Sex and Racial Disparity in Outcome of Aneurysmal Subarachnoid Hemorrhage in the United States: A 20-Year Analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage is associated with high rate of morbidity and mortality. We aimed to assess prognostic impact of sex, race, and ethnicity in these patients. METHODS: Nationwide Inpatient Sample (2000-2019) was used to identify patients presenting with aneurysmal subarachnoid hemorrhage as primary diagnosis. Patient age, sex, race/ethnicity, insurance status, socioeconomic status, comorbidities, type of the hospital, and treatment modality used for aneurysm repair were extracted. The previously validated Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale was used to estimate the clinical severity. Discharge destination and in-hospital mortality was used as outcome measured. The impact of race/ethnicity and sex on clinical outcome was analyzed using multivariate regression models. RESULTS: A total of 161 086 patients with aneurysmal subarachnoid hemorrhage were identified. Mean age was 55.0±13.8 years. Sixty-nine percent of the patients were female, 60% White patients, and 17% Black patients. There was no difference in the Nationwide Inpatient Sample Subarachnoid Hemorrhage Severity Scale score between the 2 sexes. Women had significantly lower odds of good clinical outcome (defined as discharge to home or acute rehabilitation facility; RR, 0.83 [95% CI, 0.74-0.94]; P=0.004). Hispanic patients (RR, 1.12 [95% CI, 1.07-1.17]; P<0.001) had higher odds of excellent clinical outcome compared with White patients, and lower risk of mortality were observed in Black patients (RR, 0.73 [95% CI, 0.66-0.81]) and Hispanic patients (RR, 0.78 [95% CI, 0.70-0.86]) compared with the White patients. CONCLUSIONS: In this nationally representative study, women were less likely to have excellent outcomes following aneurysmal subarachnoid hemorrhage, and White patients had disproportionately higher likelihood of worse clinical outcomes. Lower rates of mortality were seen among Black and Hispanic patients.

Intracranial Large Artery Stenosis and Past Infectious Exposures: Results From the NOMAS Cohort.

BACKGROUND: Intracranial large artery stenosis (ILAS) is an important contributor to ischemic stroke in the United States and worldwide. There is evidence to suggest that chronic exposure to certain infectious agents may also be associated with ILAS. We aimed to study this association further in an ethnically diverse, prospective, population-based sample of Northern Manhattan. METHODS: We enrolled a random sample of stroke-free participants from an urban, racially, and ethnically diverse community in 1993. Participants have been followed prospectively and a subset underwent brain magnetic resonance angiograms from 2003 to 2008. Intracranial stenoses of the circle of Willis and vertebrobasilar arteries were scored as 0=no stenosis, 1≤50% (or luminal irregularities), 2=50% to 69%, 3≥70% stenosis, and 4=flow gap. We summed the individual score of each artery to produce a global ILAS score (possible range, 0-44). Past infectious exposure to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpes simplex virus 1 and 2 was determined using serum antibody titers. RESULTS: Among 572 NOMAS (Northern Manhattan Study) participants (mean age 71.0±8.0 years, 60% women, 68% Hispanic) with available magnetic resonance angiogram and serological data, herpes simplex virus 2 (beta=0.051, P<0.001) and cytomegalovirus (beta=0.071, P<0.05) were associated with ILAS score after adjusting for demographics and vascular risk factors. Stratifying by anterior and posterior circulations, herpes simplex virus 2 remained associated with the anterior circulation (beta=0.055 P<0.01) but not with posterior circulation ILAS score. CONCLUSIONS: Chronic infectious exposures, specifically herpes simplex virus 2 and cytomegalovirus were associated with asymptomatic ILAS as seen on magnetic resonance angiogram imaging. This may represent an additional target of intervention in the ongoing effort to stem the substantial global burden of strokes related to ILAS.

National Trends in Utilization and Outcome of Endovascular Thrombectomy for Acute Ischemic Stroke in Elderly.

OBJECTIVE: Octogenarians were excluded and/or underrepresented in the major endovascular thrombectomy (EVT) randomized controlled trials, but continue to make up a growing proportion of stroke patients. To evaluate real-world trends in utilization and outcome of EVT in patients ≥80 years in a large nationally representative database. METHODS: Using the Nationwide Inpatient Sample (2014-2016), we identified patients admitted to United States hospitals with acute ischemic stroke (AIS) who also underwent EVT. The primary endpoint was good outcome (discharge to home/acute rehabilitation center). Poor outcome (discharge to skilled nursing facility or hospice and in-hospital mortality), intracerebral hemorrhage and in-hospital mortality were secondary outcome measures. RESULTS: In 376,956 patients with AIS, 6,230(1.54%) underwent EVT. 1,547(24.83%) were ≥80. The rate of EVT in AIS patients ≥80 more than doubled from 0.83%(n = 317) in 2014 to 1.83%(n = 695) in 2016. The rate of good outcome in patients ≥80 was 9%, significantly lower than younger patients (26%, p<0.001). In-hospital mortality was 19% in patients ≥80 compared to 13% in the younger cohort (p < 0.001). There was no difference in the rate of hemorrhagic transformation between octogenarians and younger patients (18.52% vs 17.01%, p=0.19). In patients ≥80 years of age, decreasing baseline comorbidity burden independently predicted good outcome (OR 0.258, 95% CI [0.674- 0.935]). CONCLUSIONS: A two-fold increase in the utilization of EVT in patients ≥80 years of age was seen from 2014 to 2016. While the comparative rate of good outcome is significantly lower in this age group, elderly patients with fewer comorbidities demonstrated better outcomes after EVT.

Carotid Artery Disease as a Predictor of In-Hospital Postoperative Stroke After Coronary Artery Bypass Grafting From 1999 to 2011.

BACKGROUND: In this study, the risk factors for stroke after coronary artery bypass grafting (CABG) were examined. In particular, the role of asymptomatic carotid artery stenosis (both unilateral and bilateral) as a predictor of in-hospital postoperative stroke was investigated. Finally, the trends surrounding in-hospital postoperative stroke from 1999 to 2011 also were examined. The purpose of the study was to appropriately identify patients at high risk for stroke after CABG and spark discussion about the perioperative management of such patients. MATERIALS AND METHODS: Data from the Nationwide Inpatient Sample from 1999 to 2011 were analyzed retrospectively. The study cohort was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification and Projection Clinical Classification Software codes. Exploratory statistics, univariate analyses, and multivariable regression were used for this study. RESULTS: The analysis demonstrated that both asymptomatic unilateral and bilateral carotid stenoses were independent risk factors for in-hospital postoperative stroke. In addition, increasing age, female sex, increasing van Walraven score, paralysis, neurologic disorders, history of infective endocarditis, asymptomatic basilar stenosis, and cerebral occlusion all were demonstrated to be statistically significant predictors of stroke. Patients with carotid stenosis and a van Walraven score >14 were found to be particularly vulnerable to in-hospital postoperative stroke. Lastly, predictors of carotid stenosis were examined, and increasing age, female sex, and increasing van Walraven score all were found to be significant predictors of asymptomatic carotid stenosis. CONCLUSIONS: This study examined risk factors for stroke after CABG in a large, longitudinal, and population-based database. The study found that both unilateral and bilateral asymptomatic carotid stenoses are indeed risk factors for in-hospital postoperative stroke. In addition, a number of other predictors were identified. These results can be used to identify patients at high risk for perioperative stroke and hopefully decrease the rate of a devastating complication of CABG.

The Prevalence and Impact of Status Epilepticus Secondary to Intracerebral Hemorrhage: Results from the US Nationwide Inpatient Sample.

BACKGROUND: Status epilepticus (SE) has been identified as a predictor of morbidity and mortality in many acute brain injury patient populations. We aimed to assess the prevalence and impact of SE after intracerebral hemorrhage (ICH) in a large patient sample to overcome limitations in previous small patient sample studies. METHODS: We queried the Nationwide Inpatient Sample for patients admitted for ICH from 1999 to 2011, excluding patients with other acute brain injuries. Patients were stratified into SE diagnosis and no SE diagnosis cohorts. We identified independent risk factors for SE and assessed the impact of SE on morbidity and mortality with multivariable logistic regression models. Logistic regression was used to evaluate the trend in SE diagnoses over time as well. RESULTS: SE was associated with significantly increased odds of both mortality and morbidity (odds ratios (OR) 1.18 [confidence intervals (CI) 1.01-1.39], and OR 1.53 [CI 1.22-1.91], respectively). Risk factors for SE included female sex (OR 1.17 [CI 1.01-1.35]), categorical van Walraven score (vWr 5-14: OR 1.68 [CI 1.41-2.01]; vWr > 14: OR 3.77 [CI 2.98-4.76]), sepsis (OR 2.06 [CI 1.58-2.68]), and encephalopathy (OR 3.14 [CI 2.49-3.96]). Age was found to be associated with reduced odds of SE (OR 0.97 [CI 0.97-0.97]). From 1999 to 2011, prevalence of SE diagnosis increased from 0.25 to 0.61% (p < 0.001). Factors associated with SE were female sex, medium and high risk vWr score, sepsis, and encephalopathy. Independent predictors associated with increased mortality from SE were increased age, pneumonia, myocardial infarction, cardiac arrest, and sepsis. CONCLUSIONS: SE is a significant, likely underdiagnosed, predictor of morbidity and mortality after ICH. Future studies are necessary to better identify which patients are at highest risk of SE to guide resource utilization.

Perioperative strokes following combined coronary artery bypass grafting and carotid endarterectomy: A nationwide perspective.

BACKGROUND: To assess the risk of perioperative stroke on in-hospital morbidity and mortality following combined coronary artery bypass grafting (CABG) and carotid endarterectomy (CEA). MATERIALS AND METHODS: Data from the National Inpatient Sample (NIS) database for all patients who underwent CABG with CEA were identified using ICD-9 codes. Combined procedures were identified as CEA and CABG procedures that happened on the same day. Various preoperative and perioperative risk factors and their association with in-hospital mortality and morbidity were studied. RESULTS: A total of 8457 patients underwent combined CABG and CEA from 1999 to 2011. The average age of the patient population was 69.98 years. A total of 6.17% (n = 521) of the patients developed perioperative strokes following combined CABG and CEA. An in-hospital mortality of 4.96% and morbidity of 66.35% was observed in the patient cohort. Patients with perioperative strokes showed a mortality of 19% and a morbidity of 89.34%. Other notable risk factors for in-hospital mortality and morbidity were heart failure, paralysis, renal failure, coagulopathy, weight loss and fluid and electrolyte disturbances, and postoperative myocardial infarction. CONCLUSION: A strong association was found to exist between perioperative stroke and in-hospital mortality and morbidity after combined CABG and CEA. CEA procedures are thought to mitigate the high stroke rate of 3-5% post-CABG, but our study found that combined procedures exhibit a similar stroke risk undercutting their effectiveness. Further investigative studies on combined CABG+CEA are needed to assess risk-stratification for better patient selection and examine other preventative strategies to minimize the risk of ischemic strokes.

Perioperative Strokes and Early Outcomes in Mitral Valve Surgery: A Nationwide Analysis.

OBJECTIVE: To demonstrate the role of perioperative stroke as an independent risk factor for in-hospital morbidity and mortality after mitral valve surgery and review the trends in the early outcomes of mitral valve surgery over the past decade. DESIGN: Using data from the National Inpatient Sample database for analysis, all patients who underwent isolated mitral valve procedures were identified using International Classification of Diseases-Ninth Revision codes. Univariate and multivariate analyses of risk factors of in-hospital mortality and morbidity were performed. SETTING: Multi-institutional. PARTICIPANTS: The study comprised patients who underwent mitral valve procedures from 1999 to 2011. INTERVENTIONS: Mitral valve repair or replacement. MEASUREMENTS AND MAIN RESULTS: Data on 21,821 patients showed an in-hospital mortality of 5.5% and morbidity of 63.30% (p<0.05). Perioperative strokes were experienced by 3.89% of the cohort after isolated mitral valve surgery (p<0.05). Independent predictors of adverse outcomes were age, female sex, emergency surgery, arrhythmias, hypertension, renal failure, coagulopathy, neurologic disorders, weight loss, anemia, postoperative cardiac arrest, and myocardial infarction. Perioperative strokes were found to be the strongest risk factor for postoperative mortality (odds ratio 2.34, 95% confidence interval 1.83-2.98) and morbidity (odds ratio 4.53, 95% confidence interval 3.34-6.15). CONCLUSION: Age, female sex, emergency surgery, arrhythmias, hypertension, renal failure, coagulopathy, neurologic disorders, weight loss, fluid and electrolyte imbalance, anemia, postoperative cardiac arrest, and myocardial infarction were found to be significant predictors of morbidity and mortality after mitral valve surgery, with perioperative strokes posing the strongest risk. The trends in the last 10 years indicated a decrease in mortality and an increase in morbidity. Preoperative risk stratification and intraoperative identification for impending strokes appear warranted.

Delirium Following Transcatheter Aortic Valve Replacement: National Inpatient Sample Analysis.

OBJECTIVE: To investigate the risk factors for postoperative delirium and the impact of delirium on mortality and morbidity following transcatheter aortic valve implantation (TAVI). DESIGN: Patients who underwent TAVI were identified using the International Classification of Diseases, 9th revision clinical modification codes from the National Inpatient Sample database. Statistical analysis of preoperative and perioperative risk factors was done to identify the independent risk factors for delirium after TAVI. SETTING: Multi-institutional. PARTICIPANTS: Patients who underwent TAVI from 2012 to 2013. INTERVENTIONS: TAVI. MEASUREMENTS AND MAIN RESULTS: Over the period of 2 years (2012-2013), 7,566 patients underwent TAVI. The incidence of delirium post-TAVI was 4.57% (345). Age >85 (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.05; p = 0.003), electrolyte abnormalities (OR 1.83; 95% CI 1.17-2.87; p = 0.008), prior neurologic illness (OR 1.67; 95% CI 1.10-3.15; p = 0.01), and weight loss in the hospital (OR 1.77; 95% CI 1.05-2.99; p = 0.03) were independent risk factors for postoperative delirium (POD). Unilateral or bilateral carotid stenosis did not predispose to the development of delirium. POD was an independent risk factor for procedural morbidity (OR 3.29; 95% CI 2.05-5.28; p < 0.001). POD did not increase the risk of in-house mortality after TAVI. CONCLUSION: Age of >85, electrolyte disturbance, pre-existing neurologic disease and weight loss were found to be independent risk factors for delirium. POD was associated significantly with morbidity. Owing to a significant increase in the morbidity, a thorough screening protocol and effective strategies to predict, prevent, and treat postoperative delirium would reduce the cost associated with TAVI.

Safety and Efficacy of Conscious Sedation Versus General Anesthesia for Distal Vessel Thrombectomy.

BACKGROUND AND OBJECTIVES: Anesthesia modality for endovascular thrombectomy (EVT) for distal and medium vessel occlusions remains an open question. General anesthesia (GA) may offer advantages over conscious sedation (CS) because of reduced patient movement facilitating catheter navigation, but concerns persist about potential delays and hypotension affecting collateral circulation. METHODS: In our prospectively maintained stroke registry from December 2014 to July 2023, we identified patients with distal and medium vessel occlusions defined as M2, M3, or M4 occlusion; A1 or A2 occlusion; and P1 or P2 occlusion, who underwent EVT for acute ischemic stroke. We compared patients who received CS with those who received GA. Primary outcomes were early neurological improvement (ENI), successful reperfusion, first-pass effect, and good outcome at 90 days. Secondary outcomes included intracerebral hemorrhage, subarachnoid hemorrhage, and 90-day mortality. RESULTS: Of 279 patients, 69 (24.7%) received GA, whereas 193 (69.2%) received CS. CS was associated with higher odds of ENI compared with GA (odds ratio [OR] 2.59, 95% CI [1.04-6.98], P < .05). CS was also associated with higher rates of successful reperfusion (OR 2.33, 95% CI [1.11-4.93], P < .05). CS nonsignificantly trended toward lower rates of mortality (OR 0.51, 95% CI [0.2-1.3], P = .16). No differences in good outcome at 90 days, intracerebral hemorrhage, subarachnoid hemorrhage, or first-pass effect were seen. CONCLUSION: The use of CS during EVT seems to be safe and feasible with regard to successful recanalization, hemorrhagic complications, clinical outcome, and mortality. In addition, it may be associated with a higher rate of ENI. Further randomized studies in this specific EVT subpopulation are warranted.

Engineered neurogenesis in naïve adult rat cortex by Ngn2-mediated neuronal reprogramming of resident oligodendrocyte progenitor cells.

Adult tissue stem cells contribute to tissue homeostasis and repair but the long-lived neurons in the human adult cerebral cortex are not replaced, despite evidence for a limited regenerative response. However, the adult cortex contains a population of proliferating oligodendrocyte progenitor cells (OPCs). We examined the capacity of rat cortical OPCs to be re-specified to a neuronal lineage both in vitro and in vivo. Expressing the developmental transcription factor Neurogenin2 (Ngn2) in OPCs isolated from adult rat cortex resulted in their expression of early neuronal lineage markers and genes while downregulating expression of OPC markers and genes. Ngn2 induced progression through a neuronal lineage to express mature neuronal markers and functional activity as glutamatergic neurons. In vivo retroviral gene delivery of Ngn2 to naive adult rat cortex ensured restricted targeting to proliferating OPCs. Ngn2 expression in OPCs resulted in their lineage re-specification and transition through an immature neuronal morphology into mature pyramidal cortical neurons with spiny dendrites, axons, synaptic contacts, and subtype specification matching local cytoarchitecture. Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Intravascular Large B-Cell Lymphoma Presenting as Acute Axonal Polyneuropathy: A Case Report and Literature Review.

Intravascular large B-cell lymphoma (ILBL) is a rare and difficult to diagnose subtype of large B-cell lymphoma. The most common locations of presentation are in the central nervous system and the skin, but there are reports of other organ involvement. Due to the indolence, nonspecific symptoms, and rarity of the disease, this form of lymphoma is most often diagnosed postmortem. In this article, we describe a case of ILBL that presented as a rapidly progressive acute axonal polyneuropathy. Acute axonal polyneuropathy is a common disease process with a wide differential diagnosis, but there is limited literature on its prevalence as the presenting symptom of ILBL. This patient was treated with R-EPOCH and intrathecal methotrexate with significant improvement in his polyneuropathy after 1 cycle, and complete remission after 6 cycles. Data on chemotherapy regimens and their success rates for this disease are lacking.

Extent of resection, molecular signature, and survival in 1p19q-codeleted gliomas.

OBJECTIVE: Genomic analysis in neurooncology has underscored the importance of understanding the patterns of survival in different molecular subtypes within gliomas and their responses to treatment. In particular, diffuse gliomas are now principally characterized by their mutation status (IDH1 and 1p/19q codeletion), yet there remains a paucity of information regarding the prognostic value of molecular markers and extent of resection (EOR) on survival. Furthermore, given the modern emphasis on molecular rather than histological diagnosis, it is important to examine the effect of maximal resection on survival in all gliomas with 1p/q19 codeletions, as these will now be classified as oligodendrogliomas under the new WHO guidelines. The objectives of the present study were twofold: 1) to assess the association between EOR and survival for patients with oligodendrogliomas in the National Cancer Database (NCDB), which includes information on mutation status, and 2) to demonstrate the same effect for all patients with 1p/19q codeleted gliomas in the NCDB. METHODS: The NCDB was queried for all cases of oligodendroglioma between 2004 and 2014, with follow-up dates through 2016. The authors found 2514 cases of histologically confirmed oligodendrogliomas for the final analysis of the effect of EOR on survival. Upon further query, 1067 1p/19q-codeleted tumors were identified in the NCDB. Patients who received subtotal resection (STR) or gross-total resection (GTR) were compared to those who received no tumor debulking surgery. Univariable and multivariable analyses of both overall survival and cause-specific survival were performed. RESULTS: EOR was associated with increased overall survival for both histologically confirmed oligodendrogliomas and all 1p/19q-codeleted-defined tumors (p < 0.001 and p = 0.002, respectively). Tumor grade, location, and size covaried predictably with EOR. When evaluating tumors by each classification system for predictors of overall survival, facility setting, age, comorbidity index, grade, location, chemotherapy, and radiation therapy were all shown to be significantly associated with overall survival. STR and GTR were independent predictors of improved survival in historically classified oligodendrogliomas (HR 0.83, p = 0.18; HR 0.69, p = 0.01, respectively) and in 1p/19q-codeleted tumors (HR 0.49, p < 0.01; HR 0.43, p < 0.01, respectively). CONCLUSIONS: By using the NCDB, the authors have demonstrated a side-by-side comparison of the survival benefits of greater EOR in 1p/19q-codeleted gliomas.

Endovascular Thrombectomy, Platelet Count, and Intracranial Hemorrhage.

BACKGROUND: Intracranial hemorrhage can be a devastating complication of endovascular thrombectomy (ET) after acute ischemic stroke increasing disability and mortality. Patients with low platelet count were excluded from major ET trials. This study explores the association between platelet count and intracranial hemorrhage after ET. METHODS: A retrospective review of patients undergoing ET for anterior circulation large vessel occlusions at a single comprehensive stroke center between January 2015 and February 2018 was performed. Demographic and clinical information including National Institutes of Health Stroke Scale score, intravenous tissue plasminogen activator administration, ASPECTS, platelet count, international normalized ratio, time from symptom onset to recanalization, and modified thrombolysis in cerebral infarction score were analyzed. Radiological imaging and clinical course in the hospital was evaluated to identify parenchymal hemorrhage and symptomatic intracranial hemorrhage (sICH). Univariable and multivariable analyses were conducted. RESULTS: A total of 555 patients underwent ET and 43% were male. The mean age and National Institutes of Health Stroke Scale score were 71 ± 14 years and 17 ± 6, respectively. Parenchymal hemorrhage-2 and sICH (European-Australian Cooperative Acute Stroke Study-III criteria) were noted in 9.7% and 5.8% patients, respectively. Rates of sICH in patients with platelet count <100,000 (n = 15), 100,000 to <150,000 (n = 59), and ≥150,000 (n = 481) were 6.7% (n = 1), 10.1% (n = 6), and 5.2% (n = 25), respectively (P = 0.25), and rates of modified Rankin Scale 0-2 at 90 days were 26.7%, 23.7%, and 36.4%, respectively (P = 0.12). Low ASPECTS was a significant predictor of sICH per European-Australian Cooperative Acute Stroke Study-III definition (P value = 0.046). Platelet count was not a predictor (P = 0.386) of sICH. CONCLUSIONS: Risk of sICH after ET is low and comparable in patients with low and normal platelet counts. Low platelets should not exclude patients from undergoing intra-arterial therapy.

Perioperative Neurological Complications Following Anterior Cervical Discectomy and Fusion: Clinical Impact on 317,789 Patients from the National Inpatient Sample.

BACKGROUND: Perioperative neurologic complication after an anterior cervical discectomy and fusion (ACDF) is uncommon but may have significant clinical consequences. OBJECTIVE: We aim to estimate the incidence of perioperative neurologic complications, identify their risk factors, and evaluate their impact on morbidity and mortality after ACDF. METHODS: ACDF cases (n = 317,789 patients) were extracted from the National Inpatient Sample between 1999 and 2011. Based on their Elixhauser-van Walraven score (VWR), patients were classified as low (VWR < 5), moderate (5-14), or high risk (>14) for surgery. The primary outcome was perioperative neurologic complications. Secondary outcomes included morbidity (hospital length of stay >14 days or discharge disposition to a location other than home) and in-hospital mortality. RESULTS: The rate of perioperative neurologic complications, morbidity, and mortality after ACDF was 0.4%, 8.4%, and 0.1%, respectively. Perioperative neurologic complications were highly associated with in-house morbidity (odds ratio [OR], 3.7 [3.1-4.4]) and mortality (OR, 8.0 [4.1-15.5]). The strongest predictors for perioperative neurologic complications were moderate- (OR, 3.1 [2.6-3.7]) and high-risk VWR (OR, 5.4 [3.3-8.9]), postoperative hematoma/seroma formation (OR, 5.4 [3.9-7.4]), and obesity (OR, 1.9 [1.6-2.3]). The rate of perioperative neurologic complications increased from 0.2% to 0.7% from 1999 to 2011, which was temporally associated with the rise in moderate- (P = 0.002) and high-risk patients (P = 0.001) undergoing ACDF. CONCLUSIONS: Perioperative neurologic complications are independent predictors of in-hospital morbidity and mortality after ACDF. Both morbidity and perioperative neurologic complications have increased between 1999 and 2011, which may be due, in part, to increasing numbers of moderate- and high-risk patients undergoing ACDF.

Craniotomy and Survival for Primary Central Nervous System Lymphoma.

BACKGROUND: Cytoreductive surgery is considered controversial for primary central nervous system lymphoma (PCNSL). OBJECTIVE: To investigate survival following craniotomy or biopsy for PCNSL. METHODS: The National Cancer Database-Participant User File (NCDB, n = 8936), Surveillance, Epidemiology, and End Results Program (SEER, n = 4636), and an institutional series (IS, n = 132) were used. We retrospectively investigated the relationship between craniotomy, prognostic factors, and survival for PCNSL using case-control design. RESULTS: In NCDB, craniotomy was associated with increased median survival over biopsy (19.5 vs 11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR] 0.80, P < .001). We found a similar trend with survival for craniotomy vs biopsy in the IS (HR 0.68, P = .15). In SEER, gross total resection was associated with increased median survival over biopsy (29 vs 10 mo, HR 0.68, P < .001). The survival benefit associated with craniotomy was greater within recursive partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P < .001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P < .001). A surgical risk category (RC) considering lesion location and number, age, and frailty was developed. Craniotomy was associated with increased survival vs biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P = .01), but not high RC in the IS. CONCLUSION: Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to benefit from cytoreductive surgery, ie, those with favorable RPA and RC.

Topoisomerase II Poisons for Glioblastoma; Existing Challenges and Opportunities to Personalize Therapy.

Despite advances in surgery, radiotherapy, and chemotherapy, glioblastoma (GBM) remains a malignancy with poor prognosis. The molecular profile of GBM is diverse across patients, and individual responses to therapy are highly variable. Yet, patients diagnosed with GBM are treated with a rather uniform paradigm. Exploiting these molecular differences and inter-individual responses to therapy may present an opportunity to improve the otherwise bleak prognosis of patients with GBM. This review aims to examine one group of chemotherapeutics: Topoisomerase 2 (TOP2) poisons, a class of drugs that enables TOP2 to induce DNA damage, but interferes with its ability to repair it. These potent chemotherapeutic agents are currently used for a number of malignancies and have shown promise in the treatment of GBM. Despite their robust efficacy in vitro, some of these agents have fallen short of achieving similar results in clinical trials for this tumor. In this review, we explore reasons for this discrepancy, focusing on drug delivery and individual susceptibility differences as challenges for effective TOP2-targeting for GBM. We critically review the evidence implicating genes in susceptibility to TOP2 poisons and categorize this evidence as experimental, correlative or both. This is important as mere experimental evidence does not necessarily lead to identification of genes that serve as good biomarkers of susceptibility for personalizing the use of these drugs.

Impact of Perioperative Neurologic Deficits on Clinical Outcomes After Posterior Cervical Fusion.

BACKGROUND: In the United States, the number of posterior cervical fusions has increased substantially. Perioperative neurologic complications associated with this procedure, such as spinal cord and peripheral nerve injuries, can have significant effects on patient health. We examined the impact of perioperative neurologic deficits on mortality in patients undergoing posterior cervical fusion. The secondary aim was to understand the risk factors for perioperative neurologic complications. METHODS: Data were collected from the National Inpatient Sample (NIS) Health Cost Utilization Project (HCUP) between 1999 and 2011. Patients younger than 18 years and older than 80 years were excluded, as were patients who underwent posterior cervical fusion caused by trauma. Patient demographics and comorbidities were compiled as well as variables that have been associated with increased risk of perioperative neurologic deficits. We used the van Walraven score, a weighted numeric surrogate for the Elixhauser comorbidity index, as a covariate to assess comorbidities that have been associated with in-hospital mortality and morbidity after posterior cervical fusion. In addition, we performed univariate comparisons between covariates and surgical outcomes. We conducted a multivariable logistic regression, adjusting for many of the covariates, as well as trend analyses. RESULTS: An analysis of 33,644 patients yielded an overall rate of perioperative neurologic deficits, morbidity, and mortality of 1.08%, 40.44%, and 1.00%, respectively. Perioperative neurologic deficits were independent risk factors predictors of in-hospital mortality (odds ratio, 5.270; P < 0.0001) and morbidity (odds ratio, 2.579; P < 0.0001). Other statistically significant predictors of mortality included increasing van Walraven score, myocardial infarction, metastatic cancer, and weight loss. These were also independent predictors of morbidity along with but not limited to age, device complications, congestive heart failure, paralysis, diabetes with chronic complications, deficiency anemias, device complications, and intraspinal abscess. CONCLUSIONS: Perioperative neurologic deficits are serious complications of posterior cervical fusion and can independently predict in-hospital mortality and morbidity. As this procedure continues to be used increasingly, attention should be directed toward preventing these complications and intervening earlier in patients who have a neurologic deficit. Future efforts should be geared toward screening for at-risk patients with the initiation of surgical prehabilitation.

Seizures After Intracerebral Hemorrhage: Incidence, Risk Factors, and Impact on Mortality and Morbidity.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is one of the most frequent causes of epilepsy in the United States. However, reported risk factors for seizure after are inconsistent, and their impact on inpatient morbidity and mortality is unclear. We aimed to study the incidence, risk factors, and impact of seizures after ICH in a nationwide patient sample. METHODS: We queried the Nationwide Inpatient Sample for patients admitted to the hospital with a primary diagnosis of ICH between the years 1999 and 2011. Patients were subsequently dichotomized into groups of those with a diagnosis consistent with seizure and those without. Multivariate logistic regression was used to assess risk factors for seizure in this patient sample, and the association between seizures and mortality and morbidity. Logistic regression was then used for trend analysis of incidence of seizure diagnoses over time. RESULTS: We identified 220,075 patients admitted with a primary diagnosis of ICH. Of these, 11.87% had a diagnosis consistent with seizure. Factors associated with increased risk of seizure after ICH included higher categorical van Walraven score, encephalopathy, alcohol abuse, solid tumor, and prior stroke. Seizure was independently associated with decreased odds of morbidity (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.92) and mortality (OR, 0.75; 95% CI, 0.72-0.77) in multivariate models controlling for existing comorbidities. CONCLUSIONS: Seizures after were associated with decreased mortality and morbidity despite attempts to correct for existing comorbidities. Continuous monitoring of these patients for seizures may not be necessary in all circumstances, despite their frequency.

Risk factors and clinical impact of perioperative neurological deficits following thoracolumbar arthrodesis.

OBJECTIVES: The rates of arthrodesis performed in the United States and globally have increased tremendously in the last 10-15 years. Amongst the most devastating complications are neurological deficits including spinal cord injury, nerve root irritation, and cauda equine syndrome. The primary purpose of this study is to understand the risk factors for perioperative neurological deficits in patients undergoing thoracolumbar fusion. PATIENTS AND METHODS: Data from the Nationwide Inpatient Sample between the years of 1999-2011 was analyzed. Patients were between the ages of 18 and 80 who had thoracolumbar fusion. Excluded were patients who underwent the procedure as a result of trauma or a malignancy. A list of covariates, including demographic variables, preoperative and postoperative variables that are known to increase the risk of perioperative neurological deficits were compiled. Statistical analysis utilized univariate and multivariate logistic regression for comparisons between these covariates and the proposed outcomes. RESULTS: The analysis of 37,899 patients yielded an overall rate of perioperative neurological deficits and mortality of 1.20% and 0.27%, respectively. Risk factors for perioperative neurological deficits included increasing age (OR 1.023 95% CI 1.018-1.029), Van Walraven 5-14 (OR 1.535 95% CI 1.054-2.235), and preoperative paralysis (OR 2.551 95% CI 1.674-3.886). Furthermore, the data showed that being 65 years old or older doubled the risk for perioperative deficit (OR 1.655, CI 1.248-2.194, p < 0.001). CONCLUSIONS: This population based study found that increasing age, higher comorbid burden, and preoperative paralysis increased the risk of perioperative neurological deficits while female gender and hypertension were found to be protective.

Carotid artery disease and perioperative stroke risk after surgical aortic valve replacement: A nationwide inpatient sample analysis.

To study the role of carotid stenosis (CS) and cerebrovascular disease as independent risk factors for perioperative stroke following surgical aortic valve replacement (SAVR). The National Inpatient Sample (NIS) database was used for our study. All patients who underwent SAVR from 1999 to 2011 were identified using ICD-9 codes. Univariate and multivariate analysis of baseline characteristics, Elixhauser comorbidities and other covariates were examined to identify independent predictors of perioperative strokes following SAVR. Data on 50,979 patients who underwent SAVR from 1999 to 2011 was obtained. The mean age of the study cohort was 60.5. The study patients were predominantly Caucasian (79.3%) and males (60.01%). The incidence of perioperative stroke was 2.48%. CS (OR 1.8, 95%CI 1.1-2.8, p=0.009) and cerebral arterial occlusion (OR 3.4, 95% CI 1.3-8.9) significantly increased perioperative stroke risk following SAVR. Infective endocarditis (OR 4.6, 95%CI 3.8-5.6, p=0.00) and neurological disorders (OR 4.8, 95% CI 4-5.8, p=0.00) appeared to be the strongest risk factors for strokes. Other risk factors found to be significant predictors of perioperative strokes (p<0.05) were - age, higher VWR scores, CS, cerebral arterial occlusion, infective endocarditis, DM, HTN, renal failure, neurological disorders, coagulopathy and hypothyroidsm. In conclusion, perioperative stroke risk has remained more or less constant despite advancements in surgical techniques with risk having gone up in patients <65years of age. CS and cerebral arterial occlusion significantly increase stroke risk following SAVR. Improved patient selection with pre-operative risk stratification and institution of preventive strategies are necessary to improve operative outcomes following SAVR.