Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice.

BACKGROUND: Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice. METHODS: RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI). RESULTS: More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning. CONCLUSIONS: LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.

Childhood adversity, such as severe deprivation and neglect, leads to structural changes in human brain development that are associated with learning deficits and behavioral difficulties. Some of the most consistent findings in individuals exposed to childhood adversity are reduced hippocampal volume and abnormal hippocampal function. This is important because the hippocampus is necessary for learning and memory, and it plays a crucial role in depression and anxiety. Although initial studies suggested more pronounced hippocampal deficits in men, additional research is needed to confirm these findings and to elucidate the mechanisms responsible for these sex differences. We found that male and female mice exposed to early impoverishment and deprivation exhibit similar structural changes to those observed in deprived children. Interestingly, adolescent male mice, but not females, display severe deficits in their ability to freeze when placed back in a box where they were previously shocked. The ability to associate "shock/danger" with a "box/place" is referred to as contextual fear conditioning and requires normal connections between the entorhinal cortex and the hippocampus. We found that these connections did not form properly in male mice exposed to impoverished conditions, but they were only minimally affected in females. These findings appear to explain why exposure to impoverished conditions impairs contextual fear conditioning in male mice but not in female mice. Additional work is needed to determine whether similar sex-specific changes in these connections are also observed in adolescents exposed to neglect and deprivation.

Frailty in intracranial meningioma resection: the risk analysis index demonstrates strong discrimination for predicting non-home discharge and in-hospital mortality.

PURPOSE: Frailty is an independent risk factor for adverse postoperative outcomes following intracranial meningioma resection (IMR). The role of the Risk Analysis Index (RAI) in predicting postoperative outcomes following IMR is nascent but may inform preoperative patient selection and surgical planning. METHODS: IMR patients from the Nationwide Inpatient Sample were identified using diagnostic and procedural codes (2019-2020). The relationship between preoperative RAI-measured frailty and primary outcomes (non-home discharge (NHD), in-hospital mortality) and secondary outcomes (extended length of stay (eLOS), complication rates) was assessed via multivariate analyses. The discriminatory accuracy of the RAI for primary outcomes was measured in area under the receiver operating characteristic (AUROC) curve analysis. RESULTS: A total of 23,230 IMR patients (mean age = 59) were identified, with frailty statuses stratified by RAI score: 0-20 "robust" (R)(N = 10,665, 45.9%), 21-30 "normal" (N)(N = 8,895, 38.3%), 31-40 "frail" (F)(N = 2,605, 11.2%), and 41+ "very frail" (VF)(N = 1,065, 4.6%). Rates of NHD (R 11.5%, N 29.7%, F 60.8%, VF 61.5%), in-hospital mortality (R 0.5%, N 1.8%, F 3.8%, VF 7.0%), eLOS (R 13.2%, N 21.5%, F 40.9%, VF 46.0%), and complications (R 7.5%, N 11.6%, F 15.7%, VF 16.0%) significantly increased with increasing frailty thresholds (p < 0.001). The RAI demonstrated strong discrimination for NHD (C-statistic: 0.755) and in-hospital mortality (C-statistic: 0.754) in AUROC curve analysis. CONCLUSION: Increasing RAI-measured frailty is significantly associated with increased complication rates, eLOS, NHD, and in-hospital mortality following IMR. The RAI demonstrates strong discrimination for predicting NHD and in-hospital mortality following IMR, and may aid in preoperative risk stratification.

Risk Analysis Index as a preoperative frailty tool for elective ventriculoperitoneal shunt surgery for idiopathic normal pressure hydrocephalus.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) predominantly occurs in older patients, and ventriculoperitoneal shunt (VPS) placement is the definitive surgical treatment. VPS surgery carries significant postoperative complication rates, which may tip the risk/benefit balance of this treatment option for frail, or higher-risk, patients. In this study, the authors investigated the use of frailty scoring for preoperative risk stratification for adverse event prediction in iNPH patients who underwent elective VPS placement. METHODS: The Nationwide Readmissions Database (NRD) was queried from 2018 to 2019 for iNPH patients aged ≥ 60 years who underwent VPS surgery. Risk Analysis Index (RAI) and modified 5-item Frailty Index (mFI-5) scores were calculated and RAI cross-tabulation was used to analyze trends in frailty scores by the following binary outcome measures: overall complications, nonhome discharge (NHD), extended length of stay (eLOS) (> 75th percentile), and mortality. Area under the receiver operating characteristic curve analysis was performed to assess the discriminatory accuracy of RAI and mFI-5 for primary outcomes. RESULTS: A total of 9319 iNPH patients underwent VPS surgery, and there were 685 readmissions (7.4%), 593 perioperative complications (6.4%), and 94 deaths (1.0%). Increasing RAI score was significantly associated with increasing rates of postoperative complications: RAI scores 11-15, 5.4% (n = 80); 16-20, 5.6% (n = 291); 21-25, 7.6% (n = 166); and ≥ 26, 11.6% (n = 56). The discriminatory accuracy of RAI was statistically superior (DeLong test, p < 0.05) to mFI-5 for the primary endpoints of mortality, NHD, and eLOS. All RAI C-statistics were > 0.60 for mortality within 30 days (C-statistic = 0.69, 95% CI 0.68-0.70). CONCLUSIONS: In a nationwide database analysis, increasing frailty, as measured by RAI, was associated with NHD, 30-day mortality, unplanned readmission, eLOS, and postoperative complications. Although the RAI outperformed the mFI-5, it is essential to account for the potentially reversible clinical issues related to the underlying disease process, as these factors may inflate frailty scores, assign undue risk, and diminish their utility. This knowledge may enhance provider understanding of the impact of frailty on postoperative outcomes for patients with iNPH, while highlighting the potential constraints associated with frailty assessment tools.

Andexanet alfa therapy showed No increased rate of thromboembolic events in spontaneous intracranial hemorrhage patients: A multicenter electronic health record study.

•Intracranial hemorrhage accounts for two out of every three major intracranial hemorrhages.•Systemic anticoagulation is routinely prescribed for prevention of cerebrovascular accidents.•The FDA approved Andexanet alfa to treat life-threatening bleeding.•Andexanet alfa relationship to outcomes requires further investigation.

Frailty as a predictor of poor outcomes in patients with chronic subdural hematoma (cSDH): A systematic review of literature.

Objective: In recent years, frailty has been reported to be an important predictive factor associated with worse outcomes in neurosurgical patients. The purpose of the present systematic review was to analyze the impact of frailty on outcomes of chronic subdural hematoma (cSDH) patients. Methods: We performed a systematic review of literature using the PubMed, Cochrane library, Wiley online library, and Web of Science databases following PRISMA guidelines of studies evaluating the effect of frailty on outcomes of cSDH published until January 31, 2023. Results: A comprehensive literature search of databases yielded a total of 471 studies. Six studies with 4085 patients were included in our final qualitative systematic review. We found that frailty was associated with inferior outcomes (including mortality, complications, recurrence, and discharge disposition) in cSDH patients. Despite varying frailty scales/indices used across studies, negative outcomes occurred more frequently in patients that were frail than those who were not. Conclusions: While the small number of available studies, and heterogenous methodology and reporting parameters precluded us from conducting a pooled analysis, the results of the present systematic review identify frailty as a robust predictor of worse outcomes in cSDH patients. Future studies with a larger sample size and consistent frailty scales/indices are warranted to strengthen the available evidence. The results of this work suggest a strong case for using frailty as a pre-operative risk stratification measure in cSDH patients.

Neurosurgical Malpractice Litigation: A Systematic Review and Meta-Analysis.

BACKGROUND & OBJECTIVES: Neurosurgery has one of the highest risks for medical malpractice claims. We reviewed the factors associated with neurosurgical malpractice claims and litigation in the United States of America (USA) and reported the outcomes through a systematic review of the literature. METHODS: We conducted a systematic review of the literature according to the PRISMA guidelines using the Medline, Embase, Cochrane, PubMed, and Google Scholar databases. We sought to identify pertinent studies containing information about medical malpractice claims and outcomes involving neurosurgeons in the USA. RESULTS: We identified 15 retrospective studies spanning from 2002 to 2023 that reviewed over 7,890 malpractice claims involving practicing neurosurgeons in the USA. Disparities were evident in neurosurgical litigation, with 474 cases linked to brain-related surgeries and a larger proportion, 1926 cases, tied to spine surgeries. The most commonly filed claims were intra-procedural errors (37.4%), delayed diagnoses (32.1%), and failure to treat (28.8 %). Less frequently filed claims included misdiagnosis or choice of incorrect procedure (18.4%), occurrence of death (17.3%), test misinterpretation (14.4%), failure to appropriately refer patients for evaluation/treatment (14.3%), unnecessary surgical procedures (13.3 %), and lack of informed consent (8.3%). The defendant was favored in 44.3% of claims, while 31.3% of lawsuits, 17.7% of verdicts favored the plaintiff, and 16.6% reached an out-of-court settlement. Only 3.5% of lawsuits found both parties liable. CONCLUSION: Neurosurgery is a high-risk specialty with one of the highest rates of malpractice claims. Spine claims had a significantly higher rate of filed malpractice claims, while cranial malpractice claims were associated with higher litigation compensation. Predictably, spinal cord injuries play a crucial role in predicting litigation. Importantly, nonsurgical treatments are also a common source of liability in neurosurgical practice.

The risk analysis index demonstrates exceptional discrimination in predicting frailty's impact on neurosurgical length of stay quality metrics.

BACKGROUND: Quality measures determine reimbursement rates and penalties in value-based payment models. Frailty impacts these quality metrics across surgical specialties. We compared the discriminatory thresholds for the risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for the outcomes of extended length of stay (LOS [eLOS]), prolonged LOS within 30 days (pLOS), and protracted LOS (LOS > 30). METHODS: Patients ≥18 years old who underwent neurosurgical procedures between 2012 and 2020 were queried from the ACS-NSQIP. We performed receiver operating characteristic analysis, and multivariable analyses to examine discriminatory thresholds and identify independent associations. RESULTS: There were 411,605 patients included, with a median age of 59 years (IQR, 48-69), 52.2% male patients, and a white majority 75.2%. For eLOS: RAI C-statistic 0.653 (95% CI: 0.652-0.655), versus mFI-5 C-statistic 0.552 (95% CI: 0.550-0.554) and increasing patient age C-statistic 0.573 (95% CI: 0.571-0.575). Similar trends were observed for pLOS- RAI: 0.718, mFI-5: 0.568, increasing patient age: 0.559, and for LOS>30- RAI: 0.714, mFI-5: 0.548, and increasing patient age: 0.506. Patients with major complications had eLOS 10.1%, pLOS 26.5%, and LOS >30 45.5%. RAI showed a larger effect for all three outcomes, and major complications in multivariable analyses. CONCLUSION: Increasing frailty was associated with three key quality metrics that is, eLOS, pLOS, LOS > 30 after neurosurgical procedures. The RAI demonstrated a higher discriminating threshold compared to both mFI-5 and increasing patient age. Preoperative frailty screening may improve quality metrics through risk mitigation strategies and better preoperative communication with patients and their families.

Rapid increase in departmental scholarly activity independent of residents demonstrates reproducibility and success of intensive research initiative in neurosurgery department.

BACKGROUND: Neurological surgery remains one of the most competitive specialties with a match rate of <70%. Historically, medical student performance was gauged through the USMLE Step 1. However, with the recent exam score change, metrics such as recommendation letters, research, and clerkship grades carry increased importance. Research experiences vary greatly between institutions and medical students depend on faculty/resident mentorship in order to facilitate scholarly activity. We previously reported our 2-year intensive research initiative (IRI) in a neurosurgery program. Here we report successful implementation of the IRI in a disparate setting, a department devoid of residents, and demonstrate the IRI's reproducibility with non-resident learners. MATERIALS & METHODS: We compared retrospective data from 2007 to 2020 with the IRI's results during the 2-year study period (July 2020-July 2022). RESULTS: The IRI resulted in a rapid exponential increase in publications, with medical student led peer-reviewed publications (PRPs) increasing 1000% and pre-residency fellow (PRF) PRPs increasing by 4900%. Learner involvement on PRPs pre-IRI was 31%, increasing to 72% post-IRI implementation. CONCLUSIONS: We present the IRI's success increasing academic productivity despite utilizing only non-resident learners. Students underrepresented in medicine and those at non-tier 1 institutions receive unequal research and clinical opportunities, therefore, prioritizing and providing sufficient opportunities/mentorship is crucial in their success in matching into competitive specialties. Our IRI allows for early faculty/resident student mentorship and gives students more flexibility as it allows medical students at varying stages to participate in research with no set time frame.

Frailty predicts non-home discharge in anterior lumbar interbody fusion patients.

BACKGROUND: Anterior lumbar interbody fusion (ALIF) is a well-established surgical approach in the treatment of degenerative pathology, trauma, infection, and neoplasia of the spine. This study sought to assess the usefulness of frailty as a predictor of non-home discharge (NHD) for patients who undergo the procedure. METHODS: Patient cases were extracted from the American College of Surgeons's National Surgical Quality Improvement Program database from 2012 to 2020. Univariable and receiver operating characteristic curve analyses were used to compare the 5-item Modified Frailty Index (mFI-5) to the Revised Risk Analysis Index (RAI-rev) in relation to NHD. RESULTS: Simple linear regression demonstrated that increasing frailty was associated with an increased likelihood of NHD among 25,317 patients (mFI-5 odds ratio: 2.13, 3.23, 8.4; RAI-rev odds ratio: 3.22, 9.6, 23.6 [P<0.001 for all]). In each instance, a Cochran-Armitage trend test was significant (P<0.001), indicating a linear association of increasing odds. The RAI-rev resulted in a C-statistic of 0.722, compared to 0.628 for the mFI-5, and was shown to have superior discriminative ability with a DeLong Test (P<0.001). CONCLUSIONS: Frailty, as measured by mFI-5 and RAI-rev, was associated with an increased likelihood of NHD in patients who underwent ALIF. This finding supports recent literature on the promising utility of these indices, especially the RAI-rev, in preoperative decision-making across multiple facets of neurosurgery.

Risk Analysis Index and 30-Day Mortality after Brain Tumor Resection: A Multicenter Frailty Analysis of 31,776 Patients from 2012 to 2020.

Introduction The aim of this study was to evaluate the discriminative accuracy of the preoperative Risk Analysis Index (RAI) frailty score for prediction of mortality or transition to hospice within 30 days of brain tumor resection (BTR) in a large multicenter, international, prospective database. Methods Records of BTR patients were extracted from the American College of Surgeons National Surgical Quality Improvement Program (2012-2020) database. The relationship between the RAI frailty scale and the primary end point (mortality or discharge to hospice within 30 days of surgery) was assessed using linear-by-linear proportional trend tests, logistic regression, and receiver operating characteristic (ROC) curve analysis (area under the curve as C-statistic). Results Patients with BTR ( N = 31,776) were stratified by RAI frailty tier: 16,800 robust (52.8%), 7,646 normal (24.1%), 6,593 frail (20.7%), and 737 severely frail (2.3%). The mortality/hospice rate was 2.5% ( n = 803) and was positively associated with increasing RAI tier: robust (0.9%), normal (3.3%), frail (4.6%), and severely frail (14.2%) ( p < 0.001). Isolated RAI was a robust discriminatory of primary end point in ROC curve analysis in the overall BTR cohort (C-statistic: 0.74; 95% confidence interval [CI]: 0.72-0.76) as well as the malignant (C-statistic: 0.74; 95% CI: 0. 67-0.80) and benign (C-statistic: 0.71; 95% CI: 0.70-0.73) tumor subsets (all p < 0.001). RAI score had statistically significantly better performance compared with the 5-factor modified frailty index and chronological age (both p < 0.0001). Conclusions RAI frailty score predicts 30-day mortality after BTR and may be translated to the bedside with a user-friendly calculator ( https://nsgyfrailtyoutcomeslab.shinyapps.io/braintumormortalityRAIcalc/ ). The findings hope to augment the informed consent and surgical decision-making process in this patient population and provide an example for future study designs.

Frailty Predicts 30-day mortality following major complications in neurosurgery patients: The risk analysis index has superior discrimination compared to modified frailty index-5 and increasing patient age.

Background: Postoperative complications after cranial or spine surgery are prevalent, and frailty can be a key contributing patient factor. Therefore, we evaluated frailty's impact on 30-day mortality. We compared the discrimination for risk analysis index (RAI), modified frailty index-5 (mFI-5) and increasing patient age for predicting 30-day mortality. Methods: Patients with major complications following neurosurgery procedures between 2012- 2020 in the ACS-NSQIP database were included. We employed receiver operating characteristic (ROC) curve and examined discrimination thresholds for RAI, mFI-5, and increasing patient age for 30-day mortality. Independent relationships were examined using multivariable analysis. Results: There were 19,096 patients included in the study and in the ROC analysis for 30-day mortality, RAI showed superior discriminant validity threshold C-statistic 0.655 (95% CI: 0.644-0.666), compared to mFI-5 C-statistic 0.570 (95% CI 0.559-0.581), and increasing patient age C-statistic 0.607 (95% CI 0.595-0.619). When the patient population was divided into subsets based on the procedures type (spinal, cranial or other), spine procedures had the highest discriminant validity threshold for RAI (Cstatistic 0.717). Furthermore, there was a frailty risk tier dose response relationship with 30-day mortalityy (p<0.001). Conclusion: When a major complication arises after neurosurgical procedures, frail patients have a higher likelihood of dying within 30 days than their non-frail counterparts. The RAI demonstrated a higher discriminant validity threshold than mFI-5 and increasing patient age, making it a more clinically relevant tool for identifying and stratifying patients by frailty risk tiers. These findings highlight the importance of initiatives geared toward optimizing frail patients, to mitigate long-term disability.

SARS-CoV-2 and spinal cord ischemia: a systematic review on clinical presentations, diagnosis, treatment, and outcomes.

BACKGROUND CONTEXT: Spinal cord ischemia is a rare but ominous clinical situation with high levels of disability. There are emerging reports on COVID-19 and spinal cord ischemic events. PURPOSE: To investigate the cardinal manifestations of SARS-CoV-2 associated spinal cord ischemia, review treatment paradigms, and follow outcomes. STUDY DESIGN: A systematic review. METHODS: The current study was conducted under Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The authors searched PubMed, Scopus, Web of Science, and Google Scholar for studies published up to February 12, 2023, on spinal cord ischemia and SARS-CoV-2 infection. Data on patient demographics, study methods, medical records, interventions, and outcomes were extracted from eligible articles. For each data set, the authors performed pooled estimates examining 3 factors of interest, which were (1) predisposing factors (2) treatment regimens, and (3) neurological rehabilitation outcomes. Neurological status was reported as the American Spinal Injury Association (ASIA) impairment scale reported by data sets. RESULTS: Six data sets were identified. The mean age of the study population was 50 years old, with 66.6% male predominance. Sixty-six percent of the patients had severe COVID-19. Five data sets reported preexisting coagulopathy. ASIA A and B were the most prevalent primary neurological status (80%). The mean interval between COVID-19 and the first neurological deficit was 13 days. Anterior spinal artery lesions were the most prevalent ischemic pattern. The most common treatment regimens were heparin and steroid therapy. Physical rehabilitation showed poor functional outcomes. CONCLUSIONS: SARS-CoV-2 is associated with spinal cord ischemia through multiple neuropathological mechanisms. Proper coagulation profile control and aggressive rehabilitation may play a promising role in the prevention and recovery of spinal cord infarction in SARS-CoV-2 patients.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

Transient Impairment in Microglial Function Causes Sex-Specific Deficits in Synaptic and Hippocampal Function in Mice Exposed to Early Adversity.

Abnormal development and function of the hippocampus are two of the most consistent findings in humans and rodents exposed to early life adversity, with males often being more affected than females. Using the limited bedding (LB) paradigm as a rodent model of early life adversity, we found that male adolescent mice that had been exposed to LB exhibit significant deficits in contextual fear conditioning and synaptic connectivity in the hippocampus, which are not observed in females. This is linked to altered developmental refinement of connectivity, with LB severely impairing microglial-mediated synaptic pruning in the hippocampus of male and female pups on postnatal day 17 (P17), but not in adolescent P33 mice when levels of synaptic engulfment by microglia are substantially lower. Since the hippocampus undergoes intense synaptic pruning during the second and third weeks of life, we investigated whether microglia are required for the synaptic and behavioral aberrations observed in adolescent LB mice. Indeed, transient ablation of microglia from P13-21, in normally developing mice caused sex-specific behavioral and synaptic abnormalities similar to those observed in adolescent LB mice. Furthermore, chemogenetic activation of microglia during the same period reversed the microglial-mediated phagocytic deficits at P17 and restored normal contextual fear conditioning and synaptic connectivity in adolescent LB male mice. Our data support an additional contribution of astrocytes in the sex-specific effects of LB, with increased expression of the membrane receptor MEGF10 and enhanced synaptic engulfment in hippocampal astrocytes of 17-day-old LB females, but not in LB male littermates. This finding suggests a potential compensatory mechanism that may explain the relative resilience of LB females. Collectively, these studies highlight a novel role for glial cells in mediating sex-specific hippocampal deficits in a mouse model of early-life adversity.

The Weight of Frailty in Neurosurgery Patients: Analyzing the Combined Effect of Frailty and Body Mass Index on 30-Day Postoperative Mortality.

OBJECTIVE: There is a rising prevalence of overweight and obese persons in the US, and there is a paucity of information about the relationship between frailty and body mass index. Therefore, we examined discrimination thresholds and independent relationships of the risk analysis index (RAI), modified frailty index-5 (mFI-5), and increasing patient age in predicting 30-day postoperative mortality. METHODS: This retrospective American College of Surgeons National Surgical Quality Improvement Program analysis compared all overweight or obese adult patients who underwent neurosurgery procedures between 2012 and 2020. We compared discrimination using receiver operating characteristic curve analysis for RAI, mFI-5, and increasing patient age. Furthermore, multivariable analyses, as well as subgroup analyses by procedure type i.e., spine, skull base, and other (vascular and functional) were performed, and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 315,725/412,909 (76.5%) neurosurgery patients, with a median age of 59 years (interquartile range: 48-68), predominately White 76.7% and male 54.3%. Receiver operating characteristic analysis for 30-day postoperative mortality demonstrated a higher discriminatory threshold for RAI (C-statistic: 0.790, 95%CI: 0.782-0.800) compared to mFI-5 (C-statistic: 0.692, 95%CI: 0.620-0.638) and increasing patient age (C-statistic: 0.659, 95%CI: 0.650-0.668). Multivariable analyses showed a dose-dependent association and a larger magnitude of effect by RAI: frail patients OR: 11.82 (95%CI: 10.57-13.24), and very frail patients OR: 31.19 (95%CI: 24.87-39.12). A similar trend was observed in all subgroup analyses i.e., spine, skull base, and other (vascular and functional) procedures (P ≤ 0.001). CONCLUSIONS: Increasing frailty was associated with a higher rate of 30-day postoperative mortality, with a dose-dependent effect. Furthermore, the RAI had a higher threshold for discrimination and larger effect sizes than mFI-5 and increasing patient age. These findings support RAI's use in preoperative assessments, as it has the potential to improve postoperative outcomes through targeted interventions.

Comparative analysis of exoscope-assisted spine surgery versus operating microscope: A systematic review.

Background: Limitations in the operative microscope (OM)'s mobility and suboptimal ergonomics created the opportunity for the development of the exoscope. This systematic review aims to evaluate the advantages and disadvantages of exoscopes and OMs in spine surgery. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic search was conducted in the major research databases. All studies evaluating the exoscopes and/or OMs in spinal procedures were included. Results: There were 602 patients included in the 16 studies, with 539 spine surgery patients, 19 vascular cases, 1 neural pathology case, 19 cranial cases, and 24 tumor pathologies. When examining surgical outcomes with the exoscope, results were mixed. Compared to the OM, exoscope usage resulted in longer operative times in 7 studies, comparable times in 3 studies, and shorter operative times in 3 studies. Two studies found similar lengths of stay (LOS) for both tools, two reported longer LOS with exoscopes, and one indicated shorter hospital LOS with exoscopes. One study reported higher exoscope-related blood loss (EBL), but four other studies consistently showed reduced EBL. In terms of image quality, illumination, dynamic range, depth perception, ergonomics and cost-effectiveness, the exoscope was consistently rated superior, while findings across studies were mixed regarding the optical zoom ratio and mean scope adjustment (MSA). The learning curve for exoscope use was consistently reported as shorter in all studies. Conclusion: Exoscopes present a viable alternative to OMs in spine surgery, offering multiple advantages, which supports their promising role in modern neurosurgical practice.

The risk analysis index demonstrates superior discriminative ability in predicting extended length of stay in pituitary adenoma resection patients when compared to the 5-point modified frailty index.

Objective: To compare the predictive abilities of two frailty indices on post-operative morbidity and mortality in patients undergoing pituitary adenoma resection. Methods: The National Surgical Quality Improvement Program (NSQIP) database was used to retrospectively collect data for patients undergoing pituitary adenoma resection between 2015-2019. To compare the predictive abilities of two of the most common frailty indices, the 5-point modified frailty index (mFI-5) and the risk analysis index (RAI), receiver operating curve analysis (ROC) and area under the curve (AUC)/Cstatistic were used. Results: In our cohort of 1,454 patients, the RAI demonstrated superior discriminative ability to the mFI-5 in predicting extended length of stay (C-statistic 0.59, 95% CI 0.56-0.62 vs. C-statistic 0.51, 95% CI: 0.48-0.54, p = 0.0002). The RAI only descriptively appeared superior to mFI-5 in determining mortality (C-statistic 0.89, 95% CI 0.74-0.99 vs. Cstatistic 0.63, 95% CI 0.61-0.66, p=0.11), and NHD (C-statistic 0.68, 95% CI 0.60-0.76 vs. C-statistic 0.60, 95% CI: 0.57-0.62, p=0.15). Conclusions: Pituitary adenomas account for one of the most common brain tumors in the general population, with resection being the preferred treatment for patients with most hormone producing tumors or those causing compressive symptoms. Although pituitary adenoma resection is generally safe, patients who experience post-operative complications frequently share similar pre-operative characteristics and comorbidities. Therefore, appropriate pre-operative risk stratification is imperative for adequate patient counseling and informed consent in these patients. Here we present the first known report showing the superior discriminatory ability of the RAI in predicting eLOS when compared to the mFI-5.

Frailty as a Predictor of Post-Surgical Outcomes in Patients With Cutaneous Malignancies of the Scalp and Neck Requiring Flap Reconstruction.

BACKGROUND: Investigate the ability of frailty status to predict post-surgical outcomes in patients with cutaneous malignancies of the scalp and neck undergoing flap reconstruction. METHODS: National Surgical Quality Improvement Program database was used to isolate patients with cutaneous malignancies of the scalp and neck who underwent surgical resection between 2015 to 2019. Univariate and multivariate analyses were performed to determine if frailty score correlated with negative post-operative outcomes. Receiver operating characteristic (ROC) curves allowed testing of the discriminative performance of age versus frailty. RESULTS: This study demonstrated an independent correlation between frailty and major complications as well as non-home discharge. In ROC curve analysis, frailty demonstrated superior discrimination compared to age for predicting major complications. CONCLUSION: Our study demonstrated an association between increasing frailty and major complications as well as the likelihood of a non-home discharge. When compared to age, frailty was also shown to be a better predictor of major complications.