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Dual biologic therapy with ocrelizumab for multiple sclerosis and vedolizumab for Crohn's disease:A case report and review of literature

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world Journal of Clinical Cases 2022年第8期10卷 2569-2576页

作者： Michael Au Nikola Mitrev rupert w leong Viraj Kariyawasam Department of Gastroenterology and Hepatology Blacktown and Mt Druitt HospitalsWestern Sydney Local Health DistrictSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversityBlacktown 2148New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustralia Endoscopy Department and Inflammatory Bowel Disease Service Concord HospitalSydney 2137New South WalesAustralia Concord Clinical School University of SydneySydney 2137New South WalesAustralia Inflammatory Bowel Disease Service Blacktown HospitalWestern Sydney Local Health DistrictBlacktown 2148New South WalesAustria

BACKGROUND Little is known about the safety and efficacy of using two or more biologics for the treatment of immune-mediated diseases,including Crohn’s disease(CD).CASE SUMMARY This case report and narrative review demonstrate the potential safety of dual biologic therapy(DBT)in a 45-year-old female with two separate immunemediated diseases.She had a history of multiple sclerosis for which she was receiving treatment with ocrelizumab,and she had been recently diagnosed with CD after presenting with diarrhoea.The CD diagnosis was confirmed radiologically,endoscopically,histologically,and biochemically.The patient received treatment with vedolizumab,a gut-specific inhibitor of theα4β7 integrin on leukocytes.No adverse reactions were observed for the duration of treatment.The safety of ocrelizumab and vedolizumab for the treatment of different immune-mediated diseases was demonstrated.CONCLUSION DBT may be a safe and effective option for the treatment of refractory disease or multiple immunemediated diseases.Newer biologics,which have improved safety profiles and gut specificity,may provide promising avenues for treatment.However,caution must be exercised in the appropriate selection of biologics given their inherent immunosuppressive properties,side effects,and efficacy profiles.Current evidence suggests that biologic therapy is not associated with a worse prognosis in patients with coronavirus disease 2019,but treatment decisions should be made in a multidisciplinary setting.Further research from controlled trials is needed to better understand the safety profile of DBT in CD.The immunopathological mechanisms underlying DBT also remain to be clarified.

关键词： Dual biologic therapy Combination Immunosuppression Safety Autoimmune Case report

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Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists

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world Journal of Gastroenterology 2023年第2期29卷 378-389页

作者： Aviv Pudipeddi Caroline Fung Britt Christensen Robert V Bryant Kavitha Subramaniam John Chetwood Sudarshan Paramsothy rupert w leong Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139Australia Faculty of Medicine and Health Concord Clinical SchoolUniversity of SydneySydney 2138Australia Department of Anatomical Pathology Concord Repatriation General HospitalSydney 2139Australia Department of Gastroenterology Royal Melbourne HospitalMelbourne 3050Australia Department of Medicine University of MelbourneMelbourne 3052Australia Department of Gastroenterology and Hepatology The Queen Elizabeth HospitalAdelaide 5011Australia Gastroenterology and Hepatology Unit Canberra HospitalCanberra 2605Australia Australian National University Medical School Australian National UniversityCanberra 2601Australia Faculty of Medicine and Health Sciences Macquarie University HospitalSydney 2109Australia

BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis(UC).However,the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.METHODS A prospective,cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted.The survey consisted of 34 questions to assess gastroenterologists’and pathologists’knowledge(score out of 19)and attitudes towards histological assessment in UC.Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines.It included knowledge of histological assessment of disease activity and dysplasia,knowledge of histological scoring systems for ulcerative colitis,uptake of histology scoring systems in routine practice,attitudes towards the role of histological activity,and the use of histological activity in clinical scenarios.RESULTS Of 89 responders(77 gastroenterologists,12 pathologists),there was almost universal acceptance that histological assessment should form part of UC evaluation[95%gastroenterologists,92%pathologists].However,gastroenterologists reported that 92%of their pathologists do not use a histological scoring system.Utilisation of a formal histological scoring system was preferred by 77%of gastroenterologists and 58%of pathologists.Both groups lacked awareness of the Geboes Score,Nancy Index and Robarts Histopathological Index scoring systems with 91%,87%,and 92%of gastroenterologists respectively;and 83%,83%,and 92%pathologists respectively,being uncertain of scoring systems’remission definitions.Histology knowledge score was not significantly different between gastroenterologists and pathologists[9/19(IQR:8-11)vs 8/19(IQR:7-1

关键词： Histology Scoring system Ulcerative colitis Survey

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Faecal microbiota transplantation as an elixir of youth

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 488-489页

作者： Craig Haifer Sudarshan Paramsothy rupert w.leong Concord Clinical School The University of SydneySydneyAustralia Gastroenterology and Liver Services Concord Repatriation General HospitalSydneyAustralia South western Clinical School UNSWSydneyAustralia

The intestinal microbiota has been increasingly seen to be responsible for various gastrointestinal disorders such as inflammatory bowel diseases(1).However,their effects on systemic physiological processes unrelated ... 详细信息

关键词： diseases gastrointestinal unrelated

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Epidemiology of inflammatory bowel disease in South America: A systematic review

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world Journal of Gastroenterology 2019年第47期25卷 6866-6875页

作者： Sriharan Selvaratnam Santiago Gullino Lisa Shim Eric Lee Alice Lee Sudarshan Paramsothy rupert w leong Department of Gastroenterology and Hepatology Macquarie University Hospital

BACKGROUND The worldwide epidemiology of inflammatory bowel disease(IBD)is rapidly changing.Increasing Crohn’s disease(CD)and ulcerative colitis(UC)incidence and prevalence have been recorded in developing regions such as Asia,Africa and Eastern Europe where it was previously thought to be uncommon.whether this is also the case in South America is not well known.Demonstration that developing regions worldwide have increasing IBD incidence would indicate that environmental change plays a significant role in the development of IBD.AIM To report the incidence,prevalence and disease characteristics of CD and UC within the South American continent.METHODS A systematic review was conducted by searching published studies in major international and regional databases(MEDLINE,EMBASE and Scopus)between January 1990 and December 2018.Outcomes considered were incidence,prevalence,phenotype,environmental and genetic factors,ethnicity and gender.A pair of independent reviewers screened and reviewed all identified articles.RESULTS One hundred and sixty two citations were initially retrieved with 18 studies included in this systematic review.The majority of included studies were from Brazil(n=13,72%).The incidence of UC ranged from 4.3-5.3/100000 personyears whilst the incidence of CD ranged from 0.74-3.5/100000 person-years.Prevalence ranged from 15.0-24.1/100000 inhabitants for UC and from 2.4-14.1/100000 inhabitants for CD.The incidence and prevalence of both UC and CD has increased significantly in Brazil over the past 21 years.Pancolitis was the most common disease distribution in patients with UC whilst colonic involvement was the most common distribution in CD.People residing in urban areas were at higher risk of developing both CD and UC.CONCLUSION The IBD burden in South America is increasing at a rate possibly even greater than other developing regions around the world.There is a paucity of highquality epidemiological studies and further robust and representative data are required to further explore modifiable risk fac

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis South America Epidemiology

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Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases

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world Journal of Gastroenterology 2014年第5期20卷 1238-1247页

作者： Yanna Ko Rhys Butcher rupert w leong Concord Hospital Gastroenterology and Liver Services and The University of New South Wales

Inflammatory bowel diseases(IBD)are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk factors.Permissive genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory studies.Exploring differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of IBD.There are few opportunities that have been offered so far.we aim to review the available migration studies on IBD,evaluate the known environmental factors associated with IBD,and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.

关键词： Inflammatory bowel disease Crohn’s dis-ease Ulcera

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Current application of proteomics in biomarker discoveryfor inflammatory bowel disease

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world Journal of Gastrointestinal Pathophysiology 2016年第1期7卷 27-37页

作者： Patrick PY Chan Valerie C wasinger rupert w leong Bioanalytical Mass Spectrometry Facility Mark Wainwright Analytical Centrethe University of NSW AustraliaKensingtonNSW 2052Australia Gastroenterology and Liver Services Concord Repatriation General HospitalConcordNSW 2137Australia

Recently, the field of proteomics has rapidly expanded in its application towards clinical research with objectives ranging from elucidating disease pathogenesis to discovering clinical biomarkers. As proteins govern and/or reflect underlying cellular processes, the study of proteomics provides an attractive avenue for research as it allows for the rapid identification of protein profiles in a biological sample. Inflammatory bowel disease(IBD) encompasses several heterogeneous and chronic conditions of the gastrointestinal tract. Proteomic technology provides a powerful means of addressing major challenges in IBD today, especially for identifying biomarkers to improve its diagnosis and management. This review will examine the current state of IBD proteomics research and its use in biomarker research. Furthermore, we also discuss the challenges of translating proteomic research into clinically relevant tools. The potential application of this growing field is enormous and is likely to provide significant insights towards improving our future understanding and management of IBD.

关键词： Proteomics Inflammatory bowel disease Biomarkers Molecular diagnostic techniques Massspectrometry

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Epstein Barr virus-positive mucocutaneous ulcer of thecolon associated Hodgkin lymphoma in Crohn＇s disease

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world Journal of Gastroenterology 2015年第19期21卷 6072-6076页

作者： Neil R Moran Bradley webster Kenneth M Lee Judith Trotman YiuLam Kwan John Napoli rupert w leong Neil R Moran Rupert gW Leong Gastroenterology and Liver Services Concord Repatriation General Hospital Sydney NSW 2137 Australia.

Epstein Barr virus （EBV） positive mucocutaneous ulcers（EBVMCU） form part of a spectrum of EBV-associatedlymphoproliferative disease. They have been reportedin the setting of immunosenescence and iatrogenicimmunosuppression, affecting the oropharyngeal mucosa,skin and gastrointestinal tract （GIT）. Case reports andseries to date suggest a benign natural history respondingto conservative management, particularly in the GIT. wereport an unusual case of EBVMCU in the colon, arisingin the setting of immunosuppression in the treatment ofCrohn＇s disease, with progression to Hodgkin lymphoma18 mo after cessation of infliximab. The patient presentedwith multiple areas of segmental colonic ulceration,histologically showing a polymorphous infiltrate withEBV positive Reed-Sternberg-like cells. A diagnosisof EBVMCU was made. The ulcers failed to regressupon cessation of infliximab and methotrexate for 18mo. Following commencement of prednisolone for herCrohn＇s disease, the patient developed widespreadHodgkin lymphoma which ultimately presented as alife-threatening lower GIT bleed requiring emergencycolectomy. This is the first report of progression ofEBVMCU to Hodgkin lymphoma, in the setting of ongoingiatrogenic immunosuppression and inflammatory boweldisease.

关键词： Epstein Barr virus Mucocutaneous ulcer Hodgkin lymphoma Inflammatory bowel disease Crohn's disease

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The pathogenesis of primary pouchitis following ileal pouch-anal anastomosis: a review of current hypotheses

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Open Journal of Gastroenterology 2011年第2期1卷 7-12页

作者： Sally Bath Christian P. Selinger rupert w.L. leong 不详

Primary pouchitis is a common complication of ileal pouch-anal anastomosis following proctocolectomy in patients treated for ulcerative colitis (UC), but is un-usual for those treated for familial adenomatous polyposis (FAP). while a number of theories as to the pathogenesis of this inflammatory condition have been proposed, no single one has been wholly satis-factory. Much research has been devoted to investi-gating a link between the pathogenic factors involved in UC, but not FAP, and those underlying pouchitis. The contribution of sulfate-producing bacteria has also been explored. The role of other intraluminal factors, such as short chain fatty acids and unconju-gated bile salts, has also been investigated. A unifying theory of a multi-step process might explain the pathogenesis of pouchitis, but further research is re-quired to proof causation. It is likely that pouchitis develops as a result of a combination of genetic, im-munological, microbial and metabolic factors. Future insight into the causes of pouchitis may eventually allow for the development of more effective treat-ments.

关键词： Pouchitis Ileo-pouch Anal Anastomosis Pathogenesis

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No generality in biodiversity-productivity relationships along elevation in temperate and subtropical forest landscapes

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Forest Ecosystems 2024年第3期11卷 255-265页

作者： Jiayun Zou Yahuang Luo rupert Seidl Dominik Thom Jie Liu Lisa Geres Tobias Richter Linjiang Ye wei Zheng Liangliang Ma Jie Song Kun Xu Dezhu Li Lianming Gao Sebastian Seibold Ecosystem Dynamics and Forest Management Research Group School of Life SciencesTechnical University of MunichHans-Carl-von-Carlowitz-Platz 285354FreisingGermany State Key Laboratory of Plant Diversity and Specialty Crops Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Germplasm Bank of wild Species Kunming Institute of BotanyChinese Academy of SciencesKunming650201YunnanChina Lijiang Forest Biodiversity National Observation and Research Station Kunming Institute of BotanyChinese Academy of SciencesLijiang674100China Berchtesgaden National Park Doktorberg 683471Germany Gund Institute for Environment University of Vermont617 Main StreetBurlingtonVT 1105405USA Faculty of Biological Sciences Institute for EcologyEvolution and DiversityConservation BiologyGoethe University FrankfurtFrankfurt am MainGermany University of Chinese Academy of Sciences Beijing10049China TUD Dresden University of Technology Forest ZoologyPienner Str.701737TharandtGermany

An improved understanding of biodiversity-productivity relationships(BPRs)along environmental gradients is crucial for effective ecosystem management and biodiversity conservation.The stress-gradient hypothesis suggests that BPRs are stronger in stressful environments compared to more favorable conditions.However,there is limited knowledge regarding the variation of BPRs along elevational gradients and their generality across different landscapes.To study how BPRs change with elevation,we harnessed inventory data on 6,431 trees from152 plots surveyed twice in eight to ten year intervals in mountain forests of temperate Europe and subtropical Asia.we quantified the relationship between aboveground productivity and different biodiversity measures,including taxonomic,functional,and phylogenetic diversity.To elucidate the processes underlying BPRs,we studied the variation of different functional traits along elevation across landscapes.we found no general pattern of BPRs across landscapes and elevations.Relationships were neutral for all biodiversity measures in temperate forests,and negative for taxonomic and functional diversity in subtropical forests.BPRs were largely congruent between taxonomic,functional and phylogenetic diversity.we found only weak support for the stress-gradient hypothesis,with BPRs turning from negative to positive(effect not significant)close to the tree line in subtropical forests.In temperate forests,however,elevation patterns were strongly modulated by species identity effects as influenced by specific traits.The effect of traits such as community-weighted mean of maximum plant height and wood density on productivity was congruent across landscapes.Our study highlights the context-dependence of BPRs across elevation gradients and landscapes.Species traits are key modulating factors of BPRs and should be considered more explicitly in studies of the functional role of biodiversity.Furthermore,our findings highlight that potential trade-offs between conserving biodiversity and fostering ecos

关键词： Biodiversity-ecosystem functioning Climate mitigation Elevation gradients Forest management Forest productivity Functional traits Nature conservation Phylogenetic diversity

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world Journal of Gastroenterology 2012年第21期18卷 2600-2608页

作者： Christian P Selinger rupert wL leong Simon Lal Department of Gastroenterology Salford Royal HospitalSalford M6 8HD United Kingdom Gastroenterology and Liver Services Sydney Local Health Network Concord HospitalNSW 2139 Sydney Australia Faculty of Medicine The University of New South WalesNSW 2052 Sydney Australia

Inflammatory bowel disease (IBD) affects women of childbearing age and can influence fertility, pregnancy and decisions regarding breastfeeding. women with IBD need to consider the possible course of disease during pregnancy, the benefits and risks associated with medications required for disease management during pregnancy and breastfeeding and the effects of mode of delivery on their disease. when indicated, aminosalicylates and thiopurines can be safely used during pregnancy. Infliximab and Adalimumab are considered probably safe during the first two trimesters. During the third trimester the placenta can be crossed and caution should be applied. Methotrexate is associated with severe teratogenicity due to its folate antagonism and is strictly contraindicated. women with IBD tend to deliver earlier than healthy women, but can have a vaginal delivery in most cases. Caesarean sections are generally recommended for women with active perianal disease or after ileo-anal pouch surgery. while the impact of disease activity and medication has been addressed in several studies, there are minimal studies evaluating patients' perspective on these issues. women's attitudes may influence their decision to have children and can positively or negatively influence the chance of conceiving, and their beliefs regarding therapies may impact on the course of their disease during pregnancy and/or breastfeeding. This review article outlines the impact of IBD and its treatment on pregnancy, and examines the available data on patients' views on this subject.

关键词：怀孕期间鸡传染性法氏囊病回肠炎症基础证据安全使用氨基水杨酸

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