Rates of operative intervention and in-hospital mortality following subarachnoid hemorrhage in patients with COVID-19.

OBJECTIVE: COVID-19 had massive effects on the healthcare system and multifactorial implications for the management of intensive care unit and cerebrovascular patients. This study aimed to assess the effect of COVID-19 on the outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The National Inpatient Sample (NIS) was used to identify patients with nontraumatic SAH (ICD-10 code I60.x). Patients with nonaneurysmal cerebrovascular malformations or traumatic intracranial injuries were excluded. Only patients managed from April to December 2020 were included in the study given the availability of an ICD-10 code for COVID-19. Data on sociodemographic factors, hospital characteristics, comorbidities, NIS SAH Severity Score (NIS-SSS), surgical treatment, and death were acquired. Multivariable analysis was used to assess predictors of both surgical intervention and in-hospital mortality. RESULTS: In total, 6984 patients met the study criteria, 359 (5.1%) of whom had COVID-19. Those with COVID-19 were more likely to be younger and male and had a higher All Patient Refined Diagnosis-Related Groups illness severity subclass, and NIS-SSS. Moreover, patients with COVID-19 were less likely to undergo surgery (10.0% vs 23.6%, OR 0.35, p < 0.0001) and had significantly higher mortality rates (48.2% vs 22.7%, p < 0.0001). When controlling for other variables, COVID-19 was an independent predictor of death (OR 1.67, p = 0.0002). Aneurysm surgery was performed in 1597 patients (317 open and 1280 endovascular procedures). There was no difference between the cohorts positive and negative for COVID-19 in terms of time to surgery or type of surgery. CONCLUSIONS: COVID-19 had significant impacts on patients with nontraumatic SAH. Specifically, patients with COVID-19 were significantly less likely to undergo surgery and had higher in-hospital mortality rates; however, for patients who did undergo procedural intervention, there was no significant difference in the type of intervention. Multiple factors, from medical acuity to healthcare system limitations, may contribute to these findings. Further retrospective research is needed to identify both specific causes of lower intervention rates and other potential nonaneurysmal causes of SAH in patients with COVID-19.

Frailty is a Predictor of Increased Readmissions and Increased Postoperative Complications After Elective Treatment of Unruptured Aneurysms.

INTRODUCTION: Frailty is a state of decreased physiologic reserve associated with adverse treatment outcomes across surgical specialties. We sought to determine whether frailty affected patient outcomes after elective treatment (open microsurgical clipping or endovascular therapy [EVT]) of unruptured cerebral aneurysms (UCAs). METHODS: The National Readmissions Database was queried from 2010 to 2014 to identify patients who had a known UCA and underwent elective clipping or EVT. Frailty was assessed using the Johns Hopkins Adjusted Clinical Groups frailty indicator tool. Multivariable exact logistic regression analyses were conducted to assess the associations between frailty and the primary outcome variables of 30- and 90-day readmissions, complications, length of stay (LOS), and patient disposition. RESULTS: Of 18,483 patients who underwent elective treatment for UCAs, 358 (1.9%) met the criteria for frailty. After adjusting for patient- and hospital-based factors, frailty (30-day: odds ratio [OR], 1.55; 95% confidence interval [CI], 1.11-2.17; P = 0.01; 90-day: OR, 1.47; 95% CI, 1.05-2.06; P = 0.02) and clipping versus EVT (30-day: OR, 2.12; 95% CI, 1.85-2.43; P < 0.000; 90-day: OR, 1.80; 95% CI, 1.59-2.03; P < 0.0001) were associated with increased readmission rates. Furthermore, frailty was associated with an increased rate of complications (surgical: OR, 2.91; 95% CI, 2.27-3.72; P < 0.0001; neurological: OR, 3.04; 95% CI, 2.43-3.81; P < 0.0001; major: OR, 2.75; 95% CI, 1.96-3.84; P < 0.0001), increased LOSs (incidence rate ratio, 3.08; 95% CI, 2.59-3.66; P < 0.0001), and an increased rate of nonroutine disposition (OR, 3.94; 95% CI, 2.91-5.34; P < 0.0001). CONCLUSIONS: Frailty was associated with an increased likelihood of 30- and 90-day readmissions after elective treatment of UCAs. Frailty was notably associated with several postoperative complications, longer LOSs, and nonroutine disposition in the treatment of UCAs.

Association of carotid endarterectomy at low-volume centers with higher likelihood of major complications and nonroutine discharge.

OBJECTIVE: Carotid artery stenosis (CAS) is associated with an annual stroke risk of 2%-5%, and revascularization with carotid endarterectomy (CEA) can reduce this risk. While studies have demonstrated that hospital CEA volume is associated with mortality and myocardial infarction, CEA volume cutoffs in studies are relatively arbitrary, and no specific analyses on broad complications and discharge disposition have been performed. In this study, the authors systematically set out to identify a cutoff at which CEA procedural volume was significantly associated with major complications and nonroutine discharge. METHODS: Asymptomatic and symptomatic CAS patients undergoing CEA were retrospectively identified in the Nationwide Readmissions Database (2010-2018). The association of CEA volume with outcomes was explored as a continuous variable using locally estimated scatterplot smoothing. The identified volume cutoff was used to generate dichotomous volume cohorts, and multivariate analyses of patient and hospital characteristics were conducted to evaluate the association of CEA volume with major complications and discharge disposition. RESULTS: Between 2010 and 2018, 308,933 asymptomatic and 32,877 symptomatic patients underwent CEA. Analysis of CEA volume with outcomes as a continuous variable demonstrated that an increase in volume was associated with a lower risk until a volume of approximately 7 cases per year (20th percentile). A total of 6702 (2.2%) asymptomatic and 1040 (3.2%) symptomatic patients were treated at the bottom 20% of hospital procedure volume. Increased rates of complications were seen at low-volume centers among asymptomatic (3.66% vs 2.77%) and symptomatic (7.4% vs 6.87%) patients. Asymptomatic patients treated at low-volume centers had an increased likelihood of major complications (OR 1.26, 95% CI 1.07-1.49; p = 0.007) and nonroutine discharge (OR 1.36, 95% CI 1.24-1.50; p < 0.0001). Symptomatic patients treated at low-volume centers were also more likely to experience major complications (OR 1.47, 95% CI 1.07-2.02; p = 0.02) and nonroutine discharge (OR 1.26, 95% CI 1.07-1.47; p = 0.005). Mortality rates were similar between low- and high-volume hospitals among asymptomatic (0.36% and 0.32%, respectively) and symptomatic (1.06% and 1.49%, respectively) patients, while volume was not significantly associated with mortality among asymptomatic (OR 1.06, 95% CI 0.67-1.65; p = 0.81) and symptomatic (OR 0.81, 95% CI 0.43-1.54; p = 0.52) patients in multivariate analysis. CONCLUSIONS: CEA patients, asymptomatic or symptomatic, are at a higher risk of major complications and nonroutine discharge at low-volume centers. Analysis of CEA as a continuous variable demonstrated a cutoff at 7 cases per year, and further study may identify factors associated with improved outcome at the lowest-volume centers.

A cross-sectional study to test equivalence of low- versus intermediate-flip angle dynamic susceptibility contrast MRI measures of relative cerebral blood volume in patients with high-grade gliomas at 1.5 Tesla field strength.

Introduction: 1.5 Tesla (1.5T) remain a significant field strength for brain imaging worldwide. Recent computer simulations and clinical studies at 3T MRI have suggested that dynamic susceptibility contrast (DSC) MRI using a 30° flip angle ("low-FA") with model-based leakage correction and no gadolinium-based contrast agent (GBCA) preload provides equivalent relative cerebral blood volume (rCBV) measurements to the reference-standard acquisition using a single-dose GBCA preload with a 60° flip angle ("intermediate-FA") and model-based leakage correction. However, it remains unclear whether this holds true at 1.5T. The purpose of this study was to test this at 1.5T in human high-grade glioma (HGG) patients. Methods: This was a single-institution cross-sectional study of patients who had undergone 1.5T MRI for HGG. DSC-MRI consisted of gradient-echo echo-planar imaging (GRE-EPI) with a low-FA without preload (30°/P-); this then subsequently served as a preload for the standard intermediate-FA acquisition (60°/P+). Both normalized (nrCBV) and standardized relative cerebral blood volumes (srCBV) were calculated using model-based leakage correction (C+) with IBNeuro™ software. Whole-enhancing lesion mean and median nrCBV and srCBV from the low- and intermediate-FA methods were compared using the Pearson's, Spearman's and intraclass correlation coefficients (ICC). Results: Twenty-three HGG patients composing a total of 31 scans were analyzed. The Pearson and Spearman correlations and ICCs between the 30°/P-/C+ and 60°/P+/C+ acquisitions demonstrated high correlations for both mean and median nrCBV and srCBV. Conclusion: Our study provides preliminary evidence that for HGG patients at 1.5T MRI, a low FA, no preload DSC-MRI acquisition can be an appealing alternative to the reference standard higher FA acquisition that utilizes a preload.

Increased time to surgery and worse perioperative outcome in benign brain tumor patients with COVID-19.

BACKGROUND: The COVID-19 pandemic caused significant disruptions to healthcare systems around the world, due to both high resource utilization and concern for disease spread. Delays in non-emergent surgeries have also affected chronic disease management, including that of benign brain tumors such as meningiomas and pituitary adenomas. To evaluate the effect of COVID-19 infection on benign brain tumor resection rates and subsequent perioperative and inpatient outcomes, this study utilized the 2020 National Inpatient Sample (NIS) to investigate rates of surgical resection, time to surgery, and mortality among benign brain tumor patients with and without COVID-19. METHODS: Patient data from April 2020 to December 2020 was extracted from the NIS. Confirmed COVID-19 diagnosis was identified using the ICD-10 diagnosis code U07.1. Patients with benign neoplasms of the cerebral meninges, cranial nerves, pituitary gland, craniopharyngeal duct, and brain were included in the study. Patient socio-demographics, hospital characteristics, and clinical comorbidities were obtained. Outcome variables included rates of surgical resection, time to surgery, in-hospital mortality, length of stay, and discharge disposition. RESULTS: The study analysis consisted of 13,053 patients with benign intracranial neoplasms who met inclusion criteria; 597 (4.6%) patients were COVID-19 positive. Patients with COVID-19 were more likely to be older and male than COVID-19 negative patients. Patients with COVID-19 had increased overall likelihood of mortality (OR 2.36, 95% CI 1.72-3.25, p < 0.0001). Even when controlling for sociodemographic/hospital factors and comorbidities, COVID-19 positive patients had a significantly longer time to surgery (8.7 days vs. 0.9 days, p < 0.0001) than COVID negative patients, and were associated with a decreased likelihood of undergoing surgery on index admission overall (OR 0.17, 95% CI 0.10-0.29, p < 0.0001). CONCLUSIONS: As expected, COVID-19 infection was associated with worse inpatient outcomes in effectively all measured categories, including longer time to surgery, decreased likelihood of receiving surgery on index admission, and increased likelihood of in-hospital mortality. These findings emphasize the effect that COVID-19 has on other aspects of patient care and highlight the importance of appropriate avenues of care for patients who are COVID-19 positive. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome for these patients is essential in efficient triage and optimizing treatment for these patients in the future. Further study is needed to elucidate causal relationships on the outcomes of benign brain tumor patients.

The effect of COVID-19 on treatment and outcomes following ischemic stroke: A national assessment.

INTRODUCTION: COVID-19 has had innumerable impacts on the healthcare system, both by worsening patient illness and impeding effective and efficient care. Further, COVID-19 has been tied to increased rates of ischemic stroke, particularly among young patients. We utilized a national database to assess associations of COVID-19 with thrombectomy rates, mortality, and discharge disposition among stroke patients. METHODS: Patients were identified from the National Inpatient Sample (NIS, 2020). Inclusion criteria selected for adult ischemic stroke patients; those with venous thrombosis or unspecified cerebral infarction were excluded. Patients were stratified by presence or absence of COVID-19 diagnosis. Outcome variables included mechanical thrombectomy, in-hospital mortality, and discharge disposition. Additional patient demographics, hospital characteristics, and disease severity metrics were collected. Statistical analysis was performed via multivariable logistic regression and log-binary regression. RESULTS: 54,368 patients were included in the study; 2116 (3.89%) were diagnosed with COVID-19. COVID-19 was associated with lower rates of mechanical thrombectomy (OR 0.94, p < 0.0001), higher rates of in-hospital mortality (OR 1.14, p < 0.0001), and unfavorable discharge disposition (OR 1.08, p < 0.0001), even when controlling for illness severity. Other relationships, such as a male predominance among stroke patients with COVID-19, were also identified. CONCLUSION: This study identified a relationship between COVID-19 diagnosis and worse outcomes for each metric assessed, including mechanical thrombectomy rates, in-hospital mortality, and discharge disposition. Several factors might underly this, ranging from systemic/multisystem inflammation and worsened disease severity to logistical barriers to treatment caused by COVID-19. Further research is needed to determine causality of these findings.

Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients.

Background: The global coronavirus disease-19 (COVID-19) pandemic has resulted in procedural delays around the world; however, timely and aggressive surgical resection for malignant brain tumor patients is essential for outcome optimization. To investigate the association between COVID-19 and outcomes of these patients, we queried the 2020 National Inpatient Sample (NIS) for differences in rates of surgical resection, time to surgery, mortality, and discharge disposition between patients with and without confirmed COVID-19 infection. Methods: Patient data were taken from the NIS from April 2020 to December 2020. COVID-19 diagnosis was determined with the International Classification of Diseases, Tenth Revision, Clinical Modification code U07.1. Results: A total of 30,671 malignant brain tumor patients met inclusion criteria and 738 (2.4%) patients had a confirmed COVID-19 diagnosis. COVID-19-positive patients had lower likelihood of receiving surgery (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63, P < 0.0001), increased likelihood of mortality (OR 2.18, 95% CI 1.78-2.66, P < 0.0001), and increased likelihood of non-routine discharge (OR 1.25, 95% CI 1.13-1.39, P < 0.0001). Notably, COVID patients receiving surgery were not associated with surgical delay (P = 0.17). Conclusion: COVID-19 infection was associated with worse patient outcome in malignant brain tumor patients, including decreased likelihood of receiving surgery, increased likelihood of mortality, and increased likelihood of non-routine discharge. Our study highlights the need to balance the risks and benefits of delaying surgery for malignant brain tumor patients with COVID-19. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome provides important insight in effective triage for these patients in the situations where resources are limited.

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases.

OBJECTIVE: Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM. METHODS: The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses. RESULTS: The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans. CONCLUSIONS: Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

Development of multifocal glioblastoma after radiotherapy for craniopharyngioma: illustrative case.

BACKGROUND: Radiation-induced glioblastoma (GBM) in patients previously treated for craniopharyngioma is a rare phenomenon. To the authors' knowledge, only seven cases have previously been documented in the literature. OBSERVATIONS: Herein, the authors report a case of a patient presenting with a new diagnosis of multifocal GBM 15 years after having received adjuvant radiotherapy for a craniopharyngioma. Magnetic resonance imaging revealed an extensive enhancing infiltrative lesion in the right frontal lobe as well as two satellite lesions in the contralateral frontal lobe. Histopathology on biopsy was consistent with GBM. LESSONS: Even though this case is rare, it is nevertheless important to recognize GBM as a potential side effect of radiation. Long-term follow-up in postradiation craniopharyngioma patients is crucial for early detection.

Carotid artery stenting for asymptomatic stenosis is associated with decreased 30-day readmission at very high volume centers.

Endovascular carotid artery stenting (CAS) is a common treatment for carotid artery stenosis and stroke prevention. Previous studies have shown that high procedural volume centers are associated with improved patient outcomes. Unplanned 30-day readmissions, which are associated with significant expenses, are increasingly used as a metric of patient outcome. Despite prior studies evaluating associations between procedural volume and multiple outcomes, the association between very high CAS volume and short-term (30-day) readmission has not yet been evaluated in a large multicenter study. The National Readmissions Database (NRD) was analyzed retrospectively from 2010 to 2015 to evaluate the association between hospital procedural volume and patient outcomes in asymptomatic and symptomatic CAS patients. Very high volume centers (VHVC) were defined as the top 10% hospitals in terms of procedural volume, performing >= 79 procedures a year. Univariate and multivariate analyses of patient and hospital characteristics evaluated associations with short-term (30-day) readmissions (SR), long-term (90-day) readmissions (LR), index mortality, discharge disposition, major complications, and neurological complications. A total of 36,128 asymptomatic patients and 8,390 symptomatic patients who underwent CAS were identified. Asymptomatic CAS patients treated at VHVCs were associated with decreased likelihood of SR (OR 0.88, 95% CI 0.80-0.95, p = 0.003) and LR (OR 0.91, 95% CI 0.85-0.99, p = 0.037) compared to asymptomatic patients at non-VHVCs. There was no significant difference in SR or LR between symptomatic CAS patients treated at a VHVC vs. non-VHVC. Our findings provide additional evidence to support the role of experience in improved CAS treatment outcomes.

Pediatric patients with malignant brain tumor treated at children's hospitals: association with fewer unplanned readmissions.

OBJECTIVE: Pediatric primary brain tumors are the leading cause of death among childhood cancers. Guidelines recommend specialized care with a multidisciplinary team and focused treatment protocols to optimize outcomes in this patient population. Furthermore, readmission is a key metric of patient outcomes and has been used to inform reimbursement. However, no prior study has analyzed national database-level records to evaluate the role of care in a designated children's hospital following pediatric tumor resection and its impact on readmission rates. The goal of this study was to investigate whether treatment at a children's hospital rather than a nonchildren's hospital has a significant effect on outcome. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to evaluate the effect of hospital designation on patient outcomes after craniotomy for brain tumor resection, and results are reported as national estimates. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if craniotomy for tumor resection at a designated children's hospital was independently associated with 30-day readmissions, mortality rate, and length of stay. RESULTS: A total of 4003 patients who underwent craniotomy for tumor resection were identified using the Nationwide Readmissions Database, with 1258 of these cases (31.4%) treated at children's hospitals. Patients treated at children's hospitals were associated with decreased likelihood of 30-day hospital readmission (OR 0.68, 95% CI 0.48-0.97, p = 0.036) compared to patients treated at nonchildren's hospitals. There was no significant difference in index mortality between patients treated at children's hospitals and those treated at nonchildren's hospitals. CONCLUSIONS: The authors found that patients undergoing craniotomy for tumor resection at children's hospitals were associated with decreased rates of 30-day readmission, with no significant difference in index mortality. Future prospective studies may be warranted to confirm this association and identify components contributing to improved outcomes in care at children's hospitals.

Myelomeningocele repair at pediatric hospitals: association with routine discharge and shorter hospital stay.

OBJECTIVE: Postnatal repair for myelomeningocele (MMC) is a time-sensitive and technically challenging procedure. More experienced hospitals may provide improved outcomes for the complexity of care associated with these patients. No prior study has investigated the impact of MMC treatment at pediatric hospitals. The authors sought to examine the effect of pediatric hospital designation on patients undergoing postnatal MMC repair to identify factors associated with maximizing improved patient outcomes. METHODS: The Nationwide Readmissions Database records from 2010 to 2018 were analyzed retrospectively to determine the effect of hospital designation on patient outcomes after postnatal MMC repair. Univariate and multivariate regression analyses of patient and hospital characteristics were conducted to evaluate if MMC repair at a designated pediatric hospital was independently associated with patient outcomes of perinatal infection rates, discharge disposition, and length of stay. RESULTS: Of the total of 6353 pediatric patients who underwent postnatal MMC repair between 2010 and 2018, 2224 (35.0%) received care at a pediatric hospital. Those with an extreme level of disease burden as defined by the all patient refined diagnosis-related group severity of illness index were more likely to be treated at a pediatric hospital (p = 0.03). Patients undergoing repair at a pediatric hospital were also associated with a decreased likelihood of perinatal infection (OR 0.54, 95% CI 0.35-0.83, p = 0.005); greater likelihood of routine disposition (OR 4.85, 95% CI 2.34-10.06, p < 0.0001); and shorter length of stay (incidence rate ratio 0.88, 95% CI 0.77-0.995, p = 0.04). CONCLUSIONS: Pediatric patients requiring intervention for postnatal repair of MMC may benefit from the multidisciplinary subspeciality care offered at pediatric hospitals. The authors found that postnatal repair of MMC at pediatric hospitals was associated with a greater likelihood of improved patient outcomes.

Mortality following mechanical thrombectomy for ischemic stroke in patients with COVID-19.

OBJECTIVES: Multiple prior studies have shown a relationship between COVID-19 and strokes; further, COVID-19 has been shown to influence both time-to-thrombectomy and overall thrombectomy rates. Using large-scale, recently released national data, we assessed the association between COVID-19 diagnosis and patient outcomes following mechanical thrombectomy. MATERIALS AND METHODS: Patients in this study were identified from the 2020 National Inpatient Sample. All patients with arterial strokes undergoing mechanical thrombectomy were identified using ICD-10 coding criteria. Patients were further stratified by COVID diagnosis (positive vs. negative). Other covariates, including patient/hospital demographics, disease severity, and comorbidities were collected. Multivariable analysis was used to determine the independent effect of COVID-19 on in-hospital mortality and unfavorable discharge. RESULTS: 5078 patients were identified in this study; 166 (3.3%) were COVID-19 positive. COVID-19 patients had a significantly higher mortality rate (30.1% vs. 12.4%, p < 0.001). When controlling for patient/hospital characteristics, APR-DRG disease severity, and Elixhauser Comorbidity Index, COVID-19 was an independent predictor of increased mortality (OR 1.13, p = 0.002). COVID-19 was not significantly related to discharge disposition (p = 0.480). Older age and increased APR-DRG disease severity were also correlated with increase morality. CONCLUSIONS: Overall, this study indicates that COVID-19 is a predictor of mortality among mechanical thrombectomy. This finding is likely multifactorial but may be related to multisystem inflammation, hypercoagulability, and re-occlusion seen in COVID-19 patients. Further research would be needed to clarify these relationships.

Interhospital transfer of pediatric patients with malignant brain tumor not associated with increased mortality, but safe routine discharge.

OBJECTIVE: Interhospital transfer (IHT) to obtain a higher level of care for pediatric patients requiring neurosurgical interventions is common. Pediatric patients with malignant brain tumors often require subspecialty care commonly provided at specialized centers. The authors aimed to assess the impact of IHT in pediatric neurosurgical patients with malignant brain tumors to identify areas of improvement in treatment of this patient population. METHODS: Pediatric patients (age < 19 years) with malignant primary brain tumors undergoing craniotomy for resection between 2010 and 2018 were retrospectively identified in the Nationwide Readmissions Database. Patient and hospital data for each index admission provided by the Nationwide Readmissions Database was analyzed by univariate and multivariate analyses. Further analysis evaluated association of IHT on specific patient- or hospital-related characteristics. RESULTS: In a total of 2279 nonelective admissions for malignant brain tumors in pediatric patients, the authors found only 132 patients (5.8%) who underwent IHT for a higher level of care. There is an increased likelihood of transfer when a patient is younger (< 7 years old, p = 0.006) or the disease process is more severe, as characterized by higher pediatric complex chronic conditions (p = 0.0004) and increased all patient refined diagnosis-related group mortality index (p = 0.02). Patients who are transferred (OR 1.87, 95% CI 1.04-3.35; p = 0.04) and patients who are treated at pediatric centers (OR 6.89, 95% CI 4.23-11.22; p < 0.0001) are more likely to have a routine discharge home. On multivariate analysis, transfer status was not associated with a longer length of stay (incident rate ratio 1.04, 95% CI 0.94-1.16; p = 0.5) or greater overall costs per patient ($20,947.58, 95% CI -$35,078.80 to $76,974.00; p = 0.50). Additionally, IHT is not associated with increased likelihood of death or major complication. CONCLUSIONS: IHT has a significant role in the outcome of pediatric patients with malignant brain tumors. Transfer of this patient population to hospitals providing subspecialized care results in a higher level of care without a significant burden on overall costs, risks, or mortality.

The abscopal effect: systematic review in patients with brain and spine metastases.

Background: The abscopal effect is a rare phenomenon whereby local radiation induces a proposed immune-mediated anti-tumor effect at distant sites. Given the growing use of immunotherapies and systemic immune checkpoint inhibitors in neuro-oncologic practice, we aimed to review prior studies pertaining to this phenomenon in the context of tumor shrinkage both within the central nervous system as well as distant disease sites. Methods: A systematic review in accordance with the PRISMA guidelines was conducted to identify all studies which assessed the abscopal effect in patients with treated metastatic cancer to the brain and/or spine. Articles were included if they reported the abscopal effect in patients (case studies) or if the abscopal effect was explicitly analyzed in case series with cohorts of patients with metastatic brain or spine tumors. Laboratory investigations and clinical trials investigating new therapies were excluded. Results: Twenty reports met inclusion criteria [16 case reports, 4 case series (n = 160), total n = 174]. Case reports of the abscopal effect were in relation to the following cancers: melanoma (6 patients), breast cancer (3), lung adenocarcinoma (2), non-small-cell lung cancer (2), hepatocellular carcinoma (1), and renal cell carcinoma (1). Eleven patients had irradiation to the brain and 2 to the spine. Patients undergoing whole brain radiotherapy (6) had an average dose of 33.6 Gy over 8-15 fractions, and those undergoing stereotactic radiosurgery (5) had an average dose of 21.5 Gy over 1-5 fractions. One patient had radiation to the body and an intracranial abscopal effect was observed. Most common sites of extracranial tumor reduction were lung and lymph nodes. Ten case studies (57%) showed complete resolution of extra-CNS tumor burden. Median progression-free survival was 13 months following radiation. Four papers investigated incidence of abscopal effects in patients with metastatic melanoma to the brain who received immune checkpoint inhibitor therapy (n = 160); two papers found an abscopal effect in 35% and 52% of patients (n = 16, 21 respectively), and two papers found no evidence of abscopal effects (n = 61, 62). Conclusions: Abscopal effects can occur following radiotherapy in patients with brain or spine metastases and is thought to be a result of increased anti-tumor immunity. The potential for immune checkpoint inhibitor therapy to be used in combination with radiotherapy to induce an abscopal effect is an area of active investigation.

Modulating glioblastoma chemotherapy response: Evaluating long non-coding RNA effects on DNA damage response, glioma stem cell function, and hypoxic processes.

Glioblastoma (GBM) is the most common and aggressive primary adult brain tumor, with an estimated annual incidence of 17 000 new cases in the United States. Current treatments for GBM include chemotherapy, surgical resection, radiation therapy, and antiangiogenic therapy. However, despite the various therapeutic options, the 5-year survival rate remains at a dismal 5%. Temozolomide (TMZ) is the first-line chemotherapy drug for GBM; however, poor TMZ response is one of the main contributors to the dismal prognosis. Long non-coding RNAs (lncRNAs) are nonprotein coding transcripts greater than 200 nucleotides that have been implicated to mediate various GBM pathologies, including chemoresistance. In this review, we aim to frame the TMZ response in GBM via exploration of the lncRNAs mediating three major mechanisms of TMZ resistance: (1) regulation of the DNA damage response, (2) maintenance of glioma stem cell identity, and (3) exploitation of hypoxia-associated responses.

Interhospital transfer of patients with malignant brain tumors undergoing resection is associated with routine discharge.

INTRODUCTION: Neurosurgical patients often undergo interhospital transfer (IHT) for specialized care. While IHT is often associated with worse outcomes in emergent neurosurgical conditions, less is known about patient outcomes after IHT for urgent diagnoses such as brain tumors. We sought to evaluate patient outcomes after IHT for malignant brain tumor resection. METHODS: Patients hospitalized for resection of malignant brain tumor resections were analyzed from the Nationwide Readmissions Database (NRD) from 2016 to 2018. Multivariate regression analyses were conducted to determine associations between transfer status and routine disposition, mortality index, and length of stay. RESULTS: Among 13,173 patients with non-elective admissions for malignant brain tumor resection, 1583 (12.0%) were transferred from another facility. In comparison to non-transferred patients, IHT patients were more likely to be male (53.8% vs. 51.1%, p < 0.04), older (rates of age ≥60 64.0% vs. 58.9%, p < 0.001), and had greater Elixhauser comorbidity scores (≥3: 75.0% vs. 56.1%, p < 0.0001). After adjustment for comorbidity burden, transfer status was associated with increased likelihood of routine discharge (OR 1.35, 95% CI 1.18-1.55, p < 0.0001). Mortality was similar for IHT patients compared to non-transferred patients (OR 0.87, CI 0.62-1.22, p = 0.405). Transfer status was associated with increased length of stay (incident rate ratio [IRR] 1.41, 95% CI 1.34-1.48, p < 0.0001). CONCLUSION: IHT for malignant brain tumor resection was not associated with worse patient outcomes with respect to discharge disposition and mortality. Length of stay was greater for IHT patients. Further research is needed to determine which patients will benefit from IHT for malignant brain tumor resection.