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Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara Vodicska Júlia déri dóra Tihanyi Edit Várkondi EnikőKispéter Róbert dóczi dóra lakatos Anna dirner Mátyás Vidermann Péter Filotás Réka Szalkai-dénes István Szegedi Katalin Bartyik Krisztina Míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss Miklós Garami István Peták Oncompass Medicine Hungary Kft Retek Str.34Budapest 1024Hungary division of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology department Velkey LászlóPaediatric Health CentreMiskolcHungary department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology department Heim Pál Children’s HospitalBudapestHungary department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(ddA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of ddA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(d in our precision oncology program,and samples from 100 patients were eligible for further *** or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the ddA algorithm for therapeutic decision ***,a molecular tumor board(MTB)evaluated the results to provide therapy *** Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the evidence *** approved the clinical use of a ddA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** ddA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

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Risk for colorectal cancer in ulcerative colitis:Changes,causes and management strategies

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World Journal of Gastroenterology 2008年第25期14卷 3937-3947页

作者： Peter Laszlo lakatos Laszlo lakatos 1st department of Medicine Semmelweis University 1st department of Medicine Csolnoky F. County Hospital

The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in-clude extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflam-mation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epide-miological trends and causes for the observed chang-es. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

关键词： Ulcerative colitis Colorectal cancer Riskfactors Surveillance Chemprevention

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Prediction of disease course in inflammatory bowel diseases

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World Journal of Gastroenterology 2010年第21期16卷 2589-2590页

作者： Peter Laszlo lakatos 1st department of Medicine Semmelweis UniversityH-1083 BudapestKoranyi S 2AHungary

Clinical presentation at diagnosis and disease course of both Crohn's disease(Cd) and ulcerative colitis are heterogeneous and variable over *** most patients have a relapsing course and most Cd patients develop complications(*** and/or perforation),much emphasis has been placed in the recent years on the determination of important predictive *** identification of these factors may eventually lead to a more personalized,tailored *** this TOPIC HIGHLIGHT series,we provide an update on the available literature regarding important clinical,endoscopic,fecal,serological/routine laboratory and genetic *** aim is to assist clinicians in the everyday practical decisionmaking when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis disease course Predictive markers Clinical Serology Genetics

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Prevalence,predictors,and clinical consequences of medical adherence in IBd:How to improve it?

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World Journal of Gastroenterology 2009年第34期15卷 4234-4239页

作者： Peter Laszlo lakatos 1st department of Medicine Semmelweis University

Inflammatory bowel diseases(IBd)are chronic diseases with a relapsing-remitting disease course necessitating lifelong ***,non-adherence has been reported in over 40%of patients,especially those in remission taking maintenance therapies for IBd. The economical impact of non-adherence to medical therapy including absenteeism,hospitalization risk, and the health care costs in chronic conditions,is *** causes of medication non-adherence are complex,where the patient-doctor relationship, treatment regimen,and other disease-related factors play key ***,subjective assessment might underestimate *** adherence may result in more frequent relapses,a disabling disease course, in ulcerative colitis,and an increased risk for colorectal *** medication adherence in patients is an important challenge for *** the different patient types,the reasons given by patients for non-adherence,simpler and more convenient dosage regimens,dynamic communication within the health care team,a self-management package incorporating enhanced patient education and physician-patient interaction,and identifying the predictors of nonadherence will help devise suitable plans to optimize patient *** editorial summarizes the available literature on frequency,predictors,clinical consequences,and strategies for improving medical adherence in patients with IBd.

关键词： Inflammatory bowel disease Crohn's disease Ulcerative colitis Therapy Adherence Compliance 5-aminosalicylate Mesalazine Azathioprine

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Smoking in inflammatory bowel diseases:Good,bad or ugly?

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World Journal of Gastroenterology 2007年第46期13卷 6134-6139页

作者： Peter Laszlo lakatos Tamas Szamosi Laszlo lakatos department of Medicine Semmelweis UniversityBudapestHungary department of Medicine Csolnoky F.County HospitalVeszpremHungary

Smoking is an important environmental factor in inflammatory bowel disease （IBd）, having different effects in ulcerative colitis （UC） and Crohn＇s disease （Cd）. A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing Crohn＇s disease and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves Crohn＇s disease. data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases.

关键词： Smoking Crohn's disease Ulcerative colitis Phenotype

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Use of new once-daily 5-aminosalicylic acid preparations in the treatment of ulcerative colitis:Is there anything new under the sun?

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World Journal of Gastroenterology 2009年第15期15卷 1799-1804页

作者： Peter Laszlo lakatos 1st department of Medicine Semmelweis University

5-aminosalicylate(5-ASA)agents remain the mainstay treatment in ulcerative colitis(UC).A number of oral 5-ASA agents are commercially available,including azobond pro-drugs,as well as delayed-and controlledrelease forms of ***,poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with ***, new,once-daily formulations of mesalazine,including the unique multi-matrix delivery system and mesalazine granules,were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC,with a good safety profile comparable to that of other oral mesalazine *** addition,they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical *** editorial summarizes the available literature on the short-and medium-term efficacy and safety of the new once-daily mesalazine formulations.

关键词： Ulcerative colitis 5-aminosalicylate Mesalazine Multi matrix system Therapy Once-daily Compliance

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Recent trends in the epidemiology of inflammatory bowel diseases:Up or down?

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World Journal of Gastroenterology 2006年第38期12卷 6102-6108页

作者： Peter Laszlo lakatos 1~(st) department of Medicine Semmelweis University Budapest Hungary

Inflammatory bowel disease (IBd) is traditionally con- sidered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBd with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemio- logic studies are needed to better define the burden of illness, explore the mechanism of association with envi- ronmental factors, and identify new risk factors.

关键词： Inflammatory bowel diseases Ulcerative colitis Crohn's disease Incidence Epidemiology

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Current concept on the pathogenesis of inflammatory bowel disease-crosstalk between genetic and microbial factors:Pathogenic bacteria and altered bacterial sensing or changes in mucosal integrity take"toll"?

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World Journal of Gastroenterology 2006年第12期12卷 1829-1841页

作者： Peter Laszlo lakatos Simon Fischer Janos Papp Laszlo lakatos Istvan Gal department of Medicine Semmelweis UniversityBudapestHungary department of Medicine Csolnoky F.County HospitalVeszpremHungary department of Medicine Kenezi Gy.County HospitalDebrecenHungary

The pathogenesis of inflammatory bowel disease （IBd） is only partially understood. Various environmental and host （e.g. genetic-, epithelial-, immune and nonimmune） factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBd itself, while others increase the risk of ulcerative colitis （UC） or Crohn＇ s disease （Cd） or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBd. The article discusses the current information on the crosstalk between microbial and genetic factors （e.g. NOd2/CARd15, SLC22A46A5 and dLG5）. The genetic data acquired in recent years help in understanding the pathogenesis of IBd and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBd.

关键词： Inflammatory bowel disease Ulcerativecolitis Crohn's disease Pathogenesis Microbial factors Genetics NOd2/CARd15 SLC22A4/A5 dLG5

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State-of-art modelling of inflammatory astrocyte-synapse interactions in injury and amyotrophic lateral sclerosis

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Neural Regeneration Research 2017年第1期12卷 75-76页

作者： András lakatos John van Geest Centre for Brain Repair Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUnited Kingdom department of Neurology Addenbrooke's HospitalCambridge University Hospitals NHS TrustCambridgeUnited Kingdom

different outcomes of astrocyte inflammatory signalling in injury and neurodegeneration：It is emerging that astrocytes have a significant impact on the neuronal network by modulating synaptic connections and neuronal... 详细信息

关键词： astrocyte amyotrophic neuronal synaptic modulating insight viability glutamate inflammation NMdAR

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Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones:Results of a retrospective,single center study between 1996-2002

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World Journal of Gastroenterology 2004年第23期10卷 3495-3499页

作者： Laszlo lakatos Gabor Mester Gyorgy Reti Attila Nagy Peter Laszlo lakatos 1~(st)department of Medicine Csolnoky FProvince HospitalVeszpremH-8200 Hungary department of Surgery Csolnoky FProvince HospitalVeszpremH-8200 Hungary 1~(st)department of Medicine Semmelweis UniversityBudapestH-8200 Hungary

AIM: The optimal treatment for bile duct stones (in terms of cost, complications and accuracy) is unclear. The aim of our study was to determine the predictive factors for preoperative endoscopic retrograde cholangiopancreatography (ERCP).METHOdS: Patients undergoing preoperative ERCP (≤90 d before laparoscopic cholecystectomy) were evaluated in this retrospective study from the 1^st of January 1996 to the 31^st of december 2002. The indications for ERCP were elevated serum bilirubin, elevated liver function tests (LFT), dilated bile duct (≥8 mm) and/or stone at US examination, coexisting acute pancreatitis and/or acute pancreatitis or jaundice in patient's history. Suspected prognostic factors and the combination of factors were compared to the result of ERCRRESULTS: Two hundred and six preoperative ERCPs were performed during the observed period. The rate of successful cannulation for ERC was (97.1%). Bile duct stones were detected in 81 patients (39.3%), and successfully removed in 79 (97.5%). The number of prognostic factors correlated with the presence of bile duct stones. The positive predictive value for one prognostic factor was 1.2%, for two 43%,for three 72.5%, for four or more 91.4%.CONCLUSION: Based on our data preoperative ERCP is highly recommended in patients with three or more positive factors (high risk patients). In contrast, ERCP is not indicated in patients with zero or one factor (low risk patients).Preoperative ERCP should be offered to patients with two positive factors (moderate risk patients), however the practice should also be based on the local conditions (*** of the endoscopist, other diagnostic tools).

关键词： Cholangiopancreatography, Endoscopic Retrograde Cholecystectomy, Laparoscopic Patient Selection Bile ducts Cholelithiasis Female Humans Male Middle Aged Predictive Value of Tests Preoperative Care Retrospective Studies

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