Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults.

Importance: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants: This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure: Immunosuppresion. Main Outcomes and Measures: Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results: Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance: In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

The use of Microsurgical Exploration of the External Carotid Artery for Removal of a Retained Microcatheter After Middle Meningeal Artery Embolization Using Live Fluoroscopy: A Technical Note.

BACKGROUND: Fragmentation, disconnection, or entrapment of an in-use microcatheter during neuro-endovascular procedures is a known risk. Often a benign entity, retained catheters are not infrequently observed, but severe complications including thrombus, thromboembolic events, pseudoaneurysm, and limb ischemia have been described, necessitating retrieval. This technical case report demonstrates the safe use of an external carotid artery (ECA) approach for ligation and removal of a retained microcatheter after middle meningeal artery (MMA) embolization. This article also demonstrates the use of live intraoperative fluoroscopy as a surgical adjunct to ensure that the catheter is fully removed without any injury, shearing, or breakage during removal. METHODS: A 66-year-old male patient presented with bilateral subdural hematomas to an outside hospital. He subsequently underwent evacuation of the hematomas followed by a right-sided MMA embolization, complicated by Onyx (Medtronic, Minneapolis, MN) entrapment of the microcatheter in the MMA. The patient was asymptomatic, but there was significant concern about continuing antiplatelet/anticoagulation therapy in the presence of the subdural hematoma. We proceeded with an open surgical approach for catheter retrieval. As the catheter was withdrawn, intraoperative fluoroscopy demonstrated complete removal without any retained fragments. RESULTS: The patient recovered without event and was discharged on postoperative day 1. On follow-up the patient continued to do well without any complications from the fragment that remained in the external carotid circulation. CONCLUSIONS: This case and accompanying video demonstrates the effective use of open ECA surgical approach to retrieve the retained microcatheter after an MMA embolization. This approach allowed for safe and effective removal of the microcatheter while significantly reducing complication risks.

Treatment of Ruptured Wide-Necked Aneurysms using a Microcatheter Injectable Biomaterial.

Ruptured wide-neck aneurysms (WNAs), especially in a setting of coagulopathy, are associated with significant morbidity and mortality. It is shown that by trapping a sub-millimeter clinical catheter inside the aneurysm sac using a flow diverter stent (FDS), instant hemostasis can be achieved by filling the aneurysm sac using a novel biomaterial, rescuing catastrophic bleeding in large-animal models. Multiple formulations of a biomaterial comprising gelatin, nanoclay (NC), and iohexol are developed, optimized, and extensively tested in vitro to select the lead candidate for further testing in vivo in murine, porcine, and canine models of WNAs, including in a subset with aneurysm rupture. The catheter-injectable and X-ray visible versions of the gel embolic agent (GEA) with the optimized mechanical properties outperform control groups, including a subset that receive a clinically used liquid embolic (Onyx, Medtronic), with and without aneurysm rupture. A combinatorial approach to ruptured WNAs with GEA and FDS may change the standard of medical practice and save lives.

Predictive Model Evaluating Risk of Hemorrhage in Intracranial Aneurysms: Analysis from Prospectively Collected HEAT Trial Database.

OBJECTIVE: We analyzed the data of patients enrolled in the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to develop and validate a model to predict the risk of aneurysmal hemorrhage. METHODS: Analysis included data from 600 patients enrolled for the HEAT trial and included single saccular aneurysms of 3-14 mm size. Baseline characteristics were compared between patients with ruptured and unruptured aneurysms. Regression analysis was performed in the training set to identify significant risk factors and was validated in the validation dataset. The complete dataset was used to formulate a scoring model in which positive and negative predictors were assigned 1 and -1 points, respectively. RESULTS: Data from 593 patients were analyzed in which 169 (28.5%) patients had ruptured aneurysms. The training (n = 297) and validation dataset (n = 296) had a comparable proportion of ruptured aneurysms (29.3% and 27.7%). Dome-to-neck ratio >2.5 (odds ratio [OR] 3.66), irregular shape (OR 3.79), daughter sac (OR 5.89), and anterior and posterior communicating artery locations (OR 3.32 and 3.56, respectively) had a higher rupture rate. Use of aspirin was associated with lower risk of hemorrhage (OR 0.16). The area under the curve from the receiver operating curve analysis was 0.88, 0.87, and 0.87 in the training, validation, and combined data set, respectively. The scoring model created a score of -1 to 2, yielding an of aneurysmal hemorrhage probability from 1.5% (score -1) to 70% (score 2). CONCLUSIONS: This prospective study identifies dome-to-neck ratio >2.5, irregular shape, presence of daughter sac, absence of aspirin use, and aneurysm location at anterior communicating and posterior communicating artery as factors associated with increased risk of hemorrhagic presentation in small- to medium-sized intracranial aneurysms. Our model provides an estimate of rupture risk based on the presence or absence of these factors.

Optimizing Door-to-Groin Puncture Time: The Mayo Clinic Experience.

Objectives: To provide a better understanding of methods that can be used to improve patient outcomes by reducing the door-to-groin puncture (DTP) time and present the results of a stroke quality improvement project (QIP) conducted by Mayo Clinic Arizona's stroke center. Methods: We conducted a systematic literature search of Ovid MEDLINE(R), Ovid EMBASE, Scopus, and Web of Science for studies that evaluated DTP time reduction strategies. Those determined eligible for the purpose of this analysis were assessed for quality. The strategies for DTP time reduction were categorized on the basis of modified Target: Stroke Phase III recommendations and analyzed using a meta-analysis. The Mayo Clinic QIP implemented a single-call activation system to reduce DTP times by decreasing the time from neurosurgery notification to case start. Results: Fourteen studies were selected for the analysis, consisting of 2277 patients with acute ischemic stroke secondary to large-vessel occlusions. After intervention, all the studies showed a reduction in the DTP time, with the pooled DTP improvement being the standardized mean difference (1.37; 95% confidence interval, 1.20-1.93; τ2=1.09; P<.001). The Mayo Clinic QIP similarly displayed a DTP time reduction, with the DTP time dropping from 125.1 to 82.5 minutes after strategy implementation. Conclusion: Computed tomography flow modifications produced the largest and most consistent reduction in the DTP time. However, the reduction in the DTP time across all the studies suggests that any systematic protocol aimed at reducing the DTP time can produce a beneficial effect. The relative novelty of mechanical thrombectomy and the consequential lack of research call for future investigation into the efficacy of varying DTP time reduction strategies.

The Characteristics of White Matter Hyperintensities in Patients With Migraine.

Background: The presence of white matter hyperintensities (WMHs) in migraine is well-documented, but the location of WMH in patients with migraine is insufficiently researched. This study assessed WMH in patients with migraine using a modified version of the Scheltens visual rating scale, a semiquantitative scale for categorizing WMH in periventricular, lobar, basal ganglia, and infratentorial regions. Methods: In total, 263 patients with migraine (31 men and232 women) enrolled in the American Registry for Migraine Research (ARMR) from Mayo Clinic Arizona and who had clinical brain magnetic resonance imaging (MRI) were included in this study. Those with imaging evidence for gross anatomical abnormalities other than WMHs were excluded. A board-certified neuroradiologist identified WMHs on axial T2 and fluid-attenuated inversion recovery (FLAIR) sequences. WMHs were characterized via manual inspection and categorized according to the scale's criteria. Results: Results showed that 95 patients (36.1%, mean age: 41.8 years) had no WMHs on axial T2 and FLAIR imaging and 168 patients (63.9%, mean age: 51.4 year) had WMHs. Of those with WMHs, 94.1% (n = 158) had lobar hyperintensities (frontal: 148/158, 93.7%; parietal: 57/158, 36.1%; temporal: 35/158, 22.1%; and occipital: 9/158, 5.7%), 13/168, 7.7% had basal ganglia WMHs, 49/168, 29.1% had periventricular WMHs, and 17/168, 10.1% had infratentorial WMHs. In addition, 101/168 patients (60.1%) had bilateral WMHs and 67/168 (39.9%) had unilateral WMHs (34 right hemisphere/33 left hemisphere). Discussion: Among ARMR participants who were enrolled by Mayo Clinic Arizona and who had clinical brain MRIs, nearly two-thirds had WMHs. The WMHs were the most common in the frontal lobes. Describing the features of WMHs in those with migraine, and comparing them with WMHs attributable to other etiologies, might be useful for developing classifiers that differentiate between migraine-specific WMH and other causes of WMH.

Administration of Glutaredoxin-1 Attenuates Liver Fibrosis Caused by Aging and Non-Alcoholic Steatohepatitis.

Liver fibrosis is a sign of non-alcoholic fatty liver disease progression towards steatohepatitis (NASH) and cirrhosis and is accelerated by aging. Glutaredoxin-1 (Glrx) controls redox signaling by reversing protein S-glutathionylation, induced by oxidative stress, and its deletion causes fatty liver in mice. Although Glrx regulates various pathways, including metabolism and apoptosis, the impact of Glrx on liver fibrosis has not been studied. Therefore, we evaluated the role of Glrx in liver fibrosis induced by aging or by a high-fat, high-fructose diet. We found that: (1) upregulation of Glrx expression level inhibits age-induced hepatic apoptosis and liver fibrosis. In vitro studies indicate that Glrx regulates Fas-induced apoptosis in hepatocytes; (2) diet-induced NASH leads to reduced expression of Glrx and higher levels of S-glutathionylated proteins in the liver. In the NASH model, hepatocyte-specific adeno-associated virus-mediated Glrx overexpression (AAV-Hep-Glrx) suppresses fibrosis and apoptosis and improves liver function; (3) AAV-Hep-Glrx significantly inhibits transcription of Zbtb16 and negatively regulates immune pathways in the NASH liver. In conclusion, the upregulation of Glrx is a potential therapeutic for the reversal of NASH progression by attenuating inflammatory and fibrotic processes.

A Renaissance in Modern and Future Endovascular Stroke Care.

Acute ischemic stroke continues to be a major cause of death and disability globally. Although the concept of endovascular treatment of ischemic stroke is relatively new, current evidence from high-quality randomized trials suggests a significant improvement in the clinical outcome with mechanical thrombectomy up to 24 hours from the stroke onset. There has been a paradigm shift from medical management to mechanical thrombectomy which is now considered standard of care in eligible patients. Not surprisingly, there has been a constant effort to further improve stroke care in the last few years with a common goal of ultra-rapid intervention along with highly effective revascularization methods. Currently, it is one of the most dynamic and rapidly changing subspecialties in the field of medicine with significant advances in all aspects of acute stroke treatment starting from triage in the field to poststroke rehabilitation.

Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks.

ABSTRACT: Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA.All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended.The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.

Clinical outcomes of first- and second-generation hydrogel coils compared with bare platinum coils: a systematic literature review.

Endovascular coiling has revolutionized intracranial aneurysm treatment; however, recurrence continues to represent a major limitation. The hydrogel coil was developed to increase packing density and improve neck healing and therefore decrease recurrence rates. In this paper, we review treatment outcomes of first- (1HCs) and second-generation (2HCs) hydrogel coils and compare them to those of bare platinum coils (BPC). A query of multiple databases was performed. Articles with at least 10 aneurysms treated with either 1HC or 2HC were selected for analysis. Collected data included aneurysm size, rupture status, initial occlusion, initial residual neck/aneurysm, packing density, mortality, morbidity, recurrence, and retreatment rates. The primary endpoint was recurrence at final follow-up. Secondary endpoints included residual neck and dome rates as well as procedure-related complications and functional dependence at final follow-up. Studies that compared 1HC to BPC showed significant lower recurrence (24% vs. 30.8%, p = 0.02) and higher packing density (58.5% vs. 24.1%, p < 0.001) in 1HC but no significant difference in initial occlusion rate (p = 0.08). Studies that compared 2HC to BPC showed lower recurrence (6.3% vs. 14.3%, p = 0.007) and retreatment rates (3.4% vs. 7.7%, p = 0.010) as well as higher packing density (36.4% vs. 29.2%, p = 0.002) in 2HC, with similar initial occlusion rate (p = 0.86). The rate of complications was not statistically different between HC (25.5%) and BPC (22.6%, p = 0.06). Based on our review, the 1HC and 2HC achieved higher packing density and lower recurrence rates compared to BPC. The safety profile was similar between both groups.

Treatment of Ruptured and Nonruptured Aneurysms Using a Semisolid Iodinated Embolic Agent.

Saccular aneurysms (SAs) are focal outpouchings from the lateral wall of an artery. Depending on their morphology and location, minimally invasive treatment options include coil embolization, flow diverter stents, stent-assisted coiling, and liquid embolics. Many drawbacks are associated with these treatment options including recanalization, delayed healing, rebleeding, malpositioning of the embolic or stent, stent stenosis, and even rupture of the SA. To overcome these drawbacks, a nanoclay-based shear-thinning hydrogel (STH) is developed for the endovascular treatment of SAs. Extensive in vitro testing is performed to optimize STH performance, visualization, injectability, and endothelialization in cell culture. Femoral artery saccular aneurysm models in rats and in pigs are created to test stability, efficacy, immune response, endothelialization, and biocompatibility of STH in both ruptured and unruptured SA. Fluoroscopy and computed tomography imaging consistently confirmed SA occlusion without recanalization, migration, or nontarget embolization; STH is also shown to outperform coil embolization of porcine aneurysms. In pigs with catastrophic bleeding due to SA rupture, STH is able to achieve instant hemostasis rescuing the pigs in long-term survival experiments. STH is a promising semisolid iodinated embolic agent that can change the standard of medical practice and potentially save lives.

A comparison of treating physician versus independent core lab assessments of post-aneurysm treatment imaging outcomes: an analysis of prospectively collected data from a randomized trial.

OBJECTIVE: Aneurysm occlusion has been used as surrogate marker of aneurysm treatment efficacy. Aneurysm occlusion scales are used to evaluate the outcome of endovascular aneurysm treatment and to monitor recurrence. These scales, however, require subjective interpretation of imaging data, which can reduce the utility and reliability of these scales and the validity of clinical studies regarding aneurysm occlusion rates. Use of a core lab with independent blinded reviewers has been implemented to enhance the validity of occlusion rate assessments in clinical trials. The degree of agreement between core labs and treating physicians has not been well studied with prospectively collected data. METHODS: In this study, the authors analyzed data from the Hydrogel Endovascular Aneurysm Treatment (HEAT) trial to assess the interrater agreement between the treating physician and the blinded core lab. The HEAT trial included 600 patients across 46 sites with intracranial aneurysms treated with coiling. The treating site and the core lab independently reviewed immediate postoperative and follow-up imaging (3-12 and 18-24 months, respectively) using the Raymond-Roy occlusion classification (RROC) scale, Meyer scale, and recanalization survey. A post hoc analysis was performed to calculate interrater reliability using Cohen's kappa. Further analysis was performed to assess whether degree of agreement varied on the basis of various factors, including scale used, timing of imaging, size of the aneurysm, imaging modality, location of the aneurysm, dome-to-neck ratio, and rupture status. RESULTS: Minimal interrater agreement was noted between the core lab reviewers and the treating physicians for assessing aneurysm occlusion using the RROC grading scale (k = 0.39, 95% CI 0.38-0.40) and Meyer scale (k = 0.23, 95% CI 0.14-0.38). The degree of agreement between groups was slightly better but still weak for assessing recanalization (k = 0.45, 95% CI 0.38-0.52). Factors that significantly improved degree of agreement were scales with fewer variables, greater time to follow-up, imaging modality (digital subtraction angiography), and wide-neck aneurysms. CONCLUSIONS: Assessment of aneurysm treatment outcome with commonly used aneurysm occlusion scales suffers from risk of poor interrater agreement. This supports the use of independent core labs for validation of outcome data to minimize reporting bias. Use of outcome tools with fewer point categories is likely to provide better interrater reliability. Therefore, the outcome assessment tools are ideal for clinical outcome assessment provided that they are sensitive enough to detect a clinically significant change.

Does General Anesthesia Compared With Conscious Sedation Result in Better Outcomes in Acute Stroke Patients Undergoing Endovascular Therapy?

BACKGROUND: There is considerable controversy surrounding the optimal use of sedation in patients with acute ischemic stroke undergoing mechanical thrombectomy. Several retrospective studies have favored conscious sedation (CS) over general anesthesia (GA) in terms of functional outcomes and mortality. Recent data from randomized controlled trials has challenged this view. OBJECTIVE: The aim was to critically assess current evidence regarding the use of CS versus GA in mechanical thrombectomy for acute ischemic stroke. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology, vascular neurosurgery, and interventional neuroradiology. RESULTS: A randomized controlled trial was selected for critical appraisal. This trial compared 128 patients with acute ischemic stroke and large vessel occlusion from a single center (Aarhus University Hospital, Denmark), 65 of whom received GA and 63 received CS. No significant difference was detected for the primary outcome of volume of infarct growth. The rate of successful thrombectomy and favorable clinical outcomes for the GA arm was significantly higher in the intention-to-treat analysis. CONCLUSIONS: GA does not result in worse tissue outcomes or worse clinical outcomes when compared with CS in acute stroke patients with large vessel occlusion undergoing mechanical thrombectomy.

Autochthonous and Travel Acquired Hepatitis E Virus in Australia.

BACKGROUND: Hepatitis E virus (HEV) is a common cause of acute viral hepatitis with significant morbidity and mortality, particularly in pregnant women. There are four major genotypes which can cause disease in humans. Genotypes 1 and 2 are usually associated with outbreaks and spread via facal/oral route or contaminated water. Genotypes 3 and 4 are zoonotic and usually associated with handling of pigs or consumption of contaminated pork. The strains circulating in Australia have never been characterized. RATIONALE/AIMS: The aims for this project are to identify the HEV genotypes found in Australia and link them to possible sources of transmission by phylogenetic analysis. MATERIALS AND METHODS: Between 2015 and 2020, 91 HEV isolates were sequenced and genotyped using an in-house PCR. Sixty-six of these were also sequenced by using the international HEVnet primers. Genotypes were determined using the BLASTn program. Relatedness to other strains in Australia was determined by phylogenetic analyses of the HEVnet sequences. Isolates were also stratified by state of origin, gender, age, predisposing factors and travel history (if known). RESULTS: Of the 91 HEV isolates sequenced, 55 (60.4%) were genotype 1. There were 34 (37.4%) genotype 3 strains and two genotype 4 (2.2%). At least 20 of the genotype 1 strains have been linked to travel in India, and another three with Pakistan. Five of the "Indian" strains were closely related and are suspected to have originated in Gujarat. Phylogenetic analysis also showed that 12 genotype 3 strains were genetically related and potentially acquired in/from New South Wales, Australia. The two genotype 4 strains may have originated in China. DISCUSSION: This is the first study to describe the HEV isolates identified in Australia. The results infer that HEV may be acquired during overseas travel as well as locally, presumably from consumption of pork or pork-related products. The phylogenetic analyses also reveal clusters of infection originating from India and Pakistan. This study provides some insight into the source and epidemiology of HEV infection in Australia which may be used to guide public health procedure and enable the implementation of measures to deal with potential outbreaks of infection.

Quality of Life of Patients with Unruptured Intracranial Aneurysms Before and After Endovascular Coiling: A HEAT Trial Secondary Study and Systematic Review of the Literature.

BACKGROUND: The study of quality of life (QOL) in patients with asymptomatic diseases receiving interventional treatment provides an essential metric for the assessment of procedural benefits in the surgical patient population. In this study, we analyzed QOL data collected from patients with unruptured intracranial aneurysms (UIAs) before and after endovascular coiling in the HEAT Trial, alongside a systematic review on QOL in unruptured brain aneurysms. METHODS: HEAT was a randomized controlled trial comparing recurrence rates in aneurysms treated with either bare platinum coils or hydrogel coils. Patients enrolled in this trial completed a short form-36 (SF-36) QOL questionnaire before treatment and at the 3- to 12- and 18- to 24-month follow-ups. The change in QOL before and after treatment was assessed. Regression analysis evaluated the effect of select baseline characteristics on QOL change. RESULTS: A total of 270 patients were eligible for analysis. There was an increase in the role physical (P = 0.043), vitality (P = 0.022), and emotional well-being (P < 0.001) QOL components at the 18- to 24-month follow-up compared with baseline scores. Regression analysis showed that age younger than 60 and absence of serious adverse events were associated with improved social functioning and vitality. The literature review showed a mixed effect of intervention on QOL in patients with UIAs. CONCLUSIONS: Our analysis has revealed that patients with 3- to 14-mm UIAs had improvements in some physical and emotional components of QOL at 18-24 months following aneurysm coiling in the HEAT study. The literature remains indeterminate on this issue. Further studies are needed to better understand the effects of the diagnosis of UIAs and their treatment on QOL.

Detection of SARS-CoV-2 in saliva: implications for specimen transport and storage.

Saliva has recently been proposed as a suitable specimen for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Use of saliva as a diagnostic specimen may present opportunities for SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing in remote and low-resource settings. Determining the stability of SARS-CoV-2 RNA in saliva over time is an important step in determining optimal storage and transport times. We undertook an in vitro study to assess whether SARS-CoV-2 could be detected in contrived saliva samples. The contrived saliva samples comprised 10 ml pooled saliva spiked with gamma-irradiated SARS-CoV-2 to achieve a concentration of 2.58×104 copies ml SARS-CoV-2, which was subsequently divided into 2 ml aliquots comprising: (i) neat saliva; and a 1 : 1 dilution with (ii) normal saline; (iii) viral transport media, and (iv) liquid Amies medium. Contrived samples were made in quadruplicate, with two samples of each stored at either: (i) room temperature or (ii) 4 °C. SARS-CoV-2 was detected in all SARS-CoV-2 spiked samples at time point 0, day 1, 3 and 7 at both storage temperatures using the N gene RT-PCR assay and time point 0, day 1 and day 7 using the Xpert Xpress SARS-CoV-2 (Cepheid, Sunnyvale, USA) RT-PCR assay. The ability to detect SARS-CoV-2 in saliva over a 1 week period is an important finding that presents further opportunities for saliva testing as a diagnostic specimen for the diagnosis of SARS-CoV-2.

Deep neural network to locate and segment brain tumors outperformed the expert technicians who created the training data.

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data.

Sample pooling is a viable strategy for SARS-CoV-2 detection in low-prevalence settings.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly increased demand on laboratory throughput and reagents for nucleic acid extraction and polymerase chain reaction (PCR). Reagent shortages may limit the expansion of testing required to scale back containment measures. The aims of this study were to investigate the viability of sample pooling as a strategy for increasing test throughput and conserving PCR reagents; and to report our early experience with pooling of clinical samples. A pre-implementation study was performed to assess the sensitivity and theoretical efficiency of two, four, and eight-sample pools in a real-time reverse transcription PCR-based workflow. A standard operating procedure was developed and implemented in two laboratories during periods of peak demand, inclusive of over 29,000 clinical samples processed in our laboratory. Sensitivity decreased (mean absolute increase in cycle threshold value of 0.6, 2.3, and 3.0 for pools of two, four, and eight samples, respectively) and efficiency increased as pool size increased. Gains from pooling diminished at high disease prevalence. Our standard operating procedure was successfully implemented across two laboratories. Increased workflow complexity imparts a higher risk of errors, and requires risk mitigation strategies. Turnaround time for individual samples increased, hence urgent samples should not be pooled. Pooling is a viable strategy for high-throughput testing of SARS-CoV-2 in low-prevalence settings.