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Circulating autoantibodies to endogenous erythropoietin are associated with chronic hepatitis C virus infection-related anemia

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 289-295页

作者： Aristotelis Tsiakalos Theoharis voumvas Alexandros Psarris Christina k oikonomou Dimitrios C Ziogas Ioannis ketikoglou Grigorios Hatzis Nikolaos v Sipsas Department of Pathophysiology Laikon General Hospital Medical School National and Kapodistrian University of Athens Athens Greece hird Department of Internal Medicine Laikon General Hospital Medical School National and Kapodistrian University of Athens Athens Greece Microbiology Department Red Cross General Hospital Athens Greece Department of Internal Medicine Hippocration General Hospital Athens Greece

BACkGROUND： Chronic hepatitis C virus （HCv） infection is associated with autoimmune phenomena and is often complicated by anemia. Circulating autoantibodies to endogenous erythropoietin （anti-EPO） have been detected in patients with chronic viral infections and were correlated to anemia. The present study aimed to determine anti-EPO prevalence in pa- tients with chronic HCv infection and investigate its possible association with anemia. METHODS： Ninety-three consecutive patients （62 males and 31 females） with chronic HCv infection, who had never re- ceived antiviral therapy or recombinant EPO, were enrolled in the study. Circulating anti-EPO were detected in the serum by using an ELISA assay. Quantitative determination of serum EPO levels was done by radioimmunoassay. HCv RNA viral load t and genotype sequencing were also performed. RESULTS： Circulating anti-EPO were detected in 10.8% of HCv-infected patients and the prevalence of anti-EPO was significantly higher in patients with anemia （19.4% vs 5.3%, P=0.040） compared to that in those without anemia. Compared to anti-EPO negative cases, anti-EPO positive patients had higher frequency of anemia （70.0% vs 34.9%, P=0.030）, lower EPO concentrations （median 16.35 vs 30.65 mU/mL, P=0.005）, and higher HCv RNA viral load （median 891.5x103 vs 367.5x 103 IU/mL, P=0.016）. In multivariate regression anal- ysis the presence of anti-EPO remained an independent predictor of anemia （adjusted OR： 14.303, 95% CI： 1.417-36.580, P=0.024）. EPO response to anemia was less prominent among anti-EPO positive patients （P=0.001）. CONCLUSIONS： Circulating anti-EPO are detected in a significant proportion of treatment-naive HCv-infected patients and are independently associated with anemia, suggesting a further implication of autoimmunity in the pathophysiology of HCv-related anemia.

关键词： hepatitis C virus erythropoietin anemia autoantibodies

Clinical impact of microbiome in patients with decompensated cirrhosis

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World Journal of Gastroenterology 2018年第34期24卷 3813-3820页

作者： Theodora oikonomou George v Papatheodoridis Michael Samarkos Ioannis Goulis Evangelos Cholongitas Fourth Department of Internal Medicine Hippokration General Hospital Medical School of Aristotle University of Thessaloniki Academic Department of Gastroenterology Laiko General Hospital Medical School of National and Kapodistrian University of Athens First Department of Internal Medicine Laiko General Hospital Medical School of National and Kapodistrian University of Athens

Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gutliver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.

关键词： Microbiome Dysbiosis Oral-gut-liver axis Hepatic encephalopathy Decompensated cirrhosis Liver carcinoma

Ternary supramolecular quantum-dot network flocculation for selective lectin detection

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Nano Research 2016年第7期9卷 1904-1912页

作者： Maria oikonomou Junyou Wang Rui Rijo Carvalho Aldrik H. velders Laboratory of BioNanoTechnology WageningenUR Dreijenplein 6 6703 HB Wageningen the Netherlands Micronit Microfluidics B.v. Colosseum 15 7521 PV Enschede the Netherlands Interventional Molecular Imaging Laboratory Department of Radiology Leiden University Medical Center 2333 ZA Leiden the Netherlands

We present a versatile, tuneable, and selective nanoparficle-based lectin biosensor, based on flocculation of ternary supramolecular nanoparticle networks （NPN）, formed through the sequential binding of three building blocks. The three building blocks are ^-cyclodextrin-capped CdTe quantum dots, tetraethylene glycol-tethered mannose-adamantane cross-linkers （ADTEGMan）, and the tetravalent lectin Concanavalin A （ConA）. The working principle of this selective sensor lies in the dual orthogonal molecular interactions of the linker, uniting adamantane-^-cyclodextrin and mannose-lectin interaction motifs, respectively. Only when the lectin is present, sequential binding takes place, leading to in situ self-organization of the sensor through the formation of ternary supramolecular networks. Monitoring the loss of fluorescence signal of the quantum dots in solution, caused by controlled network formation and consecutive flocculation and sedimentation, leads to selective, qualitative, and quantitative lectin detection. Fluorescent sedimented networks can be observed by the naked eye or under Uv illumination for a lectin concentration of up to 10 8 M. Quantitative detection is possible at 100 min with a lower detection limit of approximately 5 × 10 ^-8 M.

关键词： supramolecular cyclodextrin quantum dot sensor lectin flocculation

Fecal DNA testing for colorectal cancer screening:molecular targets and perspectives

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World Journal of Gastrointestinal Oncology 2015年第10期7卷 178-183页

作者： Amaninder Dhaliwal Panagiotis J vlachostergios katerina G oikonomou Yitzchak Moshenyat Department of Medicine NYU Lutheran Medical Center Division of Gastroenterology NYU Lutheran Medical Center

The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use.

关键词： Colorectal cancer Screening Fecal DNA Cologuard^(■) Adenoma

α2-Heremans-schmid glycoprotein(fetuin A)downregulation and its utility in inflammatory bowel disease

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World Journal of Gastroenterology 2017年第3期23卷 437-446页

作者： Anastassios C Manolakis Gregory Christodoulidis Andreas N kapsoritakis Panagiotis Georgoulias Elisavet k Tiaka kostas oikonomou varvara J Spyros P Potamianos Department of Gastroenterology University of ThessalySchool of Medicine41110 LarissaGreece Department of Surgery University of ThessalySchool of Medicine41110 LarissaGreece Laboratory of Nuclear Medicine University of ThessalySchool of Medicine41110 LarissaGreece

AIM To investigate the impact of inflammatory bowel disease (IBD) on α2-Heremans-Schmid Glycoprotein(AHSG/fetuin A) and potential associations with disease and patient *** AHSG serum levels were determined in treatment-na?ve newly-diagnosed patients, 96 with ulcerative colitis(UC), 84 with Crohn's disease (CD), 62 with diarrheapredominant or mixed irritable bowel syndrome (IBS, D- and M- types) and 180 healthy controls (HC), by an enzyme linked immunosorbent assay (ELISA).All patients were followed for a minimum period of 3 years at the Gastroenterology Department of the University Hospital of Larissa, Greece. C-reactive protein(CRP), anti-glycan antibodies, anti-Saccharomyces cerevisiae mannan antibodies Ig G, anti-mannobioside carbohydrate antibodies Ig G, anti-laminariobioside carbohydrate antibodies Ig G and anti-chitobioside carbohydrate antibodies Ig A were also determined via immunonephelometry and ELISA, *** The mean ± SE of serum AHSG, following adjustment for confounders, was 0.32 ± 0.02 g/L in IBD, 0.32 ± 0.03 g/L in CD and 0.34 ± 0.03 g/L in UC patients, significantly lower than in IBS patients(0.7 ± 0.018 g/L) and HC (0.71 ± 0.02 g/L) (P vels were comparable between the CD and UC groups. Based on AHSG levels IBD patients could be distinguished from HC with about 90% sensitivity and specificity. Further adjusted analysis verified the inverse association between AHSG and penetrating, as well as stricturing CD (partial correlation coefficient: -0.45 and -0.33, respectively) (P verse correlations between AHSG and CRP and the need for anti-TNFα therapy or surgery, were found (partial correlation coefficients:-0.31,-0.33,-0.41, respectively, P viduals who were seropositive, for at least one marker, had AHSG levels falling within the two lower quartiles (OR = 2.86, 95%CI: 1.5-5.44, P < 0.001) while

关键词： Inflammatory bowel disease Irritable bowel syndrome Fetuin A

Diabetes mellitus and atrial fibrillation-from pathophysiology to treatment

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World Journal of Diabetes 2023年第5期14卷 512-527页

作者： Marianna Leopoulou Panagiotis Theofilis Athanasios kordalis Nikolaos Papageorgiou Marios Sagris Evangelos oikonomou Dimitris Tousoulis 1^(st)Cardiology Clinic ‘Hippokration’General HospitalNational and Kapodistrian University of AthensSchool of MedicineAthens 11527Greece 3^(rd)Cardiology Clinic ‘Sotiria’Chest Diseases HospitalNational and Kapodistrian University of AthensSchool of MedicineAthens 11527Greece

Type 2 diabetes mellitus(T2DM)is a leading risk factor for cardiovascular complications around the globe and one of the most common medical *** fibrillation(AF)is the most common supraventricular arrhythmia,with a rapidly increasing prevalence.T2DM has been closely associated with the risk of AF development,identified as an independent risk *** cardiovascular complications,both AF and T2DM have been linked with high *** underlying pathophysiology has not been fully determined yet;however,it is multifactorial,including structural,electrical,and autonomic *** therapies include pharmaceutical agents in sodium-glucose cotransporter-2 inhibitors,as well as antiarrhythmic strategies,such as cardioversion and *** interest,glucose-lowering therapies may affect the prevalence of *** review presents the current evidence regarding the connection between the two entities,the pathophysiological pathways that link them,and the therapeutic options that exist.

关键词： Atrial fibrillation Diabetes mellitus Pathophysiology Treatment

Role of genetic testing in cardiomyopathies:Αprimer for cardiologists

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World Journal of Cardiology 2022年第1期14卷 29-39页

作者： Georgia vogiatzi George Lazaros Evangelos oikonomou Emilia Lazarou Emmanouil vavuranakis Dimitris Tousoulis The Third Department of Cardiology Sotiria HospitalAthens 11527Greece The First Department of Cardiology Hippokration HospitalAthens 11526Greece The First Department of Cardiology Hippokration HospitalMedical School of National and Kapodistrian University of AthensAthens 11527Greece

Recent advances in cardiovascular genetics have transformed genetic testing into a valuable part of management of families with inherited *** novel mutations have been identified,understanding when to consider genetic testing has emerged as an important consideration in the management of these *** genetic testing has a paramount importance in the risk stratification of family members,in the prognosis of probands at higher risk of a serious phenotype expression,and finally in the identification of new mutations,all of which are discussed in this *** indications for each type of cardiomyopathy are described,along with the limitations of genetic ***,the importance of public sharing of variants in large data sets is *** ultimate aim of this review is to present key messages about the genetic testing process in order to minimize potential harms and provide suggestions to specialized clinicians who act as a part of a multidisciplinary team in order to offer the best care to families with inherited cardiomyopathies.

关键词： Cardiomyopathy Genetic counselling Genetic testing variant Hereditary

Necrolytic acral erythema in a human immunodeficiency virus/hepatitis C virus coinfected patient:A case report

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World Journal of Hepatology 2019年第2期11卷 226-233页

作者： katerina G oikonomou Dost Sarpel Alexandra Abrams-Downey Adnan Mubasher Douglas T Dieterich Division of Infectious Diseases Icahn School of Medicine at Mount Sinai Department of Pathology Icahn School of Medicine at Mount Sinai Division of Liver Diseases Icahn School of Medicine at Mount Sinai

BACkGROUND Necrolytic acral erythema(NAE) is a rare dermatological disorder,which is associated with hepatitis C virus(HCv) infection or zinc *** is characterized by erythematous or violaceous lesions occurring primarily in the lower *** treatment includes systemic steroids and oral zinc *** report a case of NAE in a 66-year-old human immunodeficiency virus(HIv)/HCv co-infected woman with *** is rarely reported in co-infected patients and the exact mechanisms of pathogenesis are still *** SUMMARY A 66-year-old HIv/HCv co-infected female patient presented with painless,nonpruritic rash of extremities for one week and underwent extensive work-up for possible rheumatologic disorders including vasculitis and *** skin biopsies of right and left thigh revealed thickened parakeratotic stratum corneum most consistent with *** was started on prednisone and zinc supplementation with resolution of the lesions and improvement of *** Clinicians should maintain high clinical suspicion for early recognition of NAE in patients with rash and HCv.

关键词： Necrolytic acral erythema Human immunodeficiency virus Hepatitis C virus Zinc deficiency Case report

Prevention,diagnostic evaluation,management and prognostic implications of liver disease in critically ill patients with COvID-19

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World Journal of Clinical Cases 2023年第3期11卷 514-527页

作者： Asimina valsamaki Maria Xanthoudaki katerina G oikonomou Panagiotis J vlachostergios AntoniosPapadogoulas Periklis katsiafylloudis Ioanna voulgaridi Apostolia-Lemonia Skoura Apostolos komnos Panagiotis Papamichalis Intensive Care Unit General Hospital of LarissaLarissa 41221Greece Division of Hematology and Medical Oncology Department of MedicineWeill Cornell MedicineNew YorkNY 10065United States Department of Microbiology General Hospital of LarissaLarissa 41221Greece Transfusion Medicine Department University Hospital of LarissaLarissa 41110Greece

Coronavirus disease 2019(COvID-19),caused by severe acute respiratory syndrome coronavirus 2,broke out in December 2019 in Wuhan city of China and spread rapidly ***,by March 2020,the World Health Organization declared the disease a global *** from the respiratory system,various other organs of the human body are also seriously affected by the *** injury in patients with a severe form of COvID-19 is estimated to be 14.8%-53.0%.Elevated levels of total bilirubin,aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory *** with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver *** literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COvID-19,the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these ***,it highlighted the burden that COvID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

关键词： Coronavirus disease 2019 Severe acute respiratory syndrome coronavirus 2 Liver disease Intensive care unit Liver unit Prealbumin