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Immunotherapy of gastric cancer:Present status and future perspectives

World Journal of Gastroenterology 2024年第8期30卷 779-793页

作者： John K Triantafillidis Manousos M Konstadoulakis apostolos e papalois Inflammatory Bowel Disease Unit “Metropolitan General”HospitalHolargos 15562AtticaGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece Second Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528AtticaGreece Unit of Surgical Research and Training Second Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528AtticaGreece

In this editorial,we comment on the article entitled“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review(1999-2023),”which was published in the recent issue of the World Journal of *** focused on the results of the authors’bibliometric analysis concerning gastric cancer immunotherapy,which they analyzed in depth by compiling the relevant publications of the last 20 *** that,we briefly describe the most recent data concerning the epidemiological parameters of gastric cancer(GC)in different countries,attempting to give an interpretation based on the etiological factors involved in the etiopathogenesis of the *** then briefly discuss the conservative treatment(chemotherapy)of the various forms of this malignant *** describe the treatment of resectable tumors,locally advanced neoplasms,and unresectable(advanced)*** attention is given to modern therapeutic approaches with emphasis on immunotherapy,which seems to be the future of GC treatment,especially in combination with *** is also a thorough analysis of the results of the study under review in terms of the number of scientific publications,the countries in which the studies were conducted,the authors,and the scientific centers of origin,as well as the clinical studies in ***,an attempt is made to draw some conclusions and to point out possible future directions.

关键词： Gastric cancer Chemotherapy Immunotherapy Immune checkpoint inhibitors Bibliometrics Scientometrics

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Combination treatment of inflammatory bowel disease:Present status and future perspectives

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World Journal of Gastroenterology 2024年第15期30卷 2068-2080页

作者： John K Triantafillidis Constantinos G Zografos Manousos M Konstadoulakis apostolos e papalois Inflammatory Bowel Disease Unit "Metropolitan General"HospitalHolargos 15562AtticaGreece Hellenic Society for Gastrointestinal Oncology 354 Iera OdosChaidari 12461AtticaGreece The 2^(nd)Department of Surgery University of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece Unit of Surgical Research and Training The 2^(nd)Department of SurgeryUniversity of AthensSchool of MedicineAretaieion HospitalAthens 11528Greece

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical *** seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the *** daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical *** combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment ***,a part of these patients are going to *** recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe *** our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very *** mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal *** appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research *** this

关键词： Biologics for immune-mediated conditions Dual-targeted treatment Combination treatment Inflammatory bowel disease Crohn’s

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early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 583-597页

作者： John K Triantafillidis Konstantinos Georgiou Manousos M Konstadoulakis apostolos e papalois Department of IBD and GI endoscopy Metropolitan General HospitalHolargos 15562AthensGreece.Hellenic Society for Gastrointestinal Oncology354 Iera OdosChaidari 12461AtticaGreece 2nd Department of Surgery University of Athens School of MedicineAretaieion HospitalAthens 11528Greece

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary *** should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather *** exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be *** most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many *** existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from *** that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of *** these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive *** of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are *** this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible ***,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

关键词： Gastrointestinal cancer endoscopy epidemiology early-onset environment

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Sedation in gastrointestinal endoscopy: Current issues

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World Journal of Gastroenterology 2013年第4期19卷 463-481页

作者： John K Triantafillidis emmanuel Merikas Dimitrios Nikolakis apostolos e papalois Department of Gastroenterology and Center for Inflammatory Bowel Disease "Saint Panteleimon" General HospitalNikaia12461 HaidariGreece experimental Research Center ELPEN Pharmaceuticals19009 AthensGreece

Diagnostic and therapeutic endoscopy can successfully be performed by applying moderate(conscious) *** sedation,using midazolam and an opioid,is the standard method of sedation,although propofol is increasingly being used in many countries because the satisfaction of endoscopists with propofol sedation is greater compared with their satisfaction with conventional ***,the use of propofol is currently preferred for the endoscopic sedation of patients with advanced liver disease due to its short biologic half-life and,consequently,its low risk of inducing hepatic *** the future,propofol could become the preferred sedation agent,especially for routine *** is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with *** opioids,pethidine and fentanyl are the most popular.A number of other substances have been tested in several clinical trials with promising *** them,newer opioids,such as remifentanil,enable a faster *** controversy regarding the administration of sedation by an endoscopist or an experienced nurse,as well as the optimal staffing of en-doscopy units,continues to be a matter of *** sedation in special clinical circumstances,such as in the cases of obese,pregnant,and elderly individuals,as well as patients with chronic lung,renal or liver disease,requires modification of the dose of the drugs used for *** the great majority of patients,sedation under the supervision of a properly trained endoscopist remains the standard practice *** this review,an overview of the current knowledge concerning sedation during digestive endoscopy will be provided based on the data in the current literature.

关键词： Gastrointestinal endoscopy endoscopy Sedation Analgesia Digestive system

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effects of mycophenolate mofetil vs cyclosporine administration on graft survival and function after islet allotransplantation in diabetic rats

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World Journal of Gastroenterology 2005年第18期11卷 2733-2738页

作者： Constantin Fotiadis Paraskevi Xekouki apostolos e papalois PantelisT Antonakis Ioannis Sfiniadakis Dimitrios Flogeras eleutheria Karampela George Zografos 3~(rd) Department of Surgery Athens University Medical School Athens Greece experimentalResearch Unit eLPeN Pharma Athens Greece Department of Pathology Naval Hospital Athens Greece

AIM: To develop an experimental model of islet allotransplantation in diabetic rats and to determine the positive or adverse effects of MMF as a single agent. MeTHODS: Thirty-six male Wistar rats and 18 male Lewis rats were used as recipients and donors respectively. Diabetes was induced by the use of streptozotocin (60 mg/kg) intraperitoneally. Unpurified islets were isolated using the collagenase digestion technique and transplanted into the splenic parenchyma. The recipients were randomly assigned to one of the following three groups: group A (control group) had no immunosuppression; group B received cyclosporine (CsA) (5 mg/kg); group C receivedmycophenolate mofetil (MMF) (20 mg/kg). The animalswere killed on the 12th d. Blood and grafted tissues were obtained for laboratory and histological assessment. ReSULTS: Median allograft survival was significantly higher in the two therapy groups than that in the controls (10 and 12 d for CsA and MMF respectively vs 0 d for the control group, P＜0.01). No difference in allograft survival between the CsA and MMF groups was found. However,MMF had less renal and hepatic toxicity and allowed weight ***: Monotherapy with MMF for immunosu ppression was safe in an experimental model of islet allotransplantation and was equally effective with cyclosporine, with less toxicity.

关键词：麦考酚酸吗乙酯药物治疗器官移植糖尿病小鼠动物实验

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Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

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World Journal of Gastroenterology 2005年第43期11卷 6843-6847页

作者： John K Triantafillidis apostolos e papalois Aikaterini Parasi emmanuel Anagnostakis Stavros Burnazos Aristofanis Gikas emmanuel G Merikas emmanuel Douzinas Maria Karagianni Helen Sotiriou Department of Gastroenterology experimental Research Unit Department of Pathology

AIM: To investigate the influence of infliximab (Remicade)on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in ***: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1:colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7th d, all animals were killed. The colon was fixed in 10%buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) were also ***: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared withthe untreated ones was found (0.47±0.44, 1.09±0.86,0.43±0.31 vs 18.73±10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and ***: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in *** at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg *** at a dose of 5 mg/kg BW produces higher re

关键词：大肠炎肿瘤坏死因子病理机制临床表现

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Beneficial effect of an antibody against interleukin-2 receptor (daclizumab) in an experimental model of hepatocyte xenotransplantation

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World Journal of Gastroenterology 2007年第9期13卷 1435-1437页

作者： Dimitrios Papagoras apostolos papalois Alexandra Tsaroucha Dimitrios Lytras John Kyriazanos Nikoletta Giannakou Prodromos Laftsidis Constantine Simopoulos 2~(nd) Department of Surgery Medical School "Democritus" University of Thrace AlexandroupolisGreece 2~(nd) Department of Surgery Medical School "Democritus" University of Thrace AlexandroupolisGreeceExperimental-Research Department Elpen Pharmaceuticals Athens Greece Department of Pathology "Aghia Olga" General Hospital AthensGreece

AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with fulminant hepatic failure (FHF). MeTHODS: Two white male New Zealand rabbits were used as donors and 68 Wistar rats as recipients. FHF was induced by intravenous application of dimethylnitrosamine (DMNA). The isolated hepatocytes of the rabbits were xenotransplanted into the spleen of the rats 24 h after FHF induction. Group A (n = 13): no treatment; Group B (n = 14): FHF and XenoTx; Group C (n = 14): FHF and XenoTx and cyclosporin (CsA); Group D (n = 14): FHF and XenoTx and Dmab; Group e (n = 13): FHF and XenoTx and CsA and Dmab. The rats were followed for 15 d. ReSULTS: Statistical analysis showed better survival among groups D (92.86%) and e (76.92%) compared to group A (all rats died after 72 h), group B (28.57%) or group C (71.43%), although the differences were not statistically significant. Biochemical evaluation of the liver enzymes and histology confirmed satisfactory function and engraftment, respectively. CONCLUSION: This experimental model has shown the safe, effective and beneficial use of Dmab in a xenotransplantation model of rabbit hepatocytes in rats.

关键词：肝细胞移植异种移植实验模型抗体白介素-2受体

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Nonlinear dynamics in Divisia monetary aggregates:an application of recurrence quantification analysis

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Financial Innovation 2023年第1期9卷 467-483页

作者： Ioannis Andreadis Athanasios D.Fragkou Theodoros e.Karakasidis apostolos Serletis International School of The Hague Wijndaelerduin 12554BXThe HagueThe Netherlands Department of Civil engineering University of Thessaly38334 VolosGreece Condensed Matter Physics Laboratory Department of PhysicsUniversity of Thessaly35100 LamiaGreece University of Calgary CalgaryABCanada

We construct recurrence plots(RPs)and conduct recurrence quantification analysis(RQA)to investigate the dynamic properties of the new Center for Financial Stability(CFS)Divisia monetary aggregates for the United *** this study,we use the lat-est vintage of Divisia aggregates,maintained within *** use monthly data,from January 1967 to December 2020,which is a sample period that includes the extreme economic events of the 2007–2009 global financial *** then make comparisons between narrow and broad Divisia money measures and find evidence of a nonlinear but reserved possible chaotic explanation of their *** application of RPs to broad Divisia monetary aggregates encompasses an additional drift structure around the global financial crisis in *** the moving window RQA to the growth rates of narrow and broad Divisia monetary aggregates,we identify periods of changes in data-generating processes and associate such changes to monetary policy regimes and financial innovations that occurred during those times.

关键词： Divisia monetary aggregates Recurrence plots Moving windows Deterministic dynamics Stochastic structures

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COVID-19 pandemic:Building organisational flexibility to scale transplant programs

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World Journal of Transplantation 2020年第10期10卷 277-282页

作者： Jeevan Prakash Gopal Vassilios e papalois Imperial College Renal and Transplant Center Hammersmith HospitalImperial College Healthcare NHS TrustLondon W120HSUnited Kingdom Imperial College Renal and Transplant Center Department of Surgery and CancerHammersmith HospitalImperial College Healthcare NHS TrustLondon W120HSUnited Kingdom

The prevailing coronavirus disease 2019 pandemic has challenged our lives in an unprecedented *** pandemic has had a significant impact on transplantation *** logistics of travel restrictions,stretching of available resources,unclear risk of infection in immunosuppressed transplant recipients,and evolving guidelines on testing and transplantation are some of the factors that have unfavourably influenced transplant *** must begin to build organisational flexibility in order to restart transplantation so that we can be mindful stewards of organ donation and sincere advocates for our *** a culture of honesty and transparency(with patients,families,colleagues,societies,and authorities),keeping the channels of communication open,working in collaboration with others(at local,regional,national,and international levels),and not restarting without rethinking and appraising all elements of our practice,are the main underlying principles to increase the flexibility.

关键词： Organisational flexibility Clinical decision making COVID-19 Organ donation Care delivery Transplantation

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COVID-19 and the heart

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World Journal of Clinical Cases 2022年第28期10卷 9970-9984页

作者： Andrew Xanthopoulos Angeliki Bourazana Grigorios Giamouzis evangelia Skoularigki apostolos Dimos Alexandros Zagouras Michail Papamichalis Ioannis Leventis Dimitrios e Magouliotis Filippos Triposkiadis John Skoularigis Department of Cardiology University Hospital of LarissaLarissa 41110Greece Department of Cardiothoracic Surgery University of ThessalyLarissa BiopolisLarissa 41110Greece

An outbreak of coronavirus disease 2019(COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2(SARS-Co V-2),which is a strain of SARS-Co *** infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms,cough,fever and fatigue to severe lung injury,appearing as bilateral interstitial pneumonia or acute respiratory *** SARS-Co V-2 infection predominantly offends the respiratory system,it has been associated with several cardiovascular complications as *** example,patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary *** incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases,whereas heart failure(HF) may develop due to infiltration of the heart by inflammatory cells,destructive action of pro-inflammatory cytokines,micro-thrombosis and new onset or aggravated endothelial and respiratory ***,SARSCo V-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary,through respiratory failure or severe res-piratory distress *** this comprehensive review we summarize the COVID-19 related cardiovascular complications(acute coronary syndromes,myocarditis,HF,arrhythmias) and discuss the main underlying pathophysiological mechanisms.

关键词： COVID-19 Virus Complications Cardiac Acute coronary syndromes Heart failure Myocarditis Arrhythmias

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