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Endothelial progenitor cells mobilization after maximal exercise according to heart failure severity

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World Journal of Cardiology 2020年第11期12卷 526-539页

作者： Christos Kourek Eleftherios Karatzanos Katherina Psarra Georgios Georgiopoulos dimitrios Delis Vasiliki Linardatou Gerasimos Gavrielatos Costas papadopoulos Serafim Nanas Stavros Dimopoulos Department of Clinical Ergospirometry Exercise&Rehabilitation LaboratoryEvaggelismos HospitalAthens 10676Greece Immunology and Histocompatibility Department Evaggelismos HospitalAthens 10676Greece Department of Clinical Therapeutics Alexandra HospitalAthens 11528Greece Department of Cardiology Tzaneio General Hospital of PiraeusPiraeus 18536Greece 2nd Cardiology Department Korgialenio-Benakio Red Cross HospitalAthens 11526Greece Cardiac Surgery Intensive Care Unit Onassis Cardiac Surgery CenterAthens 17674Greece

BACKGROUND Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure(CHF).Patients with CHF are characterized by impaired vasodilation and inflammation of the vascular *** also have low levels of endothelial progenitor cells(EPCs).EPCs are bone marrow derived cells involved in endothelium regeneration,homeostasis,and *** has been shown to improve vasodilation and stimulate the mobilization of EPCs in healthy people and patients with cardiovascular ***,the effects of exercise on EPCs in different stages of CHF remain under *** To evaluate the effect of a symptom-limited maximal cardiopulmonary exercise testing(CPET)on EPCs in CHF patients of different *** Forty-nine consecutive patients(41 males)with stable CHF[mean age(years):56±10,ejection fraction(EF,%):32±8,peak oxygen uptake(VO2,mL/kg/min):18.1±4.4]underwent a CPET on a cycle *** blood was sampled before and after *** circulating endothelial populations were quantified by flow cytometry:Three subgroups of EPCs[CD34+/CD45-/CD133+,CD34+/CD45-/CD133+/VEGFR2 and CD34+/CD133+/vascular endothelial growth factor receptor 2(VEGFR2)]and two subgroups of circulating endothelial cells(CD34+/CD45-/CD133-and CD34+/CD45-/CD133-/VEGFR2).Patients were divided in two groups of severity according to the median value of peak VO2(18.0 mL/kg/min),predicted peak VO2(65.5%),ventilation/carbon dioxide output slope(32.5)and EF(reduced and mid-ranged EF).EPCs values are expressed as median(25th-75th percentiles)in cells/106 enucleated *** Patients with lower peak VO2 increased the mobilization of CD34+/CD45-/CD133+[pre CPET:60(25-76)vs post CPET:90(70-103)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133+/VEGFR2[pre CPET:1(1-4)vs post CPET:5(3-8)cells/106 enucleated cells,P<0.001],CD34+/CD45-/CD133-[pre CPET:186(141-361)vs post CPET:488(247-658)cells/106 enucleated cells,P<0.001]an

关键词： Chronic heart failure Endothelial progenitor cells Circulating endothelial cells Maximal exercise Cardiopulmonary exercise testing Severity

New generation of breast cancer clinical trials implementing molecular profiling

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Cancer Biology & Medicine 2016年第2期13卷 226-235页

作者： dimitrios Zardavas Martine Piccart-Gebhart Breast International Group(BIG) Brussels 100Belgium Medicine Department Institue Jules BordetUniversite Libre de BruxellesBrussels 100Belgium

The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as prescreening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i)longitudinal cohort studies that implement(or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

关键词： Clinical trial molecular profiling breast cancer study design

Synchronous resection of esophageal cancer and other organ malignancies: A systematic review

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World Journal of Gastroenterology 2019年第26期25卷 3438-3449页

作者： dimitrios Papaconstantinou Diamantis I Tsilimigras dimitrios Moris Adamantios Michalinos Aikaterini Mastoraki Efstratia Mpaili Natasha Hasemaki Anargyros Bakopoulos dimitrios Filippou dimitrios Schizas Third Department of Surgery National and Kapodistrian University of AthensAttikon University HospitalAthens 12462Greece Department of Surgery Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research InstituteColumbusOH 43210United States Department of Surgery Duke University Medical CenterDurhamNC 27710United States Department of Anatomy European University of CyprusNicosia 2404Cyprus First Department of Surgery National and Kapodistrian University of AthensLaikon General HospitalAthens 11527Greece Department of Anatomy and Surgical Anatomy National and Kapodistrian University of AthensMedical SchoolAthens 11527Greece

BACKGROUND Neoplasms arising in the esophagus may coexist with other solid organ or gastrointestinal tract neoplasms in 6%to 15%of *** of both tumors synchronously or in a staged procedure provides the best chances for long-term *** resection of both esophageal and second primary malignancy may be feasible in a subset of patients;however,literature on this topic remains rather *** To analyze the operative techniques employed in esophageal resections combined with gastric,pancreatic,lung,colorectal,kidney and liver resections and define postoperative outcomes in each *** We conducted a systematic review according to PRISMA *** searched the Medline database for cases of patients with esophageal tumors coexisting with a second primary tumor located in another organ that underwent synchronous resection of both *** English language articles deemed eligible for inclusion were accessed in full *** criteria included:(1)Hematological malignancies;(2)Head/neck/pharyngeal neoplasms;(3)Second primary neoplasms in the esophagus or the gastroesophageal junction;(4)Second primary neoplasms not surgically excised;and(5)Preclinical *** regarding the operative strategy employed,perioperative outcomes and longterm outcomes were extracted and analyzed using descriptive *** The systematic literature search yielded 23 eligible studies incorporating a total of 117 *** these patients,71%had a second primary neoplasm in the *** who underwent total gastrectomy had a reconstruction using either a colonic(n=23)or a jejunal(n=3)conduit while for those who underwent gastric preserving resections(i.e.,non-anatomic/wedge/distal gastrectomies)a conventional gastric pull-up was ***,in cases of patients who underwent esophagectomy combined with pancreaticoduodenectomy(15%of the cohort),the decision to preserve part of the stomach or not dictated the reconstruction met

关键词： Esophagectomy Esophageal neoplasm Second primary Multiple primary Concurrent neoplasms Management

"Moonlighting" at the power plant: how mitochondria facilitate serial killing by CD8^(+) cytotoxic T cells

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Signal Transduction and Targeted Therapy 2022年第1期7卷 15-16页

作者： dimitrios Mougiakakos Sascha Kahlfuss Department of Hematology Oncologyand Stem Cell TransplantationOtto-von-Guericke University MagdeburgMagdeburgGermany Institute of Molecular and Clinical Immunology Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany Institute of Medical Microbiology and Hospital Hygiene Medical FacultyOtto-von-Guericke University MagdeburgMagdeburgGermany Health Campus Immunology InfectiologyInflammation(GC-I3)Medical FacultyOtto-von-Guericke UniversityMagdeburgGermany Center for Health and Medical Prevention(CHaMP) Otto-von-Guericke UniversityMagdeburgGermany

Griffiths and colleagues rece ntly dem on strated in Science^(1) that mitochondrial translation is required by CD8^(+)cytotoxic T cells(CTLs)to facilitate serial killing of target ***8^(+)CTLs provide immunity to viruses and tumors by acting as serial killers that eliminate infected or transformed target cells one after *** achieve that,CTLs utilize a cytotoxic protein machinery that involves perforin and granzymes to activate effector caspases and to induce apoptosis in target cells.

关键词： cytotoxic immunity lighting

Hemobilia secondary to hepatic artery pseudoaneurysm: An unusual complication of bile leakage in a patient with a history of a resected Ⅲb Klatskin tumor

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World Journal of Gastroenterology 2005年第33期11卷 5229-5231页

作者： dimitrios Siablis Zafiria G.Papathanassiou dimitrios Karnabatidis Nikolaos Christeas Constantine Vagianos Department of Interventional Radiology Medical School University of PatrasRioGreece Department of Surgery Medical School University of PatrasRioGreece

We report a case of a 74-year-old woman with a 16-year history of a double bilo-enteric anastomosis due to resected hilar cholangiocarcinoma [Type IIIb Klatskin tumor]. The patient presented with cholangitis secondary to benign anastomotic stenosis which resulted in a large intrahepatic biloma. In order to restore the patency of the anastomosis and overcome cholangitis, several attempts took place, including endobiliary stenting, balloon-assisted biloplasty and transhepatic billiary drainage. Anastomotic patency was achieved, complicated, however, by persistent upper gastro-intestinal bleeding, presented as hemobilia. A biloma-induced pseudoaneurysm of the left hepatic artery was diagnosed. This had ruptured into the biliary tract, and presented the actual cause of the hemobilia. Selective embolism of the pseudoaneurysm resulted in control of the hemorrhage, and was successfully combined with transhepatic dilatation of the anastomosis and percutaneous drainage of the biloma. The patient was ultimately cured and seems to be in excellent condition, 5 mo after treatment.

关键词： Hepatic artery pseudoaneurysm Hemobilia Embolization

Direct adaptive regulation of unknown nonlinear systems with analysis of the model order problem

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Journal of Zhejiang University-Science C(Computers and Electronics) 2011年第1期12卷 1-16页

作者： dimitrios THEODORIDIS Yiannis BOUTALIS Manolis CHRISTODOULOU Department of Electrical and Computer Engineering Democritus University of Thrace Department of Industrial Informatics Technological Education Institute of Kavala Chair of Automatic Control University of Erlangen-Nuremberg Department of Electronic and Computer Engineering Technical University of Crete Dipartimento di Automatica et Informatica Politecnico di Torino

A new method for the direct adaptive regulation of unknown nonlinear dynamical systems is proposed in this paper,paying special attention to the analysis of the model order *** method uses a neurofuzzy (NF) modeling of the unknown system,which combines fuzzy systems (FSs) with high order neural networks (HONNs).We propose the approximation of the unknown system by a special form of an NF-dynamical system (NFDS),which,however,may assume a smaller number of states than the original unknown *** omission of states,referred to as a model order problem,is modeled by introducing a disturbance term in the approximating *** development is combined with a sensitivity analysis of the closed loop and provides a comprehensive and rigorous analysis of the stability *** adaptive modification method,termed ‘parameter hopping’,is incorporated into the weight estimation algorithm so that the existence and boundedness of the control signal are always *** applicability and potency of the method are tested by simulations on well known benchmarks such as ‘DC motor’ and ‘Lorenz system’,where it is shown that it performs quite well under a reduced model order ***,the proposed NF approach is shown to outperform simple recurrent high order neural networks (RHONNs).

关键词： Neuro-fuzzy systems Direct adaptive regulation Model order problems Parameter hopping

The structure of the human 4F2hc-LAT1 heteromeric amino acid transporter

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Science China(Life Sciences) 2019年第6期62卷 848-850页

作者： dimitrios Fotiadis Jean-Marc Jeckelmann Institute of Biochemistry and Molecular Medicine and Swiss National Centre of Competence in Research (NCCR) TransCureUniversity of Bern

Amino acids are biologically important molecules that serve as energy source, building blocks of proteins, precursors for metabolites and signaling compounds in all living *** of proteinogenic amino acids and related substances across biological membranes is mediated by membrane embedded proteins:the amino acid transporters. These membrane proteins belong to different solute carrier (SLC)families (http://***) and transfer amino acids in and out between compartments inside cells, between different cells and between organs. Amino acid transporters have diverse important physiological functions and their absence, overexpression and malfunction can lead to human diseases.

关键词： Amino acids important molecules functions and their absence

The Effects of Protruding Rock Boulders in Regulating Sediment Intrusion within the Hyporheic Zone of Mountain Streams

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Journal of Mountain Science 2014年第6期11卷 1466-1477页

作者： dimitrios DERMISIS A.N.Thanos PAPANICOLAOU Department of Chemical Civil and Mechanical Engineering Mc Neese State UniversityLake Charles LA 70609 USA Department of Civil and Environmental Engineering The University of TennesseeKnoxville TN 37996 USA

Excessive sedimentation in mountain stream ecosystems is a critical environmental problem due to the clogging of streambeds by sediment particles within the hyporheic zone,with detrimental effects on fish spawning *** this research,the effects of an array of boulders in regulating the intrusion of incoming sand within a gravel substrate were evaluated by performing detailed experiments in a laboratory flume.A unique experimental setup and two different sampling techniques were utilized for measuring the infiltrated sand within the gravel bed under two bed shear stress conditions(moderate ***).For comparison purposes,experiments were performed without and with the presence of partially submerged to the flow(protruding) boulders,which is typical for the average flow conditions found in mountain *** indicated that sand infiltrated primarily in the upper part of the gravel bed creating a surface seal which hindered the penetration of sand particles deeper into the *** exponential decrease of the amount of the infiltrated sand within the hyporheic zone was observed in all experiments regardless of the presence of ***,the presence of boulders promoted sediment intrusion of sand particles especially for the moderate applied bed shear stress condition,since the total amount of the infiltrated sand was found to be on average 44% greater whenboulders were *** findings from this study can provide additional insight regarding the role of boulders on promoting downwelling of flow and sediment within the gravel substrate with potential effects on fish habitat.

关键词： Spawning Gravel Boulders Sand Intrusion Sedimentation

Combined hepatocellular-cholangiocarcinoma:An update on epidemiology,classification,diagnosis and management

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Hepatobiliary & Pancreatic Diseases International 2020年第6期19卷 515-523页

作者： dimitrios Schizas Aikaterini Mastoraki Eleni Routsi Michail Papapanou dimitrios Tsapralis Pantelis Vassiliu Konstantinos Toutouzas Evangelos Felekouras First Department of Surgery National and Kapodistrian University of AthensLaikon General HospitalAthensGreece Fourth Department of Surgery National and Kapodistrian University of AthensAttikon University HospitalAthensGreece Surgical Department General Hospital of IerapetraIerapetraGreece First Department of Propaedeutic Surgery National and Kapodistrian University of AthensHippocration HospitalAthensGreece

Background:Combined hepatocellular-cholangiocarcinoma(CHC)is a rare subtype of primary hepatic malignancies,with variably reported incidence between 0.4%–14.2%of primary liver cancer *** study aimed to systematically review the epidemiological,clinicopathological,diagnostic and therapeutic data for this rare *** sources:We reviewed the literature of diagnostic approach of CHC with special reference to its clinical,molecular and histopathological *** analysis of the recent literature in order to evaluate the results of surgical and systemic treatment of this entity has been ***:The median age at CHC’s diagnosis appears to be between 50 and 75 *** of tumor markers[alpha fetoprotein(AFP),carbohydrate antigen 19–9(CA19–9)and carcinoembryonic antigen(CEA)]along with imaging patterns provides better opportunities for CHC’s preoperative *** clinicopathologic prognostic parameters possibly correlated with increased tumor recurrence and grimmer survival odds include advanced age,tumor size,nodal and distal metastases,vascular and regional organ invasion,multifocality,decreased capsule formation,stem-cell features verification and increased GGT as well as CA19–9 and CEA *** case of inoperable or recurrent disease,combinations of cholangiocarcinoma-directed systemic agents display superior results over ***-directed methods,such as transarterial chemoembolization(TACE),percutaneous ethanol injection(PEI),hepatic arterial infusion chemotherapy(HAIC),radioembolization and ablative therapies,demonstrate inferior efficacy than in cases of hepatocellular carcinoma(HCC)due to CHC’s common ***:CHC demonstrates an overlapping clinical and biological pattern between its malignant *** history of the disease seems to be determined by the predominant tumor *** standard for diagnosis is histology of surgical *** therapeutic int

关键词： Combined hepatocellular-cholangiocarcinoma Classification Diagnostic approach Therapeutic management