Michael Nhien Le

Dimethyl sulfoxide (DMSO) is widely used as a solvent in endovascular embolization procedures, yet its potential neurotoxic effects remain underexplored. In this correspondence, we highlight emerging evidence suggesting that DMSO exposure may contribute to the development of hydrocephalus through mechanisms involving ependymal damage and astrocyte apoptosis. Drawing on recent experimental findings, we propose that DMSO-induced neuroinflammation may play a role in post-embolization complications. We urge the research community to consider hydrocephalus as a possible, though unproven, outcome of DMSO exposure and to include it in long-term safety assessments of embolic agents.

Background/Objectives: Cannabinoid use is rising among patients undergoing spinal fusion, yet its influence on bone healing is poorly defined. The endocannabinoid system (ECS)—through cannabinoid receptors 1 (CB1) and 2 (CB2)—modulates skeletal metabolism. We reviewed preclinical, mechanistic and clinical evidence to clarify how individual cannabinoids affect fracture repair and spinal arthrodesis. Methods: PubMed, Web of Science and Scopus were searched from inception to 31 May 2025 with the terms “cannabinoid”, “CB1”, “CB2”, “spinal fusion”, “fracture”, “osteoblast” and “osteoclast”. Animal studies, in vitro experiments and clinical reports that reported bone outcomes were eligible. Results: CB2 signaling was uniformly osteogenic. CB2-knockout mice developed high-turnover osteoporosis, whereas CB2 agonists (HU-308, JWH-133, HU-433, JWH-015) restored trabecular volume, enhanced osteoblast activity and strengthened fracture callus. Cannabidiol (CBD), a non-psychoactive phytocannabinoid with CB2 bias, accelerated early posterolateral fusion in rats and reduced the RANKL/OPG ratio without compromising final union. In contrast, sustained or high-dose Δ⁹-tetrahydrocannabinol (THC) activation of CB1 slowed chondrocyte hypertrophy, decreased mesenchymal-stromal-cell mineralization and correlated clinically with 6–10% lower bone-mineral density and a 1.8–3.6-fold higher pseudarthrosis or revision risk. Short-course or low-dose THC appeared skeletal neutral. Responses varied with sex, age and genetic background; no prospective trials defined safe perioperative dosing thresholds. Conclusions: CB2 activation and CBD consistently favor bone repair, whereas chronic high-THC exposure poses a modifiable risk for nonunion in spine surgery. Prospective, receptor-specific trials stratified by THC/CBD ratio, patient sex and ECS genotype are needed to establish evidence-based cannabinoid use in spinal fusion.

Background/Objective: Smoking is known to impair fracture healing and worsen surgical outcomes, but its effect on psychological recovery in spine trauma patients remains unclear. The purpose of this study is to assess how smoking affects pain and anxiety in patients with spine fractures treated either conservatively or surgically. Methods: We conducted a retrospective analysis looking at spine fracture patients > 18 years old seen at a single institution between 11/2015 and 9/2019. Patient variables such as age, sex, race, ethnicity, mechanism of injury, fracture location, presence of spinal cord injury, surgical intervention, hospital and ICU LOS, disposition, and EQ-5D-3L at 3 and 12 months were collected and analyzed. Results: Non-operative management was selected for 403 patients, of which 304 never smoked and 99 were smokers. Surgical management was utilized for 126 patients, of which 90 never smoked and 36 were smokers. Studying non-smokers and current smokers, higher levels of extreme pain and anxiety at 3 and 12 months were reported in smokers managed conservatively. Smokers managed surgically reported higher levels of pain and anxiety than non-smokers at 3 months but not at 12 months. No significant differences were seen with regards to changes in pain or anxiety between the 3- and 12-month follow-up. Conclusions: Smoking is independently associated with higher levels of pain and anxiety in conservatively managed spine fracture patients. These findings suggest a need for early intervention and cessation efforts in the trauma setting. Further investigation is warranted to clarify whether underlying psychological or physiological phenomena are impacting patient outcomes.

Background: Thoracolumbar (TL) fractures are uncommon injuries in the pediatric population. Surgery is recommended for TL fractures with significant deformity, posterior ligamentous complex disruption, or neurological compromise. The Thoracolumbar Injury Classification and Severity Scale (TLICS) has been validated in pediatric populations and serves as a valuable tool for guiding treatment decisions. However, there remains a lack of clarity regarding the appropriate treatment for patients with a TLICS of 4. While conservative and surgical techniques have been described, most studies focused on adult populations, and there is no consensus on the appropriate management in the pediatric population. We reviewed our institutional experience of TL fractures in young children with TLICS of 4, managed both non-operatively and operatively. Methods: A retrospective review of a single institution’s experience managing pediatric patients (<18 years old) with TL fractures receiving a TLICS of 4 from 2015 to 2023 was conducted to determine the clinical outcomes following non-operative and operative treatment. Results: Among 11 pediatric patients, 4 were managed with bracing alone, primarily for posterior column fractures, using a thoracolumbar sacral orthosis (TLSO). Four patients underwent minimally invasive screw fixation (MISF), for Chance or posterior column fractures, with an average operative time of 143 min, blood loss of 29 cc, length of stay (LOS) of 9.8 days, and a follow-up interval of 6 months. Three patients received open posterior screw fixation (OPSF), most commonly for Chance fractures, with averages of 129 min operative time, 225 cc blood loss, 9.7 days LOS, and 4 months follow-up. Both MISF and OPSF utilized intra-operative imaging, with lower radiation exposure in the MISF group. One MISF patients had hardware failure evident by screw lucency on follow-up imaging. Conclusions: Bracing and surgery are safe management options for pediatric TL fractures receiving a TLICS of 4. MISF is an effective alternative treatment strategy, comparable to OPSF, with the advantage of reduced blood loss and radiation exposure. Further studies with age-matched cohorts and long-term outcomes may help determine the optimal management course.

Background: Cervical spinal cord injuries (SCIs) are the most common type of human SCI. Although various animal SCI contusion models have been developed to mirror human pathology, few have described cervical-level injuries. This study aims to validate and establish optimal impact parameters to produce consistent incomplete cervical SCIs for testing novel therapies. Methods: Using a precise impactor, 3 cervical spinal cord hemi-contusions of varying severities were induced by modifying penetration depths and controlling dwell times. Penetration depths of 2.11 mm (n = 4), 2.24 mm (n = 4), and 2.36 mm (n = 3) were used with a dwell time of 0.05 s to create mild, moderate, and severe injuries. Behavioral assessments in weeks 1, 2, 5, and 8 included grooming test, forelimb asymmetry test, and the Irvine, Beatties, and Bresnahan forelimb scale (IBB). After 8 weeks, rats were euthanized, and spinal cord histology was performed. Results: Within each group, animals exhibited consistent motor deficits and functional recovery. Mean IBB scores varied significantly between each group at week 8 (p < 0.0001). Ipsilateral forelimb usage significantly improved throughout the study period in the mild (2.11 mm) and moderate (2.24 mm) groups, while the severely (2.36 mm) injured group continued to exhibit 100% asymmetrical forelimb usage. Conclusions: This study demonstrates that a precise impactor can create reproducible models of incomplete cervical SCIs. A penetration depth of 2.24 mm resulted in moderate injury with significant motor deficits that slowly improved over time, permitting future therapeutic studies in functional recovery.

Many central nervous system (CNS) disorders lack approved treatment options. Previous research demonstrated that peptide CAQK can bind to chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix of the CNS. In vivo studies have investigated CAQK conjugated to nanoparticles containing therapeutic agents with varying methodologies/outcomes. This paper presents the first systematic review assessing its properties, applications, and outcomes secondary to its use. Following PRISMA guidelines, a comprehensive search was performed across multiple databases. Studies utilizing CAQK as a therapeutic agent/homing molecule in animal/human models were selected. Sixteen studies met the inclusion criteria. Mice and rats were the predominant animal models. All studies except one used CAQK to deliver a therapeutic agent. The reviewed studies mostly included models of brain and spinal cord injuries. Most studies had intravenous administration of CAQK. All studies demonstrated various benefits and that CAQK conjugation facilitated localization to target tissues. No studies directly evaluated the effects of CAQK alone. The data are limited by the heterogeneity in study methodologies and the lack of direct comparison between CAQK and conjugated agents. Overall, these findings present CAQK utilization to deliver a therapeutic agent as a promising targeting strategy in the management of disorders where CSPGs are upregulated.