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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw nikola sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Measures of intracranial compartments in acute intracerebral haemorrhage:data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial(RIGHT-2)

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Stroke & Vascular Neurology 2023年第2期8卷 151-160页

作者： Kailash Krishnan Zhe Kang Law Lisa J Woodhouse Rob A Dineen nikola sprigg Joanna M Wardlaw Philip M Bath Stroke Department of Acute MedicineNottingham University Hospitals NHS TrustNottinghamUK Stroke Trials Unit University of NottinghamNottinghamUK Department of Medicine National University of Malaysia Faculty of MedicineKuala LumpurMalaysia Radiological Sciences Research Group University of NottinghamNottinghamUK National Institute of Health Research Nottingham Biomedical Research Centre University of NottinghamNottinghamUK Centre for Clinical Brain Sciences UK Dementia Research InstituteChancellor's BuildingUniversity of EdinburghEdinburghUK

Background and purpose Intracerebral haemorrhage volume(ICHV)is prognostically important but does not account for intracranial volume(ICV)and cerebral parenchymal volume(CPV).We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional *** also assessed if cistern effacement,midline shift,old infarcts,leukoaraiosis and brain atrophy were associated with *** Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were *** included ICHV(using ABC/2)and ICV(XYZ/2)(by independent observers);ICHV,ICV and CPV(semiautomated segmentation,SAS);atrophy(intercaudate distance,ICD,Sylvian fissure ratio,SFR);midline shift;leukoaraiosis and cistern effacement(visual assessment).The effects of these measures on death at day 4 and poor functional outcome at day 90(modified Rankin scale,mRS of>3)was *** ICV was significantly different between XYZ and SAS:mean(SD)of 1357(219)vs 1420(196),mean difference(MD)62 mL(p<0.001).There was no significant difference in ICHV between ABC/2 and *** was very good agreement for ICV measured by SAS,CPV,ICD,SFR,leukoaraiosis and cistern score(all interclass correlations,n=10:interobserver 0.72-0.99,intraobserver 0.73-1.00).ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90,death at day 4 and acute neurological deterioration(all p<0.05),similar to *** shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts,leukoaraiosis and brain atrophy were *** Intracranial compartment measures and visual estimates are *** adjusted for ICH and CPV could be useful to prognosticate in acute *** presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

关键词： measures Tri nitrate

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Endothelial progenitor cells, potential biomarkers for diagnosis and prognosis of ischemic stroke: protocol for an observational case-control study

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Neural Regeneration Research 2020年第7期15卷 1300-1307页

作者： Kamini Rakkar Othman Othman nikola sprigg Philip Bath Ulvi Bayraktutan Stroke Division of Clinical Neuroscience University of Nottingham Clinical Sciences Building City Hospital

Ischemic stroke is a devastating,life altering event which can severely reduce patient quality of *** years of research there have been minimal therapeutic *** progenitor cells(EPCs),stem cells involved in both vasculogenesis and angiogenesis,may be a potential therapeutic *** a stroke,EPCs migrate to the site of ischemic injury to repair cerebrovascular damage,and their numbers and functional capacity may determine patients'*** study aims to determine whether the number of circulating EPCs and their functional aspects may be used as biomarkers to identify the type(cortical or lacunar)and/or severity of ischemic *** study will also investigate if there are any differences in these characteristics between healthy volunteers over and under 65 years of age.100 stroke patients(50 lacunar and 50 cortical strokes)will be recruited in this prospective,observational case-controlled *** samples will be taken from stroke patients at baseline(within 48 hours of stroke)and days 7,30 *** will be counted with flow *** plasma levels of pro-and anti-angiogenic factors and inflammatory cytokines will also be *** endothelial cells will be cultured to be used in tube formation,migration and proliferation functional *** outcome is disability or dependence on day 90 after stroke,assessed by the modified Rankin *** outcomes are changes in circulating EPC numbers and/or functional capacity between patient and healthy volunteers,between patient subgroups and between elderly and young healthy *** started in February 2017,167 participants have been *** will end in November *** Midlands-Coventry&Warwickshire Research Ethics Committee approved this study(REC number:16/WM/0304)on September8,*** version:*** Bayraktutan Dunhill Medical Trust EPC Study was registered in ***(NCT02980354)on November 15,*** st

关键词： ageing biomarkers cortical stroke endothelial progenitor cells ischemic stroke lacunar stroke observational study stem cells

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Blood pressure management in acute stroke

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Stroke & Vascular Neurology 2016年第2期1卷 72-82页

作者： Jason P Appleton nikola sprigg Philip M Bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK

Blood pressure(BP)is elevated in 75%or more of patients with acute stroke and is associated with poor *** to modulate BP in acute stroke has long been *** the loss of normal cerebral autoregulation,theoretical concerns are twofold:high BP can lead to cerebral oedema,haematoma expansion or haemorrhagic transformation;and low BP can lead to increased cerebral infarction or perihaematomal *** evidence from multiple large,high-quality,randomised trials is increasing our understanding of this challenging area,such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic *** we review the evidence for BP modulation in acute stroke,discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit.

关键词： Blood acute cerebral

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Cerebral misery perfusion due to carotid occlusive disease

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Stroke & Vascular Neurology 2017年第2期2卷 88-93页

作者： Mohana Maddula nikola sprigg Philip M Bath Sunil Munshi Acute Stroke Unit Tauranga HospitalTaurangaNew Zealand Division of Clinical Neuroscience University of NottinghamNottinghamUK Department of Stroke Nottingham University Hospitals NHS TrustNottinghamUK

Purpose Cerebral misery perfusion(CMP)is a condition where cerebral autoregulatory capacity is exhausted,and cerebral blood supply in insufficient to meet metabolic *** present an educational review of this important condition,which has a range of clinical *** A non-systematic review of published literature was undertaken on CMP and major cerebral artery occlusive disease,using Pubmed and *** Patients with CMP may present with strokes in watershed territories,collapses and transient ischaemic attacks or episodic movements associated with an orthostatic *** positron emission tomography is the gold standard investigation for misery perfusion,advanced MRI is being increasingly used as an alternative investigation *** presence of CMP increases the risk of *** addition to the devastating effect of stroke,there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease(COD)and misery *** evidence for revascularisation in the setting of complete carotid occlusion is *** management constitutes careful blood pressure management while addressing other vascular risk *** The evidence for the management of patients with COD and CMP is discussed,together with recommendations based on our local *** this review,we focus on misery perfusion due to *** Patients with CMP and COD may present with a wide-ranging clinical phenotype and therefore to many *** identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow,while avoiding potentially harmful treatment.

关键词： perfusion carotid impaired

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Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel

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Stroke & Vascular Neurology 2021年第1期6卷 103-108页

作者： Jason Philip Appleton Carla Richardson Natalia Dovlatova Jane May nikola sprigg Stan Heptinstall Philip M Bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Stroke Division Nottingham University Hospitals NHS TrustNottinghamUK Platelet Solutions Ltd Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK Platelet Research Group Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK

Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment *** primary aim was to assess the proportion of patients who are insensitive to *** secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular *** Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were *** function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or ***’general practitioners provided details on recurrent vascular events at least 90 days *** are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(MF)>500 units,clopidogrel MF>860 ***-parametric descriptors and tests were *** 63 patients were recruited:mean age 64(13.7)years,women 47%.At baseline,59(95%)patients were taking clopidogrel alone with 3(5%)on combined clopidogrel and *** of platelet surface P-selectin revealed:aspirin test 528[317,834],>50054.8%;clopidogrel test 429[303,656],>86011.3%.No participants on aspirin and clopidogrel showed aspirin ***(20.6%)patients had a recurrent cerebrovascular event;those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence:626[380,801]versus 406[265,609],p=*** Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed *** significant associations were noted between clopidogrel resistance and recurrent ischaemic events.

关键词： patients cerebral function

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Managing end-stage carcinoid heart disease:A case report and literature review

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1076-1083页

作者： nikola Bulj Vedran Tomasic Maja Cigrovski Berkovic Department of Cardiology University Hospital Centre“Sestre Milosrdnice“Zagreb 10000Croatia Division of Gastroenterology Department of Internal MedicineUniversity Hospital Centre“Sestre Milosrdnice”Zagreb 10000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare tumors,often diagnosed in an advanced stage when curative treatment is impossible and grueling symptoms related to vasoactive substance release by tumor cells affect patients’quality of *** complications of GEP-NENs,primarily tricuspid and pulmonary valve disease,and right-sided heart failure,are the leading cause of death,even compared to metastatic *** SUMMARY We present a case of a 35-year-old patient with progressive dyspnea,back pain,polyneuropathic leg pain,and nocturnal diarrhea lasting for a decade before the diagnosis of neuroendocrine carcinoma of unknown primary with extensive liver *** the initial presentation,serum biomarkers were not evaluated,and the patient received five cycles of doxorubicin,which he did not tolerate well,so he refused further therapy and was lost to *** 10 years,he presented to the emergency room with signs and symptoms of right-sided heart *** markers,serum chromogranin A,and urinary 5-hydroxyindoleacetic acid were extremely elevated(900 ng/mL and 2178µmol/L),and transabdominal ultrasound confirmed hepatic *** tomo-graphy(CT)showed liver metastases up to 6 cm in diameter and metastases in mesenteric lymph nodes and ***,an Octreoscan showed lesions in the heart,thoracic spine,duodenum,and ascendent colon.A standard trans-thoracic echocardiogram confirmed findings of carcinoid heart *** patient was not a candidate for valve *** started octreotide acetate treatment,and the dose escalated to 80 mg IM *** biochemical CONCLUSION Carcinoid heart disease occurs with carcinoid syndrome related to advanced neuroendocrine tumors,usually with liver metastases,which manifests as right-sided heart valve dysfunction leading to right-sided heart *** heart disease and tumor burden are major prognostic factors of poor surviva

关键词： Gastroenteropancreatic neuroendocrine neoplasms Carcinoid syndrome Carcinoid heart disease Diagnosis Treatment Case report

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Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

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Stroke & Vascular Neurology 2021年第2期6卷 180-186页

作者： Lucy Beishon Lisa J Woodhouse Daniel Bereczki Hanne K Christensen Ronan Collins John Gommans Christina Kruuse George Ntaios Serefnur Ozturk Stephen Phillips Stuart Pocock Szabolcs Szatmari Joanna Wardlaw nikola sprigg Philip M Bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Department of Neurology Semmelweis UniversityBudapestHungary Bispebjerg Hospital and University of Copenhagen University of CopenhagenCopenhagenDenmark Department of Geriatric and Stroke Medicine Adelaide and Meath HospitalDublinIreland Department of Medicine Hawke's Bay HospitalCamberleyNew Zealand Department of Neurology Herlev Gentofte HospitalUniversity of CopenhagenCopenhagenDenmark Department of Medicine Larissa University HospitalUniversity of ThessalyVolosGreece Department of Neurology Selcuk University Medical FacultyKonyaTurkey Department of Neurology Queen Elizabeth II Health Sciences CentreHalifaxNova ScotiaCanada Medical Statistics Unit London School of Hygiene&Tropical MedicineLondonUK Department of Neurology George Emil Palade University of MedicinePharmacyScience and Technology of Târgu MureșTargu MuresRomania Centre for Clinical Brain Sciences University of EdinburghEdinburghUK Stroke Nottingham University Hospitals NHS TrustNottinghamUK

Introduction Nitrate-induced headache is common and may signify responsive cerebral *** assessed the relationship between nitrate headache and outcome in patients with acute *** and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke *** of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were *** are adjusted for baseline prognostic factors and give OR and mean difference(MD)with 95%*** In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;p<0.001).Nitrate-related headache was associated with:younger age,female sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(p<0.05).Nitrate headache was not associated with improved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,MD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,MD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or *** and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.

关键词： headache patients nitrate

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An in vitro demonstration of a passive,acoustic metamaterial as a temperature sensor with mK resolution for implantable applications

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Microsystems & Nanoengineering 2024年第1期10卷 41-54页

作者： Lucrezia Maini Vicente Genovés Roman Furrer nikola Cesarovic Christofer Hierold Cosmin Roman Micro-and Nanosystems Department of Mechanical and Process EngineeringETH ZurichTannenstrasse 38092 ZurichSwitzerland. Translational Cardiovascular Technology Department of Health Science and TechnologyETH ZurichLeopold-Ruzicka-Weg 48093 ZurichSwitzerland. Transport at Nanoscale Interfaces Swiss Federal Laboratories for Materials Science and TechnologyEMPAÜberlandstrasse 1298600 DübendorfSwitzerland Department of Cardiothoracic and Vascular Surgery Deutsches Herzzentrum der Charite(DHZC)13353 BerlinGermany

Wireless medical sensors typically utilize electromagnetic coupling or ultrasound for energy transfer and sensor *** transfer and management is a complex aspect that often limits the applicability of implantable sensor *** this work,we report a new passive temperature sensing scheme based on an acoustic metamaterial made of silicon embedded in a polydimethylsiloxane *** to other approaches,this concept is implemented without additional electrical components in situ or the need for a customized receiving unit.A standard ultrasonic transducer is used for this demonstration to directly excite and collect the reflected *** metamaterial resonates at a frequency close to a typical medical value(5 MHz)and exhibits a high-quality *** the design features of the metamaterial with the high-temperature sensitivity of the polydimethylsiloxane matrix,we achieve a temperature resolution of 30 *** value is below the current standard resolution required in infrared thermometry for monitoring postoperative complications(0.1 K).We fabricated,simulated,in vitro tested,and compared three acoustic sensor designs in the 29-43℃(~302-316 K)temperature *** this concept,we demonstrate how our passive metamaterial sensor can open the way toward new zero-power smart medical implant concepts based on acoustic interrogation.

关键词： passive resolution utilize

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Rethinking Global Context in Crowd Counting

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Machine Intelligence Research 2024年第4期21卷 640-651页

作者： Guolei Sun Yun Liu Thomas Probst Danda Pani Paudel nikola Popovic Luc Van Gool Computer Vision Lab ETH ZurichZurich 8092Switzerland Institute for Infocomm Research A*STARSingapore 138632Singapore Magic Leap Zirich 8050Switzerland

This paper investigates the role of global context for crowd ***,a pure transformer is used to extract features with global information from overlapping image *** by classification,we add a context token to the input sequence,to facilitate information exchange with tokens corresponding to image patches throughout transformer *** to the fact that transformers do not explicitly model the tried-and-true channel-wise interactions,we propose a token-attention module(TAM)to recalibrate encoded features through channel-wise attention informed by the context *** that,it is adopted to predict the total person count of the image through regression-token module(RTM).Extensive experiments on various datasets,including ShanghaiTech,UCFQNRF,JHU-CROWD++and NWPU,demonstrate that the proposed context extraction techniques can significantly improve the performanceover the baselines.

关键词： Crowd counting vision transformer global context attention density map.

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