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Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford

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World Journal of Gastroenterology 2020年第30期26卷 4428-4441页

作者： Samba Siva Reddy Pulusu Ashish Srinivasan Krupa Krishnaprasad Daniel Cheng Jakob Begun CharlotteKeung Daniel Van Langenberg Lena Thin Tamara Mogilevski Peter De Cruz Graham Radford-Smith Emma Flanagan Sally Bell Soleiman Kashkooli Miles Sparrow Simon Ghaly Peter Bampton Elise Sawyer Susan Connor Quart-ul-ain Rizvi Jane M Andrews Gillian Mahy Paola Chivers Simon Travis Ian Craig Lawrance Centre for Inflammatory Bowel Diseases St John of God HospitalSubiaco 6008Western AustraliaAustralia Translational Gastroenterology Unit NIHR Oxford Biomedical Research CentreOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxford OX39DUUnited Kingdom Inflammatory Bowel Disease research Group Queensland institute of Medical ResearchHerston 4006QueenslandAustralia Department of Gastroenterology Mater HospitalBrisbane 4101QueenslandAustralia Department of Gastroenterology Mater HospitalSouth Brisbane 4101QueenslandAustralia of Gastroenterology Eastern HealthBox Hill 3128VictoriaAustralia Department of Gastroenterology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalFitzroy 3065VictoriaAustralia Department of Gastroenterology Northern HealthEpping 3076VictoriaAustralia Department of Gastroenterology The Alfred HospitalMelbourne 3004VictoriaAustralia Department of Gastroenterology St Vincent’s HospitalDarlinghurst 2010New South WalesAustralia Department of Gastroenterology Flinders Medical CentreBedford Park 5042South AustraliaAustralia Department of Gastroenterology Liverpool HospitalSydney 2170New South WalesAustralia Department of Gastroenterology Royal Adelaide Hospital&University of AdelaideAdelaide 5000South AustraliaAustralia Department of Gastroenterology Townsville HospitalDouglas 4814QueenslandAustralia institute for Health research University of Notre DameFremantle 6160Western AustraliaAustralia School of Medicine and Pharmacology University of Western AustraliaCrawley 6009Western AustraliaAustralia

BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)*** To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving *** A retrospective review of Australian and Oxford,United Kingdom data for UC *** response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were *** regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing *** outcomes were *** Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were *** clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo ***-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 *** VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

关键词： Vedolizumab Ulcerative colitis Outcomes

Screening for early-onset neonatal sepsis on the Kaiser Permanente sepsis risk calculator could reduce neonatal antibiotic usage by two-thirds

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Pediatric Investigation 2022年第3期6卷 171-178页

作者： Michelle Fernandes Lucinda Winckworth Lyrille Lee Madiha Akram Simon Struthers The Department of Neonatal Medicine and the Neonatal Intensive Care Unit Princess Anne HospitalUniversity Hospitals Southampton NHS Foundation TrustSouthamptonUK The MRC Lifecourse Epidemiology Centre and Human Development and Health Academic Unit Faculty of MedicineUniversity of SouthamptonSouthamptonUK Nuffield Department of Women’s and Reproductive Health John Radcliffe HospitalUniversity of OxfordOxfordUK Department of Pediatrics Royal Hampshire County HospitalWinchesterUK

Importance:Effective screening strategies for early-onset neonatal sepsis(EONS)have the potential to reduce high volume parenteral antibiotics(PAb)usage in ***:To compare management decisions for EONS,between CG149 National institute for Health and Care Excellence(NICE)guidelines and those projected through the virtual application of the Kaiser Permanente sepsis risk calculator(SRC)in a level 2 neonatal unit at a district general hospital(DGH).Methods:Hospital records were reviewed for maternal and neonatal risk factors for EONS,neonatal clinical examination findings,and microbial culture results for all neonates born at≥34 weeks’gestation between February and July 2019,who were(1)managed according to CG149-NICE guidelines or(2)received PAb within 72 h following birth at a DGH in Winchester,*** projections were obtained using its virtual risk ***:Sixty infants received PAb within the first 72 h of birth during the study *** these,19(31.7%)met SRC criteria for antibiotics;20(33.3%)met the criteria for enhanced observations and none had culture-proven *** on SRC projections,neonates with’’≥1 NICE clinical indicator and≥1 risk factor’were most likely to have a sepsis risk score(SRS)>*** below 37 weeks’gestation(risk ratio[RR]=2.31,95%confidence interval[CI]:1.02–5.22)and prolonged rupture of membranes(RR=3.14,95%CI:1.16–8.48)increased the risk of an SRS>***:Screening for EONS on the SRC could potentially reduce PAb usage by 68%in term and near-term neonates in level 2 neonatal units.

关键词： Early onset neonatal sepsis Kaiser Permanente sepsis risk calculator NICE guidelines Parenteral antibiotics

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Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

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World Journal of Gastroenterology 2017年第16期23卷 2995-3002页

作者： Shomron Ben-Horin Jane M Andrews Konstantinos H Katsanos Florian Rieder Flavio Steinwurz Konstantinos Karmiris Jae Hee Cheon Gordon William Moran Monica Cesarini Christian D Stone Doron Schwartz Marijana Protic Xavier Roblin Giulia Roda Min-Hu Chen Ofir Har-Noy Charles N Bernstein Department of Gastroenterology Sheba Medical CenterSackler School of MedicineTel-Aviv UniversityRamat-Gan 52621Israel the First Affiliated Hospital of Sun Yat-Sen University Guangzhou 510700Guangdong provinceChina Department of Gastroenterology and Hepatology Inflammatory Bowel Disease ServiceRoyal Adelaide HospitalSchool of MedicineUniversity of AdelaideAdelaideSA 5005Australia Division of Gastroenterology School of Health SciencesUniversity of IoanninaIoannina 45500Greece Department of Gastroenterology Hepatology and NutritionDigestive Disease Diseases and Surgery InstituteCleveland Clinic FoundationClevelandOH 44109United States Unit of Inflammatory Bowel Disease Hospital Israelita Albert EinsteinSao PauloSP 05652-900Brazil Department of Gastroenterology Venizeleio General HospitalHeraklion71409 CreteGreece Department of Internal Medicine Yonsei University College of MedicineSeoul 03722South Korea NIHR Nottingham Digestive Diseases Biomedical research Unit Nottingham University Hospitals NHS Trust and University of NottinghamNottingham NG7 2UHUnited Kingdom Dipartimento di Medicina Interna e SpecialitàMediche “Sapienza”University of Rome00185 RomaItaly Comprehensive Digestive institute of Nevada Las VegasNV 89113United States Department of Gastroenterology and Hepatology Soroka University Medical CenterBeer-Sheva 6400111Israel Department of Gastroenterology University Hospital ZvezdaraBelgrade 11000Serbia Department of Gastroenterology University-Hospital of Saint-Etienne42100 Saint EtienneFrance Gastroenterology Unit S.Orsola-Malpighi40138 BolognaItaly IBD Clinical and research Centre University of ManitobaWinnipegMB R3T2N2Canada

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

关键词： Inflammatory bowel disease Corticosteroids 5-aminosalicylates Ulcerative colitis

The multispeciality approach to the management of localised kidney cancer

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四川生理科学杂志 2022年第7期44卷 1169-1169页

作者： Grant D Stewart Department of Surgery University of Cambridge Cambridge Biomedical Campus Cambridge UK CRUK Cambridge Centre University of Cambridge Cambridge Biomedical Campus Cambridge UK Department of Urology Addenbrooke's Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge UK Department of Surgery University of Cambridge Cambridge Biomedical Campus Cambridge UK Department of Urology Charité - Universitätsmedizin Berlin Berlin Germany Division of Nephrology and Dialysis ASST Fatebenefratelli Sacco Fatebenefratelli Hospital Milan Italy Specialist Centre for Kidney cancer Royal Free Hospital London UK Division of Surgery and Interventional Science University College London London UK The Netherlands cancer institute Amsterdam Netherlands Department of Urology Addenbrooke's Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge UK School of Allied Health Anglia Ruskin University Cambridge UK Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland CRUK Cambridge Centre University of Cambridge Cambridge Biomedical Campus Cambridge UK Department of Radiology University of Cambridge Cambridge Biomedical Campus Cambridge UK Sir Peter MacCallum Department of Oncology University of Melbourne Peter MacCallum Cancer Centre Melbourne VIC Australia Department of Biomedical Sciences and Human Oncology University of Bari Aldo Moro Bari Italy Division of Medical Oncology AOU Consorziale Policlinico di Bari Bari Italy Division of Nephrology and Dialysis ASST Fatebenefratelli Sacco Fatebenefratelli Hospital Milan Italy Department of Clinical and Biomedical Sciences Università di Milano Milan Italy

Historically,kidney cancer was approached in a siloed single-speciality way,with urological surgeons managing the localised stages of the disease and medical oncologists caring for patients if metastases ***,improvements in the management of localised kidney cancer have occurred rapidly over the past two decades with greater understanding of the disease biology,diagnostic options,and innovations in curative *** developments are favourable for patients but provide a substantially more complex landscape for patients and clinicians to navigate,with associated challenging decisions about who to treat,how,and *** such,the skill sets needed to manage the various aspects of the disease and guide patients appropriately outstrips the capabilities of one particular specialist,and the evolution of a multispeciality approach to the management of kidney cancer is now *** this Review,we summarise the current best multispeciality practice for the management of localised kidney cancer and the areas in need of further research and development.

关键词： kidney local approach

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结直肠癌:NICE指南概要

英国医学杂志中文版 2021年第4期24卷 223-227页

作者： Nathan Bromham Maija Kallioinen Peter Hoskin R Justin Davies 廖瑜倩(译) 张宏艳(校) 无 National Guideline Alliance Royal College of Obstetricians and GynaecologistsLondon SE11SZUK Mount Vernon Hospital Northwood HA62RNUK and University of Manchester Cambridge Colorectal Unit Addenbrooke′s HospitalCambridge University Hospitals NHS Foundation TrustCambridge CB20QQUK 南昌大学第一附属医院肿瘤中心解放军总医院第五医学中心肿瘤学部 the Guideline Committee

结直肠癌(结肠、直肠或大肠癌症)是英国第4位最常见恶性肿瘤,每年新诊断患者超过42000例1。近年生存率有所提高,目前5年生存率约为60%2。本文对英国国家健康与临床优选研究所(National institute for Health and Care Excellence,NICE)... 详细信息

结直肠癌(结肠、直肠或大肠癌症)是英国第4位最常见恶性肿瘤,每年新诊断患者超过42000例1。近年生存率有所提高,目前5年生存率约为60%2。本文对英国国家健康与临床优选研究所(National institute for Health and Care Excellence,NICE)结直肠癌诊断和治疗指南更新推荐进行总结3。更新聚焦于结直肠癌的治疗,反映该领域的最新研究证据。

关键词：结直肠癌大肠癌诊断和治疗指南常见恶性肿瘤研究证据生存率

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容易漏诊？职业性哮喘

英国医学杂志中文版 2018年第2期21卷 111-113页

作者： Johanna Feary Hilary Pinnock 李双闫永吉 Department of Occupational and Environmental Medicine Royal Brompton and Harefield NHS Foundation TrustLondon SW3 6LRUK Asthma UK Centrefor Applied research Usher institute of Population Health Sciences and Informatics University of Edinburgh Medical School EdinburghUK Whitstable MedicalPractice WhltstableUK 首都医科大学附属北京朝阳医院职业病与中毒医学科

一名22岁的男子怀疑自己患有枯草热。几个月后，全科医生把他诊断为哮喘，后来发现他的症状与他在面包店的工作有关，于是把他转诊给一位职业性肺病专科医师，接着他被诊断为职业性哮喘。

关键词：职业性哮喘临床诊断症状治疗方法

The diagnostic and prognostic value of systems biology research in major traumatic and thermal injury: a review

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Burns & Trauma 2016年第3期4卷 169-179页

作者： Jon Hazeldine Peter Hampson Janet M.Lord NIHR Surgical Reconstruction and Microbiology research Centre Institute of Inflammation and AgeingBirmingham University Medical SchoolBirmingham B152TTUK NIHR Surgical Reconstruction and Microbiology research Centre Institute of Inflammation and AgeingBirmingham University Medical SchoolBirmingham B152TTUK Healing foundation Centre for Burns research Queen Elizabeth HospitalBirmingham B152WBUK

As secondary complications remain a significant cause of morbidity and mortality amongst hospitalised trauma patients,the need to develop novel approaches by which to identify patients at risk of adverse outcome is becoming increasingly *** on the idea that patients who experience"poor"outcome post trauma elicit a response to injury that is distinct from those who experience"good"outcome,tailored therapeutics is an emerging concept aimed at improving current treatment regimens by promoting patient-specific *** use of recent advancements in the fields of genomics,proteomics and metabolomics,numerous groups have undertaken a systems-based approach to analysing the acute immune and inflammatory response to major traumatic and thermal injury in an attempt to uncover a single or combination of biomarkers that can identify patients at risk of adverse *** results are encouraging,with all three approaches capable of discriminating patients with"good"outcome from those who develop nosocomial infections,sepsis and multiple organ failure,with differences apparent in blood samples acquired as early as 2 h post *** particular,genomic data is proving to be highly informative,identifying patients at risk of"poor"outcome with a higher degree of sensitivity and specificity than statistical models built upon data obtained from existing anatomical and physiological scoring ***,focussing predominantly upon human-based research,we provide an overview of the findings of studies that have investigated the immune and inflammatory response to major traumatic and thermal injury at the genomic,protein and metabolite level,and consider both the diagnostic and prognostic potential of these approaches.

关键词： Burns Cytokines Genomics Inflammation Mortality Sepsis Trauma

Genetic mechanisms of critical illness in Covid-19

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四川生理科学杂志 2020年第4期42卷 455-455页

作者： Erola Pairo-Castineira Roslin institute University of Edinburgh Edinburgh UK MRC Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Genomics England London UK Centre for Inflammation research The Queen’s Medical Research Institute University of Edinburgh Edinburgh UK Centre for Genomic and Experimental Medicine Institute of Genetics and Molecular Medicine University of Edinburgh Western General Hospital Edinburgh UK Edinburgh Clinical research Facility Western General Hospital University of Edinburgh Edinburgh UK Intensive Care National Audit & research Centre London UK institute for Molecular Bioscience The University of Queensland Brisbane Queensland Australia Biostatistics Group School of Life Sciences Sun Yat-sen University Guangzhou China The Crick institute London UK Intensive Care Unit Royal Infirmary of Edinburgh Edinburgh UK School of Life Sciences Westlake University Hangzhou China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou China Wellcome Centre for Human Genetics University of Oxford Oxford UK Department of Medicine University of Cambridge Cambridge UK Department of Intensive Care Medicine Guy’s and St Thomas’ NHS Foundation Trust London UK School of Immunology and Microbial Sciences King’s College London London UK NIHR Health Protection research Unit for Emerging and Zoonotic Infections Institute of Infection Veterinary and Ecological Sciences University of Liverpool Liverpool UK MRC-University of Glasgow Centre for Virus research Institute of Infection Immunity and Inflammation College of Medical Veterinary and Life Sciences University of Glasgow Glasgow UK William Harvey research institute Barts and the London School of Medicine and Dentistry Queen Mary University of London London UK Centre for Tropical Medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford UK Clinical research Centre at St Vincent’s University Hospital Un

Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by *** genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC(Genetics Of Mortality In Critical Care)genome-wide association study(GWAS)in 2244 critically ill Covid-19 patients from 208 UK intensive care units(ICUs).We identify and replicate novel genome-wide significant associations,on chr12q24.13(rs10735079,p=1.65[Formula:see text]10-8)in a gene cluster encoding antiviral restriction enzyme activators(OAS1,OAS2,OAS3),on chr19p13.2(rs2109069,p=2.3[Formula:see text]10-12)near the gene encoding tyrosine kinase 2(TYK2),on chr19p13.3(rs2109069,p=3.98[Formula:see text]10-12)within the gene encoding dipeptidyl peptidase 9(DPP9),and on chr21q22.1(rs2236757,p=4.99[Formula:see text]10-8)in the interferon receptor gene *** identify potential targets for repurposing of licensed medications:using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2,and high expression of TYK2,to life-threatening disease;transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe *** results identify robust genetic signals relating to key host antiviral defence mechanisms,and mediators of inflammatory organ damage in *** mechanisms may be amenable to targeted treatment with existing ***-scale randomised clinical trials will be essential before any change to clinical practice.

关键词： lung drugs critical

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Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease

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四川生理科学杂志 2020年第4期42卷 414-414页

作者： David B Beck From the National Human Genome research institute (D.B.B. A.K.O. W.P. N.B. D.L.R. D.O.C. K.M. P.H. S.R. L.X. H.O. M.N. A.J. R.S.L. N.D. J.J.C. M.C.V.M. D.N. B.D.S. W.A.G. S.M.B. I.A. D.L.K.) the National Institute of Arthritis and Musculoskeletal and Skin Diseases (M.A.F. K.A.S. S.N. W.L.T. S.G. C.C.-R. W.G. E.R. K.V.W. G.W. S.B. S.D. Z.D. R.A.C. M.J.K. M.G. P.C.G.) the National Institute of Dental and Craniofacial Research (J.C.C. A.J.A. A.W.) the Undiagnosed Diseases Program Common Fund Office of the Director (N.B. D.L.R. M.C.V.M. D.N. W.A.G.) the Hematology Branch National Heart Lung and Blood Institute (Z.W. B.P. E.M.G. F.G.-R. L.W.D. C.S.H. N.S.Y.) the National Institute of Allergy and Infectious Diseases (K.S.B.) the Laboratory of Pathology Center for Cancer Research National Cancer Institute (C.-C.R.L.) the National Institutes of Health (NIH) Intramural Sequencing Center National Human Genome Research Institute (J.M.) the Department of Laboratory Medicine (W.W. M.T. A.D.-F. K.R.C.) and the National Eye Institute (M.A.-A.) NIH Bethesda and GeneDx Gaithersburg (K.R.) — both in Maryland and the National Amyloidosis Centre Royal Free Hospital London NHS Foundation Trust and University College London London (D.R. H.J.L.) and the National Institute for Health Research–Leeds Biomedical Research Centre and Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Leeds (S.S.) — both in the United Kingdom.

Background:Adult-onset inflammatory syndromes often manifest with overlapping clinical *** in ubiquitin-related genes,previously implicated in autoinflammatory disease,may define new ***:We analyzed peripheral-blood exome sequence data independent of clinical phenotype and inheritance pattern to identify deleterious mutations in ubiquitin-related *** sequencing,immunoblotting,immunohistochemical testing,flow cytometry,and transcriptome and cytokine profiling were ***-Cas9-edited zebrafish were used as an in vivo model to assess gene function.

关键词： inflammatory clinical Adult

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