%), followed by radicular lower-extremity pain, loss of lower-extremity sensation, or incontinence/urinary retention (n = 3 each, 33.3%). In all, 63 screws were placed (32 thoracic, 31 lumbar). The accuracy for these screws was 100% overall; all screws were Gertzbein-Robbins grade A or B (96.8% grade A, 3.2% grade B). This accuracy was achieved in the thoracic spine regardless of pedicle cancellous bone morphology. CONCLUSIONS: AR-guided surgery demonstrated a 100% accuracy rate for the insertion of 63 percutaneous pedicle screws in 9 patients (100% rate of Gertzbein-Robbins grade A or B screw placement). Using an ARHMS system for the placement of percutaneous pedicle screws showed promise, but further validation using a larger cohort of patients across multiple surgeons and institutions will help to determine the true accuracy enabled by this technology.

Posterior approaches for symptomatic metastatic spinal cord compression.

Surgical interventions for spinal metastasis are commonly performed for mechanical stabilization, pain relief, preservation of neurological function, and local tumor reduction. Although multiple surgical approaches can be used for the treatment of metastatic spinal lesions, posterior approaches are commonly performed. In this study, the role of posterior surgical procedures in the treatment of spinal metastases was reviewed, including posterior laminectomy with and without instrumentation for stabilization, transpedicular corpectomy, and costotransversectomy. A review of the literature from 1980 to 2015 was performed using Medline, as was a review of the bibliographies of articles meeting preset inclusion criteria, to identify studies on the role of these posterior approaches among adults with spinal metastasis. Thirty-four articles were ultimately analyzed, including 1 randomized controlled trial, 6 prospective cohort studies, and 27 retrospective case reports and/or series. Some of the reviewed articles had Level II evidence indicating that laminectomy with stabilization can be recommended for improvement in neurological outcome and reduction of pain in selected patients. However, the use of laminectomy alone should be carefully considered. Additionally, transpedicular corpectomy and costotransversectomy can be recommended with the expectation of improving neurological outcomes and reducing pain in properly selected patients with spinal metastases. With improvements in the treatment paradigms for patients with spinal metastasis, as well as survival, surgical therapy will continue to play an important role in the management of spinal metastasis. While this review presents a window into determining the utility of posterior approaches, future prospective studies will provide essential data to better define the roles of the various options now available to surgeons in treating spinal metastases.

Alveolar soft-part sarcoma in the sacrum: a case report and review of the literature.

Alveolar soft part sarcoma (ASPS) is a rare disease of the soft tissue. Although the disease is rare, it is refractory to chemotherapy and radiation. En bloc surgical resection offers the best chance of cure. In this article we report the case of a 28-year-old woman who presented with buttock and leg pain, bowel, bladder and gait impairment and a large mass in the sacrum. Following surgical excision, the lesion was proven to be ASPS. On pathology, the mass was TFE3 (transcription factor E3) positive, indicating the presence of the ASPL-TFE3 (novel gene-transcription factor) translocation. Following surgery, the patient had improvement in her pain and ambulation; however, she refused adjuvant therapy to pursue hospice care and succumbed to her disease 2 years after surgery. On a review of the literature, it was found that ASPS of the bone constitutes a rare and formidable subset of this disease. Further, metastases related to ASPS are common in the lungs, liver, brain, and lymph nodes. The degree of dissemination is a predictor of outcome, with 5-year survival of 81-88% in patients with local disease and only 20-46% in patients with metastatic disease at the time of presentation. Brain metastases at the time of presentation portend the worst prognosis.

Comparative in vitro biomechanical analysis of a novel posterior cervical fixation technique versus conventional posterior-based constructs.

STUDY DESIGN: Comparative in vitro, cadaveric biomechanical study. OBJECTIVE: To compare the kinematic response of a new posterior cervical midline surgical technique versus that of conventional fixation techniques. SUMMARY OF BACKGROUND DATA: A new method was designed using alternating bilateral intralaminar screws connected with a single midline rod. This technique provides the theoretical benefits of less operative dissection and reduced implant cost, but the acute flexibility properties remain unknown. Using an in vitro cadaveric model, the study objective was to define the operative level(s) changes in multidirectional flexibility after posterior destabilization/reconstruction from C3 to C6. METHODS: A 6 degree of freedom spine stimulator was used to test flexibility in 7 human cadaveric specimens. Flexion-extension, lateral bending, and axial rotation were tested in the intact condition, followed by destabilization by a simulated posterior column injury from C3 to C6. Specimens were then reconstructed from C3 to C6 and tested in the following sequence: sublaminar hook rod (SH), lateral mass screw rod (LMR), midline laminectomy from C3 to C6 with LMR (MLR), and midline posterior fixation from C3 to C6 (SMF). Range of motion (ROM) and neutral zone were quantified and analyzed. RESULTS: Significant increases in ROM and neutral zone at C3 to C6 were found under all loading conditions for the destabilized condition and intact spine versus all other treatments (P<0.05). The conventional treatments: SH, LMR, and MLR resulted in significantly less ROM than the proposed SMF in flexion-extension and lateral bending (P<0.05). Axial rotation provided similar results; however, no differences were observed between the SH and SMF (P>0.05). Notably, LMR and MLR provided significantly more stability than SH in axial rotation (P<0.05). CONCLUSIONS: Data produced suggest that the new, midline rod fixation approach provides less biomechanical stability than conventional posterior cervical reconstruction techniques. In addition, the high incidence of laminar fracture during screw placement and close proximity of the screw trajectory and polyaxial heads to the dura suggest a practical limitation as well.

Transdural Ventral Sling Technique for Calcified Thoracic Disk Herniations.

BACKGROUND: Surgery for thoracic disc herniations remains an ongoing challenge, with numerous surgical approaches, all with their own inherent risks. Discectomy via a posterior laminectomy was historically the treatment of choice; however, it was deemed very high risk with elevated rates of neurologic injury. The posterior transdural approach is an alternative surgical option for soft and calcified thoracic disc herniations. METHODS: A 56-year-old female with many years of numbness/tingling in her hands and difficulty with fine motor tasks presented with progressive weakness and loss of balance in her legs. Imaging revealed a prominent focal central calcified disc herniation at the T5-T6 level causing severe effacement and distortion of the spinal cord. A posterior transdural approach for direct visualization of a large calcified disc herniation was performed, removing the calcified disc without the need for extensive exposure or entry into the thoracic cavity. A ventral sling of the dura was created to allow rotation of the spinal cord while removing the disc. RESULTS: Intraoperative ultrasound confirmed complete disc resection, restoring cerebral spinal fluid flow circumferentially without residual impingement or cerebrospinal fluid leaks. At six months postsurgery, the patient's gait imbalance had resolved, and she had full lower extremity strength (5/5). Radiographic evaluation indicated stable implants without subsidence, pullout, fracture, or alignment loss. CONCLUSIONS: The transdural approach is less invasive in nature, minimizes surgical exposure, patient morbidity, and provides better intraoperative control of the spinal cord. This constitutes an effective alternative surgical approach to both soft and calcified central thoracic disc herniations.

Minimally Invasive Approaches for Lumbosacral Plexus Schwannomas.

BACKGROUND AND OBJECTIVES: Lumbosacral plexus schwannomas (LSPSs) are benign, slow-growing tumors that arise from the myelin sheath of the lumbar or sacral plexus nerves. Surgery is the treatment of choice for symptomatic LSPSs. Conventional retroperitoneal or transabdominal approaches provide wide exposure of the lesion but are often associated with complications in the abdominal wall, lumbar or sacral plexus, ureter, and intraperitoneal organs. Advances in technology and minimally invasive (MIS) techniques have provided alternative approaches with reliable efficacy compared with traditional open surgery. We describe 3 MIS approaches using tubular retractor systems according to the lesion level. METHODS: This was a multicenter, retrospective observational cohort study to evaluate the use of MIS tubular approaches for surgical resection of LSPSs. We included 23 lumbar and upper sacral plexus schwannomas. Clinical presentation, spinal level, surgical duration, degree of resection, days of hospitalization, pathological anatomy of the tumor, approach-related surgical difficulties, and outcomes were collected. RESULTS: The posterior oblique approach was used in 43.5% of the cases, the transpsoas approach in 39.1%, and the transiliac in 17.4%. The mean operative time was 3.3 hours, and the mean hospitalization was 2.5 days. All tumors were WHO grade 1 schwannoma. Postoperative MRI confirms gross total resection in 91.3% of the patients. No patient requires instrumentation. The pros and cons of each approach were summarized. CONCLUSION: The MIS approaches adapted to the lumbar level may improve surgeons' comfort allowing a safe resection of retroperitoneal LSPS.

Current Applications and Future Implications of Artificial Intelligence in Spine Surgery and Research: A Narrative Review and Commentary.

STUDY DESIGN: Narrative review. OBJECTIVES: Artificial intelligence (AI) is being increasingly applied to the domain of spine surgery. We present a review of AI in spine surgery, including its use across all stages of the perioperative process and applications for research. We also provide commentary regarding future ethical considerations of AI use and how it may affect surgeon-industry relations. METHODS: We conducted a comprehensive literature review of peer-reviewed articles that examined applications of AI during the pre-, intra-, or postoperative spine surgery process. We also discussed the relationship among AI, spine industry partners, and surgeons. RESULTS: Preoperatively, AI has been mainly applied to image analysis, patient diagnosis and stratification, decision-making. Intraoperatively, AI has been used to aid image guidance and navigation. Postoperatively, AI has been used for outcomes prediction and analysis. AI can enable curation and analysis of huge datasets that can enhance research efforts. Large amounts of data are being accrued by industry sources for use by their AI platforms, though the inner workings of these datasets or algorithms are not well known. CONCLUSIONS: AI has found numerous uses in the pre-, intra-, or postoperative spine surgery process, and the applications of AI continue to grow. The clinical applications and benefits of AI will continue to be more fully realized, but so will certain ethical considerations. Making industry-sponsored databases open source, or at least somehow available to the public, will help alleviate potential biases and obscurities between surgeons and industry and will benefit patient care.

Clinical prediction for surgical versus nonsurgical interventions in patients with vertebral osteomyelitis and discitis.

Background: Vertebral osteomyelitis and discitis (VOD), an infection of intervertebral discs, often requires spine surgical intervention and timely management to prevent adverse outcomes. Our study aims to develop a machine learning (ML) model to predict the indication for surgical intervention (during the same hospital stay) versus nonsurgical management in patients with VOD. Methods: This retrospective study included adult patients (≥18 years) with VOD (ICD-10 diagnosis codes M46.2,3,4,5) treated at a single institution between 01/01/2015 and 12/31/2019. The primary outcome studied was surgery. Candidate predictors were age, sex, race, Elixhauser comorbidity index, first-recorded lab values, first-recorded vital signs, and admit diagnosis. After splitting the dataset, XGBoost, logistic regression, and K-neighbor classifier algorithms were trained and tested for model development. Results: A total of 1,111 patients were included in this study, among which 30% (n=339) of patients underwent surgical intervention. Age and sex did not significantly differ between the two groups; however, race did significantly differ (P<0.0001), with the surgical group having a higher percentage of white patients. The top ten model features for the best-performing model (XGBoost) were as follows (in descending order of importance): admit diagnosis of fever, negative culture, Staphylococcus aureus culture, partial pressure of arterial oxygen to fractional inspired oxygen ratio (PaO2:FiO2), admit diagnosis of intraspinal abscess and granuloma, admit diagnosis of sepsis, race, troponin I, acid-fast bacillus culture, and alveolar-arterial gradient (A-a gradient). XGBoost model metrics were as follows: accuracy =0.7534, sensitivity =0.7436, specificity =0.7586, and area under the curve (AUC) =0.8210. Conclusions: The XGBoost model reliably predicts the indication for surgical intervention based on several readily available patient demographic information and clinical features. The interpretability of a supervised ML model provides robust insight into patient outcomes. Furthermore, it paves the way for the development of an efficient hospital resource allocation instrument, designed to guide clinical suggestions.

Posterior Transdural Approach for Thoracic Corpectomies in the Setting of Complex Spine Deformity Reconstruction.

BACKGROUND AND OBJECTIVE: There are many surgical approaches for execution of a thoracic corpectomy. In cases of challenging deformity, traditional posterior approaches might not be sufficient to complete the resection of the vertebral body. In this technical note, we describe indications and technique for a transdural multilevel high thoracic corpectomy. METHODS: A 25-year-old man with a history of neurofibromatosis type 1 presented with instrumentation failure after a previous T1-T12 posterior spinal fusion, extensive laminectomy, and tumor resection. The patient presented with progressive back pain, had broad dural ectasia, and a progressive kyphotic rotational and anteriorly translated spinal deformity. To resect the medial-most aspect of the vertebral body, a bilateral extracavitary approach was attempted, but was found insufficient. A transdural approach was subsequently performed. A left paramedian durotomy was made, followed by generous arachnoid dissection, bilateral dentate ligament division, and T4 rootlet sacrifice to mobilize the spinal cord. A ventral durotomy was then made and the ventral dura was reflected over the spinal cord to protect it while drilling. The corpectomy was then completed. The ventral and dorsal durotomies were closed primarily and reinforced with fibrin glue and fibrin sealant patch. The corpectomy defect was filled with nonstructural autograft. RESULTS: The focal kyphosis was corrected with a combination of rod contouring, compression, and in situ bending. During the surgery, the patient had stable neuromonitoring data, and postoperatively had no neurological deficits. On follow-up until 1 year, the patient presented with no signs of cerebrospinal spinal leaks, no motor or sensory deficits, minimal incisional pain, and significantly improved posture. CONCLUSION: Complex high thoracic (T3-5) ventral pathology inaccessible via a bilateral extracavitary approach may be accessed via a transdural approach as opposed to an anterior/lateral transthoracic approach that requires mobilization of cardiovascular structures or scapula.

A Meta-Analysis of Surgical Outcomes in 25727 Patients Undergoing Anterior Cervical Discectomy and Fusion or Anterior Cervical Corpectomy and Fusion for Cervical Deformity.

STUDY DESIGN: Systematic Review. OBJECTIVES: To evaluate which cervical deformity correction technique between anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) produces better clinical, radiographic, and operative outcomes. METHODS: We conducted a meta-analysis comparing studies involving ACDF and ACCF. Adult patients with either original or previously treated cervical spine deformities were included. Two independent reviewers categorized extracted data into clinical, radiographic, and operative outcomes, including complications. Clinical assessments included patient-reported outcomes; radiographic evaluations examined C2-C7 Cobb angle, T1 slope, T1-CL, C2-7 SVA, and graft stability. Surgical measures included surgery duration, blood loss, hospital stay, and complications. RESULTS: 26 studies (25727 patients) met inclusion criteria and were extracted. Of these, 14 studies (19077 patients) with low risk of bias were included in meta-analysis. ACDF and ACCF similarly improve clinical outcomes in terms of JOA and NDI, but ACDF is significantly better at achieving lower VAS neck scores. ACDF is also more advantageous for improving cervical lordosis and minimizing the incidence of graft complications. While there is no significant difference between approaches for most surgical complications, ACDF is favorable for reducing operative time, intraoperative blood loss, and length of hospital stay. CONCLUSIONS: While both techniques benefit cervical deformity patients, when both techniques are feasible, ACDF may be superior with respect to VAS neck scores, cervical lordosis, graft complications and certain perioperative outcomes. Further studies are recommended to address outcome variability and refine surgical approach selection.