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BACKGROUND AND PURPOSE:The safety and efficacy of the PulseRider for the treatment of wide-neck, bifurcation aneurysms at the basilar and carotid terminus locations were studied in a prospective trial, the Adjunctive Neurovascular Support of Wide-Neck Aneurysm Embolization and Reconstruction (ANSWER) trial, reporting on initial 6-month angiographic and clinical results. This report provides insight into the longer term durability and safety with 12-month data. MATERIALS AND METHODS:Aneurysms treated with the PulseRider among enrolled sites were prospectively studied. Updated 12-month data on clinical and imaging end points are included. RESULTS:Thirty-four patients were enrolled (29 women, 5 men) with a mean age of 60.9 years. The mean aneurysm height ranged from 2.4 to 15.9 mm with a mean neck size of 5.2 mm (range, 2.3-11.6 mm). At 1 year, there were no device migrations or symptomatic in-stent stenoses. Raymond-Roy I occlusion was achieved in 53% of cases at the time of treatment and progressed to 61% and 67% at 6 and 12 months, respectively. Adequate occlusion (Raymond-Roy I/II) progressed from 88% at 6 months to 90% at 12 months. No recanalizations were observed. There was 1 delayed ischemic event. Good outcome (mRS 0-2) was achieved in 90% of patients. CONCLUSIONS:The updated 1-year results from the ANSWER trial demonstrate aneurysm stability and an acceptable safety profile for aneurysms treated at the basilar apex and carotid terminus. Prospective data from a larger set of aneurysms treated at other locations are required to assess how treatment with PulseRider compares with alternatives for treating wide-neck bifurcation aneurysms.

Out of hospital cardiac arrest (OHCA) outcomes can be improved by strengthening the chain of survival, namely prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED). However, provision of bystander CPR and AED use remains low due to individual patient factors ranging from lack of education to socioeconomic barriers and due to lack of resources such as limited availability of AEDs in the community. Although the impact of health inequalities on survival from OHCA is documented, it is imperative that we identify and implement strategies to improve public health and outcomes from OHCA overall but with a simultaneous emphasis on making care more equitable. Disparities in CPR delivery and AED use in OHCA exist based on factors including sex, education level, socioeconomic status, race and ethnicity, all of which we discuss in this review. Most importantly, we discuss the barriers to AED use, and strategies on how these may be overcome., Competing Interests: Declaration of competing interest All other authors declared that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Robotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases., Objective: To evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms., Methods: This prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events., Results: The study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites,. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2., Conclusions: This first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures., Trial Registration Number: NCT04236856., Competing Interests: Competing interests: VMP is an unpaid consultant for Siemens Healthinners Endovascular Robotics. The following authors have one or more competing interests: HR, NS, FC, DH, MP, JG, MK-O, RDT, RB. These competing interests include board membership, consultancy, employment, expert testimony grants, contract research, lectures/other education events, speakers’ bureau, and receipt of equipment or supplies, royalties, stock/stock options/other forms of ownership., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND: Cough is the key symptom of pulmonary TB (PTB) and is associated with transmission. No tool for measuring the subjective impact of cough in PTB has been previously validated. We sought to measure patientreported cough in PTB and investigate any relationship to objectively quantified daily cough frequency. METHODS: The validity of the Leicester Cough Questionnaire (LCQ) was assessed in sequential patients newly diagnosed with PTB at a UK hospital. Resulting LCQ scores were compared to non-cough clinical variables, and to 24-h, ambulatory, objective cough frequency measured using the Leicester Cough Monitor. RESULTS: The LCQ in 30 patients with PTB was acceptable to users and had high internal reliability (Cronbach's α = 0.93), concurrent validity (correlation with visual analogue scale for cough severity, Spearman's ρ = ???0.69) and responsiveness (substantial median increase score after 2 weeks of TB treatment: 5.1 points, IQR 1.8???9.7; P = 0.003). There was only moderate correlation between patient-reported cough and objectively-measured 24-h cough frequency in PTB (ρ = ???0.48, P = 0.008). CONCLUSION: The LCQ is valid for use in PTB, with applications that include monitoring treatment of the disease. However, there was a mismatch between objective and subjective assessment of cough, which has important implications for delayed diagnosis and transmissibility.

Background: The Patient Global Impression of Severity (PGI-S) scale is a self-reported, single-item categorical scale that is increasingly used when assessing chronic cough (CC)., Objective: This study aimed to establish validity, repeatability, and responsiveness of the PGI-S scale in CC and use the scale to define discrete categories of severity when measured with other commonly used patient-reported outcome (PRO) tools., Methods: Consecutive patients with CC completed the PGI-S scale, cough severity and urge to cough visual analog scales (VAS), and cough-specific health status Leicester Cough Questionnaire (LCQ) at a clinic visit. Validity, repeatability, and responsiveness were assessed, and threshold scores for PRO severity categories determined., Results: A total of 482 participants completed the assessments; the median (interquartile range [IQR]) age was 57 (46-67) years, 71% were female, and the median (IQR) duration of cough was 48 (24-120) months. They reported a median (IQR) PGI-S score of 3 (3-4; moderate severity), cough severity VAS of 57 (31-75) mm, urge to cough VAS of 62 (40-81) mm, and LCQ of 11.5 (8.7-14.4). There were strong associations between PGI-S scores and cough severity VAS (ρ = 0.81), urge to cough VAS (ρ = 0.73), and LCQ (ρ = -0.73) (all P < .001). Repeatability of the PGI-S scale was high (n = 77); the intraclass correlation coefficient (95% confidence interval) was 0.85 (0.77-0.91) (P < .001). The PGI-S scale was responsive in participants with a treatment response (P < .001). The suggested PRO thresholds to define severe cough are ≥61 mm (cough severity VAS), ≥71 mm (urge to cough VAS), and ≤10 (LCQ)., Conclusion: The PGI-S scale is a simple and valid tool that characterizes cough severity and is repeatable and responsive in CC. The proposed categorical severity thresholds for VAS and LCQ can provide intuitive meaning for patients and clinicians., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Chronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction. Chronic cough is also a common feature of the syndrome, with features of hypersensitivity, often preceding core neurological symptoms by up to 30 years or more. The genetic basis in a majority of cases of CANVAS appears to be biallelic variable repeat intron expansion sequences within RFC1, a gene normally involved in the regulation of DNA replication and repair. The same polymorphism has now been identified at an increased frequency in patients with unexplained or refractory chronic cough in the absence of defining clinical features of CANVAS. This review expands on these points, aiming to increase the awareness of CANVAS amongst clinicians and researchers working with chronic cough. We discuss the implications of a link between RFC1 disease and cough. Improved understanding of CANVAS may lead to an enhanced grasp of the pathophysiology of chronic cough, and new approaches to antitussive treatments., (© 2023. Crown.)

Chronic cough (CC; ≥8 weeks in duration) is a common and burdensome feature of respiratory diseases. The understanding of cough has progressed significantly in recent years, albeit largely in refractory (unexplained) chronic cough (RCC) in the absence of other respiratory conditions. The prevalence of CC in respiratory diseases is poorly described, but estimates have been reported: asthma (8-58%), chronic obstructive pulmonary disease (COPD; 10-74%), bronchiectasis (82-98%), interstitial lung disease (ILD; 50-89%) and sarcoidosis (3-64%). CC in respiratory conditions generally predicts impaired health status and more severe disease. It is associated with increased symptom burden and disease severity in asthma, COPD, bronchiectasis and ILD, higher exacerbation frequency in asthma and bronchiectasis, and increased mortality and lung transplantation in idiopathic pulmonary fibrosis (IPF). Physiologically, heightened cough reflex sensitivity (CRS) has been reported and postulated to be mechanistic in isolated RCC. Cough reflex hypersensitivity (CRH) has also been reported in asthma, COPD, bronchiectasis, ILD and sarcoidosis. Unlike recent advances in isolated RCC, there are limited studies and understanding of central cough neuropathways in other respiratory conditions. Of note, dysfunctional central voluntary cough suppression neuropathways and physiology were observed in isolation in RCC; cough suppression is preserved in COPD. Understanding in the mechanism of RCC cannot be simply extrapolated to other respiratory conditions. The restricted understanding of cough mechanisms in these conditions has limited cough-specific therapeutic options in this context. There is currently an unmet need to expand our understanding of cough in chronic respiratory conditions, both in order to improve the quality of life of patients, and to improve knowledge of cough in general. This review aims to describe the prevalence, impact, pathophysiology and management of CC in asthma, COPD, bronchiectasis, ILD and sarcoidosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1776/coif). The series “Novel Insights into Chronic Cough” was commissioned by the editorial office without any funding or sponsorship. SSB has received personal fees for consultancy from Merck, Bellus, Trevi, Genentech, Nerre, Kinevant, Boehringer Ingelheim and Bayer. PSPC reports two ongoing grants: EPSRC and MERCK, outside of the submitted work. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Background: The antiplatelet management in acute ischemic stroke requiring carotid artery stenting is heterogenous, with no clear guidelines to direct management., Objective: To evaluate the safety and efficacy of an intravenous eptifibatide protocol in the management of acute ischemic stroke requiring emergent carotid artery stenting., Methods: We performed a retrospective analysis of consecutive patients who underwent carotid artery stenting for acute ischemic stroke at a high-volume tertiary neuroscience center, who were managed with an intravenous eptifibatide protocol. The protocol consists of an intravenous loading eptifibatide bolus (180 mcg/kg) at the time of stenting, followed by a maintenance infusion of 1 mcg/kg/min, then oral or nasogastric loading of dual antiplatelet agents., Results: 80 patients were included for analysis. Median presenting NIHSS was 17. Sixty-six patients (83%) had a tandem intracranial occlusion. Six (7.5%) patients developed symptomatic intracranial hemorrhage (sICH). Those who received intravenous thrombolysis were not more likely to develop sICH (10% vs 5%, p = 0.40). Those patients with a presenting ASPECTS <8 were significantly more likely to develop sICH than those with ASPECTS 8-10 (25% vs 3%, p = 0.004)., Conclusions: Eptifibatide may have a role in the management of acute stroke requiring carotid stenting. Caution may be required in those with established infarct on presentation imaging.

The clinical and research discipline of cough has grown substantially over the last two decades as methods to measure cough have developed and evolved. Cough can be thought of both as a symptom and an objectively observable pathophysiological phenomenon, two aspects whose interrelationship is complicated. The following review explores the varied methods to measuring cough, both subjective, patient-reported measures and objective approaches. Specifically, symptom scores, questionnaires of cough-related quality of life, and associated mental health impacts of chronic cough are addressed, as are developments in measuring cough frequency, cough intensity, cough reflex sensitivity, and cough suppressibility. Measuring patient reported cough-severity with a simple visual analogue scale increasingly appears to be justified, but has limitations. The Leicester Cough Questionnaire has been widely used for twenty years, within varied settings and diseases, in research and routine clinical practice, and captures cough-related quality of life. Objective cough frequency has become the primary outcome measure for clinical trials of antitussives, and technology is now enabling the wider application of cough counting. Inhaled tussive challenge testing still has a role, including in the assessment of cough hypersensitivity, and in the identification of failure to supress cough. Ultimately, many measures have a contributory and complementary role, with differing merits in quantifying the multiple facets of cough, the complexity of which is being increasingly recognised., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-230/coif). The series “Novel Insights Into Chronic Cough” was commissioned by the editorial office without any funding or sponsorship. SSB has received personal fees from Merck, Bayer, Shionogi, Bellus, Nerre, Gala and Trevi, research grants from Merck, fees for LCM cough monitoring analysis and LCQ. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Control of cell size and morphology is of paramount importance for bacterial fitness. In the opportunistic pathogen Enterococcus faecalis, the formation of diplococci and short cell chains facilitates innate immune evasion and dissemination in the host. Minimisation of cell chain size relies on the activity of a peptidoglycan hydrolase called AtlA, dedicated to septum cleavage. To prevent autolysis, AtlA activity is tightly controlled, both temporally and spatially. Here, we show that the restricted localization of AtlA at the septum occurs via an unexpected mechanism. We demonstrate that the C-terminal LysM domain that allows the enzyme to bind peptidoglycan is essential to target this enzyme to the septum inside the cell before its translocation across the membrane. We identify a membrane-bound cytoplasmic protein partner (called AdmA) involved in the recruitment of AtlA via its LysM domains. This work reveals a moonlighting role for LysM domains, and a mechanism evolved to restrict the subcellular localization of a potentially lethal autolysin to its site of action., (© 2023. The Author(s).)

Background: There is a clinical need for a guide catheter with combined stability and navigability, which can be used in a biaxial system for neuroendovascular procedures in place of triaxial systems., Objective: To assess the safety and feasibility of the Q'Apel Medical Wahoo Hybrid Access System, a dual-mode 0.072″ internal diameter guide catheter, in a range of neuroendovascular procedures., Methods: We performed a retrospective analysis of consecutive cases from a high-volume tertiary center in which the Wahoo Hybrid Access System was used as the guide catheter. Characteristics of the patients, vascular lesions, procedure, and procedural complications were assessed., Results: A total of 102 patients were included for analysis. Vascular lesions were in the anterior circulation in 90 of 102 (88%), and posterior circulation in 12 of 102 (12%). Eighty-four cases were ruptured or unruptured aneurysm embolization procedures, the majority being balloon-assisted coiling (42%) and flow diversion (42%). All cases, including flow diversion, were performed as a biaxial system. There were no instances of prolapse of the catheter beyond the arterial segment in which it was initially placed. The procedure was able to be performed to completion in 101 of 102 (99%) cases. Thromboembolic complications occurred in 5 of 102 (5%); causality in two cases was unrelated to the guide catheter, and three were indeterminate., Conclusions: The Wahoo guide catheter is safe and feasible when used in a variety of neuroendovascular procedures. It can accommodate a range of devices, can be safely navigated into distal vasculature, and provides support for a range of procedures, including those which traditionally require triaxial support.

Background: Most conventional 0.088 inch guide catheters cannot safely navigate intracranial vasculature. The objective of this study is to evaluate the safety of stroke thrombectomy using a novel 0.088 inch guide catheter designed for intracranial navigation., Methods: This is a multicenter retrospective study, which included patients over 18 years old who underwent thrombectomy for anterior circulation large vessel occlusions. Technical outcomes for patients treated using the TracStar Large Distal Platform (TracStar LDP) or earlier generation TRX LDP were compared with a matched cohort of patients treated with other commonly used guide catheters. The primary outcome measure was device-related complications. Secondary outcome measures included guide catheter failure and time between groin puncture and clot engagement., Results: Each study arm included 45 patients. The TracStar group was non-inferior to the control group with regard to device-related complications (6.8% vs 8.9%), and the average time to clot engagement was 8.89 min shorter (14.29 vs 23.18 min; p=0.0017). There were no statistically significant differences with regard to other technical outcomes, including time to recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2B). The TracStar was successfully advanced into the intracranial internal carotid artery in 33 cases (73.33%); in three cases (6.67%), it was swapped for an alternate catheter. Successful reperfusion (mTICI 2B-3) was achieved in 95.56% of cases. Ninety-day follow-up data were available for 86.67% of patients, among whom 46.15% had an modified Rankin Score of 0-2%, and 10.26% were deceased., Conclusions: Tracstar LDP is safe for use during stroke thrombectomy and was associated with decreased time to clot engagement. Intracranial access was regularly achieved., Competing Interests: Competing interests: JV reports consulting agreements with Integra Life Sciences and Corindus Vascular Robotics. MM reports grants funding from the National Institutes of Health (NIH R21NS109575), consulting agreements with Medtronic and Cerenovus; stock options in Serenity Medical, Synchron, Endostream, and VICIS; and an affiliation with the JNIS editorial board. RDT reports consulting agreements with Siemens Healthineers, Johnson and Johnson, Q’Apel Medical, Rebound Therapeutics, Echovate, Viseon; stock holdings in Q’Apel Medical, Rebound Therapeutics, Echovate, Viseon, Synchron, Endostream Medical; and royalty fees from the Medical University of South Carolina. MIC reports consulting agreements with Terumo Microvention, Johnson and Johnson, Imperative Care, Medtronic Neurovascular; stock holdings in Q’Apel Medical, RIST Neurovascular, Echovate, Viseon, Synchron, Endostream Medical, and royalty fees from the Medical University of South Carolina. AST reports consulting agreements with Blockade Medical, Cardinal Consulting, Cerebrotech, Corindus Vascular Robotics, Medtronic Neurovascular, Endostream Medical, Terumo Microvention, Penumbra, Siemens Healthineers, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Stryker Neurovascular, Serenity Medical, 880 Medical, Q’Apel Medical; stock holdings in Cerebrotech, Corindus Robotics, Endostream Medical, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Synchron, Serenity Medical, BlinkTBI, Echovate, RIST, Apama, Pipe Therapeutics; is the Chief Medical Officer of Corindus Robotics; co-foundership of Imperative Care, Vastrax, National Education and Research (NEAR) Center, Neuro Technology Investors (NTI), Pipe Therapeutics; and board membership for BlinkTBI. JF reports equity in Imperative Care and an affiliation with the JNIS editorial board. RDL reports a consulting agreements with Imperative Care, Cerenovus, Siemens Healthineers; equity in Synchron, Endostream and Q’Apel Medical; and an affiliation with the JNIS editorial board. DVB, BSG, DC, RZ, and TS have no competing interest to report., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Radiomics allows information not readily available to the naked eye to be extracted from high resolution imaging modalities such as CT. Identifying that a cancer has already metastasised at the time of presentation through a radiomic signature will affect the treatment pathway. The ability to recognise the existence of metastases earlier will have a significant impact on the survival outcomes., Aim: To create a novel radiomic signature using textural analysis in the evaluation of synchronous liver metastases in colorectal cancer., Methods: CT images at baseline and subsequent surveillance over a 5-year period of patients with colorectal cancer were processed using textural analysis software. Comparison was made between those patients who developed liver metastases and those that remained disease free to detect differences in the 'texture' of the liver., Results: A total of 24 patients were divided into two matched groups for comparison. Significant differences between the two groups scores when using the textural analysis programme were found on coarse filtration (p = 0.044). Patients that went on to develop metastases an average of 18 months after presentation had higher levels of hepatic heterogeneity on CT., Conclusion: This initial study demonstrates the potential of using a textural analysis programme to build a radiomic signature to predict the development of hepatic metastases in rectal cancer patients otherwise thought to have clear staging CT scans at time of presentation., (© 2022 The Authors.)

Background: The use of a balloon-guide catheter (BGC) in acute stroke treatment has been widely adopted after demonstrating optimized procedure metrics and outcomes. Initial technical constraints of previous devices included catheter stiffness and smaller inner diameters. We aim to evaluate the performance and safety of the Walrus BGC, a variable stiffness catheter with a large bore 0.087 inch inner diameter (ID), via the the WICkED study ( W alrus Large Bore guide Catheter I mpact on re C analization first pass E ffect an D outcomes)., Methods: This is a retrospective, site adjudicated, multicenter study on consecutive patients with large vessel occlusion treated with the Walrus BGC. Baseline characteristics, procedural outcomes and functional outcomes were analyzed., Results: A total of 338 patients met the inclusion criteria. The Walrus was successfully tracked into distal vasculature and allowed therapeutic device delivery in all but 3 cases (0.9%). Large aspiration catheters ≥0.070 inch ID were used in 71.9% of cases. Stent retriever thrombectomy was used as the first-line modality in 59.2% and thromboaspiration in 40.8% of cases. The successful recanalization rate (modified treatment in cerebral ischemia (mTICI) 2b/3) was 94.4%, with 64.8% of the patients achieving mTICI 2b/3 after the first pass. The Walrus-related adverse event rate was 0.6%, corresponding to two vessel dissections. Functional independence was 50% (126/252) and mortality 25% (63/252). Unfavorable outcomes were more likely in older patients, who had unsuccessful reperfusion, longer procedure times, and a higher mean number of passes., Conclusion: In acute ischemic stroke patients presenting with large vessel occlusion, the Walrus BGC demonstrated excellent navigability and safety profile, allowed the accommodation of leading large bore aspiration catheters, and demonstrated high vessel recanalization rates., Competing Interests: Competing interests: RDT is also an employee of Siemens Healthineers and Corindus, and a consultant for Johnson and Johnson, Q’Apel Medical, Rebound Therapeutics, Integra Lifesciences, Medtronic, Echovate, Viseon; holds stock in Q’Apel Medical, Rebound Therapeutics, Echovate, Viseon, Synchron, Blockade Medical, Endostream Medical, and receives royalty fees from the Medical University of South Carolina. AHS reports grants from Coinvestigator: NIH/NINDS 1R01NS091075 Virtual Intervention of Intracranial Aneurysms; personal fees from Adona Medical, Inc, Amnis Therapeutics, BlinkTBI, Inc, Boston Scientific Corp (for purchase of Claret Medical), Buffalo Technology Partners, Inc, Cardinal Consultants, LLC, Cerebrotech Medical Systems, Inc, Cognition Medical, Endostream Medical, Ltd, Imperative Care, Inc, International Medical Distribution Partners, Neurovascular Diagnostics, Inc, Q’Apel Medical, Inc, Rebound Therapeutics Corp (purchased 2019 by Integra Lifesciences, Corp), Rist Neurovascular, Inc, Sense Diagnostics, Inc, Serenity Medical, Inc, Silk Road Medical, Spinnaker Medical, Inc, StimMed, Synchron, Three Rivers Medical, Inc, Vastrax, LLC, VICIS, Inc, Viseon, Inc, personal fees from Amnis Therapeutics, Boston Scientific, Canon Medical Systems USA, Inc, Cerebrotech Medical Systems, Inc, Cerenovus, Corindus, Inc, Endostream Medical, Ltd, Imperative Care, Inc, Integra LifeSciences Corp, Medtronic, MicroVention, Minnetronix Neuro, Inc, Northwest University, Penumbra, Q’Apel Medical, Inc, Rapid Medical, Rebound Therapeutics Corp, Serenity Medical, Inc, Silk Road Medical, StimMed, Stryker, Three Rivers Medical, Inc, VasSol, W.L. Gore & Associates, and personal fees from Cerenovus; Medtronic; MicroVention; consultant fees for opinion on the design of clinical trials. ASP is a consultant for and has received research grants from Stryker Neurovascular, Medtronic, Cerenovus. He has received NIH grants. He is also a consultant for Microvention, QApel, Perfuze Medical, Arsenal Medical, Merit Medical. Holds stock in InNeuroCo Inc, Galaxy therapeutics, Agile Medical, Perfuze medical and NTI. JM has received research grants from Stryker, Penumbra, and Microvention. He is a consultant to Endostream, Viseon, Imperative Care, RIST, Synchron, Viz.ai, Perflow, CVAid, and Cerebrotech. He is investor/stockholder at Rebound, BlinkTBI, Endostream, Viseon, Imperative Care, Serenity, Cardinal Consulting, NTI, RIST, Synchron, Viz.ai, Q’Apel Medical, and Cerebrotech. JV is a consultant for Integra Life Sciences, Corindus Vascular Robotics, Cerenovus, Integra, and Medtronic. Own equity in Truvic Medical and Visom Technologies, and he is founder and co-partner of Ceretronic LLC.IC is a consultant to Cerenovus (JNJ), Medtronic, Q’Apel Medical, Microvention, and Serenity. He is a stockholder at Truvic, Imperative care, Rist, The Near Center, Q’Apel, Cerebrotech, Synchron, Echovate, Three Rivers Medical Inc, and Serenity. AA is on an advisory board for iSchema View. AST is a consultant for Cardinal Consulting, Cerebrotech, Cerenovus, Corindus Robotics, Endostream Medical, Medtronic, Siemens, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Serenity Medical, 880 Medical, and Q’Apel; stock holder in Cerebrotech, Endostream Medical, Imperative Care, Three Rivers Medical, Vastrax, Pipe Therapeutics, Q’Apel, Shape Memory, Synchron, Serenity Medical, Blink TBI, Echovate, RIST, Apama, VIZ AI, Early Bird Medicak, Radical Medical, Spinnaker Medical; co-founder of PipeTherapeutics, Neuro Technology Investors (NTI), National Education and Research Center (NEAR), Imperative Care; on the board of BlinkTBI and provides expert testimony for Corindus Vascular Robotics. RAH is a consultant for Medtronic, Stryker, Cerenovous, Microvention, Balt, Phenox, Rapid Medical and Q’Apel. He is on advisory board for MiVI, eLum, Three Rivers, Shape Medical and Corindus. In restricted research grant from NIH, Interline Endowment, Microvention, Stryker, CNX. Investor/stockholder for InNeuroCo, Cerebrotech, eLum, Endostream, Three Rivers Medical Inc, Scientia, RisT, BlinkTBI, and Corindus. All the other authors have no disclosure to report., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: In this single-centre retrospective observational study, the 8-week safety and the efficiency of a single dose of BNT162b2 vaccine was studied in 83 HD patients., Methods: All clinically stable adult ESRD patients on chronic HD for at least 4 weeks were screened for participation in the study. Exclusion criteria for enrollment in the study included a medical history of COVID-19 infection within the last 12 weeks or delivery of both vaccine doses less than 8 weeks apart from each other. The same patients during the 8-week period that preceded the vaccination served as controls of themselves. The vaccine was administered intramuscularly in the deltoid muscle, on a dialysis day, at least 30 min either pre- or post-dialysis. The primary end-point of the study was severe COVID-19 infection, and/or death due to COVID-19 pneumonitis. Furthermore, all vaccinated patients were scrutinized for any local or systemic reactions within the first 7 days post-vaccination., Results: Amongst 113 adult HD patients in our Unit, in total 83 patients had the first 30 μg dose of the BNT162b2 vaccine and were considered eligible to be included in the study. The 8-week survival rate was 91% for the controls and 100% for the vaccine group. No life-threatening allergic reaction or other side-effect was observed post-vaccination., Conclusion: The BNT162b2 vaccine can be safely used in HD patients and seems to offer significant protection against the infection even after the first vaccine dose., (© 2021. Japanese Society of Nephrology.)

Understanding how bacteria grow and divide requires insight into both the molecular-level dynamics of ultrastructure and the chemistry of the constituent components. Atomic force microscopy (AFM) can provide near molecular resolution images of biological systems but typically provides limited chemical information. Conversely, while super-resolution optical microscopy allows localization of particular molecules and chemistries, information on the molecular context is difficult to obtain. Here, we combine these approaches into STORMForce (stochastic optical reconstruction with atomic force microscopy) and the complementary SIMForce (structured illumination with atomic force microscopy), to map the synthesis of the bacterial cell wall structural macromolecule, peptidoglycan, during growth and division in the rod-shaped bacterium Bacillus subtilis . Using "clickable" d-amino acid incorporation, we fluorescently label and spatially localize a short and controlled period of peptidoglycan synthesis and correlate this information with high-resolution AFM of the resulting architecture. During division, septal synthesis occurs across its developing surface, suggesting a two-stage process with incorporation at the leading edge and with considerable in-filling behind. During growth, the elongation of the rod occurs through bands of synthesis, spaced by ∼300 nm, and corresponds to denser regions of the internal cell wall as revealed by AFM. Combining super-resolution optics and AFM can provide insights into the synthesis processes that produce the complex architectures of bacterial structural biopolymers.

Many software solutions are available for proteomics and glycomics studies, but none are ideal for the structural analysis of peptidoglycan (PG), the essential and major component of bacterial cell envelopes. It icomprises glycan chains and peptide stems, both containing unusual amino acids and sugars. This has forced the field to rely on manual analysis approaches, which are time-consuming, labour-intensive, and prone to error. The lack of automated tools has hampered the ability to perform high-throughput analyses and prevented the adoption of a standard methodology. Here, we describe a novel tool called PGFinder for the analysis of PG structure and demonstrate that it represents a powerful tool to quantify PG fragments and discover novel structural features. Our analysis workflow, which relies on open-access tools, is a breakthrough towards a consistent and reproducible analysis of bacterial PGs. It represents a significant advance towards peptidoglycomics as a full-fledged discipline., Competing Interests: AP, RT, AR, MA, DL, IG, MC, SM none, AA None, AN Andrew Nichols is affiliated with Protein Metrics Inc. The author has no other competing interests to declare, MB Marshall Bern is affiliated with Protein Metrics Inc. The author has no other competing interests to declare, (© 2021, Patel et al.)

Background: Direct aspiration thrombectomy techniques use large bore aspiration catheters for mechanical thrombectomy. Several aspiration catheters are now available. We report a bench top exploration of a novel beveled tip catheter and our experience in treating large vessel occlusions (LVOs) using next-generation aspiration catheters., Methods: A retrospective analysis from a prospectively maintained database comparing the bevel shaped tip aspiration catheter versus non-beveled tip catheters was performed. Patient demographics, periprocedural metrics, and discharge and 90-day modified Rankin Scale (mRS) scores were collected. Patients were divided into two groups based on which aspiration catheter was used., Results: Our data showed no significant difference in age, gender, IV tissue plasminogen activator administration, admission NIH Stroke Scale score, baseline mRS, or LVO location between the beveled tip and flat tip groups. With the beveled tip, Thrombolysis in Cerebral Infarction (TICI) 2C or better recanalization was more frequent overall (93.2% vs 74.2%, p=0.017), stent retriever usage was lower (9.1% vs 29%, p=0.024), and patients had lower mRS on discharge (median 3 vs 4, p<0.001) and at 90 days (median 2 vs 4, p=0.008)., Conclusion: Patients who underwent mechanical thrombectomy with the beveled tip catheter had a higher proportion of TICI 2C or better and had a significantly lower mRS score on discharge and at 90 days., Competing Interests: Competing interests: JV is a consultant for Integra Life Sciences and Corindus Vascular Robotics. MJG has received research support from the National Institutes of Health (NIH), the United States – Israel Binational Science Foundation, Anaconda, Apic Bio, Arsenal Medical, Axovant, Cerenovus, Ceretrieve, Cook Medical, Galaxy LLC, Gentuity, Imperative Care, InNeuroCo, Insera, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Neuravi, Neurogami, Philips Healthcare, Progressive Neuro, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, ThrombX Medical and the Wyss Institute; is a consultant on a fee-per-hour basis for Cerenovus, Imperative Care, Medtronic Neurovascular, Mivi Neurosciences, Phenox, Q’Apel Medical, Route 92 Medical, and Stryker Neurovascular; holds stock in Imperative Care, InNeuroCo, and Neurogami. RDT is a consultant for Siemens Healthineers, Johnson and Johnson, Q’Apel Medical, Rebound Therapeutics, Echovate, Viseon; holds stock in Q’Apel Medical, Rebound Therapeutics, Echovate, Viseon, Synchron, Endostream Medical, and receives royalty fees from the Medical University of South Carolina. IC is a consultant for Terumo Microvention, Johnson and Johnson, Imperative Care, Medtronic Neurovascular; holds stock in Q’Apel Medical, RIST Neurovascular, Echovate, Viseon, Synchron, Endostream Medical, and receives royalty fees from the Medical University of South Carolina. AT is a consultant for Blockade Medical, Cardinal Consulting, Cerebrotech, Corindus Vascular Robotics, Medtronic Neurovascular, Endostream Medical, Terumo Microvention, Penumbra, Siemens Healthineers, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Stryker Neurovascular, Serenity Medical, 880 Medical, Q’Apel Medical; holds stock in Cerebrotech, Corindus Robotics, Endostream Medical, Imperative Care, Three Rivers Medical, Vastrax, Shape Memory, Synchron, Serenity Medical, BlinkTBI, Echovate, RIST, Apama, Pipe Therapeutics; is the Chief Medical Officer of Corindus Robotics, Imperative Care; is the co-founder of Imperative Care, Vastrax, National Education and Research (NEAR) Center, Neuro Technology Investors (NTI), Pipe Therapeutics; is a board member of BlinkTBI., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD.Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured.Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sd capsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L -1 versus 44.50±5.90 µmol·L -1 , respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sd C5 3.86±5.13 µmol·L -1 versus 45.89±3.95 µmol·L -1 , respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough: geometric mean±sd capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L -1 versus 12.80±8.33 µmol·L -1 (p<0.001) and 44.50±5.90 µmol·L -1 versus 183.2±6.37 µmol·L -1 (p=0.006), respectively. This was also the case for healthy participants (C5 versus CS5: 45.89±3.95 µmol·L -1 versus 254.40±3.78 µmol·L -1 , p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86±5.13 µmol·L -1 versus 3.34±5.04 µmol·L -1 , p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= -0.430, p=0.036 and ρ= -0.420, p=0.041, respectively.Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management., Competing Interests: Conflict of interest: P.S.P. Cho reports a grant from Merck, outside the submitted work. Conflict of interest: H.V. Fletcher has nothing to disclose. Conflict of interest: I.S. Patel has nothing to disclose. Conflict of interest: R.D. Turner has nothing to disclose. Conflict of interest: C.J. Jolley has nothing to disclose. Conflict of interest: S.S. Birring reports grants from Merck, and personal fees from Merck, Bayer, Shionogi, Bellus, Nerre, Nocion and Boehringer Ingelheim, outside the submitted work., (Copyright ©ERS 2021.)

Pediatric stroke presents with a variety of signs and symptoms. Correct modality of imaging is essential in decreasing the time from symptom onset to appropriate management. Evaluation of pediatric stroke should include both blood work as well as imaging in a parallel rather than a sequential matter. We report a case of a child with a bow hunter's stroke that was challenging to diagnose. This type of stroke happens when the vertebral artery is occluded at the atlantoaxial or subaxial level during neck rotation. This case demonstrates that workup of stroke should be comprehensive to include all mechanical and anatomic possibilities before investigating rarer hypercoagulable disorders.

Background: Cough is predictive of exacerbations of chronic obstructive pulmonary disease (COPD). Little is known about cough reflex sensitivity during exacerbation of COPD and whether it is associated with exacerbation frequency. This pilot study aimed to investigate cough reflex sensitivity during and following recovery from exacerbation of COPD, and its association with the frequency of future exacerbations. In addition, the repeatability of cough reflex sensitivity in stable COPD was investigated., Methods: Twenty participants hospitalised with exacerbation of COPD underwent inhaled capsaicin challenge during exacerbation and after 6 weeks of recovery. The frequency of future exacerbations was monitored for 12 months. The repeatability of cough reflex sensitivity was assessed in separate participants with stable COPD, who underwent 2 capsaicin challenge tests, 6 weeks apart., Results: Cough reflex sensitivity was heightened during exacerbation of COPD. Geometric mean (SD) capsaicin concentration thresholds to elicit 5 coughs (C5) during exacerbation and after 6 weeks of recovery were 1.76 (3.73) vs. 8.09 (6.25) μmol L -1 , respectively (p < 0.001). The change in C5 from exacerbation to 6-week recovery was associated with the frequency of future exacerbations (ρ = - 0.687, p = 0.003). C5 was highly repeatable over 6 weeks in stable COPD, and intraclass correlation coefficient was 0.85., Conclusion: Cough reflex sensitivity is heightened during exacerbation of COPD and reduces after recovery. The persistence of cough reflex hypersensitivity at recovery was associated with the frequency of future exacerbations.

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics 1,2 . Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor 1,3 . In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength 4-6 . Here we applied atomic force microscopy 7-12 to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent; the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface 13,14 , providing information complementary to traditional structural biology approaches.

Infectious diseases (exacerbated by antimicrobial resistance) cause death, loss of quality of life and economic burden globally. Materials with inherent antimicrobial properties offer the potential to reduce the spread of infection through transfer via surfaces or solutions, or to directly reduce microbial numbers in a host if used as implants. Additive Manufacturing (AM) techniques offer shorter supply chains, faster delivery, mass customisation and reduced unit costs, as well as highly complicated part geometries which are potentially harder to clean and sterilise. Here, we present a new approach to introducing antibacterial properties into AM, using Laser Sintering, by combining antimicrobial and base polymer powders prior to processing. We demonstrate that the mechanical properties of the resultant composite parts are similar to standard polymer parts and reveal the mode of the antibacterial activity. We show that antibacterial activity is modulated by the presence of obstructing compounds in different experimental media, which will inform appropriate use cases. We show that the material is not toxic to mammalian cells. This material could be quickly used for commercial products, and our approach could be adopted more generally to add new functionality to Laser Sintered parts.