The role of frailty in the clinical management of neurofibromatosis type 1: a mixed-effects modeling study using the Nationwide Readmissions Database.

OBJECTIVE: Frailty embodies a state of increased medical vulnerability that is most often secondary to age-associated decline. Recent literature has highlighted the role of frailty and its association with significantly higher rates of morbidity and mortality in patients with CNS neoplasms. There is a paucity of research regarding the effects of frailty as it relates to neurocutaneous disorders, namely, neurofibromatosis type 1 (NF1). In this study, the authors evaluated the role of frailty in patients with NF1 and compared its predictive usefulness against the Elixhauser Comorbidity Index (ECI). METHODS: Publicly available 2016-2017 data from the Nationwide Readmissions Database was used to identify patients with a diagnosis of NF1 who underwent neurosurgical resection of an intracranial tumor. Patient frailty was queried using the Johns Hopkins Adjusted Clinical Groups frailty-defining indicator. ECI scores were collected in patients for quantitative measurement of comorbidities. Propensity score matching was performed for age, sex, ECI, insurance type, and median income by zip code, which yielded 60 frail and 60 nonfrail patients. Receiver operating characteristic (ROC) curves were created for complications, including mortality, nonroutine discharge, financial costs, length of stay (LOS), and readmissions while using comorbidity indices as predictor values. The area under the curve (AUC) of each ROC served as a proxy for model performance. RESULTS: After propensity matching of the groups, frail patients had an increased mean ± SD hospital cost ($85,441.67 ± $59,201.09) compared with nonfrail patients ($49,321.77 ± $50,705.80) (p = 0.010). Similar trends were also found in LOS between frail (23.1 ± 14.2 days) and nonfrail (10.7 ± 10.5 days) patients (p = 0.0020). For each complication of interest, ROC curves revealed that frailty scores, ECI scores, and a combination of frailty+ECI were similarly accurate predictors of variables (p > 0.05). Frailty+ECI (AUC 0.929) outperformed using only ECI for the variable of increased LOS (AUC 0.833) (p = 0.013). When considering 1-year readmission, frailty (AUC 0.642) was outperformed by both models using ECI (AUC 0.725, p = 0.039) and frailty+ECI (AUC 0.734, p = 0.038). CONCLUSIONS: These findings suggest that frailty and ECI are useful in predicting key complications, including mortality, nonroutine discharge, readmission, LOS, and higher costs in NF1 patients undergoing intracranial tumor resection. Consideration of a patient's frailty status is pertinent to guide appropriate inpatient management as well as resource allocation and discharge planning.

Investigating the blood-spinal cord barrier in preclinical models: a systematic review of in vivo imaging techniques.

STUDY DESIGN: This study is a systematic review. OBJECTIVES: To evaluate current in vivo techniques used in the investigation of the blood-spinal cord barrier (BSCB). METHODS: Search of English language literature for animal studies that investigated the BSCB in vivo. Data extraction included animal model/type, protocol for BSCB evaluation, and study outcomes. Descriptive syntheses are provided. RESULTS: A total of 40 studies were included, which mainly investigated rodent models of experimental autoimmune encephalomyelitis (EAE) or spinal cord injury (SCI). The main techniques used were magnetic resonance imaging (MRI) and intravital microscopy (IVM). MRI served as a reliable tool to longitudinally track BSCB permeability changes with dynamic contrast enhancement (DCE) using gadolinium, or assess inflammatory infiltrations with targeted alternative contrast agents. IVM provided high-resolution visualization of cellular and molecular interactions across the microvasculature, commonly with either epi-fluorescence or two-photon microscopy. MRI and IVM techniques enabled the evaluation of therapeutic interventions and mechanisms that drive spinal cord dysfunction in EAE and SCI. A small number of studies demonstrated the feasibility of DCE-computed tomography, ultrasound, bioluminescent, and fluorescent optical imaging methods to evaluate the BSCB. Technique-specific limitations and multiple protocols for image acquisition and data analyses are described for all techniques. CONCLUSION: There are few in vivo investigations of the BSCB. Additional studies are needed in less commonly studied spinal cord disorders, and to establish standardized protocols for data acquisition and analysis. Further development of techniques and multimodal approaches could overcome current imaging limitations to the spinal cord. These advancements might promote wider adoption of techniques, and can provide greater potential for clinical translation.

Transcranial eddy current damping sensors for detection and imaging of hemorrhagic stroke: feasibility in benchtop experimentation.

OBJECTIVE: Spontaneous intracerebral hemorrhage occurs in an estimated 10% of stroke patients, with high rates of associated mortality. Portable diagnostic technologies that can quickly and noninvasively detect hemorrhagic stroke may prevent unnecessary delay in patient care and help rapidly triage patients with ischemic versus hemorrhagic stroke. As such, the authors aimed to develop a rapid and portable eddy current damping (ECD) hemorrhagic stroke sensor for proposed in-field diagnosis of hemorrhagic stroke. METHODS: A tricoil ECD sensor with microtesla-level magnetic field strengths was constructed. Sixteen gelatin brain models with identical electrical properties to live brain tissue were developed and placed within phantom skull replicas, and saline was diluted to the conductivity of blood and placed within the brain to simulate a hemorrhage. The ECD sensor was used to detect modeled hemorrhages on benchtop models. Data were saved and plotted as a filtered heatmap to represent the lesion location. The individuals performing the scanning were blinded to the bleed location, and sensors were tangentially rotated around the skull models to localize blood. Data were also used to create heatmap images using MATLAB software. RESULTS: The sensor was portable (11.4-cm maximum diameter), compact, and cost roughly $100 to manufacture. Scanning time was 2.43 minutes, and heatmap images of the lesion were produced in near real time. The ECD sensor accurately predicted the location of a modeled hemorrhage in all (n = 16) benchtop experiments with excellent spatial resolution. CONCLUSIONS: Benchtop experiments demonstrated the proof of concept of the ECD sensor for rapid transcranial hemorrhagic stroke diagnosis. Future studies with live human participants are warranted to fully establish the feasibility findings derived from this study.

A systematic review of next-generation point-of-care stroke diagnostic technologies.

OBJECTIVE: Stroke is a leading cause of morbidity and mortality. Current diagnostic modalities include CT and MRI. Over the last decade, novel technologies to facilitate stroke diagnosis, with the hope of shortening time to treatment and reducing rates of morbidity and mortality, have been developed. The authors conducted a systematic review to identify studies reporting on next-generation point-of-care stroke diagnostic technologies described within the last decade. METHODS: A systematic review was performed according to PRISMA guidelines to identify studies reporting noninvasive stroke diagnostics. The QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool was utilized to assess risk of bias. PubMed, Web of Science, and Scopus databases were utilized. Primary outcomes assessed included accuracy and timing compared with standard imaging, potential risks or complications, potential limitations, cost of the technology, size/portability, and range/size of detection. RESULTS: Of the 2646 reviewed articles, 19 studies met the inclusion criteria and included the following modalities of noninvasive stoke detection: microwave technology (6 studies, 31.6%), electroencephalography (EEG; 4 studies, 21.1%), ultrasonography (3 studies, 15.8%), near-infrared spectroscopy (NIRS; 2 studies, 10.5%), portable MRI devices (2 studies, 10.5%), volumetric impedance phase-shift spectroscopy (VIPS; 1 study, 5.3%), and eddy current damping (1 study, 5.3%). Notable medical devices that accurately predicted stroke in this review were EEG-based diagnosis, with a maximum sensitivity of 91.7% for predicting a stroke, microwave-based diagnosis, with an area under the receiver operating characteristic curve (AUC) of 0.88 for differentiating ischemic stroke and intracerebral hemorrhage (ICH), ultrasound with an AUC of 0.92, VIPS with an AUC of 0.93, and portable MRI with a diagnostic accuracy similar to that of traditional MRI. NIRS offers significant potential for more superficially located hemorrhage but is limited in detecting deep-seated ICH (2.5-cm scanning depth). CONCLUSIONS: As technology and computational resources have advanced, several novel point-of-care medical devices show promise in facilitating rapid stroke diagnosis, with the potential for improving time to treatment and informing prehospital stroke triage.

Posterolateral cervical transpedicular corpectomy for the surgical management of metastatic tumor.

Management of metastatic spinal disease in the upper cervical spine can be particularly challenging. Depending on the level of the lesion and the patient's anatomy, multiple anterior approaches have been described for resection of the cancer, followed by posterior fixation and instrumentation. Although a single-stage posterolateral approach is now well established for thoracic pathology, less is known about the applicability of these principles when applied as an approach to the cervical spine. The authors present here a case using a posterolateral transpedicular approach for corpectomy and graft placement for circumferential reconstruction as a treatment of metastatic disease in the cervical spine to illustrate the feasibility of this technique, especially in the setting where the patient's anatomy or pathology may impede an anterior or combined circumferential approach.

Combined Direct and Indirect Cerebral Revascularization Using Local and Flow-Through Flaps.

BACKGROUND: Extracranial-intracranial bypass is indicated in ischemic disease such as moyamoya, certain intracranial aneurysms, and other complex neurovascular diseases. In this article, we present our series of local and flow-through flaps for cerebral revascularization as an additional tool to provide direct and indirect revascularization and/or soft tissue coverage. METHODS: A retrospective review of a prospectively maintained database was performed identifying nine patients. Ten direct arterial bypass procedures with nine indirect revascularization and/or soft tissue reconstruction were performed. RESULTS: Indications for arterial bypass included intracranial aneurysm (n = 2) and moyamoya disease (n = 8). Indications for soft tissue transfer included infected cranioplasty (one) and indirect cerebral revascularization (eight). Four flow-through flaps and five pedicled flaps were used including a flow-through radial forearm fasciocutaneous flap (one), flow-through radial forearm fascial flaps (three), and pedicled temporoparietal fascial (TPF) flaps with distal end anastomosis (five). The superficial temporal vessels (seven) and facial vessels (two) were used as the vascular inflow. Arterial bypass was established into the middle cerebral artery (six) and anterior communicating artery (three). There were no intraoperative complications. All flaps survived with no donor-site complications. In one case of flow-through TPF flap, the direct graft failed, but the indirect flap remained vascularized. CONCLUSION: Local and flow-through flaps can improve combined direct and indirect revascularization and provide soft tissue reconstruction. Minimal morbidity has been encountered in early outcomes though long-term results remain under investigation for these combined neurosurgery and plastic surgery procedures. LEVEL OF EVIDENCE: The level of evidence is IV.

Dimensions of the cervical neural foramen in conditions of spinal deformity: an ex vivo biomechanical investigation using specimen-specific CT imaging.

PURPOSE: Patients with cervical spondylosis commonly present with neck pain, radiculopathy or myelopathy. As degenerative changes progress, multiple factors including disc height loss, thoracic kyphosis, and facetogenic changes can increase the risk of neural structure compression. This study investigated the impact of cervical deformity including forward head posture (FHP) and upper thoracic kyphosis, on the anatomy of the cervical neural foramen. METHODS: Postural changes of 13 human cervical spine specimens (Occiput-T1, age 50.6 years; range 21-67) were assessed in response to prescribed cervical sagittal malalignments using a previously reported experimental model. Two characteristics of cervical sagittal deformities, C2-C7 sagittal vertical alignment (SVA) and sagittal angle of the T1 vertebra (T1 tilt), were varied to create various cervical malalignments. The postural changes were documented by measuring vertebral positions and orientations. The vertebral motion data were combined with specimen-specific CT-based anatomical models, which allowed assessments of foraminal areas of subaxial cervical segments as a function of increasing C2-C7 SVA and changing T1 tilt. RESULTS: Increasing C2-C7 SVA from neutral posture resulted in increased neural foraminal area in the lower cervical spine (largest increase at C4-C5: 13.8 ± 15.7 %, P < 0.01). Increasing SVA from a hyperkyphotic posture (greater T1 tilt) also increased the neural foraminal area in the lower cervical segments (C5-C6 demonstrated the largest increase: 13.4 ± 9.6 %, P < 0.01). The area of the cervical neural foramen decreased with increasing T1 tilt, with greater reduction occurring in the lower cervical spine, specifically at C5-C6 (-8.6 ± 7.0 %, P < 0.01) and C6-C7 (-9.6 ± 5.6 %, P < 0.01). CONCLUSION: An increase in thoracic kyphosis (T1 tilt) decreased cervical neural foraminal areas. In contrast, an increase in cervical SVA increased the lower cervical neural foraminal areas. Patients with increased upper thoracic kyphosis may respond with increased cervical SVA as a compensatory mechanism to increase their lower cervical neural foraminal area.

Bioluminescent imaging of drug efflux at the blood-brain barrier mediated by the transporter ABCG2.

ATP-binding cassette (ABC) transporters are a group of transmembrane proteins that maintain chemical homeostasis through efflux of compounds out of organelles and cells. Among other functions, ABC transporters play a key role in protecting the brain parenchyma by efflux of xenobiotics from capillary endothelial cells at the blood-brain barrier (BBB). They also prevent the entry of therapeutic drugs at the BBB, thereby limiting their efficacy. One of the key transporters playing this role is ABCG2. Although other ABC transporters can be studied through various imaging modalities, no specific probe exists for imaging ABCG2 function in vivo. Here we show that D-luciferin, the endogenous substrate of firefly luciferase, is a specific substrate for ABCG2. We hypothesized that ABCG2 function at the BBB could be evaluated by using bioluminescence imaging in transgenic mice expressing firefly luciferase in the brain. Bioluminescence signal in the brain of mice increased with coadministration of the ABCG2 inhibitors Ko143, gefitinib, and nilotinib, but not an ABCB1 inhibitor. This method for imaging ABCG2 function at the BBB will facilitate understanding of the function and pharmacokinetic inhibition of this transporter.

Versatile utilization of real-time intraoperative contrast-enhanced ultrasound in cranial neurosurgery: technical note and retrospective case series.

OBJECTIVE: Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series. METHODS: Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions. RESULTS: Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis. CONCLUSIONS: Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of extent of resection. Further prospective studies will help standardize the role of iCEUS in neurosurgery.

Risk factors associated with the surgical management of craniopharyngiomas in pediatric patients: analysis of 1961 patients from a national registry database.

OBJECTIVE Patient demographic characteristics, hospital volume, and admission status have been shown to impact surgical outcomes of sellar region tumors in adults; however, the data available following the resection of craniopharyngiomas in the pediatric population remain limited. The authors sought to identify potential risk factors associated with outcomes following surgical management of pediatric craniopharyngiomas. METHODS The Nationwide Inpatient Sample database and Kids' Inpatient Database were analyzed to include admissions for pediatric patients (≤ 18 years) who underwent a transcranial or transsphenoidal craniotomy for resection of a craniopharyngioma. Patient-level factors, including age, race, comorbidities, and insurance type, as well as hospital factors were collected. Outcomes analyzed included mortality rate, endocrine and nonendocrine complications, hospital charges, and length of stay. A multivariate model controlling for variables analyzed was constructed to examine significant independent risk factors. RESULTS Between 2000 and 2011, 1961 pediatric patients were identified who underwent a transcranial (71.2%) or a transsphenoidal (28.8%) craniotomy for resection of a craniopharyngioma. A major predilection for age was observed with the selection of a transcranial (23.4% in < 7-year-olds, 28.1% in 7- to 12-year-olds, and 19.7% in 13- to 18-year-olds) versus transphenoidal (2.9% in < 7-year-olds, 7.4% in 7- to 12-year-olds, and 18.4% in 13- to 18-year-olds) approach. No significant outcomes were associated with a particular surgical approach, except that 7- to 12-year-old patients had a higher risk of nonendocrine complications (relative risk [RR] 2.42, 95% CI 1.04-5.65, p = 0.04) with the transsphenoidal approach when compared with 13- to 18-year-old patients. The overall inpatient mortality rate was 0.5% and the most common postoperative complication was diabetes insipidus (64.2%). There were no independent factors associated with inpatient mortality rates and no significant differences in outcomes among groups based on sex and race. The average length of stay was 11.8 days, and the mean hospital charge was $116,5 22. Hospitals with medium and large bed capacity were protective against nonendocrine complications (RR 0.53, 95% CI 0.3-0.93, p = 0.03 [medium]; RR 0.45, 95% CI 0.25-0.8, p < 0.01 [large]) and total complications (RR 0.73, 95% CI 0.55-0.97, p = 0.03 [medium]; RR 0.68, 95% CI 0.51-0.9, p < 0.01 [large]) when compared with hospitals with small bed capacity (< 200 beds). Patients admitted to rural hospitals had an increased risk for nonendocrine complications (RR 2.56, 95% CI 1.11-5.9, p = 0.03). The presence of one or more medical comorbidities increased the risk of higher total complications (RR 1.38, 95% CI 1.14-1.68), p < 0.01 [1 comorbidity]; RR 2.37, 95% CI 1.98-2.84, p < 0.01 [≥ 2 comorbidities]) and higher total hospital charges (RR 2.9, 95% CI 1.08-7.81, p = 0.04 [1 comorbidity]; RR 9.1, 95% CI 3.74-22.12, p < 0.01 [≥ 2 comorbidities]). CONCLUSIONS This analysis identified patient age, comorbidities, insurance type, hospital bed capacity, and rural or nonteaching hospital status as independent risk factors for postoperative complications and/or increased hospital charges in pediatric patients with craniopharyngioma. Transsphenoidal surgery in younger patients with craniopharyngioma was a risk factor for nonendocrine complications.

Upward transtentorial herniation following frontoorbital advancement for syndromic craniosynostosis: case report.

The authors describe the case of a boy with Muenke syndrome, an autosomal dominant disorder associated with craniosynostosis. The family history was significant for syndromic craniosynostosis in the patient's maternal grandmother, who died in adulthood after a craniofacial reconstruction. The patient, her grandson, underwent craniofacial reconstruction surgery at the age of 9 months and developed upward transtentorial herniation. Imaging findings revealed remote cerebellar hemorrhage after a large quantity of supratentorial CSF was drained during postoperative Day 1. The clinical course was further complicated by cerebral sinus thrombosis, which was diagnosed after a fourth surgical procedure. Upward transtentorial herniation can occur when a significant increase in intracranial pressure in the posterior fossa causes displacement of the central lobule and superior surfaces of the cerebellum upward through the incisura tentorii. This is a rare but well-documented phenomenon that commonly occurs in the setting of an expansive posterior fossa lesion or excessive supratentorial CSF loss. To help clinicians recognize and prevent this rare but potentially fatal complication, the authors review the postulated mechanisms by which this process may occur.

Evidence-based management of traumatic thoracolumbar burst fractures: a systematic review of nonoperative management.

OBJECT: The overall evidence for nonoperative management of patients with traumatic thoracolumbar burst fractures is unknown. There is no agreement on the optimal method of conservative treatment. Recent randomized controlled trials that have compared nonoperative to operative treatment of thoracolumbar burst fractures without neurological deficits yielded conflicting results. By assessing the level of evidence on conservative management through validated methodologies, clinicians can assess the availability of critically appraised literature. The purpose of this study was to examine the level of evidence for the use of conservative management in traumatic thoracolumbar burst fractures. METHODS: A comprehensive search of the English literature over the past 20 years was conducted using PubMed (MEDLINE). The inclusion criteria consisted of burst fractures resulting from a traumatic mechanism, and fractures of the thoracic or lumbar spine. The exclusion criteria consisted of osteoporotic burst fractures, pathological burst fractures, and fractures located in the cervical spine. Of the studies meeting the inclusion/exclusion criteria, any study in which nonoperative treatment was used was included in this review. RESULTS: One thousand ninety-eight abstracts were reviewed and 447 papers met inclusion/exclusion criteria, of which 45 were included in this review. In total, there were 2 Level-I, 7 Level-II, 9 Level-III, 25 Level-IV, and 2 Level-V studies. Of the 45 studies, 16 investigated conservative management techniques, 20 studies compared operative to nonoperative treatments, and 9 papers investigated the prognosis of conservative management. CONCLUSIONS: There are 9 high-level studies (Levels I-II) that have investigated the conservative management of traumatic thoracolumbar burst fractures. In neurologically intact patients, there is no superior conservative management technique over another as supported by a high level of evidence. The conservative technique can be based on patient and surgeon preference, comfort, and access to resources. A high level of evidence demonstrated similar functional outcomes with conservative management when compared with open surgical operative management in patients who were neurologically intact. The presence of a neurological deficit is not an absolute contraindication for conservative treatment as supported by a high level of evidence. However, the majority of the literature excluded patients with neurological deficits. More evidence is needed to further classify the appropriate burst fractures for conservative management to decrease variables that may impact the prognosis.

Surgical management of spinal pathologies in the octogenarian: a narrative review.

Optimal management paradigms of spinal pathologies in the octogenarian population are controversial given the higher incidence of comorbidities with concern for poor prognosis and fear of increased complications associated with surgical management. In this narrative review, we aim to detail the complex clinical considerations when approaching odontoid screw fixation/instrumented fusion, spinal decompression, and spinal fusion in the octogenarian. Literature review was conducted via Google Scholar and PubMed databases, with literature selected based on statistical power and clinical relevance to the following pathologies/surgical techniques: odontoid fracture, surgical decompression, and surgical fusion in the octogenarian. The aforementioned pathologies were selected based on prevalence in the advanced-age population in which surgical screening techniques and management remain nonuniform. Preoperative evaluation of the octogenarian patient increasingly includes frailty, sarcopenia, and osteopenia/osteoporosis assessments. In cases of odontoid fracture, conservative management appears to provide beneficial clinical outcomes with lower rates of complication compared to surgery; however, rates of radiographic odontoid fusion are far lower in conservatively managed patients. Regarding surgical decompression and fusion, the presence of comorbidities may be more predictive of outcome rather than age status, with the advent of minimally invasive techniques providing safety and efficacy in the surgical management of this age cohort. Age status may be less pertinent than previously thought in the decision to pursue spinal surgery for odontoid fracture, spinal decompression, or spinal fusion; however, each of these procedures has respective risks and benefits that must be considered within the context of each patient's comorbidity profile.

Prospective Validation of the Spinal Cord Shape Classification System in the Prediction of Intraoperative Neuromonitoring Data Loss: Assessing the Risk of Spinal Cord Data Loss During Spinal Deformity Correction.

BACKGROUND: The Spinal Cord Shape Classification System (SCSCS) class has been associated with spinal cord monitoring data loss during spinal deformity surgery. The objective of the current study was to prospectively validate the SCSCS as a predictor of spinal cord monitoring data loss during spinal deformity surgery. METHODS: A prospective cohort study of consecutive patients who were undergoing primary deformity surgery at a single institution from 2018 to 2023 and whose major curve was in the spinal cord region was undertaken. Spinal cord morphology at the apex of the major curve on preoperative axial T2-weighted magnetic resonance imaging was used to categorize patients into 3 spinal cord shape types based on the SCSCS. The primary outcome was intraoperative neuromonitoring (IONM) data loss related to spinal cord dysfunction. Demographics and surgical and radiographic variables were compared between patients with IONM data loss and those without loss. Predictors of IONM loss were determined using bivariate and multivariable logistic regression analyses. RESULTS: A total of 256 patients (168 adult, 88 pediatric) were included and were separated into 3 SCSCS types: 110 (43.0%) with Type I, 105 (41.0%) with Type II, and 41 (16.0%) with Type III. IONM loss was observed in 30 (11.7%) of the 256 patients, including 7 (6.4%) of 110 with SCSCS Type I, 7 (6.7%) of 105 with Type II, and 16 (39.0%) of 41 with Type III. IONM loss was associated with SCSCS Type III, the preoperative deformity angular ratio, performance of 3-column osteotomies, greater operative time, greater transfusion volume, and greater postoperative sagittal corrections. SCSCS type was the strongest independent predictor of IONM data loss. SCSCS Type III had the greatest odds of IONM loss (odds ratio [OR] = 6.68, 95% confidence interval [CI] = 2.45 to 18.23 compared with Types I and II combined). The overall predictive performance with respect to IONM loss (area under the receiver operating characteristic curve = 0.827) was considered excellent. CONCLUSIONS: This prospective cohort study of patients undergoing spinal deformity correction confirmed that patients with a Type-III spinal cord shape had greater odds of IONM loss. Inclusion of the SCSCS in preoperative risk stratification and intraoperative management of spinal deformity corrective surgery is recommended. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Evaluating osteoporosis and bone quality in the aging spine: modern considerations for surgical management in the geriatric population.

Surgical management paradigms of spinal pathologies in the aging population carry inherent substantial risks, with surgical complications being more prevalent among patients with osteoporosis compared to those with normal bone mineral density. In this narrative review, we aim to highlight important clinical understanding and considerations in perioperative evaluation and management of patients elected to undergo spinal surgery. Osteoporosis is a well-defined risk factor for mechanical complications following spinal surgery, and as such, perioperative optimization of bone health in the setting of surgery for geriatric patients remains a critical research area alongside intraoperative surgical augmentation techniques. Surgical techniques to circumvent challenges with instrumentation of poor bone mineral density have included augmentation of pedicle screw fixation, including segmental bicortical screw fixation techniques, cement augmentation with fenestrated screws, or use of expandable pedicle screws to improve bone-implant interface. Judicious selection of treatment modalities and subsequent perioperative optimization is paramount to minimize surgical complications. Contemporary guidelines and evolving paradigms in perioperative evaluation, optimization, and management of the aging spine include the advent of quantitatively evaluating computed tomography (CT) via assessment of the magnitude of Hounsfield units. Prescribing pharmacotherapeutic agents and monitoring bone health requires a multidisciplinary team approach, including endocrinologists and geriatricians to coordinate high-quality care for advanced-age patients who require surgical management of their spinal disorders.

Knee flexion compensation in postoperative adult spinal deformity patients: implications for sagittal balance and clinical outcomes.

PURPOSE: To determine whether maintaining good sagittal balance with significant knee flexion (KF) constitutes a suboptimal outcome after adult spinal deformity (ASD) correction. METHODS: This single-center, single-surgeon retrospective study, assessed ASD patients who underwent posterior spinal fusion between 2014 and 2020. Inclusion criteria included meeting at least one of the following: PI-LL ≥ 25°, T1PA ≥ 20°, or CrSVA-H ≥ 2 cm. Those with lower-extremity contractures were excluded. Patients were classified into four groups based on their 6-week postoperative cranio-hip balance and KF angle, and followed for at least 2 years: Malaligned with Knee Flexion (MKF+) (CrSVA-H > 20 mm + KFA > 10), Malaligned without Knee Flexion (MKF-) (CrSVA-H > 20 mm + KFA < 10), Aligned without Knee Flexion (AKF-) (CrSVA-H < 20 mm + KFA < 10), and Aligned with Knee Flexion (AKF+) (CrSVA-H < 20 mm + KFA > 10). The primary outcomes of this study included one and two year reoperation rates. Secondy outcomes included clinical and patient reported outcomes. RESULTS: 263 patients (mean age 60.0 ± 0.9 years, 74.5% female, and mean Edmonton Frailty Score 3.3 ± 0.2) were included. 60.8% (160/263 patients) exhibited good sagittal alignment at 6-week postop without KF. Significant differences were observed in 1-year (p = 0.0482) and 2-year reoperation rates (p = 0.0374) across sub-cohorts, with the lowest and highest rates in the AKF- cohort (5%, n = 8) and MKF + cohort (16.7%, n = 4), respectively. Multivariable Cox regression demonstrated the AKF- cohort exhibited significantly better reoperation outcomes compared to other groups: AKF + (HR: 5.24, p = 0.025), MKF + (HR: 31.7, p < 0.0001), and MKF- (HR: 11.8, p < 0.0001). CONCLUSION: Our findings demonstrate that patients relying on knee flexion compensation in the early postoperative period have inferior outcomes compared to those achieving sagittal balance without knee flexion. When compared to malaligned patients, those with CrSVA-H < 20 mm and KFA > 10 degrees experience fewer early reoperations but similar delayed reoperation rates. This insight emphasizes the importance of considering knee compensation perioperatively when managing sagittal imbalance in clinical practice.

Overlapping substrate and inhibitor specificity of human and murine ABCG2.

ABCG2 (also known as breast cancer resistance protein) is an ATP-binding cassette (ABC) transporter localized to the plasma membrane where it mediates the efflux of xenobiotics, including potential therapeutics. Studies investigating Abcg2 function at the blood-brain barrier in mouse models are often compared with human ABCG2 function. It is critical to understand the nature of species differences between mouse and human ABCG2, since extrapolations are made from murine data to humans. Two independent drug-selected cell line pairs expressing human or mouse ABCG2 were compared for efflux of fluorescent substrates using flow cytometry. To this end, we developed and characterized a new mouse Abcg2-expressing subline that demonstrated efflux of known fluorescent ABCG2 substrates and increased resistance to mitoxantrone, which is reduced in the presence of the ABCG2 inhibitor Ko143. Our results indicate that the substrate specificity of human and mouse ABCG2 is very similar. We identified a new human and mouse ABCG2 substrate, a porphyrin analog, purpurin-18 (Pp-18), which is not a substrate for P-glycoprotein or multidrug resistance protein 1. The ability of inhibitors to block efflux activity of ABCG2 was assessed using Pp-18. Inhibitors also demonstrated similar effects on human and mouse ABCG2. Chrysin, benzoflavone, and cyclosporin A inhibited Pp-18 efflux in both human and mouse ABCG2. The similarity of the substrate and inhibitor specificity of human and mouse ABCG2 supports interpretation of mouse models in understanding the clinical, pharmacological, and physiologic roles of ABCG2.

The "Sandwich" Extended Pedicle Subtraction Osteotomy for the Treatment of Fixed Sagittal Malalignment: Technical Description, Case Series, and Early Results With 2-Year Outcomes.

BACKGROUND AND OBJECTIVES: Adult spinal deformity (ASD) with fixed sagittal malalignment (FSM) may require a pedicle subtraction osteotomy (PSO) for greater focal lordosis and restoration of global alignment. Despite growing trends in minimizing PSOs given their associated high risks, a considerable portion of patients with ASD still require a lumbar PSO most commonly because of iatrogenic flat back deformity. The purpose of this article is to describe a modified extended PSO technique with additional anterior column support coined the "sandwich" extended PSO (SE-PSO) to promote arthrodesis and report the outcomes in a consecutive case series. METHODS: Patients with ASD treated with a lumbar SE-PSO at a single institution from 2015 to 2020 were analyzed. Complications, radiographic data, and patient-reported outcomes were compared preoperatively, at immediate postoperative follow-up, and at a 2-year postoperative follow-up (FU). RESULTS: Fourteen patients who underwent revision operations for FSM were included. Improvements in segmental lordosis across the PSO site (14.8 ± 6.8 vs 39.9 ± 7.1, P < .0001), overall lumbar lordosis (14.6 ± 15.4 vs 44.6 ± 12.1, P < .0001), sacral slope (21.0 ± 10.5 31.1 ± 10.7, P = .0150), C7 sagittal vertical axis (140.1 ± 59.0 mm vs 35.9 ± 28.5, P < .0001), and spinopelvic mismatch (52.5 ± 21.3 vs 18.6 ± 14.1, P = .0001) were obtained in all patients. Eight patients experienced perioperative complications, with intraoperative durotomy being the most common (n = 7). Eight patients had a 2-year FU and demonstrated improvements in their segmental lordosis across the PSO site (14.3 ± 7.0 vs 41.3 ± 7.3, P = .0003), overall lumbar lordosis (8.7 ± 17.8 vs 46.1 ± 14.2, P = .0014), sacral slope (19.1 ± 12.8 vs 32.3 ± 12.5, P = .0479), C7 sagittal vertical axis (173.6 ± 54.4 mm vs 35.8 ± 30.0, P < .0001), and spinopelvic mismatch (63.0 ± 19.7 vs 21.1 ± 18.3, P < .0001), all of which were maintained at final FU (P > .05). At 2 years, a significant increase in Scoliosis Research Society-22r total score (2.5 ± 0.8 vs 3.6 ± 0.7, P = .0023 was reported. There were no reports of symptomatic pseudarthrosis or mechanical complications. CONCLUSION: SE-PSO is an effective technique to correct FSM and is associated with low complications, improved patient-reported outcomes, and spinopelvic parameters that are maintained at 2 years.

The performance of frailty in predictive modeling of short-term outcomes in the surgical management of metastatic tumors to the spine.

BACKGROUND CONTEXT: The concept of frailty has become increasingly recognized, and while patients with cancer are at increased risk for frailty, its influence on perioperative outcomes in metastatic spine tumors is uncertain. Furthermore, the impact of frailty can be confounded by comorbidities or metastatic disease burden. PURPOSE: The purpose of this study was to evaluate the influence of frailty and comorbidities on adverse outcomes in the surgical management of metastatic spine disease. STUDY DESIGN/SETTING: Retrospective analysis of a nationwide database to include patients undergoing spinal fusion for metastatic spine disease. PATIENT SAMPLE: A total of 1,974 frail patients who received spinal fusion with spinal metastasis, and 1,975 propensity score matched non-frail patients. OUTCOME MEASURES: Outcomes analyzed included mortality, complications, length of stay (LOS), nonroutine discharges and costs. METHODS: A validated binary frailty index (Johns Hopkins Adjusted Clinical Groups) was used to identify frail and non-frail groups, and propensity score-matched analysis (including demographics, comorbidities, surgical and tumor characteristics) was performed. Sub-group analysis of levels involved was performed for cervical, thoracic, lumbar and junctional spine. Multivariable-regression techniques were used to develop predictive models for outcomes using frailty and the Elixhauser Comorbidity Index (ECI). RESULTS: 7,772 patients underwent spinal fusion with spinal metastasis, of which 1,974 (25.4%) patients were identified as frail. Following propensity score matching for frail (n=1,974) and not-frail (n=1,975) groups, frailty demonstrated significantly greater medical complications (OR=1.58; 95% CI 1.33-1.86), surgical complications (OR=1.46; 95% CI 1.15-1.85), LOS (OR=2.65; 95% CI 2.09-3.37), nonroutine discharges (OR=1.79; 95% CI 1.46-2.20) and costs (OR=1.68; 95% CI 1.32-2.14). Differences in mortality were only observed in subgroup analysis and were greater in frail junctional and lumbar spine subgroups. Models using ECI alone (AUC=0.636-0.788) demonstrated greater predictive ability compared to those using frailty alone (AUC=0.633-0.752). However, frailty combined with ECI improved the prediction of increased LOS (AUC=0.811), cost (AUC=0.768), medical complications (AUC=0.723) and nonroutine discharges (AUC=0.718). Predictive modeling of frailty in subgroups demonstrated the greatest performance for mortality (AUC=0.750) in the lumbar spine, otherwise performed similarly for LOS, costs, complications, and discharge across subgroups. CONCLUSIONS: A high prevalence of frailty existed in the current patient cohort. Frailty contributed to worse short-term adverse outcomes and could be more influential in the lumbar and junctional spine due to higher risk of deconditioning in the postoperative period. Predictions for short term outcomes can be improved by adding frailty to comorbidity indices, suggesting a more comprehensive preoperative risk stratification should include frailty.

Evaluating the predictive value of comorbidity indices in pituitary surgery: a mixed-effects modeling study using the Nationwide Readmissions Database.

OBJECTIVE: Although pituitary adenomas (PAs) are common intracranial tumors, literature evaluating the utility of comorbidity indices for predicting postoperative complications in patients undergoing pituitary surgery remains limited, thereby hindering the development of complex models that aim to identify high-risk patient populations. We utilized comparative modeling strategies to evaluate the predictive validity of various comorbidity indices and combinations thereof in predicting key pituitary surgery outcomes. METHODS: The Nationwide Readmissions Database was used to identify patients who underwent pituitary tumor operations (n = 19,653) in 2016-2017. Patient frailty was assessed using the Johns Hopkins Adjusted Clinical Groups (ACG) System. The Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) were calculated for each patient. Five sets of generalized linear mixed-effects models were developed, using as the primary predictors 1) frailty, 2) CCI, 3) ECI, 4) frailty + CCI, or 5) frailty + ECI. Complications of interest investigated included inpatient mortality, nonroutine discharge (e.g., to locations other than home), length of stay (LOS) within the top quartile (Q1), cost within Q1, and 1-year readmission rates. RESULTS: Postoperative mortality occurred in 73 patients (0.4%), 1-year readmission was reported in 2994 patients (15.2%), and nonroutine discharge occurred in 2176 patients (11.1%). The mean adjusted all-payer cost for the procedure was USD $25,553.85 ± $26,518.91 (Q1 $28,261.20), and the mean LOS was 4.8 ± 7.4 days (Q1 5.0 days). The model using frailty + ECI as the primary predictor consistently outperformed other models, with statistically significant p values as determined by comparing areas under the curve (AUCs) for most complications. For prediction of mortality, however, the frailty + ECI model (AUC 0.831) was not better than the ECI model alone (AUC 0.831; p = 0.95). For prediction of readmission, the frailty + ECI model (AUC 0.617) was not better than the frailty model alone (AUC 0.606; p = 0.10) or the frailty + CCI model (AUC 0.610; p = 0.29). CONCLUSIONS: This investigation is to the authors' knowledge the first to implement mixed-effects modeling to study the utility of common comorbidity indices in a large, nationwide cohort of patients undergoing pituitary surgery. Knowledge gained from these models may help neurosurgeons identify high-risk patients who require additional clinical attention or resource utilization prior to surgical planning.