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World Journal of Gastroenterology 2014年第10期20卷 2564-2577页

作者： Nora Sipeki peter Antal-Szalmas peter l lakatos Maria Papp Institute of Medicine Department of Gastroenterology University of Debrecen H-4032 DebrecenHungary Department of laboratory Medicine University of Debrecen H-4032 Debrecen Hungary 1st Department of Medicine Semmelweis University H-1083 Budapest Hungary

Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver *** the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology *** bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical *** and chronic exposure to bacteria and/or their products,however,can result in variable clinical *** immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic *** this review we give a detailed overview of acquired immune dysfunction and its consequences for *** demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory ***,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver *** and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.

关键词： Cirrhosis Immune dysfunction Endotoxemia

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Mucosal healing and deep remission: What does it mean?

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World Journal of Gastroenterology 2013年第43期19卷 7552-7560页

作者： Gerhard Rogler Stephan Vavricka Alain Schoepfer peter l lakatos Division of Gastroenterology and Hepatology Department of Internal MedicineUniversity Hospital Zürich8091 ZürichSwitzerland Zurich Center for Integrative Human Physiology University of Zurich8006 ZürichSwitzerland Gastroenterology Triemli Spital8063 ZürichSwitzerland Division of Gastroenterology and Hepatology Centre Hospitalier Universitaire Vaudois et Université de Lausanne1011 LausanneSwitzerland Division of Gastroenterology and Hepatology 1st Department of MedicineSemmelweis UniversityH1083 BudapestHungary

The use of specific terms under different meanings and varying definitions has always been a source of confusion in *** we point our efforts towards an evidence based medicine for inflammatory bowel diseases(IBD)the same is true:Terms such as"mucosal healing"or"deep remission"as endpoints in clinical trials or treatment goals in daily patient care may contribute to misconceptions if meanings change over time or definitions are *** appears to be useful to first have a look at the development of terms and their definitions,to assess their intrinsic and context-independent problems and then to analyze the different relevance in present-day clinical studies and *** purpose of such an attempt would be to gain clearer insights into the true impact of the clinical findings behind the *** may also lead to a better defined use of those terms for future *** terms"mucosal healing"and"deep remission"have been introduced in recent years as new therapeutic targets in the treatment of IBD *** clinical trials,cohort studies or inception cohorts provided data that the long term disease course is better,when mucosal healing is ***,it is still unclear whether continued or increased therapeutic measures will aid or improve mucosal healing for patients in clinical *** trials are under way to answer this *** should be paid to clearly address what levels of IBD activity are looked *** the present review article authors aim to summarize the current evidence available on mucosal healing and deep remission and try to highlight their value and position in the everyday decision making for gastroenterologists.

关键词： Inflammatory bowel disease Mucosal healing Deep remission Treatment targets Clinical activity

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Positioning of old and new biologicals and small molecules in the treatment of inflammatory bowel diseases

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World Journal of Gastroenterology 2018年第32期24卷 3567-3582页

作者： Jason Reinglas lorant Gonczi Zsuzsanna Kurt Talat Bessissow peter l lakatos Department of Gastroenterology McGill University Health CenterMontrealQuébec H4A 3J1Canada First Department of Medicine Semmelweis UniversityH-1083BudapestKoranyi S.2AHungary

The past decade has brought substantial advances in the management of inflammatory bowel diseases(IBD). The introduction of tumor necrosis factor(TNF) antagonists, evidence for the value of combination therapy, the recog-nition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The thera-peutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn's disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older' anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severityand response to therapy.

关键词： Inflammatory bowel disease Small molecule Positioning Biologic Therapeutic

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Quality of care in inflammatory bowel diseases: What is the best way to better outcomes?

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World Journal of Gastroenterology 2018年第22期24卷 2363-2372页

作者： Matthew Strohl lorant Gonczi Zsuzsanna Kurt Talat Bessissow peter l lakatos Division of Gastroenterology McGill University Health Center First Department of Medicine Semmelweis University

Inflammatory bowel disease(IBD) is a lifelong, progres-sive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large economic burden seen across all health care systems. Quality in-dicators(QI) have been created to assess the different fa?ades of disease management including structure, process and outcome components. Their development serves to provide a means to target and measure quality of care(Qo C). Multiple different QI sets have been published in IBD, but all serve the same purpose of trying to achieve a standard of care that can be attained on a national and international level, since there is still a major variation in clinical practice. There have been many recent innovative developments that aim to improve Qo C in IBD including telemedicine, home biomarker assessment and rapid access clinics. These are some of the novel advancements that have been shown to have great potential at improving Qo C, while offloading some of the burden that IBD can have vis-a-vis emergency room visits and hospital admissions. The aim of the current review is to summarize and discuss available QI sets and recent developments in IBD care including telemedicine, and to give insight into how the utilization of these tools could benefit the Qo C of IBD patients. Additionally, a treating-to-target structure as well as evidence surrounding aggressive management directed at tighter disease control will be presented.

关键词： Inflammatory bowel disease Telemedicine Quality indicators Quality of care Treat-to-target

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Inflammatory bowel disease course in Crohn's disease:Is the natural history changing?

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World Journal of Gastroenterology 2014年第12期20卷 3198-3207页

作者： Petra A Golovics Michael D Mandel Barbara D lovasz peter l lakatos First Department of Medicine Semmelweis University

Crohn’s disease (CD) is a multifactorial potentially debilitating disease. It has a variable disease course, but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability. Studies on the natural history of CD provide invaluable data on its course and clinical predictors, and may help to identify patient subsets based on clinical phenotype. Most data are available from referral centers, however these outcomes may be different from those in population-based cohorts. New data suggest the possibility of a change in the natural history in Crohn’s disease, with an increasing percentage of patients diagnosed with inflammatory disease behavior. Hospitalization rates remain high, while surgery rates seem to have decreased in the last decade. In addition, mortality rates still exceed that of the general population. The impact of changes in treatment strategy, including increased, earlier use of immunosuppressives, biological therapy, and patient monitoring on the natural history of the disease are still conflictive. In this review article, the authors summarize the available evidence on the natural history, current trends, and predictive factors for evaluating the disease course of CD.

关键词： Crohn’ s disease, Natural history, Surgery, Mortality, Disease course, Inflammatory bowel disease

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Endoscopic management of Crohn's strictures

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World Journal of Gastroenterology 2018年第17期24卷 1859-1867页

作者： Talat Bessissow Jason Reinglas Achuthan Aruljothy peter l lakatos Gert Van Assche Division of Gastroenterology Department of Medicine McGill University Health Center 1~(st) Department of Medicine Semmelweis University Division of Gastroenterology and Hepatology University Hospitals Leuven Belgium and University of Leuven

Symptomatic intestinal strictures develop in more than one third of patients with Crohn's disease(CD) within 10 years of disease onset. Strictures can be inflammatory, fibrotic or mixed and result in a significant decline in quality of life, frequently requiring surgery for palliation of symptoms. Patients under the age of 40 with perianal disease are more likely to suffer from disabling ileocolonic disease thus may have a greater risk for fibrostenotic strictures. Treatment options for fibrostenotic strictures are limited to endoscopic and surgical therapy. Endoscopic balloon dilatation(EBD) appears to be a safe, less invasive and effective alternative modality to replace or defer surgery. Serious complications are rare and occur in less than 3% of procedures. For non-complex strictures without adjacent fistulizaation or perforation that are less than 5 cm in length, EBD should be considered as first-line therapy. The aim of this review is to present the current literature on the endoscopic management of small bowel and colonic strictures in CD, which includes balloon dilatation, adjuvant techniques of intralesional injection of steroids and anti-tumor necrosis factor, and metal stent insertion. Short and long-term outcomes, complications and safety of EBD will be discussed.

关键词： Endoscopy Crohn’s disease Stricture Stenosis Inflammatory bowel disease Endoscopic balloon dilation

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Elderly patients with inflammatory bowel disease: Updated review of the therapeutic landscape

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World Journal of Gastroenterology 2019年第30期25卷 4158-4171页

作者： Jean-Frédéric leBlanc Daniel Wiseman peter l lakatos Talat Bessissow Department of Adult Gastroenterology McGill University Health CentreMontrealQC H3G 1A4Canada Department of Medicine McGill University Health CentreMontrealQC H3G 1A4Canada 1^st Department of Medicine Semmelweis UniversityBudapest 1083Hungary

High-quality data remains scarce in terms of optimal management strategies in the elderly inflammatory bowel disease(IBD)***,available trials have been mostly retrospective,of small sample size,likely owing to underrepresentation of such a population in the major randomized controlled ***,in the last five years,there has been a steady increase in the number of published trials,helping clarify the estimated benefits and toxicity of the existing IBD *** the Everhov trial,prescription strategies were recorded over an average follow-up of 4.2 years.A minority of elderly IBD patients(1%-3%)were treated with biologics within the five years following diagnosis,whilst almost a quarter of these patients were receiving corticosteroid therapy at year five of follow-up,despite its multiple *** low use of biologic agents in real-life settings likely stems from limited data suggesting lower efficacy and higher *** minireview will aim to highlight current outcome measurements as it portends the elderly IBD patient,as well as summarize the available therapeutic strategies in view of a growing body of evidence.

关键词： Inflammatory bowel disease Elderly Outcomes Glucocorticoids Biological therapy Surgery

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Prevalence, significance and predictive value of antiphospholipid antibodies in Crohn's disease

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World Journal of Gastroenterology 2015年第22期21卷 6952-6964页

作者： Nora Sipeki laszlo Davida Eszter Palyu Istvan Altorjay Jolan Harsfalvi peter Antal Szalmas Zoltan Szabo Gabor Veres Zakera Shums Gary l Norman peter l lakatos Maria Papp Division of Gastroenterology Department of Internal Medicine Faculty of Medicine University of Debrecen Clinical Research Center Faculty of MedicineUniversity of Debrecen Department of laboratory Medicine Faculty of Medicine University of Debrecen Division of Emergency Medicine Department of Internal Medicine Faculty of Medicine University of Debrecen 1~(st) Department of Medicine Semmelweis University Inova Diagnostics Inc. San Diego California

AIM: To assess the prevalence and stability of different antiphospholipid antibodies(APlAs) and their association with disease phenotype and progression in inflammatory bowel diseases(IBD) ***: About 458 consecutive patients [Crohn's disease(CD): 271 and ulcerative colitis(UC): 187] were enrolled into a follow-up cohort study in a tertiary IBD referral center in Hungary. Detailed clinical phenotypes were determined at enrollment by reviewing the patients' medical charts. Disease activity, medical treatment and data about evolvement of complications or surgical interventions were determined prospectively during the follow-up. Disease course(development f complicated disease phenotype and need for surgery),occurrence of thrombotic events, actual state of diseaseactivity according to clinical, laboratory and endoscopic scores and accurate treatment regime were recorded during the follow-up,(median, 57.4 and 61.6 mo for CD and UC). Sera of IBD patients and 103 healthy controls(HC) were tested on individual anti-β2-Glycoprotein-I(anti-β2-GPI IgA/M/G), anti-cardiolipin(ACA IgA/M/G)and anti-phosphatidylserine/prothrombin(anti-PS/PT IgA/M/G) antibodies and also anti-Saccharomyces cerevisiae antibodies(ASCA IgA/G) by enzyme-linked immunosorbent assay(ElISA). In a subgroup of CD(n = 198) and UC patients(n = 103), obtaining consecutive samples over various arbitrary timepoints during the disease course, we evaluated the intraindividual stability of the APlA status. Additionally,we provide an overview of studies, performed so far, in which significance of APlAs in IBD were ***: Patients with CD had significantly higher prevalence of both ACA(23.4%) and anti-PS/PT(20.4%) antibodies than UC(4.8%, p lence of anti-β2-GPI between different groups(7.2%-9.7%). In CD, no association was found between APlA and ASCA status of the *** of a

关键词： Crohn's disease Ulcerative colitis Diseaseprogression Antiphospholipid antibodies Anti-β2-Glycoprotein-I antibodies Anti-phosphatidylserine/prothrombin Anti-cardiolipin antibodies Thrombosis

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Systematic review and meta-analysis of colon cleansing preparations in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2017年第32期23卷 5994-6002页

作者： Sophie Restellini Omar Kherad Talat Bessissow Charles Ménard Myriam Martel Maryam Taheri Tanjani peter l lakatos Alan N Barkun division of gastroenterology department of medicine mcgill university health center division of internal medicine department of medicine la tour hospital and university of geneva division of gastroenterology department of medicine university of sherbrooke department of family medicine queens universitykingston department of clinical epidemiology mcgill university and the mcgill university health center

AIM To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel *** Systematic searches were performed( January 1980-September 2016) using MEDlINE, EMBASE, Scopus, CENTRAl and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high(> 3 l) or low-volume(2 l or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-torepeat the procedure and side effects/*** Out of 439 citations, 4 trials fulfilled our inclusion criteria(n = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol(PEG) 4 l with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume vs PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84(0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations vs high-volume; OR = 5.11(1.31-20.0). CONClUSION In inflammatory bowel disease population, PEG lowvolume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-torepeat. Further additional research is urgently required to compare contemporary products in this population.

关键词： Inflammatory bowel disease Polyethylene glycol Colonoscopy Meta-analysis

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Access to biologicals in Crohn's disease in ten European countries

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World Journal of Gastroenterology 2017年第34期23卷 6294-6305页

作者： Márta Péntek peter l lakatos Talitha Oorsprong lászló Gulácsi Milena Pavlova Wim Groot Fanni Rencz Valentin Brodszky Petra Baji Crohn’s Disease Research Group department of health economics corvinus university of budapest mcgill university muhcmontreal general hospital 1st department of internal medicine semmelweis university department of health services research caphrimaastricht university medical centrefaculty of healthmedicine and life sciencesmaastricht university top institute evidence based education research (tier) teachers academymaastricht university 不详

AIM To analyze access(availability, affordability and acceptability) to biologicals for Crohn's disease(CD) in ten European countries and to explore the associations between these dimensions, the uptake of biologicals and economic *** A questionnaire-based survey combined with desk research was carried out in May 2016. Gastroenterologists from the Czech Republic, France, Germany, Hungary, latvia, Poland, Romania, Slovakia, Spain and Sweden were invited to participate and provide data on the availability of biologicals/biosimilars, reimbursement criteria, clinical practice and prices, and use of biologicals. An availability score was developed to evaluate the restrictiveness of eligibility and administrative criteria applied in the countries. Affordability was defined as the annual cost of treatment as a share of gross domestic product(GDP) per capita. Correlations with the uptake of biologicals, dimensions of access and GDP per capita were *** At the time of the survey, infliximab and adalimumab were reimbursed in all ten countries, and vedolizumab was reimbursed in five countries(France, Germany, latvia, Slovakia, Sweden). Reimbursement criteria were the least strict in Sweden and Germany, and the strictest in Hungary, Poland and Slovakia. Between countries, the annual cost of different biological treatments differed 1.6-3.3-fold. Treatments were the most affordable in Sweden(13%-37% of the GDP per capita) and the least affordable in the Central and Eastern European countries, especially in Hungary(87%-124%) and Romania(141%-277%). Biosimilars made treatments more affordable by driving down the annual costs. The number of patients with CD on biologicals per 100000 population was strongly correlated with GDP per capita(0.91), although substantial differences were found in the uptake among countries with similar economic development. Correlation between the number of patients with CD on biologicals per 100000 population and the availabi

关键词： Crohn’s disease Biological therapy Access Inequality Europe

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