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.

Pedicle screw placement in the cervical vertebrae using augmented reality-head mounted displays: a cadaveric proof-of-concept study.

BACKGROUND: The accurate and safe positioning of cervical pedicle screws is crucial. While augmented reality (AR) use in spine surgery has previously demonstrated clinical utility in the thoracolumbar spine, its technical feasibility in the cervical spine remains less explored. PURPOSE: The objective of this study was to assess the precision and safety of AR-assisted pedicle screw placement in the cervical spine. STUDY DESIGN: In this experimental study, 5 cadaveric cervical spine models were instrumented from C3 to C7 by 5 different spine surgeons. The navigation accuracy and clinical screw accuracy were evaluated. METHODS: Postprocedural CT scans were evaluated for clinical accuracy by 2 independent neuroradiologists using the Gertzbein-Robbins scale. Technical precision was assessed by calculating the angular trajectory (°) and linear screw tip (mm) deviations in the axial and sagittal planes from the virtual pedicle screw position as recorded by the AR-guided platform during the procedure compared to the actual pedicle screw position derived from postprocedural imaging. RESULTS: A total of forty-one pedicle screws were placed in 5 cervical cadavers, with each of the 5 surgeons navigating at least 7 screws. Gertzbein-Robbins grade of A or B was achieved in 100% of cases. The mean values for tip and trajectory errors in the axial and sagittal planes between the virtual versus actual position of the screws was less than 3 mm and 30°, respectively (p<.05). None of the cervical screws violated the cortex by more than 2 mm or displaced neurovascular structures. CONCLUSIONS: AR-assisted cervical pedicle screw placement in cadavers demonstrated clinical accuracy comparable to existing literature values for image-guided navigation methods for the cervical spine. CLINICAL SIGNIFICANCE: This study provides technical and clinical accuracy data that supports clinical trialing of AR-assisted subaxial cervical pedicle screw placement.

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.

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.

Preoperative Mobile Health Data Improve Predictions of Recovery From Lumbar Spine Surgery.

BACKGROUND AND OBJECTIVES: Neurosurgeons and hospitals devote tremendous resources to improving recovery from lumbar spine surgery. Current efforts to predict surgical recovery rely on one-time patient report and health record information. However, longitudinal mobile health (mHealth) assessments integrating symptom dynamics from ecological momentary assessment (EMA) and wearable biometric data may capture important influences on recovery. Our objective was to evaluate whether a preoperative mHealth assessment integrating EMA with Fitbit monitoring improved predictions of spine surgery recovery. METHODS: Patients age 21-85 years undergoing lumbar surgery for degenerative disease between 2021 and 2023 were recruited. For up to 3 weeks preoperatively, participants completed EMAs up to 5 times daily asking about momentary pain, disability, depression, and catastrophizing. At the same time, they were passively monitored using Fitbit trackers. Study outcomes were good/excellent recovery on the Quality of Recovery-15 (QOR-15) and a clinically important change in Patient-Reported Outcomes Measurement Information System Pain Interference 1 month postoperatively. After feature engineering, several machine learning prediction models were tested. Prediction performance was measured using the c-statistic. RESULTS: A total of 133 participants were included, with a median (IQR) age of 62 (53, 68) years, and 56% were female. The median (IQR) number of preoperative EMAs completed was 78 (61, 95), and the median (IQR) number of days with usable Fitbit data was 17 (12, 21). 63 patients (48%) achieved a clinically meaningful improvement in Patient-Reported Outcomes Measurement Information System pain interference. Compared with traditional evaluations alone, mHealth evaluations led to a 34% improvement in predictions for pain interference (c = 0.82 vs c = 0.61). 49 patients (40%) had a good or excellent recovery based on the QOR-15. Including preoperative mHealth data led to a 30% improvement in predictions of QOR-15 (c = 0.70 vs c = 0.54). CONCLUSION: Multimodal mHealth evaluations improve predictions of lumbar surgery outcomes. These methods may be useful for informing patient selection and perioperative recovery strategies.

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.

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.

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.

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.

Rapid Implementation of a 3-Dimensional-Printed Patient-Specific Titanium Sacrum Implant for Severe Neuropathic Spinal Arthropathy and Guide to Compassionate US Regulatory Approval.

BACKGROUND AND OBJECTIVE: Rapid design and production of patient-specific 3-dimensional-printed implants (3DPIs) present a novel opportunity to restore the biomechanically demanding integrity of the lumbopelvic junction. We present a unique case of a 61-year-old patient with severe neuropathic spinal arthropathy (Charcot spine) who initially underwent a T4-to-sacrum spinal fusion. Massive bone destruction led to dissociation of his upper body from his pelvis and legs. Reconstruction of the spinopelvic continuity was planned with the aid of a personalized lumbosacral 3DPI. METHOD: Using high-resolution computed tomography scans, the custom 3DPI was made using additive titanium manufacturing. The unique 3DPI consisted of (1) a sacral platform with iliac screws, (2) modular corpectomy device with rigid connection to the sacral platform, and (3) anterior plate connection with screws for proximal fixation. The procedures to obtain compassionate use Food and Drug Administration approval were followed. The patient underwent debridement of a chronically open wound before undertaking the 3-stage reconstructive procedure. The custom 3DPI and additional instrumentation were inserted as part of a salvage rebuilding procedure. RESULTS: The chronology of the rapid implementation of the personalized sacral 3DPI from decision, design, manufacturing, Food and Drug Administration approval, and surgical execution lasted 28 days. The prosthesis was positioned in the defect according to the expected anatomic planes and secured using a screw-rod system and a vascularized fibular bone strut graft. The prosthesis provided an ideal repair of the lumbosacral junction and pelvic ring by merging spinal pelvic fixation, posterior pelvic ring fixation, and anterior spinal column fixation. CONCLUSION: To the best of our knowledge, this is the first case of a multilevel lumbar, sacral, and sacropelvic neuropathic (Charcot) spine reconstruction using a 3DPI sacral prosthesis. As the prevalence of severe spine deformities continues to increase, adoption of 3DPIs is becoming more relevant to offer personalized treatment for complex deformities.

Predictors of Postoperative Segmental and Overall Lumbar Lordosis in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Consecutive Case Series.

STUDY DESIGN: Retrospective Case-Series. OBJECTIVES: Due to heterogeneity in previous studies, the effect of MI-TLIF on postoperative segmental lordosis (SL) and lumbar lordosis (LL) remains unclear. Therefore, we aim to identify radiographic factors associated with lordosis after surgery in a homogenous series of MI-TLIF patients. METHODS: A single-center retrospective review identified consecutive patients who underwent single-level MI-TLIF for grade 1 degenerative spondylolisthesis from 2015-2020. All surgeries underwent unilateral facetectomies and a contralateral facet release with expandable interbody cages. PROs included the ODI and NRS-BP for low-back pain. Radiographic measures included SL, disc height, percent spondylolisthesis, cage positioning, LL, PI-LL mismatch, sacral-slope, and pelvic-tilt. Surgeries were considered "lordosing" if the change in postoperative SL was ≥ +4° and "kyphosing" if ≤ -4°. Predictors of change in SL/LL were evaluated using Pearson's correlation and multivariable regression. RESULTS: A total of 73 patients with an average follow-up of 22.5 (range 12-61) months were included. Patients experienced significant improvements in ODI (29% ± 22% improvement, P < .001) and NRS-BP (3.3 ± 3 point improvement, P < .001). There was a significant increase in mean SL (Δ3.43° ± 4.37°, P < .001) while LL (Δ0.17° ± 6.98°, P > .05) remained stable. Thirty-eight (52%) patients experienced lordosing MI-TLIFs, compared to 4 (5%) kyphosing and 31 (43%) neutral MI-TLIFs. A lower preoperative SL and more anterior cage placement were associated with the greatest improvement in SL (ß = -.45° P = .001, ß = 15.06° P < .001, respectively). CONCLUSIONS: In our series, the majority of patients experienced lordosing or neutral MI-TLIFs (n = 69, 95%). Preoperative radiographic alignment and anterior cage placement were significantly associated with target SL following MI-TLIF.

Study of the Rv1417 and Rv2617c Membrane Proteins and Their Interactions with Nicotine Derivatives as Potential Inhibitors of Erp Virulence-Associated Factor in Mycobacterium tuberculosis: An In Silico Approach.

The increasing emergence of Mycobacterium tuberculosis (Mtb) strains resistant to traditional anti-tuberculosis drugs has alarmed health services worldwide. The search for new therapeutic targets and effective drugs that counteract the virulence and multiplication of Mtb represents a challenge for the scientific community. Several studies have considered the erp gene a possible therapeutic target in the last two decades, since its disruption negatively impacts Mtb multiplication. This gene encodes the exported repetitive protein (Erp), which is located in the cell wall of Mtb. In vitro studies have shown that the Erp protein interacts with two putative membrane proteins, Rv1417 and Rv2617c, and the impairment of their interactions can decrease Mtb replication. In this study, we present five nicotine analogs that can inhibit the formation of heterodimers and trimers between these proteins. Through DFT calculations, molecular dynamics, docking, and other advanced in silico techniques, we have analyzed the molecular complexes, and show the effect these compounds have on protein interactions. The results show that four of these analogs can be possible candidates to counteract the pathogenicity of Mtb. This study aims to combine research on the Erp protein as a therapeutic target in the search for new drugs that serve to create new therapies against tuberculosis disease.

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.

Feasibility and Acceptability of a Preoperative Multimodal Mobile Health Assessment in Spine Surgery Candidates.

BACKGROUND: Rapid growth in smartphone use has expanded opportunities to use mobile health (mHealth) technology to collect real-time patient-reported and objective biometric data. These data may have important implication for personalized treatments of degenerative spine disease. However, no large-scale study has examined the feasibility and acceptability of these methods in spine surgery patients. OBJECTIVE: To evaluate the feasibility and acceptability of a multimodal preoperative mHealth assessment in patients with degenerative spine disease. METHODS: Adults undergoing elective spine surgery were provided with Fitbit trackers and sent preoperative ecological momentary assessments (EMAs) assessing pain, disability, mood, and catastrophizing 5 times daily for 3 weeks. Objective adherence rates and a subjective acceptability survey were used to evaluate feasibility of these methods. RESULTS: The 77 included participants completed an average of 82 EMAs each, with an average completion rate of 86%. Younger age and chronic pulmonary disease were significantly associated with lower EMA adherence. Seventy-two (93%) participants completed Fitbit monitoring and wore the Fitbits for an average of 247 hours each. On average, participants wore the Fitbits for at least 12 hours per day for 15 days. Only worse mood scores were independently associated with lower Fitbit adherence. Most participants endorsed positive experiences with the study protocol, including 91% who said they would be willing to complete EMAs to improve their preoperative surgical guidance. CONCLUSION: Spine fusion candidates successfully completed a preoperative multimodal mHealth assessment with high acceptability. The intensive longitudinal data collected may provide new insights that improve patient selection and treatment guidance.

Clinically meaningful improvement in disabilities of arm, shoulder, and hand (DASH) following cervical spine surgery.

BACKGROUND CONTEXT: Patients with cervical spine disease suffer from upper limb disability. At present, no clinical benchmarks exist for clinically meaningful change in the upper limb function following cervical spine surgery. PURPOSE: Primary: to establish clinically meaningful metrics; the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) of upper limb functional improvement in patients following cervical spine surgery. Secondary: to identify the prognostic factors of MCID and SCB of upper limb function following cervical spine surgery. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients ≥18 years of age who underwent cervical spine surgery from 2012 to 2016. OUTCOME MEASURES: Patient-reported outcomes: Neck disability index (NDI) and Disabilities of Arm, Shoulder, and Hand (DASH). METHODS: MCID was defined as minimal improvement and SCB as substantial improvement in the DASH score at last follow-up. The anchor-based methods (ROC analyses) defined optimal MCID and SCB thresholds with area under curve (AUC) in discriminating improved vs. non-improved patients. The MCID was also calculated by distribution-based methods: half standard-deviation (0.5-SD) and standard error of the mean (SEM) method. A multivariable logistic regression evaluated the impact of baseline factors in achieving the MCID and SCB in DASH following cervical spine surgery. RESULTS: Between 2012 and 2016, 1,046 patients with average age of 57±11.3 years, 53% males, underwent cervical spine surgery. Using the ROC analysis, the threshold for MCID was -8 points with AUC of 0.73 (95% CI: 0.67-0.79) and the SCB was -18 points with AUC of 0.88 (95% confidence interval [CI]: 0.85-0.91). The MCID was -11 points by 0.5-SD and -12 points by SEM-method. On multivariable analysis, patients with myelopathy had lower odds of achieving MCID and SCB, whereas older patients and those with ≥6 months duration of symptoms had lower odds of achieving DASH MCID and SCB respectively. CONCLUSIONS: In patients undergoing cervical spine surgery, MCID of -8 points and SCB of -18 points in DASH improvement may be considered clinically significant. These metrics may enable evaluation of minimal and substantial improvement in the upper extremity function following cervical spine surgery.

Leveraging Artificial Intelligence and Synthetic Data Derivatives for Spine Surgery Research.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Leveraging electronic health records (EHRs) for spine surgery research is impeded by concerns regarding patient privacy and data ownership. Synthetic data derivatives may help overcome these limitations. This study's objective was to validate the use of synthetic data for spine surgery research. METHODS: Data came from the EHR from 15 hospitals. Patients that underwent anterior cervical or posterior lumbar fusion (2010-2020) were included. Real data were obtained from the EHR. Synthetic data was generated to simulate the properties of the real data, without maintaining a one-to-one correspondence with real patients. Within each cohort, ability to predict 30-day readmissions and 30-day complications was evaluated using logistic regression and extreme gradient boosting machines (XGBoost). RESULTS: We identified 9,072 real and 9,088 synthetic cervical fusion patients. Descriptive characteristics were nearly identical between the 2 datasets. When predicting readmission, models built using real and synthetic data both had c-statistics of .69-.71 using logistic regression and XGBoost. Among 12,111 real and 12,126 synthetic lumbar fusion patients, descriptive characteristics were nearly the same for most variables. Using logistic regression and XGBoost to predict readmission, discrimination was similar with models built using real and synthetic data (c-statistics .66-.69). When predicting complications, models derived using real and synthetic data showed similar discrimination in both cohorts. Despite some differences, the most influential predictors were similar in the real and synthetic datasets. CONCLUSION: Synthetic data replicate most descriptive and predictive properties of real data, and therefore may expand EHR research in spine surgery.

Association Between Neighborhood-Level Socioeconomic Disadvantage and Patient-Reported Outcomes in Lumbar Spine Surgery.

BACKGROUND: Despite an increased understanding of the impact of socioeconomic status on neurosurgical outcomes, the impact of neighborhood-level social determinants on lumbar spine surgery patient-reported outcomes remains unknown. OBJECTIVE: To evaluate the impact of geographic social deprivation on physical and mental health of lumbar surgery patients. METHODS: A single-center retrospective cohort study analyzing patients undergoing lumbar surgery for degenerative disease from 2015 to 2018 was performed. Surgeries were categorized as decompression only or decompression with fusion. The area deprivation index was used to define social deprivation. Study outcomes included preoperative and change in Patient-Reported Outcomes Measurement (PROMIS) physical function (PF), pain interference (PI), depression, and anxiety (mean follow-up: 43.3 weeks). Multivariable imputation was performed for missing data. One-way analysis of variance and multivariable linear regression were used to evaluate the association between area deprivation index and PROMIS scores. RESULTS: In our cohort of 2010 patients, those with the greatest social deprivation had significantly worse mean preoperative PROMIS scores compared with the least-deprived cohort (mean difference [95% CI]-PF: -2.5 [-3.7 to -1.4]; PI: 3.0 [2.0-4.1]; depression: 5.5 [3.4-7.5]; anxiety: 6.0 [3.8-8.2], all P < .001), without significant differences in change in these domains at latest follow-up (PF: +0.5 [-1.2 to 2.2]; PI: -0.2 [-1.7 to 2.1]; depression: -2 [-4.0 to 0.1]; anxiety: -2.6 [-4.9 to 0.4], all P > .05). CONCLUSION: Lumbar spine surgery patients with greater social deprivation present with worse preoperative physical and mental health but experience comparable benefit from surgery than patients with less deprivation, emphasizing the need to further understand social and health factors that may affect both disease severity and access to care.