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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(s)were involved 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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Compared efficacy of preservation solutions on the outcome of liver transplantation:Meta-analysis

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World Journal of Gastroenterology 2018年第16期24卷 1812-1824页

作者： Agnes Lilla szilágyi Péter Mátrai Péter Hegyi Eszter Tuboly Daniella Pécz András garami Margit solymár Erika Pétervári Márta Balaskó Gábor Veres László Czopf Bastian Wobbe Dorottya szabó Juliane Wagner Petra Hartmann Institute of surgical Research University of SzegedSzeged H-6720Hungary Institute of Bioanalysis University of PécsPécs H-7624Hungary Institute for Translational Medicine and First Department of Medicine University of PécsPécs H-7624Hungary MTA-sZTE Translational Gastroenterology Research Group Szeged H-6720Hungary János szentágothai Research Center University of PécsPécs H-7624Hungary 1^st Department of Paediatrics University of SemmelweisBudapest H-1085Hungary Department of Cardiology 1^st Department of MedicineUniversity of PécsPécs H-7624Hungary

AIM To compare the effects of the four most commonly used preservation solutions on the outcome of liver *** A systematic literature search was performed using MEDLINE, scopus, EMBAsE and the Cochrane Library databases up to January 31^(st), 2017. The inclusion criteria were comparative, randomized controlled trials(RCTs) for deceased donor liver(DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin(UW) solution or histidinetryptophan-ketoglutarate(HTK), Celsior(Cs) and Institut Georges Lopez(IGL-1) solutions. Fifteen RCTs(1830 livers) were included; the primary outcomes were primary non-function(PNF) and one-year posttransplant graft survival(OGs-1). REsULTs All trials were homogenous with respect to donor and recipient characteristics. There was no statistical difference in the incidence of PNF with the use of UW, HTK, Cs and IGL-1(RR = 0.02, 95%CI: 0.01-0.03, P = 0.356). Comparing OGs-1 also failed to reveal any difference between UW, HTK, Cs and IGL-1(RR = 0.80, 95%CI: 0.80-0.80, P = 0.369). Two trials demonstrated higher PNF levels for UW in comparison with the HTK group, and individual studies described higher rates of biliary complications where HTK and Cs were used compared to the UW and IGL-1 solutions. However, the meta-analysis of the data did not prove a statistically significant difference: the UW, Cs, HTK and IGL-1 solutions were associated with nearly equivalent *** Alternative solutions for UW yield the same degree of safety and effectiveness for the preservation of DDLs, but further well-designed clinical trials are warranted.

关键词： Liver transplantation Preservation solution Primary non-function One-year post-transplant graft survival systematic review Meta-analysis

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急性脑缺血时紧急联合应用颈内动脉/经颅多普勒超声检查的有效性和精确性

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世界核心医学期刊文摘（神经病学分册） 2005年第6期1卷 49-50页

作者： Chernyshev O.Y. garami Z. Callejas. A.V. Alexandrov 雷翀 University of Texas- Houston Department of Neurology MSB 7044 6431 Fannin Street Houston TX 77005 United States Dr.

Background and Purpose - We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). Methods - NVUE was performed with portable carotid duplex and TCD using standardized fast- track (s) insonation protocols. Digital subtraction angiography (DsA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near- occlusions, ≥ 50% stenoses or thrombus in the symptomatic artery. Results - One hundred and fifty patients (70 women, mean age 66± 15 years)- underwent NVUE at median 128 minutes after symptom onset. Fifty- four patients (36% ) received intravenous or intra- arterial thrombolysis (median National Institutes of Health stroke scale (NIHss) score 14, range 4 to 29; 81% had NIHss ≥ 10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), PsA was performed in 30 patients on average 230 minutes after NVUE. Compared with DsA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. Conclusions - Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DsA.

关键词：颈内动脉急性脑缺血血管超声检查脑缺血患者颈动脉超声急性卒中双侧颈动脉超声波检查动脉溶栓金标准

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经颅多普勒超声（TCD）的实践标准——第2部分：临床适应证和预期结果

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国际脑血管病杂志 2012年第1期20卷 1-11页

作者： Andrei V. Alexandrov Michael A. sloan Charles H. Tegeler David N. Newell Alan Lumsden Zsolt garami Christopher R. Levy Lawrence K.s. Wong Colleen Douville Manfred Kaps 李海峰（译）李宏（译）李展秀（译） From the Comprehensive stroke Center University of Alabama at Birmingham Birmingham AL 青岛大学医学院附属医院神经内科

引言：经颅多普勒（transcranial Doppler，TCD）已被证实为一种安全有效的生理学超声检查技术。尽管成像设备可以在结构影像的基础上显示颅内血流，但成像性双功能超声或非成像性TCD检查提供的最终结果是通过频谱波形来评价生理学血流... 详细信息

引言：经颅多普勒（transcranial Doppler，TCD）已被证实为一种安全有效的生理学超声检查技术。尽管成像设备可以在结构影像的基础上显示颅内血流，但成像性双功能超声或非成像性TCD检查提供的最终结果是通过频谱波形来评价生理学血流参数。总结概要：多学科专家小组确定的TCD临床适应证包括：镰状细胞病、恼缺血、右向左分流（right—to—left shunt，RLs）、蛛网膜下腔出血、脑死亡以及围手术期或术中监测。TCD检查可常规应用于住院或门诊患者的一些临床实践活动：通过完整或部分TCD检查以检测正常、狭窄或闭塞的颅内血管和侧支循环来判断动脉闭塞位置，并进一步完善颈动脉超声或无创性血管造影结果；通过血管运动反应性检查来识别首发或复发性卒中的高危患者；通过栓子监测对脑栓塞进行实时检查、定位和量化；在怀疑反常性栓塞或考虑分流封堵术治疗的患者中进行RLs检测；对溶栓治疗进行监测以促进血管再通和检测再闭塞；在血管内支架置入术、颈动脉内膜切除术和心脏外科手术中进行监测以发现围手术期栓塞、血栓形成、低灌注或高灌注。结论：通过界定实践范围，这些标准将在TCD检查的申请、检查和评价过程中给开申请单的医生、发报告的医生以及第三方提供帮助。

关键词： TCD 适应证应用结果

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脑卒中并发急性A型主动脉夹层时实施紧急手术修复是否安全

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世界核心医学期刊文摘(心脏病学分册) 2007年第5期 61-61页

作者： Estrera A.L. garami Z. Miller C.C. 黄浙勇 Department of Cardiothoracic and Vascular surgery The University of Texas-Houston Medical School Memorial Hermann Heart and Vascular InstituteHouston Tex United States

目的:脑卒中并发急性A型主动脉夹层是否进行紧急手术干预尚存在争议;因在这种情况下脑再灌注可能加重神经系统症状。本研究旨在报道和分析关于脑卒中并发急性A型主动脉夹层的经验。方法:1999年9月至2005年3月间共有151例急性A型主动脉... 详细信息

目的:脑卒中并发急性A型主动脉夹层是否进行紧急手术干预尚存在争议;因在这种情况下脑再灌注可能加重神经系统症状。本研究旨在报道和分析关于脑卒中并发急性A型主动脉夹层的经验。方法:1999年9月至2005年3月间共有151例急性A型主动脉夹层患

关键词：主动脉夹层手术修复脑卒中

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