CRISPRi screen of long non-coding RNAs identifies LINC03045 regulating glioblastoma invasion.

INTRODUCTION: Glioblastoma (GBM) invasion studies have focused on coding genes, while few studies evaluate long non-coding RNAs (lncRNAs), transcripts without protein-coding potential, for role in GBM invasion. We leveraged CRISPR-interference (CRISPRi) to evaluate invasive function of GBM-associated lncRNAs in an unbiased functional screen, characterizing and exploring the mechanism of identified candidates. METHODS: We implemented a CRISPRi lncRNA loss-of-function screen evaluating association of lncRNA knockdown (KD) with invasion capacity in Matrigel. Top screen candidates were validated using CRISPRi and oligonucleotide(ASO)-mediated knockdown in three tumor lines. Clinical relevance of candidates was assessed via The Cancer Genome Atlas(TCGA) and Genotype-Tissue Expression(GTEx) survival analysis. Mediators of lncRNA effect were identified via differential expression analysis following lncRNA KD and assessed for tumor invasion using knockdown and rescue experiments. RESULTS: Forty-eight lncRNAs were significantly associated with 33-83% decrease in invasion (p<0.01) upon knockdown. The top candidate, LINC03045, identified from effect size and p-value, demonstrated 82.7% decrease in tumor cell invasion upon knockdown, while LINC03045 expression was significantly associated with patient survival and tumor grade(p<0.0001). RNAseq analysis of LINC03045 knockdown revealed that WASF3, previously implicated in tumor invasion studies, was highly correlated with lncRNA expression, while WASF3 KD was associated with significant decrease in invasion. Finally, WASF3 overexpression demonstrated rescue of invasive function lost with LINC03045 KD. CONCLUSION: CRISPRi screening identified LINC03045, a previously unannotated lncRNA, as critical to GBM invasion. Gene expression is significantly associated with tumor grade and survival. RNA-seq and mechanistic studies suggest that this novel lncRNA may regulate invasion via WASF3.

Procedural volume is linearly associated with mortality, major complications, and readmissions in patients undergoing malignant brain tumor resection.

PURPOSE: Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions. We hypothesized that a linear volume-outcome relationship can estimate likelihood of adverse outcomes when comparing any two volumes. METHODS: The patient cohort was identified with ICD-10 coding in the Nationwide Readmissions Database(NRD). The association of volume and mortality, major complications, and 30-/90-day readmissions were evaluated in multivariate analyses. Volume was used as a continuous variable with two/three-piece splines, with various knot positions to reflect the best model performance, based on the Quasi Information Criterion(QIC). RESULTS: From 2016 to 2018, 34,486 patients with malignant brain tumors underwent resection. When volume was analyzed as a continuous variable, mortality risk decreased at a steady rate of OR 0.988 per each additional procedure increase for hospitals with 1-65 cases/year(95% CI 0.982-0.993, p < 0.0001). Risk of major complications decreased from 1 to 41 cases/year(OR 0.983, 95% CI 0.979-0.988, p < 0.0001), 30-day readmissions from 1 to 24 cases/year(OR 0.987, 95% CI 0.979-0.995, p = 0.001) and 90-day readmissions from 1 to 23 cases/year(OR 0.989, 95% CI 0.983-0.995, p = 0.0003) and 24-349 cases/year(OR 0.9994, 95% CI 0.999-1, p = 0.01). CONCLUSION: In multivariate analyses, institutional procedural volume remains linearly associated with mortality, major complications, and 30-/90-day readmission up to specific cutoffs. The resulting linear association can be used to calculate relative likelihood of adverse outcomes between any two volumes.

Differences in Surgical Cancer Care Delivery and Outcomes Between Safety-Net and Non-Safety-Net Hospitals in the United States: A Comprehensive Systematic Review.

BACKGROUND: Studies evaluating the association of safety-net hospitals (SNHs) with outcomes of surgical care in cancer patients have demonstrated mixed results. We sought to systematically investigate the association of SNH status with measures of surgical cancer care delivery and outcomes. METHODS: A comprehensive review of the literature identified from the MEDLINE/PubMed, Embase, Web of Science, and Cochrane databases was performed according to the PRISMA guidelines. Risk of bias assessment was conducted using the Joanna Briggs Institute's tool. The findings were synthesized qualitatively. RESULTS: Of the 1749 records identified, 33 retrospective studies were included, 79% of which investigated national databases. Risk of bias assessment revealed average score of 78%. Among studies assessing each outcome, lower likelihood of receiving appropriate surgical interventions in SNH patients was reported by 85%; longer intervals to surgery by 100%; and prolonged hospital stays by 73%. Most studies reported no differences in survival (65%) or readmission (67%). Results were mixed regarding complications and mortality. Patient characteristics and shortage of resources and interdisciplinary teams were frequently proposed factors for observed disparities. CONCLUSIONS: Cancer patients at SNHs may be less likely to undergo some surgical treatments and experience longer intervals to treatment but achieve largely comparable short- and long-term outcomes to non-SNH patients.

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.

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.

Increasing Prevalence of Frailty and Its Association with Readmission and Mortality Among Hospitalized Patients with IBD.

BACKGROUND: Although age is often used as a clinical risk stratification tool, recent data have suggested that adverse outcomes are driven by frailty rather than chronological age. AIMS: In this nationwide cohort study, we assessed the prevalence of frailty, and factors associated with 30-day readmission and mortality among hospitalized IBD patients. METHODS: Using the Nationwide Readmission Database, we examined all patients with IBD hospitalized from 2010 to 2014. Based on index admission, we defined IBD and frailty using previously validated ICD codes. We used univariable and multivariable regression to assess risk factors associated with all-cause 30-day readmission and 30-day readmission mortality. RESULTS: From 2010 to 2014, 1,405,529 IBD index admissions were identified, with 152,974 (10.9%) categorized as frail. Over this time period, the prevalence of frailty increased each year from 10.20% (27,594) in 2010 to 11.45% (33,507) in 2014. On multivariable analysis, frailty was an independent predictor of readmission (aRR 1.16, 95% CI: 1.14-1.17), as well as readmission mortality (aRR 1.12, 95% CI 1.02-1.23) after adjusting for relevant clinical factors. Frailty also remained associated with readmission after stratification by IBD subtype, admission characteristics (surgical vs. non-surgical), age (patients ≥ 60 years old), and when excluding malnutrition, weight loss, and fecal incontinence as frailty indicators. Conversely, we found older age to be associated with a lower risk of readmission. CONCLUSIONS: Frailty, independent of age, comorbidities, and severity of admission, is associated with a higher risk of readmission and mortality among IBD patients, and is increasing in prevalence. Given frailty is a potentially modifiable risk factor, future studies prospectively assessing frailty within the IBD patient population are needed.

Postpartum Psychiatric Admissions in the United States.

OBJECTIVE: This study aimed to assess risk for postpartum psychiatric admissions in the United States. STUDY DESIGN: This study used the 2010 to 2014 Nationwide Readmissions Database to identify psychiatric admissions during the first 60 days after delivery hospitalization. Timing of admission after delivery discharge was determined. We fit multivariable log-linear regression models to assess the impact of psychiatric comorbidity on admission risk, adjusting for patient, obstetrical, and hospital factors. RESULTS: Of 15.7 million deliveries from 2010 to 2014, 11,497 women (0.07%) were readmitted for a primary psychiatric diagnosis within 60 days postpartum. Psychiatric admissions occurred relatively consistently across 10-day periods after delivery hospitalization discharge. Psychiatric diagnoses were present among 5% of women at delivery but 40% of women who were readmitted postpartum for a psychiatric indication. In the adjusted model, women with psychiatric diagnoses at delivery hospitalization were 9.7 times more likely to be readmitted compared with those without psychiatric comorbidity. Women at highest risk for psychiatric admission were those with Medicare and Medicaid, in lower income quartiles, and of younger age. CONCLUSION: While a large proportion of psychiatric admissions occurred among a relatively small proportion of at-risk women, admissions occurred over a broad temporal period relative to other indications for postpartum admission.

Acute Venous Thromboembolism Risk Highest Within 60 Days After Discharge From the Hospital in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients with inflammatory bowel diseases (IBDs) have a high risk of venous thromboembolism (VTE). We assessed the timing and risk factors associated with readmission to the hospital for VTE among patients with IBD. METHODS: We collected data from the Nationwide Readmissions Database on IBD index admissions resulting in readmission to the hospital for VTE within 60 days, from 2010 through 2014. We used univariable and multivariable regression to assess risk factors associated with VTE readmission with unadjusted risk ratio (RR) and adjusted RR (aRR) as measures of effect. Time to VTE readmission was assessed in 10-day intervals, for up to 90 days. RESULTS: We identified 872,122 index admissions of patients with IBD; 1160 resulted in readmission with VTE. More than 90% of readmissions occurred within 60 days of discharge from the index admission. Factors associated with hospital readmission with VTE included prior VTE, longer length of hospital stay, comorbidities, having a flexible sigmoidoscopy or colonoscopy at index admission, and age older than 18 years. Additional risk factors included Clostridium difficile infection at index admission (aRR, 1.47; 95% CI, 1.17-1.85) and discharge to a skilled nursing facility or intermediate care facility (aRR, 1.39; 95% CI, 1.14-1.70) or discharge with home health services (aRR, 1.65; 95% CI, 1.41-1.94). CONCLUSIONS: Among patients admitted to the hospital with IBD, most readmissions with VTE occur within 60 days of discharge. Readmission with VTE is associated with C difficile infection and discharge to a skilled nursing facility, intermediate care facility, or with home health services. Studies are needed to evaluate the potential benefit of extending VTE prophylaxis for patients admitted to the hospital with IBD for up to 2 months after discharge, to minimize risk.

Increased 30-day readmission rate after craniotomy for tumor resection at safety net hospitals in small metropolitan areas.

PURPOSE: Unplanned readmission of post-operative brain tumor patients is often attributed to hospital and patient characteristics and is associated with higher mortality and cost. Previous studies demonstrate multiple patient outcome disparities in safety net hospitals (SNHs) when compared to non-SNHs. This study uses the Nationwide Readmissions Database (NRD) to determine if initial brain tumor resection at SNHs is associated with increased 30-day non-elective readmission rates. METHODS: Patients with benign or malignant primary or metastatic brain tumor undergoing craniotomy for surgical resection were retrospectively identified in the NRD from 2010 to 2014. SNHs were defined as hospitals with Medicaid and uninsured patient burden in the top quartile. Descriptive and multivariate analyses employing survey-adjusted logistic regression evaluated patient and hospital level factors influencing 30-day readmissions. RESULTS: During the study period, 83,367 patients met inclusion criteria. 44.7% of patients had a benign tumor, and 55.3% had a malignant tumor. Secondary CNS neoplasm (5.99%), post-operative infection (5.96%), and septicemia (4.26%) caused most readmissions within 30 days. Patients had increased unplanned readmission rates if they underwent craniotomy for tumor resection at a SNH in a small metropolitan area (OR 1.11, 95% CI 1.02-1.21, p = 0.01), but not at a SNH in a large metropolitan area (OR 0.99, 95% CI 0.93-1.05, p = 0.73). CONCLUSION: This finding may reflect differences in access to care and disparities in neurosurgical resources between small and large metropolitan areas. Inequities in expertise and capacity are relevant as surgical volume was also related to readmission rates. Further studies may be warranted to address such disparities.

Comorbid depression associated with non-routine discharge following craniotomy for low-grade gliomas and benign tumors - a nationwide readmission database analysis.

PURPOSE: Prior studies have demonstrated elevated rates of depression in patients with malignant brain tumor; however, the prevalence and effect on surgical outcomes in patients with low-grade gliomas (LGG) and benign brain tumors (BBT) remain unknown. Readmission and non-routine discharge, which includes discharge to skilled nursing, rehabilitative, and other inpatient facilities, are well-established quality of care indicators. We sought to analyze the association between comorbid depression and non-routine discharge, readmission, and other post-operative inpatient outcomes in patients with LGG and BBT. METHODS: The Nationwide Readmissions Database from 2010 to 2014 was retrospectively queried to select for surgically treated patients with LGG and BBT. Multivariable logistic regression models adjusting for patient and hospital characteristics were used to determine the effects of comorbid depression on post-operative outcomes. Interaction of gender and depression on non-routine disposition was analyzed. RESULTS: We identified 31,654 craniotomies for resection of BBT and LGG (2010-2014). The majority of patients (64.1%) were female. The rate of depression comorbid with BBT and LGG was 11.9%. Depression was associated with non-routine discharge after surgery (OR 1.19, p 0.0002*), but was not associated with increased morbidity, mortality, or readmission at 30 or 90 days. The rate of comorbid depression was higher among female than male patients (14.0 vs. 8.0%). Depression in males was associated with a 38% increased likelihood of non-routine disposition (p = 0.0002*), while depression in females was associated with a 13% increased likelihood of non-routine disposition (p = 0.03*). CONCLUSION: Depression is prevalent in patients with LGG and BBT and is associated with increased risk of non-routine discharge following surgical intervention. The increased likelihood of non-routine disposition is greater for males than that for females. Awareness of the risk factors for depression may aid in early screening and intervention and improve overall patient outcomes.

Predictors of readmission after craniotomy for meningioma resection: a nationwide readmission database analysis.

BACKGROUND: Meningiomas are the most common benign primary brain tumors. The mainstay of treatment, surgical resection, is often curative. Given the excellent prognosis of these lesions, minimizing perioperative complications is of the utmost importance. With the establishment of the National Readmissions Database (NRD), researchers are now able to identify variables associated with postoperative complications beyond the index admission. OBJECTIVE: In this study, we sought to identify the leading causes for non-elective readmission and variables associated with increased likelihood of readmission at 30 and 90 days after discharge following a craniotomy for meningioma resection. METHODS: Adult inpatients who underwent craniotomy for meningioma resection between 2010 and 2014 were queried from the NRD. All-cause readmissions following craniotomy at 30 and 90 days were identified, and a multivariable logistic regression model was used to characterize independent risk factors. RESULTS: Among 26,034 patients who received craniotomy for meningioma resection, 2825 (10.9%) were readmitted at 30 days and 3436 (16.1%) were readmitted at 90 days. Postoperative wound infection was the most common readmission diagnosis, occurring in 9.32% and 10.2% of 30- and 90-day readmissions respectively. Patient factors associated with increased likelihood of readmission included male gender, greater illness severity, non-routine discharge, index length of hospitalization, and having Medicare or Medicaid insurance. CONCLUSIONS: Readmission following craniotomy for meningioma resection occurs at a clinically significant rate. Several patient factors were identified in association with all-cause 30- and 90-day readmissions. Further studies are required to identify means for preventing complications following discharge in these vulnerable patient populations.

Postpartum venous thromboembolism readmissions in the United States.

BACKGROUND: There are limited data on when postpartum readmissions for thromboembolism occur after delivery hospitalizations on a population basis in the United States. OBJECTIVE: We sought to characterize risk factors for and timing of postpartum venous thromboembolism readmission after delivery hospitalization discharge. STUDY DESIGN: The Healthcare Cost and Utilization Project Nationwide Readmissions Database for calendar years 2013 and 2014 was used to perform a retrospective cohort study evaluating risk for readmission for venous thromboembolism within 60 days of discharge from a delivery hospitalization. Risks for deep vein thrombosis and pulmonary embolism were individually assessed. Obstetric, medical, demographic, and hospital factors associated with postpartum readmission for venous thromboembolism were analyzed. Risk was characterized as odds ratios with 95% confidence intervals. Both unadjusted and adjusted analyses were performed. Adjusted analyses included relevant obstetric, medical, demographic, and hospital factors within logistic regression models. RESULTS: From Jan. 1 through Oct. 31 in 2013 and 2014, 6,269,641 delivery hospitalizations were included in the analysis. In all, 2975 cases of readmission for any venous thromboembolism were identified (4.7 per 10,000 delivery hospitalizations) including 1170 cases of deep vein thrombosis and 1805 cases of pulmonary embolism. In all, 69.6% of readmissions for any venous thromboembolism occurred within the first 20 days of discharge vs 22.3% and 8.0% at 21-40 and 41-60 days after discharge. Median times to readmission were 12.7, 14.0, and 11.7 days for venous thromboembolism, deep vein thrombosis, and pulmonary embolism, respectively. Women readmitted for any venous thromboembolism were more likely to have a history of venous thromboembolism (4.2% vs 0.3%, P < .01), to have had a cesarean delivery (54.4% vs 32.4%, P < .01), to have a thrombophilia (1.8% vs 0.4%, P < .01), to have had a longer delivery hospitalization of >3 days for vaginal delivery and >4 days for cesarean (18.0% vs 6.6%, P < .01), to have been diagnosed with gestational hypertension or preeclampsia (19.7% vs 8.2%, P < .01), and to have had postpartum hemorrhage with transfusion (2.6% vs 0.5%, P < .01). These factors retained significance in adjusted models. History of venous thromboembolism and hemorrhage with transfusion were associated with the largest odds of readmission (odds ratio, 9.5; 95% confidence interval, 6.6-13.6, and odds ratio, 3.6; 95% confidence interval, 2.4-5.5, respectively). Other factors associated with increased odds included thrombophilia (odds ratio, 2.0; 95% confidence interval, 1.2-3.5), cesarean delivery (odds ratio, 2.0; 95% confidence interval, 1.8-2.3), longer delivery hospitalization (odds ratio, 1.8; 95% confidence interval, 1.5-2.2), and preeclampsia or gestational hypertension (odds ratio, 2.0; 95% confidence interval, 1.6-2.4). CONCLUSION: While the majority of events occurred within 20 days of discharge, risk factors other than thrombophilia and prior venous thromboembolism were generally associated with modestly increased odds of events, and only a small proportion of readmissions occurred among women with thrombophilia and prior events. Our data demonstrate both the challenging nature and urgent need for further research to determine which clinical practices and interventions may reduce risk for venous thromboembolism readmissions on a population basis.

Predictors of 30- and 90-day readmission following craniotomy for malignant brain tumors: analysis of nationwide data.

Hospital readmissions are a major contributor to increased health care costs and are associated with worse patient outcomes after neurosurgery. We used the newly released Nationwide Readmissions Database (NRD) to describe the association between patient, hospital and payer factors with 30- and 90-day readmission following craniotomy for malignant brain tumor. All adult inpatients undergoing craniotomy for primary and secondary malignant brain tumors in the NRD from 2013 to 2014 were included. We identified all cause readmissions within 30- and 90-days following craniotomy for tumor, excluding scheduled chemotherapeutic procedures. We used univariate and multivariate models to identify patient, hospital and administrative factors associated with readmission. We identified 27,717 admissions for brain tumor craniotomy in 2013-2014, with 3343 (13.2%) 30-day and 5271 (25.7%) 90-day readmissions. In multivariate analysis, patients with Medicaid and Medicare were more likely to be readmitted at 30- and 90-days compared to privately insured patients. Patients with two or more comorbidities were more likely to be readmitted at 30- and 90-days, and patients discharged to skilled nursing facilities or home health care were associated with increased 90-day readmission rates. Finally, hospital procedural volume above the 75th percentile was associated with decreased 90-day readmission rates. Patients treated at high volume hospitals are less likely to be readmitted at 90-days. Insurance type, non-routine discharge and patient comorbidities are predictors of postoperative non-scheduled readmission. Further studies may elucidate potentially modifiable risk factors when attempting to improve outcomes and reduce cost associated with brain tumor surgery.

Infection rate correlated with time to repair of open neural tube defects (myelomeningoceles): an institutional and national study.

BACKGROUND: The optimal time to closure of a newborn with an open neural tube defect (NTD-myelomeningocele) has been the subject of a number of investigations. One aspect of timing that has received attention is its relationship to repair site and central nervous system (CNS) infection that can lead to irreversible deficits and prolonged hospital stays. No studies have evaluated infection as a function of surgical timing at a national level. We hypothesized an increase in wound infection in those patients with delays in myelomeningocele repair when evaluated in both a single-center and national database. METHODS: Treatment outcomes following documented times to transfer and closure were evaluated at Children's Hospital of Los Angeles (CHLA) for the years 2004 to 2014. Data of newborns with a myelomeningocele with varying time to repair were also obtained from non-overlapping abstracts of the 2000-2010 Kids' Inpatient Database (KID) and Nationwide Inpatient Sample (NIS). Poisson multivariable regression analyses were used to assess the effect of time to repair on infection and time to discharge. RESULTS: At CHLA, 95 neonates who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Six (6 %) patients were noted to have postrepair complications. CHLA data was not sufficiently powered to detect a difference in infection following delay in closure. In the NIS, we identified 3775 neonates with repaired myelomeningocele of whom infection was reported in 681 (18 %) patients. There was no significant difference in rates of infection between same-day and 1-day wait times (p = 0.22). Wait times of two (RR = 1.65 [1.23, 2.22], p < 0.01) or more days (RR = 1.88 [1.39, 2.54], p < 0.01), respectively, experienced a 65 % and 88 increase in rates of infection compared to same-day procedures. Prolonged wait time was 32 % less likely at facilities with increased myelomeningocele repair volume (RR = 0.68 [0.56 0.83], p < 0.01). The presence of infection was associated with a 54 % (RR = 1.54 [1.36, 1.74], p < 0.01) increase in the length of stay when compared to neonates without infection. CONCLUSION: Myelomeningocele closure, when delayed more than 1 day after birth, is associated with an increased rate of infection and length of stay in the national cohort. High-volume centers are associated with fewer delays to repair. Though constrained by limitations of a national coded database, these results suggest that early myelomeningocele repair decreases the rate of infection.

Prevention of percutaneous spinal cord stimulation electrode migration: a 15-year experience.

OBJECTIVES: Percutaneous spinal cord stimulation electrodes have a propensity to migrate longitudinally, which is a costly complication that often compromises therapeutic effect. After implementing simple changes to our percutaneous electrode anchoring technique, we no longer encounter this migration. The current retrospective study updates previously reported results. MATERIALS AND METHODS: We retrospectively examined data in a consecutive series of patients in whom we had secured a new percutaneous electrode by injecting < 0.1 cm(3) of adhesive into the silicone elastomer lead anchor. From 1998 through 2006, we used whichever anchor was supplied with each lead until we observed one case of migration through a short anchor; thereafter, we used a long, tapered anchor exclusively. From 2007 through 2013, we further modified our technique by adding a fascial incision to accommodate the tip of the anchor and by increasing the strength of our suture material. RESULTS: In the first series of 291 patients, followed through July 2007 (mean 4.75 years, range 1.1-9.0 years), 4 (1.37%) experienced electrode migration requiring surgical revision. Only one lead had moved with respect to its anchor; the other three anchors remained securely bonded to their leads. No migration (0.00%) occurred in the second series of 142 patients, followed through 2013 (mean follow-up 2.86 years, range 0.10-5.45 years). CONCLUSION: Improvements to our simple, inexpensive technique apparently have eliminated the most common complication of spinal cord stimulation.

Racial and socioeconomic disparities in access to mechanical revascularization procedures for acute ischemic stroke.

BACKGROUND: Mechanical revascularization procedures performed for treatment of acute ischemic stroke have increased in recent years. Data suggest association between operative volume and mortality rates. Understanding procedural allocation and patient access patterns is critical. Few studies have examined these demographics. METHODS: Data were collected from the 2008 Nationwide Inpatient Sample database. Patients hospitalized with ischemic stroke and the subset of individuals who underwent mechanical thrombectomy were characterized by race, payer source, population density, and median wealth of the patient's zip code. Demographic data among patients undergoing mechanical thrombectomy procedures were examined. Stroke admission demographics were analyzed according to thrombectomy volume at admitting centers and patient demographics assessed according to the thrombectomy volume at treating centers. RESULTS: Significant allocation differences with respect to frequency of mechanical thrombectomy procedures among stroke patients existed according to race, expected payer, population density, and wealth of the patient's zip code (P < .0001). White, Hispanic, and Asian/Pacific Islander patients received endovascular treatment at higher rates than black and Native American patients. Compared with the white stroke patients, black (P < .001), Hispanic (P < .001), Asian/Pacific Islander (P < .001), and Native American stroke patients (P < .001) all demonstrated decreased frequency of admission to hospitals performing mechanical thrombectomy procedures at high volumes. Among treated patients, blacks (P = .0876), Hispanics (P = .0335), and Asian/Pacific Islanders (P < .001) demonstrated decreased frequency in mechanical thrombectomy procedures performed at high-volume centers when compared with whites. While present, socioeconomic disparities were not as consistent or pronounced as racial differences. CONCLUSIONS: We demonstrate variances in endovascular acute stroke treatment allocation according to racial and socioeconomic factors in 2008. Efforts should be made to monitor and address potential disparities in treatment utilization.

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.

Multi-Site Benchmark Study for Standardized Relative Cerebral Blood Volume in Untreated Brain Metastases Using the DSC-MRI Consensus Acquisition Protocol.

BACKGROUND AND PURPOSE: A national consensus recommendation for the collection of DSC (dynamic susceptibility contrast) MRI perfusion data, used to create maps of relative cerebral blood volume (rCBV), has been recently established for primary and metastatic brain tumors. The goal was to reduce inter-site variability and improve ease of comparison across time and sites, fostering widespread use of this informative measure. To translate this goal into practice the prospective collection of consensus DSC-MRI data and characterization of derived rCBV maps in brain metastases is needed. The purpose of this multi-site study was to determine rCBV in untreated brain metastases in comparison to glioblastoma and normal appearing brain using the national consensus protocol. MATERIALS AND METHODS: Subjects from three sites with untreated enhancing brain metastases underwent DSC-MRI according to a recommended option that uses a mid-range flip angle, GRE-EPI acquisition and the administration of both a pre-load and 2nd DSC-MRI dose of 0.1 mmol/kg GBCA. Quantitative maps of standardized rCBV (sRCBV) were generated and enhancing lesion ROIs determined from post-contrast T1-weighted images alone or calibrated difference maps, termed delta T1 (dT1) maps. Mean sRCBV for metastases were compared to normal appearing white matter (NAWM) and glioblastoma (GBM) from a previous study. Comparisons were performed using either the Wilcoxon signed-rank test for paired comparisons or the Mann-Whitney nonparametric test for unpaired comparisons. RESULTS: 49 patients with a primary histology of lung (n=25), breast (n=6), squamous cell carcinoma (SCC) (n=1), melanoma (n=5), gastrointestinal (GI) (n=3) and genitourinary (GU) (n=9) were included in comparison to GBM (n=31). The mean sRCBV of all metastases (1.83+/-1.05) were significantly lower (p=0.0009) than mean sRCBV for GBM (2.67±1.34) with both statistically greater (p<0.0001) than NAWM (0.68 +/- 0.18). Histologically distinct metastases are each statistically greater than NAWM (p<0.0001) with lung (p=0.0002) and GU (p=.02) sRCBV being significantly different than GBM sRCBV. CONCLUSIONS: 49 patients with a primary histology of lung (n=25), breast (n=6), squamous cell carcinoma (SCC) (n=1), melanoma (n=5), gastrointestinal (GI) (n=3) and genitourinary (GU) (n=9) were included in comparison to GBM (n=31). The mean sRCBV of all metastases (1.83+/-1.05) were significantly lower (p=0.0009) than mean sRCBV for GBM (2.67+1.34) with both statistically greater (p<0.0001) than NAWM (0.68 +/- 0.18). Histologically distinct metastases are each statistically greater than NAWM (p<0.0001) with lung (p=0.0002) and GU (p=.02) sRCBV being significantly different than GBM sRCBV. ABBREVIATIONS: dT1=delta T1; GBCA=gadolinium-based contrast agent; NAWM=normal appearing white matter; normalized relative cerebral blood volume=nRCBV; relative cerebral blood volume=rCBV; standardized relative cerebral blood volume=sRCBV.

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.