Elder, Benjamin D.

Abstract The development of biocompatible and biologically responsive scaffolds remains a key challenge for bone tissue engineering. Here, we report an enzyme-degradable, metal-free click-cross-linked organic–inorganic nanohybrid (Enz-Deg-Click-ON) scaffold with high biocompatibility for bone repair. The formulation was synthesized using a cyclooctyne-functionalized poly(propylene fumarate) polyphosphoester (PPF-poly(PE-BCN)) and azide-terminated dendritic polycaprolactone (PCL) with a polyhedral oligomeric silsesquioxane core (POSS-PCL-N3) via strain-promoted alkyne-azide cycloaddition (SPAAC) bioorthogonal click chemistry. The incorporation of phosphate-containing linkages enabled alkaline phosphatase (ALP)-responsive degradation. The scaffold exhibited rapid catalyst-free crosslinking, tunable swelling, and suitable mechanical properties. In vitro studies demonstrated excellent cytocompatibility, robust stem cell proliferation, and enhanced osteogenic differentiation with an elevated level of ALP and Runx2 expression. Enzyme-triggered degradation was confirmed in the presence of ALP. In the in vivo rat calvarial defect model, the scaffold significantly improved bone regeneration, as shown by an increased bone volume, mineral density, and defect coverage. Histological and immunofluorescence analyses revealed enhanced collagen deposition, angiogenesis, and osteogenesis. These results indicate that the Enz-Deg-Click-ON system provides a dynamic, bioresponsive platform for bone repair.

Assessing balance is crucial in neurological rehabilitation, yet while wearable sensors enable real-world monitoring, identifying reliable digital biomarkers remains challenging. This study utilized a high-fidelity instrumented walkway to determine which gait parameters best predict balance impairment, providing robust targets for future wearable applications. We analyzed 49 steady-state gait metrics from 140 individuals with diverse neurological conditions. Using statistical analysis and machine learning, we evaluated these parameters against objective force plate sway scores and clinical fall-history labels. Group analysis identified 16 parameters significantly distinguishing fallers from non-fallers, and a neural network classified fallers with an area under the curve of 0.75. Across all analytical approaches, overall gait variability, e.g., Stride Width S.D. and the Gait Variability Index, emerged as a universal predictor of balance impairment and fall risk. Furthermore, while traditional linear models emphasized spatial postural control, machine learning classification uniquely identified inter-limb asymmetry as a premier driver of fall prediction. These findings indicate that instrumented gait analysis effectively identifies digital biomarkers for balance deficits. Isolating these specific metrics provides a clear blueprint for meaningful metrics required for continuous objective monitoring and future development of personalized, adaptive rehabilitation strategies.

OBJECTIVE Multisegmental pathological autofusion is a hallmark feature of ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), creating a rigid, brittle spine highly susceptible to three-column fractures and devastating neurological injury. This study aimed to evaluate survival outcomes in this patient population and identify clinical and demographic predictors of mortality. METHODS Adults with DISH or AS who sustained a fracture and were admitted to a single tertiary care center for spinal fracture were retrospectively identified using ICD-10 diagnostic codes. Data were extracted on demographics, clinical presentation, fracture characteristics, and details of treatment. RESULTS A total of 383 patients (median age 78 years, 75.2% male) were included. Over a median follow-up of 17.3 months, overall mortality was 38.1%, in-hospital mortality was 5.2%, 30-day mortality was 5.7%, and 1-year mortality was 18.0%. Initial treatment consisted of external orthosis in 220 (57.4%) and surgery in 144 (37.6%), while 19 (5.0%) were left untreated. Patients who died were older (median 83 vs 74 years, p < 0.001), had a lower BMI (29.4 vs 32.3 kg/m 2 , p < 0.001), had higher frailty on the 5-item modified frailty index (mFI-5), and more commonly had congestive heart failure (CHF), cancer, functional dependency, and chronic kidney disease (CKD) (all p < 0.01). Mortality was not associated with fracture location, mechanism of injury, fracture number, or the presence of neurological deficits. Univariable time-to-event analysis showed that decreased survival was predicted by older age (HR 1.08, p < 0.0001), lower BMI (HR per kg/m 2 0.93, p < 0.0001), functional dependency (HR 2.05, p < 0.001), cancer (HR 1.55 p = 0.01), CKD (HR 1.48, p = 0.019), CHF (HR 2.18, p < 0.001), and higher mFI-5 score (HR per point 1.34, p < 0.001). On multivariable analysis, older age (HR 1.06 per year, p < 0.001), lower BMI (HR per kg/m 2 0.95, p < 0.001), and mFI-5 score (HR per patient 1.37, p < 0.001) remained significant independent predictors of mortality. Treatment modality did not predict mortality. CONCLUSIONS AS- or DISH-associated spinal fractures have a high associated mortality, regardless of mechanism or severity. Treatment modality did not affect odds of survival, suggesting that nonoperative management with an external orthosis may be an appropriate option, particularly in older and medically complex patients.

Background: The purpose of this study was to determine whether placement of triangular titanium implants (TTI) suprajacent to S2-alar-iliac (S2AI) pelvic fixation screws during multilevel spinal fusion surgery for adult spine deformity reduces pelvic fixation failures. Methods: This prospective, multicenter, international, partially blinded randomized clinical trial included 222 patients scheduled for multilevel spinal fusion surgery with S2AI-based pelvic fixation. In the S2AI+TTI group, the mean age was 64.9 years, 54.1% were female, 3.7% were Hispanic, 5.5% were African American, and 1.8% were Asian. In the S2AI-alone group, the mean age was 64.8 years, 58.4% were female, 3.5% were Hispanic, 7.1% were African American, and 0.9% were Asian. Subjects were randomized to pelvic fixation using S2AI screws alone versus S2AI+TTI. Scheduled follow-up included a 24-month full-spine radiograph and a high-resolution computed tomography (CT) scan, which was independently interpreted. Results: The primary composite radiographic end point (S2AI screw breakage, lucency, or pullout, or posterior spinal rod breakage distal to S1) occurred less frequently in the S2AI+TTI group than in the S2AI-alone group (11.0% versus 20.4%, p = 0.0415). Except for rod-screw dissociation and rod fracture distal to S1, all components of the primary composite end point occurred less frequently in the S2AI+TTI group. TTI placement did not affect sagittal or coronal spinal alignment parameters. The rate of rod fracture throughout the spinal construct was slightly higher in the S2AI+TTI group (9.2% versus 5.3%) but the difference was not significant (p = 0.197). Conclusions: Placement of TTI suprajacent to S2AI screws reduced the rate of pelvic fixation failure in patients undergoing multilevel spinal fusion with pelvic fixation. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Background/Objectives: To identify predictors of successful fusion and adjacent segment disease (ASD) following ALIF. Methods: Records of patients undergoing one- or two-level ALIF were queried for baseline and postoperative radiographic data, demographics, operative notes, and implant characteristics. All had ≥1 year of follow-up with CT, and multivariable Cox regression was used to identify predictors of radiographic fusion through the interbody, ASD, and ASD requiring reoperation. Results: In total, 177 patients (median 59 yr; 52.5% male) were treated at 245 unique levels, of which 193 fused (81.3% with posterior fixation and 59.6% with standalone), 43 had ASD (17.6%), and 14 had ASD requiring reoperation (5.7%). Fusion was predicted by anterior cage placement (HR 0.94/mm; 95% CI [0.90, 0.98]; p = 0.003) and BMP use (HR 1.92; [1.15, 3.18]; p = 0.012). Radiographic ASD was predicted by older age (HR 1.08 per year; [1.03, 1.14]; p < 0.001), undergoing a revision [vs. index] fusion operation (HR 3.51; [1.44; 8.59]; p = 0.006), lower preoperative disc height (HR 0.83/mm; [0.74, 0.94]; p = 0.003), and preoperative facet vacuum phenomenon (HR 2.46; [1.18, 5.15]; p = 0.017). None of the extracted variables predicted reoperation for ASD. Conclusions: BMP use along with anterior cage placement and posterior fixation may improve the odds of fusion through the interbody following one- or two-level ALIF. Adjacent segment pathology is more common in patients with greater preoperative degenerative pathology (vacuum sign; more collapsed disc) and advanced age. Pelvic fixation did not improve fusion odds, but the data highlight the benefits of supplementary posterior fixation vs. standalone ALIF.

Study Design: Retrospective cohort. Objective: This study aims to assess the effects of CT-based subsidence on lumbar sagittal alignment and patient-reported outcome measures (PROMs) after transforaminal lumbar interbody fusion (TLIF), and to determine if subsidence and cage properties are independent predictors of postoperative changes in regional lordosis. Summary of Background Data: Subsidence is a well-known complication following interbody fusion and has previously been associated with recurrence of preoperative symptoms and higher reoperation rates. There is incomplete evidence to characterize the effects of subsidence on lumbar alignment and PROMs following TLIF. Methods: All adult patients who underwent 1- or 2-level TLIF at a multi-institutional academic center between 2017 and 2019 were retrospectively identified. Interbody subsidence at the superior and inferior endplate of each TLIF level was directly measured on both coronal and sagittal CT scans obtained between 6 months and 1 year postoperatively. Patients were grouped based on the maximum subsidence at each operative level: mild-moderate (<4 mm) or severe (≥4 mm). Preoperative, immediate (<3 mo), and intermediate (>6 mo) postoperative radiographic outcomes (local and global lumbar alignment) and PROMs (VAS Back, Oswestry Disability Index, PROMIS Physical Function and Mood) were collected. Univariate and multivariate analysis compared patient demographics, surgical factors, and changes in radiographic measures and PROMs across subsidence groups. Multiple linear regression analyzed independent effects of subsidence and cage characteristics on alignment. Results: Sixty-seven patients with 85 unique fusion levels were included (55 with mild-moderate subsidence, 30 with severe subsidence). Levels with severe subsidence demonstrated significantly less regional lordosis at final follow-up than nonseverely subsided levels (6.4 vs. 9.1 degrees, P =0.032). No PROM significantly differed between severe and nonsevere subsidence subgroups. Linear regression analysis revealed that severe subsidence was a strong independent predictor of regional lordosis ( P =0.029) at final follow-up. Conclusions: Severe subsidence negates perioperative improvements in regional lordosis following TLIF, while changes in regional alignment are maintained in the absence of severe subsidence. Level of Evidence: Level III.

BACKGROUND Bertolotti syndrome is an underrecognized cause of chronic low back pain. Back pain generated from Bertolotti syndrome is believed to result from altered weight dissipation mechanics and/or instability of the pseudoarticulation, while local nerve root compression may result in radiculopathy. Here, the authors describe the findings of a patient with treatment-refractory low back pain found to have a cystic lesion arising from a Bertolotti joint causing L5 nerve root compression. To their knowledge, this has not been previously described in the literature. OBSERVATIONS Despite early recognition of Bertolotti syndrome, the patient’s back pain remained resistant to many years of both conservative and surgical management. The novel finding of a cyst arising from the pseudoarticulation complicated the management. The patient is scheduled to undergo further surgery this year. LESSONS This case highlights a pseudocyst associated with a Bertolotti joint. The cyst introduced additional clinical uncertainty to what is already an uncommon and difficult to treat condition. Resection of the Bertolotti joint failed to improve the patient’s symptoms. Postoperatively, a complex hemorrhagic pseudocyst was seen on imaging, possibly due to the pseudoarticulation with persistent motion. Ongoing efforts to characterize Bertolotti syndrome and its associated imaging findings are necessary to better optimize management strategies in these patients. https://thejns.org/doi/10.3171/CASE25948

BACKGROUND AND OBJECTIVES: Ventriculoperitoneal shunt (VPS) placement is a common treatment for idiopathic normal pressure hydrocephalus (iNPH), but patients may require VPS revision. This study aims to evaluate the effectiveness of a standardized VPS placement protocol by comparing indications and rates of shunt revision compared with a historical institutional cohort. METHODS: All patients treated with VPS for “suspected” iNPH at a tertiary care center between January 2000 and January 2023 were retrospectively reviewed and divided into temporally distinct historical (before 2017) and standardized (after 2017) cohorts. Cumulative incidence and timing of VPS revision were compared using competing risks analyses. RESULTS: A total of 561 patients (median age 75.0 years) were identified with 324 (57.8%) in the historical and 237 (42.2%) in the standardized cohorts. Significant variations in surgical technique and shunt hardware were noted between the cohorts. With a median follow-up of 11.4 months for historical and 12.4 months for standardized cohort, shunt revisions occurred in 19.4% and 8.4% of patients in the historical and standardized cohorts, respectively ( P < .001). Revision indications also varied significantly with lower rates of overdrainage ( P < .001), infection ( P < .001), and proximal malfunction ( P = .042) but higher rate of distal malfunction ( P = .03) in the standardized cohort. Notably, no infections were noted in the standardized cohort. CONCLUSION: Risk of shunt revision among iNPH patients may be associated with modifiable factors related to surgical technique and shunt hardware selection. Importantly, no short-term complications such as hemorrhage, infection, or catheter malposition were observed with the standardized protocol. Development and refinement of standardized shunt protocols for iNPH patients should be commonplace to facilitate tracking, identification, and modification of modifiable technical risk factors.

Background: Anterior cervical discectomy and fusion (ACDF) is a widely performed procedure for treating degenerative cervical spine conditions. While it effectively addresses neural decompression and restores segmental alignment, the interplay of baseline alignment and implant-specific factors on postoperative segmental alignment remains underexplored. This study evaluates the influence of preoperative cervical alignment and interbody cage design on segmental alignment changes following 1- to 3-level ACDF. Methods: Following institutional review board approval, we identified 258 patients undergoing ACDF for degenerative pathology between 1 January 2010 and 31 December 2023. Preoperative and postoperative radiographs were analyzed for cervical alignment, disc height, and segmental lordosis. Cage dimensions, lordosis, and positioning relative to vertebral landmarks were recorded. Multivariable linear regression models evaluated predictors of postoperative disc height, segmental lordosis, and their respective changes. Results: Postoperative disc height was positively associated with greater cage height (β = 1.13 mm per mm, p < 0.001) and negatively associated with greater cage lordosis (β = −0.10 mm per °, p = 0.001). Segmental lordosis was positively influenced by cage height (β = 0.78° per mm, p = 0.002) and lordosis (β = 0.42° per °, p = 0.002) but was negatively correlated with the distance of the cage from the anterior edge of the cranial vertebra (β = −1.76° per mm, p = 0.004). Greater preoperative segmental kyphosis predicted more significant postoperative lordosis correction (β = −1.07° per °, p < 0.001). Conclusions: This study underscores the importance of preoperative alignment and interbody cage design in achieving optimal segmental correction following ACDF. While cage height primarily drives disc height restoration, surgical technique, particularly anterior placement of the cage, is pivotal for enhancing segmental lordosis. These findings support personalized surgical planning to optimize alignment and patient outcomes.