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Dual inhibition of sirtuins 1 and 2:reprogramming metabolic energy dynamics in chronicmyeloid leukemia as an immunogenic anticancer strategy

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Cancer Communications 2024年第8期44卷 921-925页

作者： Michael Schnekenburger Anne lorant Sruthi Reddy Gajulapalli Ridhika Rajora Jin-Young Lee Aloran Mazumder Haeun Yang Christo Christov Hyoung Jin Kang Bernard Pirotte Marc Diederich Laboratoire de Biologie Moleculaire et Cellulaire du Cancer LuxembourgLuxembourg Research Institute of Pharmaceutical Sciences&Natural Products Research Institute College of PharmacySeoul National UniversitySeoulRepublic of Korea Faculte de Medecine Universite de LorraineVandoeuvre-les-NancyFrance Department of Pediatrics Seoul National University College of MedicineSeoul National University Cancer Research InstituteSeoul National University Children’s HospitalSeoulRepublic of Korea Laboratory of Medicinal Chemistry Center for Interdisciplinary Research on Medicines(CIRM)University of LiegeLiegeBelgium

Chronicmyeloid leukemia(CML)is a lethal hematopoietic malignancy with a global incidence primarily attributed to the breakpoint cluster region-Abelson(BCR-ABL1)fusion oncogene in over 95%of *** introduction of tyrosine kinase inhibitors(TKIs)has revolutionized CML management;however,a subset of patients encounters challenges such as resistance and relapse,hindering the achievement of complete *** these challenges in CML also requires addressing persistent leukemia stem cells(LSCs)with inherent resistance *** regulators of LSC metabolism,proliferation,and survival,as well as genetic and epigenetic alterations,provide potential targets[1].

关键词： metabolism myeloid alterations

Disease monitoring strategies in inflammatory bowel diseases: What do we mean by “tight control”?

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World Journal of Gastroenterology 2019年第41期25卷 6172-6189页

作者： lorant Gonczi Talat Bessissow Peter Laszlo Lakatos First Department of Medicine Semmelweis UniversityBudapest H-1083Hungary Division of Gastroenterology McGill University Health CentreMontreal H3G 1A4QuebecCanada

In recent years,there has been a critical change in treatment paradigms in inflammatory bowel diseases(IBD)triggered by the arrival of new effective treatments aiming to prevent disease progression,bowel damage and *** insufficiency of symptomatic disease control and the well-known discordance between symptoms and objective measures of disease activity lead to the need of reviewing conventional treatment algorithms and developing new concepts of optimal therapeutic *** treat-to-target strategies,defined by the selecting therapeutic targets in inflammatory bowel disease consensus recommendation,move away from only symptomatic disease control and support targeting composite therapeutic endpoints(clinical and endoscopical remission)and timely *** data suggest that early therapy using a treat-to-target approach and an algorithmic therapy escalation using regular disease monitoring by clinical and biochemical markers(fecal calprotectin and C-reactive protein)leads to improved *** review aims to present the emerging strategies and supporting evidence in the current therapeutic paradigm of IBD including the concepts of“early intervention”,“treat-to-target”and“tight control”*** also discuss the real-word experience and applicability of these new strategies and give an overview on the future perspectives and areas in need of further research and potential improvement regarding treatment targets and(“tight”)disease monitoring strategies.

关键词： Crohn’s disease Ulcerative colitis Treat-to-target Tight control Monitorting Biomarker

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

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

Therapeutic drug monitoring in inflammatory bowel disease:The dawn of reactive monitoring

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World Journal of Gastroenterology 2021年第37期27卷 6231-6247页

作者： Farah Albader Petra Anna Golovics lorant Gonczi Talat Bessissow Waqqas Afif Peter Laszlo Lakatos Department of Internal Medicine McGill UniversityMontreal H3G1A4QuebecCanada Division of Gastroenterology Hungarian Defence ForcesMedical CentreBudapest H-1062Hungar Division of Gastroenterology McGill UniversityMontreal H3G 1A4QuebecCanada First Department of Medicine Semmelweis UniversityBudapest H-1083Hungary Division of Gastroenterology McGill University Health CentreMontreal H3G 1A4QuebecCanada

Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its *** drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution,there remains a proportion of patients that do not respond or lose response to *** drug monitoring(TDM)involves measuring levels of serum drug concentrations and anti-drug *** of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory *** was then introduced in IBD to rationalize primary non-response or secondary loss of response,given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment *** aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment *** review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations,in everyday practice.A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management,through an electronic search using PubMed and *** has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in *** a trend towards an association between clinical outcomes and drug concentrations,proactive TDM based strategies have not been shown to achieve clear benefit in long-term *** the clinical setting,TDM has proven to be useful in managing IBD patients,and its use in the reactive setting,as an additional tool to help manage patients with treatment failure,is being promoted as newer guidelines and consensus groups implement

关键词： Therapeutic drug monitoring Inflammatory bowel disease Biologic therapies Loss of response Reactive Proactive

Benefits of implementing a rapid access clinic in a high-volume inflammatory bowel disease center:Access, resource utilization and outcomes

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World Journal of Gastroenterology 2020年第7期26卷 759-769页

作者： Sofia Nene lorant Gonczi Zsuzsanna Kurti Isabelle Morin Kelly Chavez Christine Verdon Jason Reinglas Rita Kohen Talat Bessissow Waqqas Afif Gary Wild Ernest Seidman Alain Bitton Peter Laszlo Lakatos Division of Gastroenterology McGill University Health CentreQuebecMontreal H3G1A4Canada First Department of Medicine Semmelweis UniversityBudapest H-1083Hungary

BACKGROUND Emergency situations in inflammatory bowel diseases(IBD)put significant burden on both the patient and the healthcare *** To prospectively measure Quality-of-Care indicators and resource utilization after the implementation of the new rapid access clinic service(RAC)at a tertiary IBD *** Patient access,resource utilization and outcome parameters were collected from consecutive patients contacting the RAC between July 2017 and March 2019 in this observational *** comparing resource utilization and healthcare costs,emergency department(ED)visits of IBD patients with no access to RAC services were evaluated between January 2018 and January *** to appointment,diagnostic methods,change in medical therapy,unplanned ED visits,hospitalizations and surgical admissions were calculated and *** 488 patients(Crohn’s disease:68.4%/ulcerative colitis:31.6%)contacted the RAC with a valid medical *** time to visit with an IBD specialist following the index contact was 2 *** had objective clinical and laboratory assessment(C-reactive protein and fecal calprotectin in 91%and 73%).Fast-track colonoscopy/sigmoidoscopy was performed in 24.6%of the patients,while computed tomography/magnetic resonance imaging in only 8.1%.Medical therapy was changed in 54.4%.ED visits within 30 d following the RAC visit occurred in 8.8%(unplanned ED visit rate:5.9%).Diagnostic procedures and resource utilization at the ED(n=135 patients)were substantially different compared to RAC users:Abdominal computed tomography was more frequent(65.7%,P<0.001),coupled with multiple specialist consults,more frequent hospital admission(P<0.001),higher steroid initiation(P<0.001).Average medical cost estimates of diagnostic procedures and services per patient was$403 CAD vs$1885 CAD comparing all RAC and ED *** Implementation of a RAC improved patient care by facilitating easier access to IBD specific medical care,optimized resource uti

关键词： Crohn’s disease Ulcerative colitis Rapid access Quality-of-care Emergency department

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林肯传

林肯传

作者： S.·洛伦特(S. lorant)

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奥斯本全自动造型线

中国铸造装备与技术 1966年第6期 32-34页

作者： M.lorant 朱奕庆

美国奥斯本(Osborn)制造公司新造了一条砂箱连续周转的全自动造型线。用了这种高度专门化的生产方法,铸造工业就能达到像加工工业已很普遍的相类似的高度自动化程度。下面要详细叙述的这条造型线安装在美国俄亥俄州克利夫兰的欧勃哈特(E... 详细信息

美国奥斯本(Osborn)制造公司新造了一条砂箱连续周转的全自动造型线。用了这种高度专门化的生产方法,铸造工业就能达到像加工工业已很普遍的相类似的高度自动化程度。下面要详细叙述的这条造型线安装在美国俄亥俄州克利夫兰的欧勃哈特(Eberhard)制造公司的可锻铸铁车间中。这整套装置中的核心部分是一台在铸件重30克至1.1公斤时每小时生产300个铸型的奥斯本自动造型机,在这种情况下每秒要生产1至

关键词：砂箱工位落砂长度辊道自动造型机造型线铸模铸型奥斯本输送小车起模

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林肯传 2版（修订版）