How the science of practice will improve evidence-based care.

This review article analyzes the present evidence-based medicine (EBM) algorithm, compares it to the science of practice (SOP) algorithm, and demonstrates how the SOP can evolve from a quality assurance and quality improvement tool into a clinical research tool. Using appropriately constructed prospective observational databases (PODs), the SOP algorithm can be used to draw causal inferences from nonrandomized data, perform innovative comparative effectiveness research, and generate reliable information that can be used to guide treatment decisions.

Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis.

OBJECTIVE: Although several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture. METHODS: Patients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population. RESULTS: The proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48). CONCLUSIONS: Smoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification.

National trends in cerebral bypass for unruptured intracranial aneurysms: a National (Nationwide) Inpatient Sample analysis of 1998-2015.

OBJECTIVEThe development and recent widespread dissemination of flow diverters may have reduced the utilization of surgical bypass procedures to treat complex or giant unruptured intracranial aneurysms (UIAs). The aim of this retrospective cohort study was to observe trends in cerebral revascularization procedures for UIAs in the United States before and after the introduction of flow diverters by using the National (Nationwide) Inpatient Sample (NIS).METHODSThe authors extracted data from the NIS database for the years 1998-2015 using the ICD-9/10 diagnostic and procedure codes. Patients with a primary diagnosis of UIA with a concurrent bypass procedure were included in the study. Outcomes and hospital charges were analyzed.RESULTSA total of 216,212 patients had a primary diagnosis of UIA during the study period. The number of patients diagnosed with a UIA increased by 128% from 1998 (n = 7718) to 2015 (n = 17,600). Only 1328 of the UIA patients (0.6%) underwent cerebral bypass. The percentage of patients who underwent bypass in the flow diverter era (2010-2015) remained stable at 0.4%. Most patients who underwent bypass were white (51%), were female (62%), had a median household income in the 3rd or 4th quartiles (57%), and had private insurance (51%). The West (33%) and Midwest/North Central regions (30%) had the highest volume of bypasses, whereas the Northeast region had the lowest (15%). Compared to the period 1998-2011, bypass procedures for UIAs in 2012-2015 shifted entirely to urban teaching hospitals (100%) and to an elective basis (77%). The median hospital stay (9 vs 3 days, p < 0.0001), median hospital charges ($186,746 vs $66,361, p < 0.0001), and rate of any complication (51% vs 17%, p < 0.0001) were approximately threefold higher for the UIA patients with bypass than for those without bypass.CONCLUSIONSDespite a significant increase in the diagnosis of UIAs over the 17-year study period, the proportion of bypass procedures performed as part of their treatment has remained stable. Therefore, advances in endovascular aneurysm therapy do not appear to have affected the volume of bypass procedures performed in the UIA population. The authors' findings suggest a potentially ongoing niche for bypass procedures in the contemporary treatment of UIAs.

Plea for an international Aneurysm Data Bank: description and perspectives.

The disease resulting in the formation, growth, and rupture of intracranial aneurysms is complex. Research is accumulating evidence that the disease is driven by many different factors, some constant and others variable over time. Combinations of factors may induce specific biophysical reactions at different stages of the disease. A better understanding of the biophysical mechanisms responsible for the disease initiation and progression is essential to predict the natural history of the disease. More accurate predictions are mandatory to adequately balance risks between observation and intervention at the individual level as expected in the age of personalized medicine. Multidisciplinary exploration of the disease also opens an avenue to the discovery of possible preventive actions or medical treatments. Modern information technologies and data processing methods offer tools to address such complex challenges requiring 1) the collection of a high volume of information provided globally, 2) integration and harmonization of the information, and 3) management of data sharing with a broad spectrum of stakeholders.Over the last decade an infrastructure has been set up and is now made available to the academic community to support and promote exploration of intracranial disease, modeling, and clinical management simulation and monitoring.The background and purpose of the infrastructure is reviewed. The infrastructure data flow architecture is presented. The basic concepts of disease modeling that oriented the design of the core information model are explained. Disease phases, milestones, cases stratification group in each phase, key relevant factors, and outcomes are defined. Data processing and disease model visualization tools are presented. Most relevant contributions to the literature resulting from the exploitation of the infrastructure are reviewed, and future perspectives are discussed.

Comprehensive review of imaging of intracranial aneurysms and angiographically negative subarachnoid hemorrhage.

Intracranial aneurysms confer the risk of subarachnoid hemorrhage (SAH), a potentially devastating condition, though most aneurysms will remain asymptomatic for the lifetime of the patient. Imaging is critical to all stages of patient care for those who harbor an unruptured intracranial aneurysm (UIA), including to establish the diagnosis, to determine therapeutic options, to undertake surveillance in patients who elect not to undergo treatment or whose aneurysm(s) portends such a low risk that treatment is not indicated, and to perform follow-up after treatment. Neuroimaging is equally as important in patients who suffer an SAH. DSA remains the reference standard for imaging of intracranial aneurysms due to its high spatial and temporal resolution. As noninvasive imaging technology, such as CTA and MRA, improves, the diagnostic accuracy of such tests continues to increasingly approximate that of DSA. In cases of angiographically negative SAH, imaging protocols are necessary not only for diagnosis but also to search for an initially occult vascular lesion, such as a thrombosed, ruptured aneurysm that might be detected in a delayed fashion. Given the crucial role of neuroimaging in all aspects of care for patients with UIAs and SAH, it is incumbent on those who care for these patients, including cerebrovascular neurosurgeons, interventional neurologists and neuroradiologists, and diagnostic radiologists and neurointensivists, to understand the role of imaging in this disease and how individual members of the multispecialty team use imaging to ensure best practices to deliver cutting-edge care to these often complex cases. This review expounds on the role of imaging in the management of UIAs and ruptured intracranial aneurysms and in the workup of angiographically negative subarachnoid hemorrhage.

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms.

OBJECTIVE: Unruptured intracranial aneurysms (UIAs) are relatively common lesions that may cause devastating intracranial hemorrhage, thus producing considerable suffering and anxiety in those affected by the disease or an increased likelihood of developing it. Advances in the knowledge of the pathobiology behind intracranial aneurysm (IA) formation, progression, and rupture have led to preclinical testing of drug therapies that would prevent IA formation or progression. In parallel, novel biologically based diagnostic tools to estimate rupture risk are approaching clinical use. Arterial wall remodeling, triggered by flow and intramural stresses and mediated by inflammation, is relevant to both. METHODS: This review discusses the basis of flow-driven vessel remodeling and translates that knowledge to the observations made on the mechanisms of IA initiation and progression on studies using animal models of induced IA formation, study of human IA tissue samples, and study of patient-derived computational fluid dynamics models. RESULTS: Blood flow conditions leading to high wall shear stress (WSS) activate proinflammatory signaling in endothelial cells that recruits macrophages to the site exposed to high WSS, especially through macrophage chemoattractant protein 1 (MCP1). This macrophage infiltration leads to protease expression, which disrupts the internal elastic lamina and collagen matrix, leading to focal outward bulging of the wall and IA initiation. For the IA to grow, collagen remodeling and smooth muscle cell (SMC) proliferation are essential, because the fact that collagen does not distend much prevents the passive dilation of a focal weakness to a sizable IA. Chronic macrophage infiltration of the IA wall promotes this SMC-mediated growth and is a potential target for drug therapy. Once the IA wall grows, it is subjected to changes in wall tension and flow conditions as a result of the change in geometry and has to remodel accordingly to avoid rupture. Flow affects this remodeling process. CONCLUSIONS: Flow triggers an inflammatory reaction that predisposes the arterial wall to IA initiation and growth and affects the associated remodeling of the UIA wall. This chronic inflammation is a putative target for drug therapy that would stabilize UIAs or prevent UIA formation. Moreover, once this coupling between IA wall remodeling and flow is understood, data from patient-specific flow models can be gathered as part of the diagnostic workup and utilized to improve risk assessment for UIA initiation, progression, and eventual rupture.

Microsurgical treatment for unruptured intracranial aneurysms: a modern single surgeon series.

With the rise of endovascular treatments for the management of unruptured intracranial aneurysms (UIAs), advances in microsurgical techniques are underrepresented in modern surgical series, which largely consist of patients with aneurysms unfit for coiling. We report a modern series of microsurgical treatment for UIAs performed by a single surgeon as the preferred treatment modality. We retrospectively reviewed the charts of all patients with UIAs treated by the senior author with microsurgical clipping over an 11-year period. Procedure-related mortality, major neurologic morbidity (modified Rankin Score 3-5), complications, and persistent neurologic deficits were recorded. Risk factors for persistent neurologic deficits and major morbidity or mortality were analyzed using multivariate logistic regression analysis. We identified 329 patients with 400 UIAs treated in 353 surgeries. The average age was 52 years, 80% of patients were women, and 13% had a previous subarachnoid hemorrhage. The average aneurysm size was 7 mm and 92% were in the anterior circulation. The mean follow-up was 15 months (range 0.5-125). There was one procedure-related death (0.3%), and two patients suffered major morbidity (0.6%). Twenty procedures (5.6%) resulted in a persistent neurologic deficit. Risk factors for death and major morbidity were increasing age and posterior circulation, while risk factors for persistent neurologic deficits were increasing aneurysm size and posterior circulation. We conclude that microsurgical clipping is safe, effective, and should be given strong consideration as the primary treatment modality for younger patients with small to medium sized UIAs in the anterior circulation.

Unruptured aneurysms in the elderly: perioperative outcomes and cost analysis of endovascular coiling and surgical clipping.

OBJECTIVE Observation and neurosurgical intervention for unruptured intracranial aneurysms (UIAs) in the elderly population is rapidly increasing. Cerebral aneurysm coiling (CACo) is favored over cerebral aneurysm clipping (CAC) in elderly patients, yet some elderly individuals still undergo CAC. The cost-effectiveness of treating UIAs requires further exploration. Understanding the effect of intervention on hospital charges and length of stay (LOS) as well as perioperative mortality and complications can further shed light on its economic impact. The purpose of this study was to analyze the cost and perioperative outcomes of UIAs in elderly patients (≥ 65 years of age) after CACo or CAC intervention. METHODS Retrospective cohorts of CACo and CAC admissions were extracted from National (Nationwide) Inpatient Sample data obtained between 2002 and 2013, forming parallel intervention groups to compare the following outcomes between elderly and nonelderly patients: average LOS and mean hospital admission costs, in-hospital mortality, and complications. Covariates included sex, race or ethnicity, and comorbidities. RESULTS Elderly patients undergoing CAC experienced an average LOS of 8.0 days, whereas elderly patients undergoing CACo stayed an average of 3.2 days. The mean hospital charges incurred during admission totaled $95,960 in the elderly patients who underwent CAC versus $87,960 in the ones who underwent CACo. Elderly patients in whom CAC was performed had a 2.2% rate of in-hospital mortality, with a 2.6 greater adjusted odds of in-hospital mortality than nonelderly patients treated with CAC. In contrast, elderly patients who underwent CACo had a 1.36 greater adjusted odds of in-hospital mortality than their nonelderly counterparts. Compared to nonelderly patients receiving both interventions, elderly individuals had a significantly higher prevalence of various comorbidities and incidence of complications. Elderly patients who received CAC experienced a 10.3% incidence rate of perioperative stroke, whereas their CACo counterparts experienced this complication at a rate of 3.5%. Elderly patients treated with CAC had greater odds of perioperative acute renal failure, whereas their CACo counterparts had greater odds of perioperative deep venous thrombosis and pulmonary embolism. CONCLUSIONS Intervention with CAC and CACo in the elderly is resource intensive and is associated with higher risk than in the nonelderly. Those deciding between intervention and conservative management should consider these risks and costs, especially the 2.2% postoperative mortality rate associated with CAC in the elderly population. Further comparative cost-effectiveness research is needed to weigh these costs and outcomes against those of conservative management.

Sex-dependent characteristics and outcomes after clipping of unruptured intracranial aneurysms: a multicenter propensity score-matched study.

OBJECTIVE: Disparities in the epidemiology and growth rates of aneurysms between the sexes are known. However, little is known about sex-dependent outcomes after microsurgical clipping of unruptured intracranial aneurysms (UIAs). The aim of this study was to examine sex differences in characteristics and outcomes after microsurgical clipping of UIAs and to perform a propensity score-matched analysis using an international multicenter cohort. METHODS: This retrospective cohort study involved the participation of 15 centers spanning four continents. It included adult patients who underwent clipping of UIAs between January 2016 and December 2020. Patients were stratified according to their sex and analyzed for differences in morbidities and aneurysm characteristics. Based on this stratification, female patients were matched to male patients in a 1:1 ratio with a caliper width of 0.1 using propensity score matching. Endpoints included postoperative complications, neurological performance, and aneurysm occlusion at discharge and 24 months after clip placement. RESULTS: A total of 2245 patients with a mean age of 57.3 (range 20-87) years were included. Of these patients, 1675 (74.6%) were female. Female patients were significantly older (mean 57.6 vs 56.4 years, p = 0.03) but had fewer comorbidities. Aneurysms of the internal carotid artery (7.1% vs 4.2%), posterior communicating artery (6.9% vs 1.9%), and ophthalmic artery (6.0% vs 2.8%) were more commonly treated surgically in females, while clipping of aneurysms of the anterior communicating artery was more frequent in males (17.0% vs 25.3%; all p < 0.001). After propensity score matching, female patients were found to have had significantly fewer pulmonary complications (1.4% vs 4.2%, p = 0.01). However, general morbidity (24.5% vs 25.2%, p = 0.72) and mortality (0.5% vs 1.1%, p = 0.34), as well as neurological performance (p = 0.58), were comparable at discharge in both sexes. Lastly, rates of aneurysm occlusion at the time of discharge (95.5% vs 94.9%, p = 0.71) and 24 months after surgery (93.8% vs 96.1%, p = 0.22) did not significantly differ between male and female patients. CONCLUSIONS: Despite overall differences between male and female patients in demographics, comorbidities, and treated aneurysm location, sex did not relevantly affect surgical performance or perioperative complication rates.

The impact of running versus interrupted anastomosis on ureterointestinal stricture rate after radical cystectomy.

PURPOSE: Benign ureterointestinal anastomotic stricture is not uncommon after radical cystectomy and urinary diversion. We studied the impact of the running vs the interrupted technique on the ureterointestinal anastomotic stricture rate. MATERIALS AND METHODS: From July 2007 to December 2008 interrupted end-to-side anastomoses were created and from January 2009 to July 2010 running anastomoses were created. The primary study end point was time to ureterointestinal anastomotic stricture. RESULTS: Of 266 consecutive patients 258 were alive 30 days after radical cystectomy, including 149 and 109 with an interrupted and a running anastomosis, respectively. The groups did not differ in age, gender, body mass index, age adjusted Charlson comorbidity index, receipt of chemotherapy or radiation, blood loss, operative time, diversion type or postoperative pathological findings. The stricture rate per ureter was 8.5% (25 of 293) and 12.7% (27 of 213) in the interrupted and running groups, respectively (p = 0.14). Univariate analysis suggested that postoperative urinary tract infection (HR 2.1, 95% CI 1.1-4.1, p = 0.04) and Clavien grade 3 or greater complications (HR 2.6, 95% CI 1.4-4.9, p <0.01) were associated with ureterointestinal anastomotic stricture. On multivariate analysis postoperative urinary tract infection (HR 2.4, 95% CI 1.2-5.1, p = 0.02) and running technique (HR 1.9, 95% CI 1.0-3.7, p = 0.05) were associated with ureterointestinal anastomotic stricture. Median time to stricture and followup was 289 (IQR 120-352) and 351 days (IQR 132-719) in the running cohort vs 213 (IQR 123-417) and 497 days (IQR 174-1,289) in the interrupted cohort, respectively. Of the 52 strictures 33 (63%) developed within 1 year. Kaplan-Meier analysis controlling for differential followup showed a trend toward higher freedom from stricture for the interrupted ureterointestinal anastomosis (p = 0.06). CONCLUSIONS: A running anastomosis and postoperative urinary tract infection may be associated with ureterointestinal anastomotic stricture. Larger series with multiple surgeons are needed to confirm these findings.

Morphological features predicting in-stent stenosis after pipeline implantation for unruptured intracranial aneurysm.

Purpose: Elongation denotes the regularity of an aneurysm and parent artery. This retrospective research study was conducted to identify the morphological factors that could predict postoperative in-stent stenosis (ISS) after Pipeline Embolization Device (PED) implantation for unruptured intracranial aneurysms (UIAs). Methods: Patients with UIA and treated with PED at our institute between 2015 and 2020 were selected. Preoperative morphological features including both manually measured shape features and radiomics shape features were extracted and compared between patients with and without ISS. Logistic regression analysis was performed for factors associated with postoperative ISS. Results: A total of 52 patients (18 men and 34 women) were involved in this study. The mean angiographic follow-up time was 11.87 ± 8.26 months. Of the patients, 20 of them (38.46%) were identified with ISS. Multivariate logistic analysis showed that elongation (odds ratio = 0.008; 95% confidence interval, 0.001-0.255; p = 0.006) was an independent risk factor for ISS. The area under the curve (AUC) of the receiver operating characteristic curve(ROC) was 0.734 and the optimal cut-off value of elongation for ISS classification was 0.595. The sensitivity and specificity of prediction were 0.6 and 0.781, respectively. The ISS degree of elongation of less than 0.595 was larger than the ISS degree of elongation of more than 0.595. Conclusion: Elongation is a potential risk factor associated with ISS after PED implantation for UIAs. The more regular an aneurysm and parent artery, the less likelihood of an ISS occurrence.

Short-term and long-term outcomes of intracorporeal "V-O manner" ureter-ileal anastomosis in robotic-assisted laparoscopic radical cystectomy with urinary diversion: a retrospective cohort study.

Background: There are several ways to perform ureter-ileal anastomosis (UIA), but there is currently no universally recognized standard approach. Unfortunately, these approaches may increase the risk of urine leakage or stricture. The aim of this study is we to describe an intracorporeal "V-O manner" UIA in robotic-assisted laparoscopic radical cystectomy (RARC) with urinary diversion, and to evaluate the short- and long-term patient outcomes. Methods: Between May 2012 and September 2018, 28 patients of bladder urothelial carcinomas (clinical stage T2-4aN0M0) who underwent RARC with intracorporeal urinary diversion (IUD) were included. All the patients received regular postoperative follow-up for 6-76 months. During the procedure of intracorporeal diversion, a "V-O manner" of UIA imitating the pyeloplasty in ureteropelvic junction (UPJ) obstruction was used to perform a mucosa-to-mucosa anastomosis. We observed short-term outcomes (operative time, blood loss, transfusion rate, length of hospital stay, 90-day mortality, and surgical complications) as well as long-term outcomes including kidney function and urinary diversion. Results: Intracorporeal orthotopic ileal neobladder (OIN) was performed in 23 patients whereas intracorporeal ileal conduit (ICD) was performed in 5 patients. The "V-O manner" UIA was applied in all the cases. The average duration of bilateral UIA was about 40 min. The median pelvic lymph node yield was 26 (range, 14-43). All patients ambulated on postoperative 2 to 3 days, and bowel function recovered on postoperative day 3 to 4. The median length of hospital stay was 14 days [interquartile range (IQR), 9-18 days]. A total of 9 patients experienced complications. Postoperative images confirmed satisfying drainage of bilateral ureters without urine leakage or stricture. During the follow up (median 29 months), all participants showed normal renal functions with satisfactory urinary diversion without hydronephrosis. Conclusions: We describe a feasible intracorporeal "V-O manner" UIA in RARC with urinary diversion, which provides improved outcomes in avoiding urine leakage or stricture and preventing the occurrence of hydronephrosis. Larger randomized controlled trials and longer duration of follow-up needs to be required in the future.

Both coiling and clipping induce the time-dependent release of endogenous neuropeptide Y into serum.

Background: The vaso- and psychoactive endogenous Neuropeptide Y (NPY) has repeatedly been shown to be excessively released after subarachnoid hemorrhage and in numerous psychiatric disorders. NPY is stored in sympathetic perivascular nerve fibers around the major cerebral arteries. This prospective study was designed to analyze the impact of microsurgical and endovascular manipulation of the cerebral vasculature versus cranio- and durotomy alone on the serum levels of NPY. Methods: 58 patients (drop-out n = 3; m:f = 26:29; mean age 52.0 ± 14.1 years) were prospectively enrolled. The vascular group underwent repair for unruptured intracranial aneurysms (UIA) of the anterior circulation [endovascular aneurysm occlusion (EV) n = 13; microsurgical clipping (MS) n = 17]; in the non-vascular group, 14 patients received microsurgical resection of a small-sized convexity meningioma (CM), and 11 patients with surgically treated degenerative lumbar spine disease (LD) served as control. Plasma was drawn (1) before treatment (t0), (2) periprocedurally (t1), (3) 6 h postprocedurally (t2), (4) 72 h postprocedurally (t3), and (5) at the 6-week follow-up (FU; t4) to determine the NPY levels via competitive enzyme immunoassay in duplicate serum samples. We statistically evaluated differences between groups by calculating one-way ANOVA and for changes along the time points using repeated measure ANOVA. Results: Except for time point t0, the serum concentrations of NPY ranged significantly higher in the vascular than in the non-vascular group (p < 0.001), with a slight decrease in both vascular subgroups 6 h postprocedurally, followed by a gradual increase above baseline levels until FU. At t3, the EV subgroup showed significantly higher NPY levels (mean ± standard deviation) than the MS subgroup (0.569 ± 0.198 ng/mL vs. 0.415 ± 0.192 ng/mL, p = 0.0217). The highest NPY concentrations were measured in the EV subgroup at t1, t3, and t4, reaching a climax at FU (0.551 ± 0.304 ng/mL). Conclusion: Our study reveals a first insight into the short-term dynamics of the serum levels of endogenous NPY in neurosurgical and endovascular procedures, respectively: Direct manipulation within but also next to the major cerebral arteries induces an excessive release of NPY into the serum. Our findings raise the interesting question of the potential capacity of NPY in modulating the psycho-behavioral outcome of neurovascular patients.

Case Report: The Different Fates of Three Aneurysms: Diagnosis and Treatment Strategies for Unruptured Intracranial Aneurysms With Other Intracranial Diseases.

Intracranial aneurysms are vascular diseases characterized by local aneurysms of intracranial arteries. Their etiology involves a variety of environmental and genetic factors. Unruptured intracranial aneurysms (UIAs) are more common in intracranial aneurysms, but once an aneurysm is ruptured, the fatality rate and disability rate are extremely high. Therefore, accurate assessment of each step in the detection of intracranial aneurysms, assessment of the risk of rupture, formulation of treatment strategies, and treatment benefits will help to better treat the disease. At present, the treatment of intracranial aneurysms is limited. Except for surgical intervention, there are no other effective methods. Therefore, when a patient has a UIA, the formulation of treatment and management strategies is a difficult issue facing neurosurgery. This article introduces the choice of different treatment strategies for 3 patients with intracranial aneurysms complicated with other diseases and reviews the literature.

IL-6 Quotient (The Ratio of Cerebrospinal Fluid IL-6 to Serum IL-6) as a Biomarker of an Unruptured Intracranial Aneurysm.

BACKGROUND: Studies conducted so far have focused mainly on the assessment of IL-6 levels in patients with ruptured brain aneurysms. Carrying out detailed studies in patients with un-ruptured brain aneurysms (UIA) would be extremely important, as it would answer the question of whether IL-6 plays also a role in primary aneurysm formation and growth. METHODS: IL-6, S100, NSE, and albumin concentrations in 67 UIA patients and 17 individuals without vascular lesions in the brain were tested using in vitro diagnostic immunoassays according to the manufacturers' instructions. IL-6 Quotient was calculated by dividing cerebrospinal fluid (CSF) IL-6 by serum IL-6. RESULTS: We showed that IL-6 Quotient was significantly higher in UIA patients (1.78) compared to the control group (0.87; p<0.001). Multivariate logistic regression analysis demonstrated that a growth in IL-6 Quotient increases the probability of UIA diagnosis. In UIA patients CSF IL-6 concentration was significantly higher (4.55 pg/ml) compared to the serum concentration (2.39 pg/ml; p<0.001). In both the study and control group, the blood-brain barrier was intact, thus the CSF-blood gradient of the IL-6 concentration in UIA patients was likely to be the expression of local synthesis of the cytokine within the central nervous system. Patients with multiple brain aneurysms had significantly higher CSF IL-6 levels (5.08 pg/ml) compared to individuals with a single aneurysm (4.14 pg/ml; p=0.0227). CONCLUSION: This totality of the may suggest IL-6 as a biomarker for UIA formation; however, further studies are needed to unequivocally confirm clinical application of IL-6 concentration evaluation.

Ratio of IL-8 in CSF versus Serum Is Elevated in Patients with Unruptured Brain Aneurysm.

Only scarce data pertaining to interleukin 8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) chemokines in human aneurysm can be found in the current literature. Therefore, the aim of this study was the evaluation of cerebrospinal fluid (CSF) and serum IL-8 and MCP-1 concentration in unruptured intracranial aneurysm (UIA) patients (n = 25) compared to the control group (n = 20). IL-8 and MCP-1 concentrations were measured with ELISA method. We demonstrated that CSF IL-8 concentration of UIA patients is significantly higher (p < 0.001) than that presented in the serum, which can indicate its local synthesis within central nervous system. CSF IL-8 concentration was also significantly related to aneurysm size, which may reflect the participation of IL-8 in the formation and development of brain aneurysms. IL-8 Quotient (CSF IL-8 divided by serum IL-8) in UIA patients was statistically higher compared to control individuals (p = 0.045). However, the diagnostic utility analysis did not equivocally indicate the diagnostic usefulness of the IL-8 Quotient evaluation in brain aneurysm patients. Nevertheless, this aspect requires further study.

Management of carotid artery stenosis in patients with coexistent unruptured intracranial aneurysms.

OBJECTIVE: Concomitant unruptured intracranial aneurysms (UIAs) are present in patients with carotid artery stenosis not infrequently and result in unique management challenges. Thus, we investigated the risk of rupture of an aneurysm after revascularization of a carotid artery in a contemporary consecutive series of patients seen at our institution. METHODS: Data from patients who underwent a carotid revascularization in the presence of at least one concomitant UIA at our institution from 1991 to 2018 were retrospectively reviewed. Patients were evaluated for the incidence of aneurysm rupture within 30 days (early period) and after 30 days (late period) of carotid revascularization, as well as for the incidence of periprocedural complications from the treatment of carotid stenosis and/or UIA. RESULTS: Our study included 53 patients with 63 concomitant UIAs. There was no rupture within 30 days of carotid revascularization. The overall risk of rupture was 0.87% per patient-year. Treatment (coiling or clipping) of a concomitant UIA, if pursued, could be performed successfully after carotid revascularization. CONCLUSIONS: Carotid artery revascularization in the setting of a concomitant UIA can be performed safely without an increased 30-day or late-term risk of rupture. If indicated, treatment of the UIA can take place after the patient recovers from the carotid procedure.

Comparative effectiveness analysis of Pipeline device versus coiling in unruptured aneurysms smaller than 10 mm.

OBJECTIVE: Both endovascular coiling and the Pipeline embolization device (PED) have been shown to be safe and clinically effective for treatment of small (< 10 mm) aneurysms. The authors conducted a comparative effectiveness analysis to compare the utility of these treatment methods in terms of health benefits. METHODS: A decision-analytical study was performed with Markov modeling methods to simulate patients with small unruptured aneurysms undergoing endovascular coiling, stent-assisted coiling (SAC), or PED placement for treatment. Input probabilities were derived from prior literature, and 1-way, 2-way, and probabilistic sensitivity analyses were performed to assess model and input parameter uncertainty. RESULTS: The base case calculation for a 50-year-old man reveals PED to have a higher health benefit (17.48 quality-adjusted life years [QALYs]) than coiling (17.44 QALYs) or SAC (17.36 QALYs). PED is the better option in 6020 of the 10,000 iterations in probabilistic sensitivity analysis. When the retreatment rate of PED is lower than 9.53%, and the coiling retreatment is higher than 15.6%, PED is the better strategy. In the 2-way sensitivity analysis varying the retreatment rates from both treatment modalities, when the retreatment rate of PED is approximately 14% lower than the retreatment rate of coiling, PED is the more favorable treatment strategy. Otherwise, coiling is more effective. SAC may be better than PED when the unfavorable outcome risk of SAC is lower than 70% of its reported current value. CONCLUSIONS: With the increasing use of PEDs for treatment of small unruptured aneurysms, the current study indicates that these devices may have higher health benefits due to lower rates of retreatment compared to both simple coiling and stent-assisted techniques. Longer follow-up studies are needed to document the rates of recurrence and retreatment after coiling and PED to assess the cost-effectiveness of these strategies.

Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion.

OBJECTIVE: Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion. METHODS: The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined. RESULTS: Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2. CONCLUSIONS: Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

Contemporary trends in extracranial-intracranial bypass utilization: analysis of data from 2008 to 2016.

OBJECTIVE: The impact of FDA approval of flow-diversion technology for the treatment of supraclinoid internal carotid artery aneurysms and the publication of the Carotid Occlusion Surgery Study, both of which occurred in 2011, on the utilization of extracranial-intracranial (EC-IC) bypasses is not known. METHODS: The National Inpatient Sample (NIS) was queried for hospitalizations for EC-IC bypass performed from 2008 to 2016. Diagnoses of interest included an unruptured intracranial aneurysm (UIA), subarachnoid hemorrhage (SAH), carotid occlusive disease (COD), and moyamoya disease. The authors assessed trends in EC-IC bypass utilization for these diagnoses and the incidence of adverse discharges, defined as discharge to locations other than home, and the rate of mortality. RESULTS: A total of 1640 EC-IC bypass procedures were performed at 558 hospitals during the study period, with 1148 procedures at 448 hospitals performed for a diagnosis of interest. The most frequent surgical indication was moyamoya disease (65.7%, n = 754), followed by COD (23.2%, n = 266), SAH (3.2%, n = 37), and a UIA (7.9%, n = 91). EC-IC bypass utilization for COD decreased from 0.21 per 100 admissions of COD in 2010 to 0.09 per 100 admissions in 2016 (p = 0.023). The frequency of adverse discharges increased during the study period from 22.3% of annual admissions in 2008 to 31.2% in 2016 (p = 0.030) when analysis was limited to procedures performed for a diagnosis of interest. Per volume, the top 5th percentile of hospitals, on average, performed 18.4 procedures (SD 13.2) per hospital during the study period, compared to 1.3 procedures (SD 1.3) that were performed in hospitals within the bottom 95th percentile. The rate of adverse discharges was higher at low-volume institutions when compared to that at high-volume institutions (33.8% vs 28.7%; p = 0.029). Over the study period, the authors noted a trend toward a reduced percentage of total surgical volume performed at high-volume hospitals (p < 0.001). CONCLUSIONS: The authors observed a decrease in the utilization of EC-IC bypass for COD during the study period. An increase in the rate of adverse discharges was also noted, coinciding with more procedures being performed at lower-volume centers.