Regional variations in morbidity and mortality among neonates with intraventricular hemorrhage: a national database analysis.

BACKGROUND: Intraventricular hemorrhage (IVH) often affects newborns of low gestational age and low birth weight, requires critical care for neonates, and is linked to long-term neurodevelopmental outcomes. Assessing regional differences in the U.S. in care for neonatal IVH and subsequent outcomes can shed light on ways to mitigate socioeconomic disparities. METHODS: Using the 2016-2019 National Inpatient Sample (NIS), patients with a primary diagnosis of IVH were identified using ICD-10-CM codes. A retrospective cohort study was conducted with patients stratified by hospital region. Demographics, comorbidities, presentation, intraoperative variables, and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as > 75th percentile of LOS), exorbitant cost (defined as > 75th percentile of cost), and mortality. RESULTS: Included in this study were 1630 newborns with IVH. A larger portion of patients in the South and Midwest were Black, compared to the Northeast and West (Northeast: 12.2% vs Midwest: 30.2% vs South: 22.8% vs West: 5.8%, p < 0.001), while a greater percentage of patients in the West and South were Hispanic (Northeast: 7.3% vs Midwest: 9.5% vs South: 22.8% vs West: 36.2%, p < 0.001). LOS was similar among all regions. Factors associated with prolonged LOS included hydrocephalus and CSF diversions. Median total cost of admission was highest in the West, while the South was associated with decreased odds of exorbitant cost. LOS was associated with exorbitant cost, and large bed-volume hospital, VLBW, and permanent CSF shunt were associated with mortality. CONCLUSIONS: Demographic variables, but not presenting or intraoperative variables, differed among regions, pointing to possible geographic health disparities. The West had the highest total cost of admission, while the South was associated with reduced odds of exorbitant admission costs.

Insurance Disparities in Patient Outcomes and Healthcare Resource Utilization Following Neonatal Intraventricular Hemorrhage.

BACKGROUND: Within the field of pediatric neurosurgery, insurance status has been shown to be associated with surgical delay, longer time to referral, and longer hospitalization in epilepsy treatment, myelomeningocele repair, and spasticity surgery.1,2 The aim of this study was to investigate the association of insurance status with inpatient adverse events (AEs), length of stay (LOS), and costs for newborns diagnosed with intraventricular hemorrhage (IVH). METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Patients with a primary diagnosis of intraventricular hemorrhage were identified using ICD-10-CM diagnostic and procedural codes. Patients were categorized based on insurance status: Medicaid or Private Insurance (PI). Multivariate logistic regression analyses were used to identify the impact of insurance status on extended LOS (defined as >75th percentile of LOS) and exorbitant cost (defined as >75th percentile of cost). RESULTS: Demographics differed significantly between groups, with the majority of newborns in the PI cohort being White (Medicaid: 35.8% vs. PI: 60.3%, P < 0.001) and the majority of Medicaid patients being in the 0-25th quartile of household income (Medicaid: 40.9% vs. PI: 12.9%, P < 0.001). While insurance status was not independently associated with increased odds of extended LOS or exorbitant cost, Medicaid patients had a greater mean LOS and total cost of admission than PI patients. CONCLUSIONS: Demographic characteristics, mean LOS, and mean total cost differed significantly between Medicaid and PI patients, indicating potential disparities based on insurance status. However, insurance status was not independently associated with increased healthcare utilization, necessitating further research in this area of study.

Reduced racial disparities among newborns with intraventricular hemorrhage.

INTRODUCTION: Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. METHODS: Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. RESULTS: Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. CONCLUSIONS: Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Selected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases.

INTRODUCTION: With the diminishing use of whole-brain radiotherapy (WBRT), there is increasing debate regarding the maximum number of brain metastases that should be treated with stereotactic radiosurgery (SRS). In patients with >10-15 lesions, some groups are proposing a new approach - selected-lesion SRS (SL-SRS) - where only a subset of intracranial lesions are chosen for irradiation. This study is an initial look into this practice. METHODS: This is a cross-sectional exploratory survey study. A survey of 19 questions was created by the International Radiosurgery Research Foundation (IRRF) using open-ended and multiple-choice style questions on SL-SRS practices and indications with the goal of qualitatively understanding how SL-SRS is being implemented worldwide. The survey was distributed to physicians in the United States (US) and internationally who are members of the IRRF and who perform SRS frequently. Ten out of 50 IRRF institutions provided responses reflecting the practices of 16 physicians. RESULTS: SL-SRS is being performed at 8/10 institutions. The most common reasons for using SL-SRS included patients with prior WBRT, patients with progressing systemic disease with central nervous system (CNS)-penetrating or immunotherapies available, specific requests from medical oncology, and cooperative studies using this approach. Lesion size was cited as the most important factor when choosing to irradiate any single lesion. The majority of respondents reported 30 mm and 40 mm as size cutoffs (by largest dimension) for treatment of a lesion in eloquent and non-eloquent locations, respectively. Eloquence of lesion location and attributable symptoms were also considered important. Progression of untreated lesions was the most common reason reported for bringing patients back for additional treatment. CONCLUSION: The responses to this survey show that SL-SRS is being used, allowing for small/asymptomatic brain metastases to be left safely unirradiated. It is currently used in patients who have >10-15 lesions with prior WBRT, those with progression of extracranial disease but with acceptable systemic treatment options, and those with poor functional status. The incorporation of this new approach into clinical trials should be considered for the safe study of the efficacy of new CNS-penetrating systemic therapies.

Frailty and postoperative outcomes in brain tumor patients: a systematic review subdivided by tumor etiology.

PURPOSE: Frailty has gained prominence in neurosurgical oncology, with more studies exploring its relationship to postoperative outcomes in brain tumor patients. As this body of literature continues to grow, concisely reviewing recent developments in the field is necessary. Here we provide a systematic review of frailty in brain tumor patients subdivided by tumor type, incorporating both modern frailty indices and traditional Karnofsky Performance Status (KPS) metrics. METHODS: Systematic literature review was performed using PRISMA guidelines. PubMed and Google Scholar were queried for articles related to frailty, KPS, and brain tumor outcomes. Only articles describing novel associations between frailty or KPS and primary intracranial tumors were included. RESULTS: After exclusion criteria, systematic review yielded 52 publications. Amongst malignant lesions, 16 studies focused on glioblastoma. Amongst benign tumors, 13 focused on meningiomas, and 6 focused on vestibular schwannomas. Seventeen studies grouped all brain tumor patients together. Seven studies incorporated both frailty indices and KPS into their analyses. Studies correlated frailty with various postoperative outcomes, including complications and mortality. CONCLUSION: Our review identified several patterns of overall postsurgical outcomes reporting for patients with brain tumors and frailty. To date, reviews of frailty in patients with brain tumors have been largely limited to certain frailty indices, analyzing all patients together regardless of lesion etiology. Although this technique is beneficial in providing a general overview of frailty's use for brain tumor patients, given each tumor pathology has its own unique etiology, this combined approach potentially neglects key nuances governing frailty's use and prognostic value.

Surgical strategies for older patients with glioblastoma.

OBJECTIVE: While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored. METHODS: Clinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed. RESULTS: The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (<70) showed significant improvement at postoperative 6 weeks (P<0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks. CONCLUSIONS: Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.

Association of baseline frailty status and age with postoperative morbidity and mortality following intracranial meningioma resection.

PURPOSE: Although numerous studies have established advanced patient age as a risk factor for poor outcomes following intracranial meningioma resection, large-scale evaluation of frailty for preoperative risk assessment has yet to be examined. METHODS: Weighted discharge data from the National Inpatient Sample were queried for adult patients undergoing benign intracranial meningioma resection from 2015 to 2018. Complex samples multivariable logistic regression models and receiver operating characteristic curve analysis were performed to evaluate adjusted associations and discrimination of frailty, quantified using the 11-factor modified frailty index (mFI), for clinical endpoints. RESULTS: Among 20,250 patients identified (mean age 60.6 years), 35.4% (n = 7170) were robust (mFI = 0), 34.5% (n = 6985) pre-frail (mFI = 1), 20.1% (n = 4075) frail (mFI = 2), and 10.0% (n = 2020) severely frail (mFI ≥ 3). On univariable analysis, these sub-cohorts stratified by increasing frailty were significantly associated with the development of Clavien-Dindo grade IV (life-threatening) complications (inclusive of those resulting in mortality) (1.3% vs. 3.1% vs. 6.5% vs. 9.4%, p < 0.001) and extended length of stay (eLOS) (15.4% vs. 22.5% vs. 29.3% vs. 37.4%, p < 0.001). Following multivariable analysis, increasing frailty (aOR 1.40, 95% CI 1.17, 1.68, p < 0.001) and age (aOR 1.20, 95% CI 1.05, 1.38, p = 0.009) were both independently associated with development of life-threatening complications or mortality, whereas increasing frailty (aOR 1.20, 95% CI 1.10, 1.32, p < 0.001), but not age, was associated with eLOS. Frailty (by mFI-11) achieved superior discrimination in comparison to age for both endpoints (AUC 0.69 and 0.61, respectively). CONCLUSION: Frailty may be more accurate than advanced patient age alone for prognostication of adverse events and outcomes following intracranial meningioma resection.

The immense heterogeneity of frailty in neurosurgery: a systematic literature review.

The aim of this study was to review and analyze the neurosurgery body of literature to document the current knowledge of frailty within neurosurgery, standardizing terminology and how frailty is defined, including the different levels of frailty, while determining what conclusions can be drawn about frailty's impact on neurosurgical outcomes. While multiple studies on frailty in neurosurgery exist, no literature reviews have been conducted. Therefore, we performed a literature review in order to organize, tabulate, and present findings from the data to broaden the understanding about what we know from frailty and neurosurgery. We performed a PubMed search to identify studies that evaluated frailty and neurosurgery. The terms "frail," "frailty," "neurosurgery," "spine surgery," "craniotomy," and "neurological surgery" were all used in the query. We then organized, analyzed, and summarized the comprehensive frailty and neurosurgical literature. The literature contained 25 published studies analyzing frailty in neurosurgery between December 2015 and December 2018. Five of these studies were cranial neurosurgical studies, the remaining studies focused on spinal neurosurgery. Over 100,000 surgical cases were analyzed among the 25 studies. Of these, 18 studies demonstrated that increasing frailty was associated with increased rate of complications, 10 studies showed that frailty was associated with higher mortality rates, 11 studies demonstrated an association between frailty and increased hospital length of stay, and 5 studies noted that higher frailty was associated with discharge to a higher level of care. The current body of literature repeatedly demonstrates that frailty is associated with worse outcomes across the neurosurgical subspecialties.

Frailty predicts worse outcomes after intracranial meningioma surgery irrespective of existing prognostic factors.

OBJECTIVE: Frailty has been recognized as a predictor of adverse surgical outcomes across multiple surgical disciplines, but until now the relationship between frailty and intracranial meningioma surgery has not been studied. The goal of the present study was to determine the relationship between increasing frailty (determined using the modified Frailty Index [mFI]) and intracranial meningioma resection outcomes (including hospital length of stay [LOS], discharge location, and reoperation and readmission rates). METHODS: This is a single-center retrospective cohort study of patients who underwent intracranial meningioma resection between August 2012 and May 2018. Seventy-six patients met the inclusion criteria. RESULTS: Frailty was associated with increased hospital LOS (p = 0.0218), increased reoperation rate (p = 0.029), and discharge to a higher level of care: an inpatient rehabilitation facility or a skilled nursing facility (p = 0.0002). After multivariable analysis, frailty was determined to be an independent risk factor for increased LOS, worse discharge disposition, and subsequent readmission. CONCLUSIONS: Frailty is an independent risk factor for worse outcomes following intracranial meningioma resection, including increased LOS, reoperations, and worse discharge disposition. Frailty may help stratify preoperative surgical risk, and thus may provide important clinical information to help neurosurgeons and elderly patients weigh the risks and benefits of resection.

What Does it Mean for a Surgeon to "Run Two Rooms"? A Comprehensive Literature Review of Overlapping and Concurrent Surgery Policies.

The aim of this study was to review and analyze all of the "concurrent surgery" (CS) and "overlapping surgery" (OS) literature with the goal of: standardizing terminology, defining discrepancies in the literature and proposing solutions for the current challenges of regulating surgery to achieve maximal safety and efficiency. The CS and OS literature has grown exponentially over the past two years. Before this, there were no significant publications addressing this topic. There is an extremely wide variance on how "running two rooms" is defined and whether it should be permitted. These differences affect our patients' perception of this practice. The literature lacks any comprehensive review of the topic and terminology. We performed a PubMed search to identify studies that considered the issue of OS. The terms "overlapping surgery", "concurrent surgery", and "simultaneous surgery" (SS) were used in the query. We then analyzed the publications identified. The literature contained 18 published studies analyzing OS safety between November 2016 and June 2018. Eight were neurosurgical studies, three were orthopedic, and the remaining seven articles were in other surgical specialties. A total of 1,207,155 surgical cases (range 250->500,000 patients) were analyzed among the 18 studies. There were 57,880 (5.04%) OS cases. The OS rates in the individual studies ranged from 1.2 to 68 per cent (Table 1). Neurosurgical studies had the highest average OS rate of 54 per cent (range 37-68%), whereas the average OS rate in orthopedic surgery was 43 per cent (range 2.7-68%). Approximately one-third of the studies were multicenter investigations (27.7%). The studies measured more than 20 distinct outcomes, but there were only five outcomes that were included in the majority of the studies: mortality rates, reoperation rates, procedure length of time, readmission rates, and hospital length of stay. The current body of literature repeatedly demonstrates that OS is a safe and effective option when undertaken by experienced surgeons who practice it frequently. For successful OS, the Mandatory Attending Portion for two surgeries must not overlap and Unnecessary Anesthesia Time must be prohibited. Hospitals and surgical specialty organizations must implement policies to assure the safe practice of OS.

Correction: Cerebral microbleeds in a neonatal rat model.

[This corrects the article DOI: 10.1371/journal.pone.0171163.].

Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus.

The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.

Cerebral microbleeds in a neonatal rat model.

BACKGROUND: In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. METHODS: Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. RESULTS: mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. CONCLUSIONS: In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development.