Assessment of targeted therapy opportunities in sinonasal cancers using patient-derived functional tumor models.

Malignant tumors derived from the epithelium lining the nasal cavity region are termed sinonasal cancers, a highly heterogeneous group of rare tumors accounting for 3 - 5 % of all head and neck cancers. Progress with next-generation molecular profiling has improved our understanding of the complexity of sinonasal cancers and resulted in the identification of an increasing number of distinct tumor entities. Despite these significant developments, the treatment of sinonasal cancers has hardly evolved since the 1980s, and an advanced sinonasal cancer presents a poor prognosis as targeted therapies are usually not available. To gain insights into potential targeted therapeutic opportunities, we performed a multiomics profiling of patient-derived functional tumor models to identify molecular characteristics associated with pharmacological responses in the different subtypes of sinonasal cancer. METHODS: Patient-derived ex vivo tumor models representing four distinct sinonasal cancer subtypes: sinonasal intestinal-type adenocarcinoma, sinonasal neuroendocrine carcinoma, sinonasal undifferentiated carcinoma and SMARCB1 deficient sinonasal carcinoma were included in the analyses. Results of functional drug screens of 160 anti-cancer therapies were integrated with gene panel sequencing and histological analyses of the tumor tissues and the ex vivo cell cultures to establish associations between drug sensitivity and molecular characteristics including driver mutations. RESULTS: The different sinonasal cancer subtypes display considerable differential drug sensitivity. Underlying the drug sensitivity profiles, each subtype was associated with unique molecular features. The therapeutic vulnerabilities correlating with specific genomic background were extended and validated with in silico analyses of cancer cell lines representing different human cancers and with reported case studies of sinonasal cancers treated with targeted therapies. CONCLUSION: The results demonstrate the importance of understanding the differential biology and the molecular features associated with the different subtypes of sinonasal cancers. Patient-derived ex vivo tumor models can be a powerful tool for investigating these rare cancers and prioritizing targeted therapeutic strategies for future clinical development and personalized medicine.

PET imaging of unruptured intracranial aneurysm inflammation (PET-IA) study: a feasibility study protocol.

INTRODUCTION: Positron emission tomography (PET) imaging can be used to evaluate arterial wall inflammation in extracranial vascular diseases. However, the application of PET imaging in unruptured intracranial aneurysms (UIA) remains unexplored. Our objective is to investigate feasibility of PET imaging using 18F-FDG and 68Ga-DOTANOC tracers to evaluate arterial wall inflammation in UIA. METHODS AND ANALYSIS: This PET imaging feasibility study will enrol patients scheduled for surgical treatment of UIA. The study subjects will undergo PET imaging of the intracranial arteries within 1 month before planned surgery. The imaging protocol includes 18F-FDG PET MRI, MRA with gadolinium enhancement, and 68Ga-DOTANOC PET CT. The study will also involve preoperative blood samples, intraoperative cerebrospinal fluid (CSF) samples, and aneurysm sac biopsy. Planned sample size is at least 18 patients. Primary outcome is uptake of 18F-FDG or 68Ga-DOTANOC in intracranial arterial aneurysms compared with contralateral normal vessel as maximum standardised uptake value or target-to-blood pool ratio and correlation of uptake of 18F-FDG or 68Ga-DOTANOC to aneurysm histological findings. Secondary outcomes include estimating the correlations between uptake of 18F-FDG or 68Ga-DOTANOC and histological findings with blood and CSF miRNA-levels, arterial wall enhancement in gadolinium enhanced MRA, aneurysm size and shape, smoking, hypertension, and location of the aneurysm. ETHICS AND DISSEMINATION: This study is approved by the Human Research Ethics Committee of the Hospital District of Southwest Finland, Finnish Medicines Agency Fimea, and Turku University Hospital. Findings will be disseminated through peer-reviewed journal articles and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04715503.

Positive Correlation Between Thoracic Aortic Diameter and Intracranial Aneurysm Size-An Observational Cohort Study.

OBJECTIVE: To investigate the association between intracranial aneurysms (IAs) and thoracic aortic diameter. METHODS: This observational cohort study examined thoracic aortic diameters in patients with IA. Patients were categorized by IA size (<7 mm and ≥7 mm) and IA status (ruptured/unruptured) based on radiologic findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses. RESULTS: A total of 409 patients were included. Mean age was 60 (±11.7) years and 63% were women. Thoracic aortic diameters were greater among patients who had an IA ≥7 mm versus IA <7 mm (P < 0.05). In the univariate analysis, the diameter of the ascending aorta (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.129 per 1 mm; P = 0.002), aortic arch (OR, 1.10; 95% CI, 1.04-1.15 per 1 mm; P < 0.001), and descending aorta (OR, 1.10; 95% CI, 1.03-1.16 per 1 mm; P = 0.003) were associated with IAs ≥7 mm. In the multivariable regression model, larger ascending aorta (OR, 1.09; 95% CI, 1.01-1.17 per 1 mm; P = 0.018), aortic arch (OR, 1.12; 95% CI, 1.02-1.22 per 1 mm; P = 0.013), and descending aorta (OR, 1.20; 95% CI, 1.08-1.33 per 1 mm; P < 0.001) were associated with ruptured IA. CONCLUSIONS: Greater thoracic aortic diameters are associated with a higher risk of IA being larger than 7 mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides a basis for future considerations regarding screening and risk management.

Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries-A Prospective Cohort Study.

Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients' outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53-89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83-65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.

Low and Borderline Ankle-Brachial Index Is Associated With Intracranial Aneurysms: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: A low ankle-brachial index (ABI) has been linked to systemic inflammation and an elevated risk of cardiovascular events, most notably myocardial infarction and stroke. Intracranial aneurysms (IAs) share similar risk factors with other cardiovascular diseases. However, the association between low ABI and IAs has not been sufficiently investigated. Our objective was to investigate the potential connection between ABI values and the prevalence of unruptured IAs. METHODS: This retrospective cohort study reviewed 2751 patients who had ABI measurements at a public tertiary hospital from January 2011 to December 2013. Patients with available cerebrovascular imaging or a diagnosis of ruptured IA were included in the study (n = 776) to examine the association between ABI and saccular IAs. The patients were classified into 4 groups: low ABI (≤0.9, n = 464), borderline ABI (0.91-0.99; n = 47), high ABI (>1.4, n = 57), and normal ABI (1.00-1.40; n = 208). RESULTS: The prevalence of IAs was 20.3% (18.1% unruptured IAs) in the low ABI group, 14.9% (12.8% unruptured IAs) in the borderline ABI group, 7.0% (5.3% unruptured IAs) in the high ABI group, and 2.4% (1.9% unruptured IAs) in the normal ABI group (P < .001). There were no significant differences in the prevalence of ruptured IAs between the ABI groups (P = .277). Sex- and age-adjusted multinomial regression, including clinically relevant variables, revealed that low ABI (odds ratio [OR], 13.02; 95% CI, 4.01-42.24), borderline ABI (OR, 8.68; 95% CI, 2.05-36.69), and smoking history (OR, 2.01; 95% CI, 1.07-3.77) were associated with unruptured IAs. CONCLUSION: The prevalence of unruptured IAs was 9-fold higher in the low ABI group and nearly 7-fold higher in the borderline ABI group when compared with the normal ABI group. ABI measurements could be clinically relevant for identifying individuals at higher risk of IAs and may help guide screening and preventive strategies.

Detection Rates and Trends of Asymptomatic Unruptured Intracranial Aneurysms From 2005 to 2019.

BACKGROUND AND OBJECTIVES: The trend in detection rates of asymptomatic unruptured intracranial aneurysms (UIAs) on brain computed tomography angiography/magnetic resonance angiography (CTA/MRA) is not well established. Our objective was to evaluate time trends in asymptomatic UIA detection rates on brain CTA/MRA between 2005 and 2019. METHODS: We conducted a retrospective study of all brain computed tomography/magnetic resonance scans (n = 288 336 scans in 130 621 patients) performed between January 2005 and December 2019 at a tertiary referral hospital. Patients who underwent brain CTA/MRA examinations were included (n = 81 261 scans in 48 037 patients). The annual detection rate of new UIA cases was calculated based on the first brain CTA/MRA imaging. Detection rates were compared between three periods and across different age groups. RESULTS: The number of first CTA/MRA examinations increased significantly from 2005 to 2009 (n = 12 190 patients) to 2010-2014 (n = 14 969 patients) and 2015-2019 (n = 20 878 patients) ( P < .001). The UIA detection rate also increased significantly from 1.7% in 2005-2009 to 2.5% in 2010-2014 and 3.4% in 2015-2019 ( P < .001). The UIA detection rate increased significantly from 2010-2014 to 2015-2019 (relative risk [RR], 1.33; 95% CI, 1.17-1.51), particularly in patients aged 60-69 years (RR, 1.29; 95% CI, 1.01-1.63), 70-79 years (RR, 1.71; 95% CI, 1.30-2.25), and >79 years (RR, 2.33; 95% CI, 1.56-3.47). Furthermore, the detection rate of <5-mm UIAs increased from 2010-2014 to 2015-2019 (RR, 1.51; 95% CI, 1.28-1.77). CONCLUSION: The detection rate of asymptomatic UIAs, particularly in elderly patients, has increased significantly over the past 15 years, coinciding with the increased use of CTA/MRA imaging. Furthermore, the size of the identified UIAs has decreased. These findings raise concerns about the management strategies for UIAs, indicating the need for further research.

Outcome and survival of surgically treated acute subdural hematomas and postcraniotomy hematomas - A retrospective cohort study.

Background: The morbidity and mortality of acute subdural hematoma (aSDH) remains high. Several factors have been reported to affect the outcome and survival of these patients. In this study, we explored factors potentially associated with the outcome and survival of surgically treated acute subdural hematoma (aSDH), including postcraniotomy hematomas (PCHs). Methods: This retrospective cohort study was conducted in a single tertiary university hospital between 2008 and 2012 and all aSDH patients that underwent surgical intervention were included. A total of 132 cases were identified for collection of demographics, clinical, laboratory, and imaging data. Univariate and multivariable analyses were performed to assess factors associated with three-month Glasgow Outcome Scale (GOS) and survival at one- and five-year. Results: In this study, PCH (n = 14, 10.6%) was not associated with a worse outcome according to the 3- month GOS (p = 0.37) or one (p = 0.34) and five-year (p = 0.37) survival. The multivariable analysis showed that the volume of initial hematoma (p = 0.009) and Abbreviated Injury Scale score (p = 0.016) were independent predictors of the three-month GOS. Glasgow Coma Scale (GCS) score (p < 0.001 and p = 0.037) and age (p = 0.048 and p = 0.003) were predictors for one and five-year survival, while use of antiplatelet drug (p = 0.030), neuroworsening (p = 0.005) and smoking (p = 0.026) were significant factors impacting one year survival. In addition, blood alcohol level on admission was a predictor for five-year survival (p = 0.025). Conclusions: These elucidations underscore that, although PCHs are pertinent, a comprehensive appreciation of multifarious variables is indispensable in aSDH prognosis. These findings are observational, not causal. Expanded research endeavors are advocated to corroborate these insights.

Effect of xenon on brain injury, neurological outcome, and survival in patients after aneurysmal subarachnoid hemorrhage-study protocol for a randomized clinical trial.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest. METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain. DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.

A summary of the first 100 neurointerventional procedures performed with the Rist radial access device in a Finnish neurovascular center.

BACKGROUND AND PURPOSE: Transradial access (TRA) has increased popularity among neurointerventionalists during a short time period but until recently there have been no devices designed especially for radial use. MATERIALS AND METHODS: Consecutive neurointerventional procedures with an intention to perform TRA with the Rist radial access guide catheter between April 2021 and May 2022 were retrospectively reviewed. Possible access site complications, other procedure-related complications and information on successful catherization of the target vessel as well as whether the procedure had been successful were collected. RESULTS: Information from 100 patients was included in the study. The most general procedure was flow diversion (29%) followed by WEB embolization (20 %). Four patients (4%) needed conversion to femoral access. The triaxial system was used in 76% of the procedures. Four patients (4%) experienced access site or device related complications, none of those were serious. Six patients had clinically relevant procedure related complications. CONCLUSIONS: It is concluded that the Rist device can be used safely for a large variety of neurointerventions with a short learning curve.

Motor dysfunction as a primary symptom predicts poor outcome: multicenter study of glioma symptoms.

Background and objectives: The objectives of this study were to investigate the prognostic value of primary symptoms and leading symptoms in adult patients with diffuse infiltrating glioma and to provide a clinical perspective for evaluating survival. Methods: This study included a retrospective cohort from two tertiary university hospitals (n = 604, 2006-2013, Tampere University Hospital and Turku University Hospital) and a prospective cohort (n = 156, 2014-2018, Tampere University Hospital). Preoperative symptoms were divided into primary and leading symptoms. Results were validated with the newer WHO 2021 classification criteria. Results: The most common primary symptoms were epileptic seizure (30.8% retrospective, 28.2% prospective), cognitive disorder (13.2% retrospective, 16.0% prospective), headache (8.6% retrospective, 12.8% prospective), and motor paresis (7.0% retrospective, 7.1% prospective). Symptoms that predicted better survival were epileptic seizure and visual or other sense-affecting symptom in the retrospective cohort and epileptic seizure and headache in the prospective cohort. Predictors of poor survival were cognitive disorder, motor dysfunction, sensory symptom, tumor hemorrhage, speech disorder and dizziness in the retrospective cohort and cognitive disorder, motor dysfunction, sensory symptom, and dizziness in the prospective cohort. Motor dysfunction served as an independent predictor of survival in a multivariate model (OR = 1.636). Conclusion: Primary and leading symptoms in diffuse gliomas are associated with prognoses in retrospective and prospective settings. Motor paresis was an independent prognostic factor for poor survival in multivariate analysis for grade 2-4 diffuse gliomas, especially in glioblastomas.

Brain white matter hyperintensities in Kawasaki disease: A case-control study.

Background: Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke. Purpose: To investigate whether childhood KD is associated with WMHs and other cerebrovascular findings later in adulthood. Materials and methods: In this case-control study, patients diagnosed with KD (cases) at our tertiary hospital between 1978 and 1995 were invited to brain magnetic resonance (MRI) between 2016 and 2017. Migraine patients (controls) with available brain MRI were matched with cases (ratio 4:1) by age (±2 years) and sex. Two blinded neuroradiologists evaluated independently cerebrovascular findings from the brain MRI scans. Modified Scheltens' visual rating scale was used to evaluate WMH burden and the total WMH volume was measured using manual segmentation. Results: Mean age [years, (SD)] at the time of brain MRI was 33.3 (3.8) and 32.8 (4.0) for cases (n = 40) and controls (n = 160), respectively (P = 0.53). Mean follow-up time for cases was 29.5 years (4.3). Total volume of WMHs (median) was 0.26 cm3 (IQR 0.34) for cases and 0.065 cm3 (IQR 0.075) for controls, P = 0.039. Cases had higher total WMH burden (P = 0.003), deep WMH burden (P = 0.003), and more periventricular WMHs (prevalence 7.5 vs. 0%, P = 0.008) than controls. Cases had greater risk of having total Scheltens' score ≥2 vs. < 2 (odds ratio, 6.88; 95% CI: 1.84-25.72, P = 0.0041) and ≥3 vs. < 3 (odds ratio, 22.71; 95% CI: 2.57-200.53, P = 0.0049). Diabetes type 1/type 2, hypertension, smoking status or hypercholesterolemia were not risk factors for WMH burden, p > 0.1. Myocarditis at the acute phase of KD increased the risk for periventricular WMHs (P < 0.05). Three cases (7.5%) and three controls (1.9%) had lacune of presumed vascular origin (P = 0.0096). Conclusion: History of KD could be associated with an increased WMH burden. More studies are needed to confirm our results.

The prevalence of cardiac complications and their impact on outcomes in patients with non-traumatic subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a serious condition, and a myocardial injury or dysfunction could contribute to the outcome. We assessed the prevalence and prognostic impact of cardiac involvement in a cohort with SAH. This is a prospective observational multicenter study. We included 192 patients treated for non-traumatic subarachnoid hemorrhage. We performed ECG recordings, echocardiographic examinations, and blood sampling within 24 h of admission and on days 3 and 7 and at 90 days. The primary endpoint was the evidence of cardiac involvement at 90 days, and the secondary endpoint was to examine the prevalence of a myocardial injury or dysfunction. The median age was 54.5 (interquartile range [IQR] 48.0-64.0) years, 44.3% were male and the median World Federation of Neurological Surgeons (WFNS) score was 2 (IQR 1-4). At day 90, 22/125 patients (17.6%) had left ventricular ejection fractions ≤ 50%, and 2/121 patients (1.7%) had evidence of a diastolic dysfunction as defined by mitral peak E-wave velocity by peak e' velocity (E/e') > 14. There was no prognostic impact from echocardiographic evidence of cardiac complications on neurological outcomes. The overall prevalence of cardiac dysfunction was modest. We found no demographic or SAH-related factors associated with 90 days cardiac dysfunction.

Physical exertion as a risk factor for perimesencephalic nonaneurysmal subarachnoid hemorrhage.

BACKGROUND: Perimesencephalic and nonperimesencephalic nonaneurysmal subarachnoid hemorrhage (PM-naSAH and NPM-naSAH) have a different bleeding pattern and clinical course. The etiology and risk factors for PM-naSAH and NPM-naSAH are unclear. The objective of this study was to compare risk factors and triggering events between PM-naSAH and NPM-naSAH. METHODS: We reviewed retrospectively all patients (n = 3475) who had undergone cerebral digital subtraction angiography between 2003 and 2020 at our tertiary hospital. Of these, 119 patients had 6-vessel angiography negative subarachnoid hemorrhage (47 (39%) PM-naSAH and 72 (61%) NPM-naSAH) and accurate information about the triggering event was available in 42 (89%) PM-NASAH and 64 (89%) NPM-naSAH patients. RESULTS: PM-naSAH were younger compared to NPM-naSAH (mean age [SD]; 55.3 [11.1] years vs. 59.6 [12.2] years, p = .045. PM-naSAH was triggered during the physical exertion in 79% of patients and 16% of patients with NPM-naSAH (relative risk 5.4; 95% CI, 2.9-10.1, p < .0001). There were no significant difference in sex, smoking, alcohol abuse, hypertension, diabetes, hyperlipidemia, or anticoagulation/antithrombotic usage between PM-naSAH and NMP-naSAH, p > .05. CONCLUSION: Physical exertion was a triggering factor in most of the PM-naSAH cases and the risk was five times greater than in NMP-naSAH. More studies are needed to confirm our results and to study pathophysiology of PM-naSAH and NPM-naSAH.

Glycans as Potential Diagnostic Markers of Traumatic Brain Injury.

The diagnosis of mild traumatic brain injury (TBI) is challenging in the acute setting because the symptoms are nonspecific and often transient, or they develop with a delay. In these cases, the criteria for acute head imaging are frequently not fulfilled. This may lead to missed diagnoses in emergency care. There is a need for developing a rapid diagnostic test to verify the presence of TBI using body fluids. Blood, urine, and saliva samples from 11 adult patients (mean age 64 years, SD 24 years) with acute and clinically diagnosed TBI, and 12 healthy volunteers were collected at Turku University Hospital during a period of 5 months. The injuries necessitated hospitalization for at least one day. The TBIs were classified mild in nine cases and severe in two cases. The mean period between the trauma and the time for obtaining the samples was 27 h, SD 11 h. The samples were analyzed in an ISO-certified laboratory for the number of lectin-bound glycan molecules indicating destruction of nerve tissue. The screening was performed on several possible glycans for binding, and the measurement by degree of fluorescence. In the analysis, the group of patients with TBI was compared with healthy volunteers. The results showed a significant decrease (p < 0.05, Wilcoxon rank-sum two-sided test) in the level of two glycans in plasma, but no significant increase for any glycan; in saliva, one glycan showed a significant increase in the TBI group; in urine, three glycans were significantly different between the groups (one showed an increase, whereas two showed a decrease). The results support the idea of conducting more research on how diagnostic glycans could be detected in body fluids after TBI. As a proof-of-concept, significant changes in the concentration of five glycans were found in plasma, saliva, and urine between TBI patients and healthy controls. This may enable the development of a rapid body fluid-based point-of-care test to identify patients with TBI after a head injury.

Risk of Rupture After Intracranial Aneurysm Growth.

Importance: Unruptured intracranial aneurysms not undergoing preventive endovascular or neurosurgical treatment are often monitored radiologically to detect aneurysm growth, which is associated with an increase in risk of rupture. However, the absolute risk of aneurysm rupture after detection of growth remains unclear. Objective: To determine the absolute risk of rupture of an aneurysm after detection of growth during follow-up and to develop a prediction model for rupture. Design, Setting, and Participants: Individual patient data were obtained from 15 international cohorts. Patients 18 years and older who had follow-up imaging for at least 1 untreated unruptured intracranial aneurysm with growth detected at follow-up imaging and with 1 day or longer of follow-up after growth were included. Fusiform or arteriovenous malformation-related aneurysms were excluded. Of the 5166 eligible patients who had follow-up imaging for intracranial aneurysms, 4827 were excluded because no aneurysm growth was detected, and 27 were excluded because they had less than 1 day follow-up after detection of growth. Exposures: All included aneurysms had growth, defined as 1 mm or greater increase in 1 direction at follow-up imaging. Main Outcomes and Measures: The primary outcome was aneurysm rupture. The absolute risk of rupture was measured with the Kaplan-Meier estimate at 3 time points (6 months, 1 year, and 2 years) after initial growth. Cox proportional hazards regression was used to identify predictors of rupture after growth detection. Results: A total of 312 patients were included (223 [71%] were women; mean [SD] age, 61 [12] years) with 329 aneurysms with growth. During 864 aneurysm-years of follow-up, 25 (7.6%) of these aneurysms ruptured. The absolute risk of rupture after growth was 2.9% (95% CI, 0.9-4.9) at 6 months, 4.3% (95% CI, 1.9-6.7) at 1 year, and 6.0% (95% CI, 2.9-9.1) at 2 years. In multivariable analyses, predictors of rupture were size (7 mm or larger hazard ratio, 3.1; 95% CI, 1.4-7.2), shape (irregular hazard ratio, 2.9; 95% CI, 1.3-6.5), and site (middle cerebral artery hazard ratio, 3.6; 95% CI, 0.8-16.3; anterior cerebral artery, posterior communicating artery, or posterior circulation hazard ratio, 2.8; 95% CI, 0.6-13.0). In the triple-S (size, site, shape) prediction model, the 1-year risk of rupture ranged from 2.1% to 10.6%. Conclusion and Relevance: Within 1 year after growth detection, rupture occurred in approximately 1 of 25 aneurysms. The triple-S risk prediction model can be used to estimate absolute risk of rupture for the initial period after detection of growth.

Intracranial aneurysm is predicted by abdominal aortic calcification index: A retrospective case-control study.

BACKGROUND AND AIMS: Patients with intracranial aneurysms (IA) have excess mortality for cardiovascular diseases, but little is known on whether atherosclerotic manifestations and IA coexist. We investigated abdominal aortic calcification index (ACI) association with unruptured and ruptured IAs. METHODS: This retrospective case-control study reviews all tertiary centers patients (n = 24,660) who had undergone head computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA) for any reason between January 2003 and May 2018. Patients (n = 2020) with unruptured or ruptured IAs were identified, and patients with available abdominal CT were included. IA patients were matched by sex and age to controls (available abdomen CT, no IAs) in ratio of 1:3. ACI was measured from abdomen CT scans and patient records were reviewed. RESULTS: 1720 patients (216 ruptured IA (rIA), 246 unruptured IA (UIA) and 1258 control) were included. Mean age was 62.9 ± 11.9 years and 58.2% were female. ACI (OR 1.02 per increment, 95%CI 1.01-1.03) and ACI>3 (OR 5.77, 95%CI 3.29-10.11) increased risk for rIA compared to matched controls. UIA patients' ACI was significantly higher but ACI did not increase odds for UIA compared to matched controls. History of coronary artery disease was less frequent in rIA patients. There was no calcification in aorta in 8.8% rIA and 13.6% UIA patients (matched controls 25.7% and 22.6% respectively, p < 0.01). CONCLUSIONS: Aortic calcification is greater in rIA and UIA patients than matched controls. ACI increases risk for rIAs.

A comprehensive p75 neurotrophin receptor gene network and pathway analyses identifying new target genes.

P75 neurotrophic receptor (p75NTR) is an important receptor for the role of neurotrophins in modulating brain plasticity and apoptosis. The current understanding of the role of p75NTR in cellular adaptation following pathological insults remains blurred, which makes p75NTR's related signaling networks an interesting and challenging initial point of investigation. We identified p75NTR and related genes through extensive data mining of a PubMed literature search including published works related to p75NTR from the past 20 years. Bioinformatic network and pathway analyses of identified genes (n = 235) were performed using ReactomeFIViz in Cytoscape based on the highly reliable Reactome functional interaction network algorithm. This approach merges interactions extracted from human curated pathways with predicted interactions from machine learning. Genome-wide pathway analysis showed total of 16 enriched hierarchical clusters. A total of 278 enriched single pathways were also identified (p < 0.05, false discovery rate corrected). Gene network analyses showed multiple known and new targets in the p75NTR gene network. This study provides a comprehensive analysis and investigation into the current knowledge of p75NTR signaling networks and pathways. These results also identify several genes and their respective protein products as involved in the p75NTR network, which have not previously been clearly studied in this pathway. These results can be used to generate novel hypotheses to gain a greater understanding of p75NTR in acute brain injuries, neurodegenerative diseases and general response to cellular damage.

Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam.

BACKGROUND: Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH. METHODS: Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4 µg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20 mm Hg above the baseline. RESULTS: Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean ± SD) 1.20 ± 0.14, 1.17 ± 0.13 (P = .93), 1.14 ± 0.09 (P = .72) and 1.19 ± 0.18 (P = 1.0) and sROR% was 150.89 ± 84.37, 75.22 ± 27.75 (P = .08), 128.25 ± 58.35 (P = .84) and 104.82 ± 36.92 (P = .42) at baseline and during 0.7, 1.0 and 1.4 µg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0 µg/kg/h dexmedetomidine (P = .02). CONCLUSIONS: Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.

The Need for Surgical Safety Checklists in Neurosurgery Now and in the Future-A Systematic Review.

Safety checklists have been studied among various surgical patient groups, but evidence of their benefits in neurosurgery remains sparse. Since the implementation of the World Health Organization's Surgical Safety Checklist, their use has become widespread. The aim of this review was to systematically review the state of the literature on surgical safety checklists in neurosurgery. Also, in the new era of robotics and artificial intelligence, there is a need to re-evaluate patient safety procedures in neurosurgery. A systematic review was conducted on PubMed, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for articles published between 2008 and 2016 using MeSH (medical subject heading) terms and keywords describing postoperative complications and surgical adverse events, and some additional searches were carried out until January 2019. Twenty-six original studies or reviews were eligible for this review. They were categorized into studies with patient-related outcomes, personnel-related outcomes, or previous reviews. Checklist use in neurosurgery was found to reduce hospital-acquired infectious complications and to enhance operating room safety culture. Checklists seem to improve patient safety in neurosurgery, although the amount of evidence is still limited. Despite their shortcomings, checklists are here to stay, and new research is required to update checklists to meet the requirements of the transforming working environment of the neurosurgery operating room.