Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection.

Background: Postoperative infection is a complication of spinal fusion surgery resulting in increased patient morbidity. Strategies including intraoperative application of powdered vancomycin have been proposed to reduce the incidence of infection; however, such antimicrobial effects are short-lived. Methods: Instrumentation of the L4-L5 vertebrae was performed mimicking pedicle screw and rod fixation in 30 rats. Titanium instrumentation inoculated with either PBS or 1×105 CFU bioluminescent MRSA, along with biomimetic bone grafts infused with varying concentrations of vancomycin and 125 µg of rhBMP-2 (BioMim-rhBMP-2-VCM) were implanted prior to closure. Infection was quantified during the six-week postoperative period using bioluminescent imaging. Arthrodesis was evaluated using micro-CT. Results: Infected animals receiving a bone graft infused with low-dose (0.18 mg/g) or high-dose vancomycin (0.89 mg/g) both exhibited significantly lower bioluminescent signal over the six-week postoperative period than control animals inoculated with MRSA and implanted with bone grafts lacking vancomycin (p=.019 and p=.007, respectively). Both low and high-dose vancomycin-infused grafts also resulted in a statistically significant reduction in average bioluminescence when compared to control animals (p=.027 and p=.047, respectively), independent of time. MicroCT analysis of animals from each group revealed pseudoarthrosis only in the control group, suggesting a correlation between infection and pseudoarthrosis. MRSA-inoculated control animals also had significantly less bone volume formation on micro-CT than the PBS-inoculated control cohort (p<.001), the MRSA+low-dose vancomycin-infused bone graft cohort (p<.001), and the MRSA+high-dose vancomycin-infused bone graft cohort (p<.001). Conclusion: BioMim-rhBMP-2-VCM presents a novel tissue engineering approach to simultaneously promoting arthrodesis and antimicrobial prophylaxis in spinal fusion. Despite mixed evidence of potential osteotoxicity of vancomycin reported in literature, BioMim-rhBMP-2-VCM preserved arthrodesis and osteogenesis with increasing vancomycin loading doses due to the graft's osteoinductive composition.

Rapid Operationalization of COVID-19 Immunization Clinics With Medical and Physician Assistant Students Serving as Vaccinators.

Introduction: In anticipation of institutional and community-wide COVID-19 immunization clinics, an educational program for the administration of COVID-19 vaccines was developed, collaborating with the Virginia Department of Health to train doctor of medicine and physician assistant students to serve as vaccinators. Faculty and students also worked with state legislatures to propose and enact a bill that would enable such students to vaccinate patients. Methods: Between January 2021 and August 2022, 263 student volunteers completed 3,685 person-hours, administering 48,279 doses. On the basis of community need, the majority of vaccines were administered at mass vaccination clinics in Chesapeake (47%) and Norfolk (22%) in Virginia. One year after the first COVID-19 immunization clinic, the authors surveyed students who assisted with clinics, utilizing a Likert scale and free-text responses to elicit feedback about the training and volunteer experience. Results: Volunteers ranked the vaccination clinics among the top third of established volunteer experiences offered at Eastern Virginia Medical School, and 75% of respondents believed that this training should be a permanent part of their program curriculum. Conclusions: This paper presents a strategy for preparing students to serve as vaccinators during public health emergencies and show how other institutions of medical education can prepare for and engage student participation in vaccination campaigns and emergent health initiatives.

Augmented reality in spine surgery - past, present, and future.

BACKGROUND CONTEXT: Augmented reality (AR) is increasingly recognized as a valuable tool in spine surgery. Here we provides an overview of the key developments and technological milestones that have laid the foundation for AR applications in this field. We also assess the quality of existing studies on AR systems in spine surgery and explore potential future applications. PURPOSE: The purpose of this narrative review is to examine the role of AR in spine surgery. It aims to highlight the evolution of AR technology in this context, evaluate the existing body of research, and outline potential future directions for integrating AR into spine surgery. STUDY DESIGN: Narrative review. METHODS: We conducted a thorough literature search to identify studies and developments related to AR in spine surgery. Relevant articles, reports, and technological advancements were analyzed to establish the historical context and current state of AR in this field. RESULTS: The review identifies significant milestones in the development of AR technology for spine surgery. It discusses the growing body of research and highlights the strengths and weaknesses of existing investigations. Additionally, it presents insights into the potential for AR to enhance spine surgical education and speculates on future applications. CONCLUSIONS: Augmented reality has emerged as a promising adjunct in spine surgery, with notable advancements and research efforts. The integration of AR into the spine surgery operating room holds promise, as does its potential to revolutionize surgical education. Future applications of AR in spine surgery may include real-time navigation, enhanced visualization, and improved patient outcomes. Continued development and evaluation of AR technology are essential for its successful implementation in this specialized surgical field.

Examination of residency program websites for the use of gendered language and imagery.

BACKGROUND: Significant disparity in gender distribution exists among medical specialties. Residency program websites are a main source of preliminary program information for candidates, and website content may influence a prospective applicant's sense of belongingness within a particular program. Given the importance of the residency program website as a recruiting tool, this study sought to examine and compare the presence of gendered language and imagery on residency program websites across various specialties. METHODS: A list of words considered masculine or feminine was used to evaluate residency program websites of the two most male-dominated specialties (orthopedic and thoracic surgery), female-dominated specialties (pediatrics and obstetrics and gynecology), and gender-balanced specialties (dermatology and family medicine) in the United States in 2022. Forty-five residency programs were randomly selected from each specialty across different regions of the US, with the exception of thoracic surgery of which there are only 33 programs. Masculine and feminine words were evaluated using a parsing and scraping program. Representation of female and male-presenting team members in photos on program websites was also evaluated. RESULTS: Masculine wording occurred more frequently in male-dominated specialties compared to gender-balanced (p = 0.0030), but not female-dominated specialties (p = 0.2199). Feminine language was used more frequently in female-dominated compared to male dominated fields (p = 0.0022), but not gender balanced (p = 0.0909). The ratio of masculine-to-feminine words used was significantly higher in male-dominated specialties compared to both gender-balanced (p < 0.0001) and female-dominated specialties. (p < 0.0001). There was an average of 1, 7, and 10 female-presenting residency team members pictured on each male-dominated, gender balanced, and female-dominated specialty RPW respectively, with significantly more female-presenting team members pictured in the photographs on female-dominated specialty websites when compared to male-dominated and gender-balanced specialty websites (p < 0.0001, p = 0.014). CONCLUSIONS: The use of gendered language and female representation in photographs varies significantly across specialties and is directly correlated with gender representation within the specialty. Given that students' perceptions of specialty programs may be affected by the use of language and photos on residency program websites, programs should carefully consider the language and pictures depicted on their program websites.

Reduction of cervicothoracic spondyloptosis in an ambulatory patient: when traction fails.

INTRODUCTION: Cervical spondyloptosis is a rare complication of high-energy trauma which often results in significant patient morbidity and mortality. The authors present a case of spondyloptosis of C7 over T1 with minimal radicular symptoms and otherwise complete spinal cord sparing. This case highlights the surgical challenges faced with cervical spondyloptosis and the techniques used when traction fails. CASE PRESENTATION: A 21-year-old man with no significant past medical history presented after a high-speed motor vehicle collision with cervicothoracic pain and mild hand grip weakness in addition to numbness of the fourth and fifth digits bilaterally (American Spinal Injury Association Impairment Scale Grade D). Computed tomography imaging revealed spondyloptosis of C7 over T1, a fracture of the C2 vertebral body, and a burst fracture of C3. To relieve spinal cord compression and restore sagittal realignment, closed reduction was attempted, however this resulted in perching of the bilateral C7-T1 facets, leading to an open posterior approach. The patient underwent C7 laminectomy, bilateral C7-T1 facetectomy, and manual reduction using a Mayfield skull clamp followed by C2-T3 fixation. Postoperatively, pain was diminished, sensory disturbances were resolved and the patient was otherwise neurologically stable. DISCUSSION: There is a role for closed traction for reduction of cervical spondyloptosis, however, its role is debated especially when the patient is predominately neurologically intact. In this setting, the spine surgeon may be required to change traction and operative strategies in order to minimize potentially harmful manipulation while restoring sagittal realignment and stabilizing the spine for preservation of neurological function.

Patient Optimization for the Prevention of Proximal Junctional Kyphosis.

Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are well-recognized challenges of surgery for adult spinal deformity (ASD). Multiple risk factors have been identified for PJK/PJF, including osteoporosis, frailty, neurodegenerative disease, obesity, and smoking. Several surgical techniques to mitigate risk of PJK/PJF have been identified; however, patient optimization is also critical. This review summarizes the data behind these 5 risk factors (osteoporosis, frailty, neurodegenerative disease, obesity, and smoking) and details the related recommendations for patients undergoing surgery for ASD.

A novel rodent model of chronic spinal implant-associated infection.

BACKGROUND CONTEXT: Bacterial infection of spinal instrumentation is a significant challenge in spinal fusion surgery. Although the intraoperative local application of powdered vancomycin is common practice for mitigating infection, the antimicrobial effects of this route of administration are short-lived. Therefore, novel antibiotic-loaded bone grafts as well as a reliable animal model to permit the testing of such therapies are needed to improve the efficacy of infection reduction practices in spinal fusion surgery. PURPOSE: This study aims to establish a clinically relevant rat model of spinal implant-associated infection to permit the evaluation of antimicrobial bone graft materials used in spinal fusion. STUDY DESIGN: Rodent study of chronic spinal implant-associated infection. METHODS: Instrumentation anchored in and spanning the vertebral bodies of L4 and L5 was inoculated with bioluminescent methicillin-resistant Staphylococcus aureus bacteria (MRSA). Infection was monitored using an in vivo imaging system (IVIS) for 8 weeks. Spines were harvested and evaluated histologically, and colony-forming units (CFUs) were quantified in harvested implants and spinal tissue. RESULTS: Postsurgical analysis of bacterial infection in vivo demonstrated stratification between MRSA and phosphate-buffered saline (PBS) control groups during the first 4 weeks of the 8-week infection period, indicating the successful establishment of acute infection. Over the 8-week chronic infection period, groups inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU demonstrated significantly higher bioluminescence than groups inoculated with PBS control (p = 0.009 and p = 0.041 respectively). Histological examination at 8 weeks postimplantation revealed the presence of abscesses localized to implant placement in all MRSA inoculation groups, with the most pervasive abscess formation in samples inoculated with 1 × 105 MRSA CFU and 1 × 106 MRSA CFU. Quantification of CFU plated from harvested spinal tissue at 8 weeks post-implantation revealed the 1 × 105 MRSA CFU inoculation group as the only group with a significantly greater average CFU count compared to PBS control (p = 0.017). Further, CFU quantification from harvested spinal tissue was greater than CFU quantification from harvested implants across all inoculation groups. CONCLUSION: Our model demonstrated that the inoculation dosage of 1 × 105 MRSA CFU exhibited the most robust chronic infection within instrumented vertebral bodies. This dosage had the greatest difference in bioluminescence signal from control (p < 0.01), the lowest mortality (0% compared to 50% for samples inoculated with 1 × 106 MRSA CFU), and a significantly higher amount of CFUs from harvested spine samples than CFUs from control harvested spine samples. Further, histological analysis confirmed the reliability of this novel rodent model of implanted-associated infection to establish infection and biofilm formation of MRSA for all inoculation groups. CLINICAL SIGNIFICANCE: This model is intended to simulate the infection of instrumentation used in spinal fusion surgeries concerning implant locality and material. This model may evaluate potential antimicrobial and osteogenic biomaterials and investigate the relationship between implant-associated infection and failed fusion.

Spinal dysraphism in exstrophy: a single-center study of a 39-year prospective database.

OBJECTIVE: The two main objectives of this study were to explore the rate of spinal dysraphism within bladder and cloacal exstrophy and to analyze the relationship between spinal dysraphism surgery, including timing of spinal dysraphism surgery, with urological and neurological outcomes. METHODS: A prospectively maintained IRB-approved database of pediatric exstrophy patients treated from 1982 to 2021 was retrospectively reviewed for patients with spinal dysraphism. Spinal dysraphism was categorized into the following 7 subtypes: lipoma-based closed defect, myelomeningocele, meningocele, diastematomyelia, myelocystocele, low-lying conus with tethered cord/fatty filum, and sacral bony defect. Other factors assessed included patient demographic characteristics, type of spinal dysraphism procedure, reoperation, complication, presence of other neurological problems (e.g., hydrocephalus, Chiari malformation), neurological status, and urological function. RESULTS: Analysis revealed that 114/1401 patients had coexisting spinal dysraphism. Of these 114, sufficient records including type of dysraphism were available for 54. Spinal dysraphism was most common within cloacal exstrophy (83.3% [45/54 patients]), followed by cloacal exstrophy variants (9.3% [5/54]), classic bladder exstrophy (3.7% [2/54]), and classic bladder exstrophy variants (3.7% [2/54]). Within spinal dysraphism, lipoma-based closed defects (63.0% [34/54]) and low-lying conus with tethered cord/fatty filum (11.1% [6/54]) were most common. Hydrocephalus and Chiari malformation occurred in 24.1% (13/54) and 11.1% (6/54) of patients. All 13 patients with hydrocephalus underwent shunt placement. Among those who underwent neurosurgical intervention, the complication rate for spinal dysraphism was 14.6% (7/48). Motor function data were available for 41 patients and revealed that motor function declined for 2/41 (4.8%) patients and improved for 6/41 (14.6%) after neurosurgery. There was no statistical difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure. CONCLUSIONS: The authors have reported the surgical management and outcomes of patients with exstrophy and coexisting spinal dysraphism (n = 54). In 54 patients, spinal dysraphism was most common in the subset of patients with cloacal exstrophy (83.3%). Lipoma-based closed defects (63.0%) and low-lying conus with tethered cord/fatty filum (11.1%) were the most common, and the rates of hydrocephalus and Chiari malformation were 24.1% and 11.1%, respectively. There was no difference in lower-extremity motor outcome related to timing of neurosurgery and exstrophy closure.

The abscopal effect: inducing immunogenicity in the treatment of brain metastases secondary to lung cancer and melanoma.

PURPOSE: The phenomenon of radiation therapy (RT) causing regression of targeted lesions as well as lesions outside of the radiation field is known as the abscopal effect and is thought to be mediated by immunologic causes. This phenomena has been described following whole brain radiation (WBRT) and stereotactic radiosurgery (SRS) of brain metastasis (BM) in advanced melanoma and non-small-cell lung cancer (NSCLC). We systematically reviewed the available literature to identify which radiation modality and immunotherapy (IT) combination may elicit the abscopal effect, the optimal timing of RT and IT, and potential adverse effects inherent to the combination of RT and IT. METHODS: Using PRISMA guidelines, a search of PubMed, Medline, and Web of Science was conducted to identify studies demonstrating the abscopal effect during treatment of NSCLC or melanoma with BM. RESULTS: 598 cases of irradiated BM of melanoma or NSCLC in 18 studies met inclusion criteria. The most commonly administered ITs included PD-1 or CTLA-4 immune checkpoint inhibitors (ICI), with RT most commonly administered within 3 months of ICI. Synergy between ICI and RT was described in 16 studies including evidence of higher tumor response within and outside of the irradiated field. In the 12 papers (n = 232 patients) that reported objective response rate (ORR) in patients with BM treated with RT and concurrent systemic IT, the non-weighted mean ORR was 49.4%; in the 5 papers (n = 110 patients) that reported ORR for treatment with RT or IT alone, the non-weighted mean ORR was 27.8%. No studies found evidence of significantly increased toxicity in patients receiving RT and ICI. CONCLUSION: The combination of RT and ICIs may enhance ICI efficacy and induce more durable responses via the abscopal effect in patients with brain metastases of melanoma or NSCLC.

Fine motor deficits exhibited in rat string-pulling behavior following exposure to sleep fragmentation and deep space radiation.

Deep space flight missions will expose astronauts to multiple stressors, including sleep fragmentation and space radiation. There is debate over whether sleep disruptions are an issue in deep space. While these stressors independently impair sensorimotor function, the combined effects on performance are currently unknown. String-pulling behavior involves highly organized bimanual reach-to-grasp and withdraw movements. This behavior was examined under rested wakeful conditions and immediately following one session of sleep fragmentation in Sham and irradiated rats 3 months after exposure (10 cGy 4Helium or 5-ion simulated Galactic Cosmic Radiation). Sleep fragmentation disrupted several aspects of string-pulling behavior, such that rats' ability to grasp the string was reduced, reach endpoint concentration was more variable, and distance traveled by the nose increased in the Y-range compared to rested wakeful performance. Overall, irradiated rats missed the string more than Sham rats 3 months post-exposure. Irradiated rats also exhibited differential impairments at 3 months, with additional deficits unveiled after sleep fragmentation. 4Helium-exposed rats took longer to approach the string after sleep fragmentation. Further, rats exposed to 4Helium traveled shorter withdraw distances 3 months after irradiation, while this only emerged in the other irradiated group after sleep fragmentation. These findings identify sleep fragmentation as a risk for fine motor dysfunction in Sham and irradiated conditions, in addition to radiation exposure. There may be complex temporal alterations in performance that are stressor- and ion-dependent. Thus, it is critical to implement appropriate models of multi-flight stressors and performance assessments in preparation for future deep space flight missions.

Management of traumatic sacral spondyloptosis: illustrative case.

BACKGROUND: Grade V spondylolisthesis, or spondyloptosis, is a complication of high-energy trauma that is most commonly reported at the lumbosacral junction. Sacral intersegmental spondyloptosis is extremely rare. The authors present a case of spondyloptosis of S1 on S2 with a comminuted fracture of S2 and complex fractures of the L4 and L5 transverse processes, resulting in severe stenosis of the lumbosacral nerve roots. OBSERVATIONS: The patient was a 70-year-old woman with a history of a fall 3 weeks prior and progressive L5 and S1 radiculopathy. Instrumentation and fusion were undertaken, extending from L3 to the pelvis because degenerative stenosis at L3-4 and L4-5 was also found. Reduction was achieved, leading to diminished pain and partial resolution of weakness. LESSONS: Traumatic sacral spondyloptosis adds a degree of difficulty to reduction, fixation, and fusion. The technique presented herein achieved sagittal realignment via a distraction maneuver of S1-2 in which rods were attached to bilateral dual S2 alar-iliac screws with reduction screws placed at S1, ultimately pulling L5 and S1 up to the rod for fixation.

CD40-CD40L in Neurological Disease.

Immune-inflammatory conditions in the central nervous system (CNS) rely on molecular and cellular interactions which are homeostatically maintained to protect neural tissue from harm. The CD40-CD40L interaction upregulates key proinflammatory molecules, a function best understood in the context of infection, during which B-cells are activated via CD40 signaling to produce antibodies. However, the role of CD40 in neurological disease of non-infectious etiology is unclear. We review the role of CD40-CD40L in traumatic brain injury, Alzheimer's Disease, Parkinson's Disease, stroke, epilepsy, nerve injury, multiple sclerosis, ALS, myasthenia gravis and brain tumors. We also highlight therapeutic advancements targeting the CD40 system to either attenuate the neuroinflammatory response or leverage the downstream effects of CD40 signaling for direct tumor cell lysis.