Opioid-related xylazine toxicity manifesting as myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema.

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022. A 27-year-old woman with opioid use disorder, active intravenous drug use, and prior bacteremia presented to our institution's emergency department (ED) with left lower extremity pain and associated weakness, new acute bilateral hearing loss, multiple electrolyte derangements, and cerebral infarcts followed by cerebral edema, leading to an emergent sub-occipital decompressive craniectomy and placement of an external ventricular drain. A definitive mechanism was not determined; however, we hypothesized that xylazine toxicity played a role in her clinical presentation, which could have future clinical implications, including the possibility to incorporate xylazine as part of toxicology screens.

Dose optimization of second window indocyanine green in meningioma patients.

OBJECTIVE: Surgery remains the first line treatment for meningiomas and can benefit from fluorescence-guided surgical techniques such as second-window indocyanine green (SWIG). In the current study, we compared the use of the standard SWIG dose of 5.0 mg/kg relative to 2.5 mg/kg indocyanine green (ICG) in meningioma patients. METHODS: Patients were prospectively enrolled in an IRB-approved study of SWIG and received either the standard dose of 5.0 mg/kg or a reduced dose of 2.5 mg/kg of ICG around 24 h prior to their surgery. Intraoperative near-infrared fluorescence imaging was performed with exo- and endoscopic systems. Signal-to-background ratio (SBR) was calculated to quantify fluorescence and was compared between 5.0 mg/kg and 2.5 mg/kg ICG. All patients received pre-operative MRI and, in select cases, the pre-operative MRI was correlated to intraoperative fluorescence imaging. RESULTS/DISCUSSION: In the current study, we found no significant difference in the SBR of meningiomas in patients that were administered with either 5.0 mg/kg or 2.5 mg/kg ICG. However, in five patients that received the standard-dose SWIG regimen of 5.0 mg/kg ICG we observed dose-related fluorescence quenching - referred to as "inversion" - that interfered with tumor visualization during fluorescence-guided surgery (FGS). When correlated to pre-operative MRI, a similar rim pattern was observed around the primary tumor on T2 FLAIR, which, in retrospect, could be used as a predictor for inversion during FGS in meningioma patients receiving standard-dose ICG. CONCLUSION: This study demonstrated that a reduced ICG dose was as effective as standard-dose SWIG in meningioma patients. We therefore recommend to adjust the standard ICG dose for meningioma patients to 2.5 mg/kg particularly when rim enhancement is observed on pre-operative T2 FLAIR.

Outcomes from 871,441 Consecutive Surgical Procedures without Overlap or with Maximally Permissible Non-Concurrent Overlap.

OBJECTIVE: To isolate the impact of subsumed surgery (a shorter procedure completed entirely during overlapping non-critical portions of a longer antecedent procedure) on patient outcomes. SUMMARY BACKGROUND DATA: The American College of Surgeons recently recommended the elimination of "concurrent surgery" with overlap during a procedure's critical portions. Guidelines for non-concurrent overlap have been established, but the safety of subsumed surgery remains to be examined. METHODS: All consecutive procedures from 2013 to 2021 within a multihospital academic medical center were included (n=871,441). Simple logistic regression was performed to compare postoperative events between patients undergoing non-overlap surgery (n=533,032) and completely subsumed surgery (n=11,319). Thereafter, coarsened exact matching was used to match patients with non-overlap and subsumed surgery 1:1 on CPT code, 18 demographic features, baseline health characteristics, and procedural variables (n=7,146). Exact-matched cases were subsequently limited to pairs performed by the same surgeon (n=5,028). Primary outcomes included 30-day readmission, ED visits, and reoperations. RESULTS: Univariate analysis suggested that subsumed surgery had a higher 30-day risk of readmission (OR 1.55, P<0.0001), ED evaluation (OR 1.19, P<0.0001), and reoperation (OR 1.98, P<0.0001). When comparison was limited to the exact same procedure and patients were matched on demographics and health characteristics, there were no outcome differences between patients with subsumed surgery and non-overlapping surgery, even when limiting analyses to the same surgeon. CONCLUSIONS: Similar surgeries for similar patients result in similar outcomes whether there is completely subsumed or no overlap. Individual surgeons performing a specific procedure have no outcome differences with subsumed and non-overlapping cases.

Low Household Income Increases Hospital Length of Stay and Decreases Home Discharge Rates in Lumbar Fusion.

STUDY DESIGN: Retrospective Matched Cohort Study. OBJECTIVES: Low median household income (MHI) has been correlated with worsened surgical outcomes, but few studies have rigorously controlled for demographic and medical factors at the patient level. This study isolates the relationship between MHI and surgical outcomes in a lumbar fusion cohort using coarsened exact matching. METHODS: Patients undergoing single-level, posterior lumbar fusion at a single institution were consecutively enrolled and retrospectively analyzed (n = 4263). Zip code was cross-referenced to census data to derive MHI. Univariate regression correlated MHI to outcomes. Patients with low MHI were matched to those with high MHI based on demographic and medical factors. Outcomes evaluated included complications, length of stay, discharge disposition, 30- and 90 day readmissions, emergency department (ED) visits, reoperations, and mortality. RESULTS: By univariate analysis, MHI was significantly associated with 30- and 90 day readmission, ED visits, reoperation, and non-home discharge, but not mortality. After exact matching (n = 270), low-income patients had higher odds of non-home discharge (OR = 2.5, P = .016) and higher length of stay (mean 100.2 vs 92.6, P = .02). There were no differences in surgical complications, ED visits, readmissions, or reoperations between matched groups. CONCLUSIONS: Low MHI was significantly associated with adverse short-term outcomes from lumbar fusion. A matched analysis controlling for confounding variables uncovered longer lengths of stay and higher rates of discharge to post-acute care (vs home) in lower MHI patients. Socioeconomic disparities affect health beyond access to care, worsen surgical outcomes, and impose costs on healthcare systems. Targeted interventions must be implemented to mitigate these disparities.

Association Between Race and Short-Term Outcomes Across 3988 Consecutive Single-Level Spinal Fusions.

BACKGROUND AND OBJECTIVES: Race has implications for access to medical care. However, the impact of race, after access to care has been attained, remains poorly understood. The objective of this study was to isolate the relationship between race and short-term outcomes across patients undergoing a single, common neurosurgical procedure. METHODS: In this retrospective cohort study, 3988 consecutive patients undergoing single-level, posterior-only open lumbar fusion at a single, multihospital, academic medical center were enrolled over a 6-year period. Among them, 3406 patients self-identified as White, and 582 patients self-identified as Black. Outcome disparities between all White patients vs all Black patients were estimated using logistic regression. Subsequently, coarsened exact matching controlled for outcome-mitigating factors; White and Black patients were exact-matched 1:1 on key demographic and health characteristics (matched n = 1018). Primary outcomes included 30-day and 90-day hospital readmissions, emergency department (ED) visits, reoperations, mortality, discharge disposition, and intraoperative complication. RESULTS: Before matching, Black patients experienced increased rate of nonhome discharge, readmissions, ED visits, and reoperations (all P < .001). After exact matching, Black patients were less likely to be discharged to home (odds ratio [OR] 2.68, P < .001) and had higher risk of 30-day and 90-day readmissions (OR 2.24, P < .001; OR 1.91, P < .001; respectively) and ED visits (OR 1.79, P = .017; OR 2.09, P < .001). Black patients did not experience greater risk of intraoperative complication (unintentional durotomy). CONCLUSION: Between otherwise homogenous spinal fusion cohorts, Black patients experienced unfavorable short-term outcomes. These disparities were not explained by differences in intraoperative complications. Further investigation must characterize and mitigate institutional and societal factors that contribute to outcome disparities.

Racial disparities in short-term spinal fusion outcomes across 4263 consecutive patients.

OBJECTIVE: Race plays a salient role in access to surgical care. However, few investigations have assessed the impact of race within surgical populations after care has been delivered. The objective of this study was to employ an exact matching protocol to a homogenous population of spine surgery patients in order to isolate the relationships between race and short-term postoperative outcomes. METHODS: In total, 4263 consecutive patients who underwent single-level, posterior-only lumbar fusion at a single multihospital academic medical center were retrospectively enrolled. Of these patients, 3406 patients self-identified as White and 857 patients self-identified as non-White. Outcomes were initially compared across all patients via logistic regression. Subsequently, White patients and non-White patients were exactly matched on the basis of key demographic and health characteristics (1520 matched patients). Outcome disparities were evaluated between the exact-matched cohorts. Primary outcomes were readmissions, emergency department (ED) visits, reoperations, mortality, intraoperative complications, and discharge disposition. RESULTS: Before matching, non-White patients were less likely to be discharged home and more likely to be readmitted, evaluated in the ED, and undergo reoperation. After matching, non-White patients experienced higher rates of nonhome discharge, readmissions, and ED visits. Non-White patients did not have more surgical complications either before or after matching. CONCLUSIONS: Between otherwise similar cohorts of spinal fusion cases, non-White patients experienced unfavorable discharge disposition and higher risk of multiple adverse postoperative outcomes. However, these findings were not accounted for by differences in surgical complications, suggesting that structural factors underlie the observed disparities.

A surgical decision aid for occipital neuralgia with literature review and single center case series.

BACKGROUND: Occipital neuralgia (ON) is a debilitating headache disorder. Due to the rarity of this disorder and lack of high-level evidence, a clear framework for choosing the optimal surgical approach for medically refractory ON incorporating shared decision making with patients does not exist. METHODS: A literature review of studies reporting pain outcomes of patients who underwent surgical treatment for ON was performed, as well as a retrospective chart review of patients who underwent surgery for ON within our institution. RESULTS: Thirty-two articles met the inclusion criteria. A majority of the articles were retrospective case series (22/32). The mean number of patients across the studies was 34 (standard deviation (SD) 39). Among the 13 studies that reported change in pain score on 10-point scales, a study of 20 patients who had undergone C2 and/or C3 ganglionectomies reported the greatest reduction in pain intensity after surgery. The studies evaluating percutaneous ablative methods including radiofrequency ablation and cryoablation showed the smallest reduction in pain scores overall. At our institution from 2014 to 2023, 11 patients received surgical treatment for ON with a mean follow-up of 187 days (SD 426). CONCLUSION: Based on these results, the first decision aid for selecting a surgical approach to medically refractory ON is presented. The algorithm prioritizes nerve sparing followed by non-nerve sparing techniques with the incorporation of patient preference. Shared decision making is critical in the treatment of ON given the lack of clear scientific evidence regarding the superiority of a particular surgical method.

The Impact of Neighborhood Socioeconomic Disadvantage on Operative Outcomes after Single-Level Lumbar Fusion.

INTRODUCTION: The relationship between socioeconomic status and neurosurgical outcomes has been investigated with respect to insurance status or median household income, but few studies have considered more comprehensive measures of socioeconomic status. This study examines the relationship between Area Deprivation Index (ADI), a comprehensive measure of neighborhood socioeconomic disadvantage, and short-term postoperative outcomes after lumbar fusion surgery. METHODS: 1861 adult patients undergoing single-level, posterior-only lumbar fusion at a single, multihospital academic medical center were retrospectively enrolled. An ADI matching protocol was used to identify each patient's 9-digit zip code and the zip code-associated ADI data. Primary outcomes included 30- and 90-day readmission, emergency department visits, reoperation, and surgical complication. Coarsened exact matching was used to match patients on key demographic and baseline characteristics known to independently affect neurosurgical outcomes. Odds ratios (ORs) were computed to compare patients in the top 10% of ADI versus lowest 40% of ADI. RESULTS: After matching (n = 212), patients in the highest 10% of ADI (compared to the lowest 40% of ADI) had significantly increased odds of 30- and 90-day readmission (OR = 5.00, P < 0.001 and OR = 4.50, P < 0.001), ED visits (OR = 3.00, P = 0.027 and OR = 2.88, P = 0.007), and reoperation (OR = 4.50, P = 0.039 and OR = 5.50, P = 0.013). There was no significant association with surgical complication (OR = 0.50, P = 0.63). CONCLUSIONS: Among otherwise similar patients, neighborhood socioeconomic disadvantage (measured by ADI) was associated with worse short-term outcomes after single-level, posterior-only lumbar fusion. There was no significant association between ADI and surgical complications, suggesting that perioperative complications do not explain the socioeconomic disparities in outcomes.

Intraoperative molecular imaging: 3rd biennial clinical trials update.

Significance: This third biennial intraoperative molecular imaging (IMI) conference shows how optical contrast agents have been applied to develop clinically significant endpoints that improve precision cancer surgery. Aim: National and international experts on IMI presented ongoing clinical trials in cancer surgery and preclinical work. Previously known dyes (with broader applications), new dyes, novel nonfluorescence-based imaging techniques, pediatric dyes, and normal tissue dyes were discussed. Approach: Principal investigators presenting at the Perelman School of Medicine Abramson Cancer Center's third clinical trials update on IMI were selected to discuss their clinical trials and endpoints. Results: Dyes that are FDA-approved or currently under clinical investigation in phase 1, 2, and 3 trials were discussed. Sections on how to move benchwork research to the bedside were also included. There was also a dedicated section for pediatric dyes and nonfluorescence-based dyes that have been newly developed. Conclusions: IMI is a valuable adjunct in precision cancer surgery and has broad applications in multiple subspecialties. It has been reliably used to alter the surgical course of patients and in clinical decision making. There remain gaps in the utilization of IMI in certain subspecialties and potential for developing newer and improved dyes and imaging techniques.

Second window ICG predicts postoperative MRI gadolinium enhancement in high grade gliomas and brain metastases.

A prospective trial evaluating the utility of second window indocyanine green (SWIG) in predicting postoperative MRI gadolinium enhancement was performed on high-grade gliomas (HGGs) and brain metastases. Compared to white light alone, SWIG demonstrated a higher sensitivity, negative predictive value, and accuracy in predicting residual neoplasm on MRI. The specificity of SWIG for predicting MRI enhancement was higher in HGGs than brain metastases. Clinically, near-infrared (NIR) imaging was better able to predict tumor recurrence than postoperative MRI. These results illustrate how SWIG is able to take advantage of gadolinium-like distribution properties to extravasate into the tumor microenvironment, enabling guidance in surgical resection. The video can be found here: https://stream.cadmore.media/r10.3171/2021.10.FOCVID21204.

Cholesterol-dependent plasma membrane order (Lo) is critical for antigen-specific clonal expansion of CD4+ T cells.

Early "T cell activation" events are initiated within the lipid microenvironment of the plasma membrane. Role of lipid membrane order (Lo) in spatiotemporal signaling through the antigen receptor in T cells is posited but remains unclear. We have examined the role of membrane order (Lo)/disorder (Ld) in antigen specific CD4+ T cell activation and clonal expansion by first creating membrane disorder, and then reconstituting membrane order by inserting cholesterol into the disordered plasma membrane. Significant revival of antigen specific CD4+ T cell proliferative response was observed after reconstituting the disrupted membrane order with cholesterol. These reconstitution experiments illustrate Koch's postulate by demonstrating that cholesterol-dependent membrane order (Lo) is critical for responses generated by CD4+ T cells and point to the importance of membrane order and lipid microenvironment in signaling through T cell membrane antigen receptors.