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Clinical management of cerebral small vessel disease:a call for a holistic approach

Chinese medical Journal 2021年第2期134卷 127-142页

作者： Una Clancy Jason P.Appleton Carmen Arteaga Fergus N.Doubal philip m.bath Joanna m.Wardlaw Centre for Clinical Brain Sciences and UK Dementia Research InstituteUniversity of EdinburghChancellor's Building49 Little France CrescentEdinburghEH164SPUK Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottingham NG51PBUK Stroke University Hospitals Birmingham NHS Foundation TrustMindelsohn WayEdgbastonBirmingham B152GWUK Stroke Nottingham University Hospitals NHS TrustNottingham NG51PBUK.

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric *** brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(mRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing *** have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of *** this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on mRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle *** core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’*** approach should integrate clinical expertise in stroke neurology,cognitive,and physical *** requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel *** essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

关键词： Dementia magnetic resonance imaging mild cognitive impairment Risk factors Small vessel disease Stroke Symptoms Treatment

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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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Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 146-153页

作者： philip C.muller matthias Pfister Dilmurodjon Eshmuminov Kuno Lehmann Department of Surgery and Transplantation University Hospital ZurichRämistrasse 100Zurich CH-8091Switzerland

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELm)is still in *** comparing LT with liver resection(LR)for NELm are scarce,as patient selection is heterogeneous and experience is *** goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of *** sources:A scoping literature search on LT and LR for NELm was performed with Pubmed,including English articles up to march ***:International guidelines recommend LR for NELm in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed *** liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free *** highly selected patients(based on the milan criteria)with unresectable NELm,oncologic results of LT are *** factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic *** on low-level evi-dence,LT for low-grade NELm within the milan criteria resulted in improved disease-free survival and overall survival compared to *** benefits of LT were lost in patients beyond the milan ***:With adherence to strict selection criteria especially tumor biology,LT for NELm is becoming a valuable option providing oncologic benefits compared to *** evidence suggests even stricter selection criteria with regard to tumor biology.

关键词： Liver transplantation Neuroendocrine liver metastases Liver resection Selection criteria Tumor biology

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A novel homozygous missense variant in ARSK causes mPS X,a new subtype of mucopolysaccharidosis

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Genes & Diseases 2024年第3期11卷 87-90页

作者： miao Sun Cornelia K.Kaminsky philip Deppe mai-Brittllse Frederic m.Vaz Barbara Plecko Torben Lubke Linda m.Randolph Division of Genomic medicine Department of Pathology and Laboratory MedicineChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Radiology Children's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA Department of Chemistry BiochemistryBielefeld UniversityBielefeld 33615Germany Amsterdam UmC Location University of Amsterdam Department of Clinical Chemistry and PediatricsLaboratory Genetic Metabolic DiseasesEmma Children's HospitalMeibergdreef 9Amsterdam 1100 DEthe Netherlands Amsterdam Gastroenterology Endocrinology metabolism Inborn Errors of MetabolismAmsterdam 1105 BKthe Netherlands Core Facility metabolomics Amsterdam UMC Location University of AmsterdamAmsterdam 1100DDthe Netherlands Department of Pediatrics Division of General PediatricsMedical Universityof GrazGraz8036Austria Division of medical Genetics Department of PediatricsChildren's Hospital Los Angeles/Keck School of Medicine of USCLos AngelesCA 90027USA

mucopolysaccharidoses(mPS)are a group of rare inborn errors of metabolism caused by defective lysosomal enzymes which prevent cells from degrading and recycling certain carbohydrates and fats,resulting in the storage of glycosaminoglycans in cells throughout the *** leads to multisystem abnormalities involving bone,connective tissues,brain,blood,spinal cord,skin,and other tissues.

关键词： metabolism doses polys

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A rat model of multicompartmental traumatic injury and hemorrhagic shock induces bone marrow dysfunction and profound anemia

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Animal models and Experimental medicine 2024年第3期7卷 367-376页

作者： Lauren S.Kelly Jennifer A.munley Erick E.Pons Kolenkode B.Kannan Elizabeth m.Whitley Letitia E.Bible philip A.Efron Alicia m.mohr Department of Surgery and Sepsis and Critical Illness Research Center University of Florida College of MedicineGainesvilleFloridaUSA Pathogenesis LLCGainesvilleFloridaUSA

Background:Severe trauma is associated with systemic inflammation and organ *** rodent trauma models are the mainstay of postinjury research but have been criticized for not fully replicating severe human *** aim of this study was to create a rat model of multicompartmental injury which recreates profound traumatic ***:male Sprague-Dawley rats were subjected to unilateral lung contusion and hemorrhagic shock(LCHS),multicompartmental polytrauma(PT)(unilateral lung contusion,hemorrhagic shock,cecectomy,bifemoral pseudofracture),or na?ve ***,plasma toll-l ike receptor 4(TLR4),hemoglobin,spleen to body weight ratio,bone marrow(Bm)erythroid progenitor(CFU-GEmm,BFU-E,and CFU-E)growth,plasma granulocyte colony-stimulating factor(G-CSF)and right lung histologic injury were assessed on day 7,with significance defined as p valuesma resulted in markedly more profound inhibition of weight gain compared to LCHS(p=0.0002)along with elevated plasma TLR4(pmoglobin(pmonstrated suppression of CFU-E and BFU-E growth compared to naive(pma G-CSF was elevated in PT compared to both na?ve and LCHS(pmonstrated significant histologic right lung injury with poor alveolar wall integrity and interstitial ***:multicompartmental injury as described here establishes a reproducible model of multicompartmental injury with worsened anemia,splenic tissue enlargement,weight loss,and increased inflammatory activity compared to a less severe *** may serve as a more effective model to recreate profound traumatic injury to replicate the human inflammatory response postinjury.

关键词： anemia i nflammation polytrauma pseudofracture shock

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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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Distinct vibrational signatures and complex phase behavior in metallic oxygen

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matter and Radiation at Extremes 2024年第2期9卷 4-11页

作者： philip Dalladay-Simpson Bartomeu monserrat Li Zhang Federico Gorelli Center for High Pressure Science Technology Advanced Research 1690 Cailun RoadShanghai 201203China Department of materials Science and metallurgy University of Cambridge27 Charles Babbage RoadCambridge CB3 OFSUnited Kingdom Cavendish Laboratory University of CambridgeJ.J.Thomson AvenueCambridge CB3 OHEUnited Kingdom Istituto Nazionale di Ottica Consiglio Nazionale delle Ricerche(CNR-INO)50125 FlorenceItaly Shanghai Advanced Research in Physical Sciences(SHARPS) ShanghaiChina

Evidence for metallization in dense oxygen has been reported for over 30 years[Desgreniers et al.,***.94,1117(1990)]at a now routinely accessible 95 GPa[Shimizu et al.,Nature 393,767(1998)].However,despite the longevity of this result and the technological advances since,the nature of the metallic phase remains poorly constrained[Akahama et al.,***.74,4690(1995);Goncharov et al.,***.B 68,224108(2003);ma,***.B 76,064101(2007);and Weck et al.,***.102,255503(2009)].In this work,through Raman spectroscopy,we report the distinct vibrational characteristics of metallicζ-O_(2) from 85 to 225 *** comparison with numerical simulations,weﬁnd reasonable agreement with the candidate structure up to about 150 *** higher pressures,the C2/mstructure is found to be unstable and incompatible with experimental *** candidate structures,and Ci,with C2/m C2/conly two molecules in the primitive unit cell,are found to be stable and more compatible with measurements above 175 GPa,indicative of the dissociation of(O_(2))4 ***,we report and discuss a strong hysteresis and metastability with the precursory phaseϵ-O_(2).Theseﬁndings will reinvigorate experimental and theoretical work into the dense oxygen system,which will have importance for oxygen-bearing chemistry,prevalent in the deep Earth,as well as fundamental physics.

关键词： metallic phase vibrational

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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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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(pment 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 pmilar 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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