The proteomic landscape and temporal dynamics of mammalian gastruloid development.

Gastrulation is the highly coordinated process by which the early embryo breaks symmetry, establishes germ layers and a body plan, and sets the stage for organogenesis. As early mammalian development is challenging to study in vivo, stem cell-derived models have emerged as powerful surrogates, e.g. human and mouse gastruloids. However, although single cell RNA-seq (scRNA-seq) and high-resolution imaging have been extensively applied to characterize such in vitro embryo models, a paucity of measurements of protein dynamics and regulation leaves a major gap in our understanding. Here, we sought to address this by applying quantitative proteomics to human and mouse gastruloids at four key stages of their differentiation (naïve ESCs, primed ESCs, early gastruloids, late gastruloids). To the resulting data, we perform network analysis to map the dynamics of expression of macromolecular protein complexes and biochemical pathways, including identifying cooperative proteins that associate with them. With matched RNA-seq and phosphosite data from these same stages, we investigate pathway-, stage- and species-specific aspects of translational and post-translational regulation, e.g. finding peri-gastrulation stages of human and mice to be discordant with respect to the mitochondrial transcriptome vs. proteome, and nominating novel kinase-substrate relationships based on phosphosite dynamics. Finally, we leverage correlated dynamics to identify conserved protein networks centered around congenital disease genes. Altogether, our data (https://gastruloid.brotmanbaty.org/) and analyses showcase the potential of intersecting in vitro embryo models and proteomics to advance our understanding of early mammalian development in ways not possible through transcriptomics alone.

Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences.

Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years.

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.

Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

Tiny swabs: nasal swabs integrated into tube caps facilitate large-scale self-collected SARS-CoV-2 testing.

The COVID-19 pandemic spurred the development of innovative solutions for specimen collection and molecular detection for large-scale community testing. Among these developments is the RHINOstic nasal swab, a plastic anterior nares swab built into the cap of a standard matrix tube that facilitates automated processing of up to 96 specimens at a time. In a study of unsupervised self-collection utilizing these swabs, we demonstrate comparable analytic performance and shipping stability compared to traditional anterior nares swabs, as well as significant improvements in laboratory processing efficiency. The use of these swabs may allow laboratories to accommodate large numbers of sample collections during periods of high testing demand. Automation-friendly nasal swabs are an important tool for high-throughput processing of samples that may be adopted in response to future respiratory viral pandemics.

CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

Triple therapy versus dual-antiplatelet therapy for dolichoectatic vertebrobasilar fusiform aneurysms treated with flow diverters.

BACKGROUND: Dolichoectatic vertebrobasilar fusiform aneurysms (DVBFAs) have poor natural history when left untreated and high morbimortality when treated with microsurgery. Flow diversion (FD) with dual-antiplatelet therapy (DAPT) is feasible but carries high risk of perforator occlusion and progression of brainstem compression. Elaborate antithrombotic strategies are needed to preserve perforator patency while vessel remodeling occurs. We compared triple therapy (TT (DAPT plus oral anticoagulation)) and DAPT alone in patients with DVBFAs treated with FD. METHODS: Retrospective comparison of DAPT and TT in patients with DVBFAs treated with FD at eight US centers. RESULTS: The groups (DAPT=13, TT=14) were similar in age, sex, clinical presentation, baseline disability, and aneurysm characteristics. Radial access use was significantly higher in the TT group (71.4% vs 15.3%; P=0.006). Median number of flow diverters and adjunctive coiling use were non-different between groups. Acute ischemic stroke rate during the oral anticoagulation period was lower in the TT group than the DAPT group (7.1% vs 30.8%; P=0.167). Modified Rankin Scale score decline was significantly lower in the TT group (7.1% vs 69.2%; P=0.001). Overall rates of hemorrhagic complications (TT, 28.6% vs DAPT, 7.7%; P=0.162) and complete occlusion (TT, 25% vs DAPT, 54.4%; P=0.213) were non-different between the groups. Rate of moderate-to-severe disability at last follow-up was significantly lower in the TT group (21.4% vs 76.9%; P=0.007). CONCLUSIONS: Patients with DVBFAs treated with FD in the TT group had fewer ischemic strokes, less symptom progression, and overall better outcomes at last follow-up than similar patients in the DAPT group.

Trends in Risk Factors and Symptoms Associated With SARS-CoV-2 and Rhinovirus Test Positivity in King County, Washington, June 2020 to July 2022.

Importance: Few US studies have reexamined risk factors for SARS-CoV-2 positivity in the context of widespread vaccination and new variants or considered risk factors for cocirculating endemic viruses, such as rhinovirus. Objectives: To evaluate how risk factors and symptoms associated with SARS-CoV-2 test positivity changed over the course of the pandemic and to compare these with the risk factors associated with rhinovirus test positivity. Design, Setting, and Participants: This case-control study used a test-negative design with multivariable logistic regression to assess associations between SARS-CoV-2 and rhinovirus test positivity and self-reported demographic and symptom variables over a 25-month period. The study was conducted among symptomatic individuals of all ages enrolled in a cross-sectional community surveillance study in King County, Washington, from June 2020 to July 2022. Exposures: Self-reported data for 15 demographic and health behavior variables and 16 symptoms. Main Outcomes and Measures: Reverse transcription-polymerase chain reaction-confirmed SARS-CoV-2 or rhinovirus infection. Results: Analyses included data from 23 498 individuals. The median (IQR) age of participants was 34.33 (22.42-45.08) years, 13 878 (59.06%) were female, 4018 (17.10%) identified as Asian, 654 (2.78%) identified as Black, and 2193 (9.33%) identified as Hispanic. Close contact with an individual with SARS-CoV-2 (adjusted odds ratio [aOR], 3.89; 95% CI, 3.34-4.57) and loss of smell or taste (aOR, 3.49; 95% CI, 2.77-4.41) were the variables most associated with SARS-CoV-2 test positivity, but both attenuated during the Omicron period. Contact with a vaccinated individual with SARS-CoV-2 (aOR, 2.03; 95% CI, 1.56-2.79) was associated with lower odds of testing positive than contact with an unvaccinated individual with SARS-CoV-2 (aOR, 4.04; 95% CI, 2.39-7.23). Sore throat was associated with Omicron infection (aOR, 2.27; 95% CI, 1.68-3.20) but not Delta infection. Vaccine effectiveness for participants fully vaccinated with a booster dose was 93% (95% CI, 73%-100%) for Delta, but not significant for Omicron. Variables associated with rhinovirus test positivity included being younger than 12 years (aOR, 3.92; 95% CI, 3.42-4.51) and experiencing a runny or stuffy nose (aOR, 4.58; 95% CI, 4.07-5.21). Black race, residing in south King County, and households with 5 or more people were significantly associated with both SARS-CoV-2 and rhinovirus test positivity. Conclusions and Relevance: In this case-control study of 23 498 symptomatic individuals, estimated risk factors and symptoms associated with SARS-CoV-2 infection changed over time. There was a shift in reported symptoms between the Delta and Omicron variants as well as reductions in the protection provided by vaccines. Racial and sociodemographic disparities persisted in the third year of SARS-CoV-2 circulation and were also present in rhinovirus infection. Trends in testing behavior and availability may influence these results.

Local-Scale phylodynamics reveal differential community impact of SARS-CoV-2 in metropolitan US county.

SARS-CoV-2 transmission is largely driven by heterogeneous dynamics at a local scale, leaving local health departments to design interventions with limited information. We analyzed SARS-CoV-2 genomes sampled between February 2020 and March 2022 jointly with epidemiological and cell phone mobility data to investigate fine scale spatiotemporal SARS-CoV-2 transmission dynamics in King County, Washington, a diverse, metropolitan US county. We applied an approximate structured coalescent approach to model transmission within and between North King County and South King County alongside the rate of outside introductions into the county. Our phylodynamic analyses reveal that following stay-at-home orders, the epidemic trajectories of North and South King County began to diverge. We find that South King County consistently had more reported and estimated cases, COVID-19 hospitalizations, and longer persistence of local viral transmission when compared to North King County, where viral importations from outside drove a larger proportion of new cases. Using mobility and demographic data, we also find that South King County experienced a more modest and less sustained reduction in mobility following stay-at-home orders than North King County, while also bearing more socioeconomic inequities that might contribute to a disproportionate burden of SARS-CoV-2 transmission. Overall, our findings suggest a role for local-scale phylodynamics in understanding the heterogeneous transmission landscape.

SwabExpress: An End-to-End Protocol for Extraction-Free COVID-19 Testing.

BACKGROUND: The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse-transcription PCR (RT-qPCR). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce. To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. METHODS: We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral inactivation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. RESULTS: After optimization, SwabExpress has a low limit of detection at 2-4 molecules/µL, 100% sensitivity, and 99.4% specificity when compared side by side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. CONCLUSION: SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

Neuroophthalmological manifestations of congenital aqueductal stenosis.

OBJECTIVE: Congenital aqueductal stenosis (CAS) is a common etiology of hydrocephalus that occurs in a subset of infants and may be linked to an increased incidence of ophthalmological abnormalities and delayed developmental milestones. Although hydrocephalus is common and widely studied, sparse literature exists on patients with isolated (no identifiable genetic link) CAS along with analysis of ophthalmological manifestations. In this study, the authors sought to describe the ophthalmological abnormalities and delayed developmental milestones of patients with isolated CAS. METHODS: Data of patients with CAS were prospectively entered and monitored in a surgical database maintained by the Department of Neurological Surgery at Children's Hospital of Pittsburgh from January 2005 to October 2016. Patients with a family history of congenital hydrocephalus, positive testing for genetic forms of aqueductal stenosis, other congenital abnormalities suggesting an underlying genetic syndrome, and stenosis/obstruction due to secondary causes were excluded from this study. Prenatal and perinatal history, CSF diversion history, and a variety of outcomes, including ophthalmological deficits and developmental milestones, were collected and analyzed. RESULTS: A total of 41 patients with isolated CAS were identified, with a mean follow-up duration of 6 years. Among that cohort, 26 patients (63.4%) developed neuroophthalmological complications, which were further stratified. Fourteen patients (34.1%) developed strabismus and 11 (26.8%) developed astigmatism, and 1 patient (2.4%) with papilledema was recorded. Among patients with ophthalmological abnormalities, 76.9% had delayed developmental milestones (p = 0.045). CONCLUSIONS: Patients with CAS were found to have increased risk of ophthalmological abnormalities requiring correction, along with an increased risk of delayed developmental milestones. Importantly, there was a significant correlation between the development of ophthalmological abnormalities and delayed developmental milestones that was independent of CSF diversion history. Larger patient cohort studies are required to explore whether earlier development of hydrocephalus, as is the case in CAS, causes elevated rates of neurological and ophthalmological complications, and if earlier CSF diversion correlates with improved outcomes.

Myocardial infarction secondary to coronary embolus in a patient with left ventricular non-compaction cardiomyopathy: a case report.

BACKGROUND: Coronary embolism is a rare cause of myocardial infarction (MI). We present a case report which emphasizes the importance of intracoronary imaging in these cases to identify the pathophysiological mechanism of MI. CASE SUMMARY: A 53-year-old male with no past medical history presented to the hospital with typical angina. Electrocardiogram and serum troponin I level trend confirmed non-ST-elevation myocardial infarction. Coronary angiography showed no evidence of any obstructive coronary artery disease, but two small thrombi were noted in the distal first obtuse marginal branch. Optical coherence tomography imaging confirmed this finding in absence of any underlying atherosclerotic plaque rupture or erosion. Cardiac magnetic resonance imaging revealed the diagnosis of non-compaction cardiomyopathy with severely depressed left ventricular function. Transmural MI was revealed by late gadolinium enhancement in the mid-lateral wall. Based on the pathophysiology of the MI confirmed by intracoronary imaging, antiplatelet medications were discontinued, and the patient was discharged on warfarin. Medical therapy was initiated for his cardiomyopathy. The patient recovered well and was asymptomatic at 1-year follow-up visit. DISCUSSION: Intracoronary imaging plays an important role to supplement coronary angiography to confirm the pathophysiology of MI in coronary embolism cases. This is important as it alters management in these patients.

Monitoring for Chemotherapy-Related Cardiotoxicity in the Form of Left Ventricular Systolic Dysfunction: A Review of Current Recommendations.

Cardiotoxicity is a well-established complication of multiple cancer therapeutics, and the one of the most prominent effects that limits the use of these agents is in the form of left ventricular dysfunction, otherwise known as chemotherapy-induced cardiomyopathy (CIMP). Because CIMP can worsen patient outcomes and interfere with a patient's life-saving cancer treatments, it is important to implement a monitoring strategy for patients undergoing potentially cardiotoxic treatments. Efforts have been made by multiple societies to provide recommendations for screening and monitoring for CIMP in at-risk patients, with slight variations between guideline documents and expert consensuses. Most of the recommendations for monitoring for CIMP are specific to anthracyclines and the human epidermal growth factor receptor 2-antagonist trastuzumab, with very limited guidance for other cardiotoxic agents such as Tyr kinase inhibitors and proteasome inhibitors, which we cover in this article. Echocardiography remains the mainstay for imaging surveillance because of its safety profile and widespread availability, but the accuracy of cardiac magnetic resonance imaging (CMR) makes it an important modality when there are discrepancies in left ventricular ejection fraction assessment. Subclinical cardiotoxicity may be detected using laboratory biomarkers such as cardiac troponin and brain natriuretic peptide as well as myocardial deformation (strain) imaging by echocardiography or CMR. Specific recommendations for timing and frequency of laboratory biomarker assessment remain up for debate, but myocardial deformation imaging should be performed with every echocardiogram or CMR assessment. Future studies are needed to evaluate the efficacy of established surveillance recommendations and to develop specific recommendations for novel cancer therapeutics.

Bortezomib-Induced Reversible Cardiomyopathy: Recovered With Guideline-Directed Medical Therapy.

Bortezomib (BTZ) is a proteasome inhibitor (PI) used for the treatment of several hematologic malignancies, including multiple myeloma (MM), and various lymphomas including mantle cell lymphoma (MCL). It acts via disruption of the ubiquitin-proteasome pathway which plays a major role in regulating cell cycle and inhibiting synthesis of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB). The ubiquitin-proteasome pathway is also important in maintaining the integral signaling in cardiac myocytes. By inhibiting this system, BTZ induces cellular apoptosis in cancer cells, and possibly the cardiomyocytes. BTZ-induced cardiotoxicity in monotherapy and combination treatments is not well described in the literature. We observed a series of three patients who developed cardiotoxicity after treatment with BTZ. All patients had echocardiograms every 3 months until recovery to assess ejection fraction (EF) and global longitudinal strain (GLS). Two of the patients had a cardiac MRI (CMR) conducted during follow-up to assess for late gadolinium enhancement (LGE).  The median age of our patients was 55 years (range 37-74). Two of them had MM, while one patient had MCL. Table 1 demonstrates patient demographics, past medical histories, and the cumulative dose and duration of BTZ therapy. Of the three patients, only one had a heart failure exacerbation at diagnosis. The other two patients were diagnosed with asymptomatic left ventricular systolic dysfunction on routine pre-transplant echocardiograms. Most importantly, all three patients had improvement or normalization of cardiac function with discontinuation of BTZ and initiation of guideline-directed medical therapy (GDMT) for heart failure. The median duration to recovery was 5 months (range 3-13). One patient had underlying non-compaction cardiomyopathy, and although EF did not normalize, it recovered to his previous baseline. All 3 patients had improvement in GLS. Two patients underwent CMRI at the time of cardiomyopathy diagnosis and neither of them had any late gadolinium enhancement. Since there was no routine pre-treatment echocardiogram, using the GLS trend to detect subclinical cardiac dysfunction was not possible. This case series demonstrates that BTZ-induced cardiomyopathy is potentially reversible with discontinuation of the drug and early initiation of GDMT. Further studies are needed to determine the ideal surveillance strategy for BTZ-induced cardiomyopathy.

More expansive horizons: a review of endovascular therapy for patients with low NIHSS scores.

While the landmark 2015 stroke trials demonstrated that endovascular therapy (EVT) was superior to medical management for the treatment of acute ischemic stroke due to large vessel occlusion, the efficacy of EVT for patients presenting with a low NIHSS score remains undetermined. We conducted a review of the EVT low National Institutes of Health Stroke Scale (NIHSS) stroke literature, identifying 24 quantitative and six qualitative publications. Details of study designs and outcome were extracted and critically discussed.All identified qualitative studies were retrospective. There was significant study design heterogeneity, with 18 unique study designs between the 24 identified quantitative manuscripts. Study investigations included low NIHSS EVT feasibility (n=6), EVT versus best medical management (BMM; n=10), EVT versus intravenous therapy (IVT, n=3), and low NIHSS score versus high NIHSS score (n=3). From single-arm EVT feasibility studies, the reported ranges of modified Thrombolysis in Cerebral Infarction and symptomatic intracranial hemorrhage were 78-97% and 0-10%, respectively. The EVT versus BMM literature had heterogeneous results with 40% reporting benefit with EVT and 60% reporting neutral findings. None of the studies comparing EVT with IVT reported a difference between the two revascularization therapies. The four identified meta-analyses had incongruent inclusion criteria and conflicting results. Two randomized trials are currently investigating EVT in patients with a low NIHSS score. Selected meta-analyses do suggest a potential benefit of EVT over BMM; however, current and future randomized clinical trials will better elucidate the efficacy of EVT in this patient population.

SwabExpress: An end-to-end protocol for extraction-free COVID-19 testing.

BACKGROUND: The urgent need for massively scaled clinical testing for SARS-CoV-2, along with global shortages of critical reagents and supplies, has necessitated development of streamlined laboratory testing protocols. Conventional nucleic acid testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab in transport medium, nucleic acid extraction, and quantitative reverse transcription PCR (RT-qPCR) (1). As testing has scaled across the world, the global supply chain has buckled, rendering testing reagents and materials scarce (2). To address shortages, we developed SwabExpress, an end-to-end protocol developed to employ mass produced anterior nares swabs and bypass the requirement for transport media and nucleic acid extraction. METHODS: We evaluated anterior nares swabs, transported dry and eluted in low-TE buffer as a direct-to-RT-qPCR alternative to extraction-dependent viral transport media. We validated our protocol of using heat treatment for viral activation and added a proteinase K digestion step to reduce amplification interference. We tested this protocol across archived and prospectively collected swab specimens to fine-tune test performance. RESULTS: After optimization, SwabExpress has a low limit of detection at 2-4 molecules/uL, 100% sensitivity, and 99.4% specificity when compared side-by-side with a traditional RT-qPCR protocol employing extraction. On real-world specimens, SwabExpress outperforms an automated extraction system while simultaneously reducing cost and hands-on time. CONCLUSION: SwabExpress is a simplified workflow that facilitates scaled testing for COVID-19 without sacrificing test performance. It may serve as a template for the simplification of PCR-based clinical laboratory tests, particularly in times of critical shortages during pandemics.

Ballast and NeuronMax in stroke thrombectomy.

BACKGROUND: Comparative evaluation of long sheath performance in stroke thrombectomy has not been performed. OBJECTIVE: To review an initial experience with the new Ballast 6F long sheath compared with the NeuronMax, to evaluate comparative benchmarks in trackability, navigability, and procedural outcomes. METHODS: A prospectively maintained thrombectomy database was evaluated over a 6-month period to compare procedural and angiographic results between a cohort of patients treated with the historical institutional standard long sheath (NeuronMax) and another with the new Ballast long sheath via a transfemoral approach. RESULTS: Of 156 stroke thrombectomy cases, 69 were performed using NeuronMax and 40 using Ballast via a transfemoral approach; the remainder of cases employed alternative long sheaths or were performed via initial radial access. There was no significant difference in patient age, medical history, baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT Score, arch type, tissue plasminogen activator use, and clot location between the two groups. Single-pass case frequency (41% for NeuronMax vs 44% for Ballast, p=0.84), and final successful revascularization (TICI 2b or greater) were similar between the two cohorts (91% vs 98%, p=0.42). Good 90-day outcome (modified Rankin Scale score 0-2) was also similar (33% for NeuronMax, 43% for Ballast, p=0.41). Excluding tandem occlusions, mean procedural time was 31 min for NeuronMax and 25 min for Ballast (p=0.09). Puncture to long sheath access and angiography in the base target vessel was faster for Ballast than NeuronMax (6.5 min vs 9.2 min, p=0.04). CONCLUSION: Among a cohort of practitioners with historical, preferential experience with NeuronMax for stroke thrombectomy, faster procedural times were achieved with Ballast with similar final angiographic results.

Urgent Treatment for Symptomatic Carotid Stenosis: The Pittsburgh Revascularization and Treatment Emergently After Stroke (PIRATES) Protocol.

BACKGROUND: Patients with symptomatic carotid stenosis remain at high risk of early recurrent stroke without revascularization. This risk must be balanced against a higher rate of periprocedural complications associated with early revascularization. OBJECTIVE: To analyze prospectively recorded data from an institutional protocol that standardized the urgent (<48 h) treatment of patients presenting with symptomatic carotid stenosis and underwent either carotid stenting (CAS) or carotid endarterectomy (CEA). METHODS: All patients presenting over 28 mo to a comprehensive stroke center with symptomatic carotid stenosis within 48 h of index event were screened for inclusion. All patients were given dual-antiplatelet therapy. If there was clinical equipoise between CEA and CAS, patients underwent angiography and subsequently revascularization if digital subtraction angiography demonstrated ≥50% stenosis. The primary outcome was a composite of stroke or death within 30 d. RESULTS: This study included 178 patients with a diagnosis of recently symptomatic carotid stenosis; 120 patients (67%) met the criteria. A total of 59 patients underwent CEA and 61 patients underwent CAS. There were not significant differences in the primary outcome; 3 patients (5.1%) in the CEA arm and 3 patients (4.9%) in the CAS arm met the primary outcome. CONCLUSION: In this prospective analysis, urgent revascularization for symptomatic carotid stenosis can be done with equivalently low rates of stroke or death, regardless of revascularization strategy.

Incorporation of transradial approach in neuroendovascular procedures: defining benchmarks for rates of complications and conversion to femoral access.

BACKGROUND: The transradial approach (TRA) has gained increasing popularity for neuroendovascular procedures. However, the experience with TRA in neuroangiography is still in early stages in most centers, and the safety and feasibility of this approach have not been well established. The purpose of this study is to report the safety and feasibility of TRA for neuroendovascular procedures. METHODS: We reviewed charts from six institutions in the USA to include consecutive patients who underwent diagnostic or interventional neuroendovascular procedures through TRA from July 2018 to July 2019. Collected data included baseline characteristics, procedural variables, complications, and whether there was a crossover to transfemoral access. RESULTS: A total of 2203 patients were included in the study (age 56.1±15.2, 60.8% women). Of these, 1697 (77%) patients underwent diagnostic procedures and 506 (23%) underwent interventional procedures. Successfully completed procedures included aneurysm coiling (n=97), flow diversion (n=89), stent-assisted coiling (n=57), balloon-assisted coiling (n=19), and stroke thrombectomy (n=76). Crossover to femoral access was required in 114 (5.2%). There were no major complications related to the radial access site. Minor complications related to access site were seen in 14 (0.6%) patients. CONCLUSION: In this early stage of transforming to the 'radial-first' approach for neuroendovascular procedures, TRA was safe with low complication rates for both diagnostic and interventional procedures. A wide range of procedures were completed successfully using TRA.

Transradial versus transfemoral approaches for diagnostic cerebral angiography: a prospective, single-center, non-inferiority comparative effectiveness study.

BACKGROUND: Interventional cardiology produced level 1 evidence recommending radial artery-first for coronary angiography given lower vascular complications. Neuroendovascular surgeons have not widely adopted the transradial approach. This prospective, single center, non-inferiority comparative effectiveness study aims to compare the transradial and transfemoral approaches for diagnostic cerebral angiography with respect to efficacy, safety and patient satisfaction. METHODS: Consecutive patients presenting for diagnostic cerebral angiography were selected to undergo right radial or femoral access based on date of presentation. Primary outcome was ability to answer the predefined diagnostic goal of the cerebral angiogram using the initial access site and was assessed with a non-inferiority design. Secondary outcomes included technical success per vessel, complications, procedure times and patient satisfaction. RESULTS: A total of 312 patients were enrolled, 158 and 154 for right radial and femoral access, respectively. The diagnostic goal of the angiogram was achieved in 152 of 154 (99%) patients who underwent attempted femoral access compared with 153 of 158 (97%) patients who underwent radial access, confirming non-inferiority of the transradial approach. Secondary outcomes showed equivalent technical success by vessel, no major complications, and similar frequency of minor complications between the two approaches. In-room time was similar between approaches, though post-procedure recovery room time was significantly shorter for transradial patients. Patient satisfaction results significantly favored the radial approach. CONCLUSIONS: In patients undergoing diagnostic cerebral angiography, transfemoral and transradial access achieve procedural goals with similar effectiveness and safety, though patients strongly prefer the radial approach. Findings support consideration of adopting a radial-first strategy for diagnostic cerebral angiography.