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Article ; Online: Hepcidin as a Sensitive and Treatment-Responsive Acute-Phase Marker in Patients with Bacteremia

Kreon Koukoulas / Vasiliki Lygoura / Philip Kartalidis / Nikolaos K. Gatselis / Efthymia Petinaki / George N. Dalekos / George Simos

Diagnostics, Vol 12, Iss 1404, p

A Pilot Study

2022 Volume 1404

Abstract: Hepcidin regulates iron metabolism by inhibiting intestinal iron absorption and iron release from iron stores. In addition to iron overload, inflammatory conditions also up-regulate hepcidin synthesis, which may serve as an antimicrobial defense by ... ...

Abstract	Hepcidin regulates iron metabolism by inhibiting intestinal iron absorption and iron release from iron stores. In addition to iron overload, inflammatory conditions also up-regulate hepcidin synthesis, which may serve as an antimicrobial defense by reducing iron availability to the invading microbes. The purpose of this study is to test this hypothesis in human patients by determining serum hepcidin concentration by enzyme linked immunosorbent assay (ELISA) in healthy blood donors ( n = 60) and patients hospitalized because of bacteremia ( n = 50), before (day 0) and after seven days (day 7) of appropriate antibiotic treatment. Serum hepcidin was significantly increased in patients with bacteremia, both at day 0 and at day 7, compared to healthy controls. However, there was significant reduction of serum hepcidin after 7-day treatment, in concert with changes in serum C-reactive protein (CRP). The hepcidin changes were similar for both Gram-negative and Gram-positive single infection cases, while CRP was significantly reduced only in the former. In contrast to hepcidin, the levels of serum ferritin in the patients remained high after treatment, irrespective of infection type. These data confirm the stimulation of hepcidin secretion in human subjects upon different types of systemic microbial infection and suggest that hepcidin is a more sensitive and treatment-responsive acute-phase marker than ferritin in bacteremia, which needs to be explored with bigger-sized and better-matched patient cohorts.
Keywords	hepcidin ; bacteremia ; ferritin ; CRP ; acute phase marker ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: FibroMeter scores for the assessment of liver fibrosis in patients with autoimmune liver diseases

Kalliopi Zachou / Vasiliki Lygoura / Pinelopi Arvaniti / Georgios Giannoulis / Nikolaos K. Gatselis / George K. Koukoulis / George N. Dalekos

Annals of Hepatology, Vol 22, Iss , Pp 100285- (2021)

2021

Abstract: Introduction and Objectives: We assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], ...

Abstract	Introduction and Objectives: We assessed FibroMeter virus (FMvirus) and FibroMeter vibration-controlled transient elastography (FMVCTE) in 134 patients with autoimmune liver diseases [ALD, autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC)], in order to assess new potential non-invasive biomarkers of liver fibrosis in patients with ALD, as similar data are missing. Patients and Methods: The following groups were included: group 1: n = 78 AIH; group 2: n = 56 PBC. FMvirus and FMVCTE were determined in all 134 patients who underwent liver biopsy and TE the same day with sera collection. In addition, APRI and FIB-4 scores were calculated. Results: The AUCs for TE and FMVCTE were significantly better (0.809; p < 0.001 and 0.772; p = 0.001, respectively for AIH and 0.997; p < 0.001 and 1; p < 0.001, for PBC) than the other three markers in predicting ≥ F3 fibrosis irrespective of the biochemical activity. FMVCTE and TE had good diagnostic accuracy (75.6% and 73%, respectively) for predicting severe fibrosis in AIH and performed even better in PBC (94.6% and 96.4%, respectively). The cut-offs of TE and FMVCTE had the best sensitivity and specificity in predicting ≥ F3 fibrosis in both AIH and PBC. Conclusions: FMVCTE seems to detect severe fibrosis equally to TE in patients with ALD but with better specificity. Biochemical disease activity did not seem to affect their diagnostic accuracy in ALD and therefore, could be helpful for the assessment of fibrosis, especially if they are performed sequentially (first TE with the best sensitivity and then FMVCTE with the best specificity).
Keywords	FMVCTE ; FMvirus ; Liver fibrosis ; Autoimmune hepatitis ; Primary biliary cholangitis ; Specialties of internal medicine ; RC581-951
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Calprotectin and Imbalances between Acute-Phase Mediators Are Associated with Critical Illness in COVID-19

Georgios Kassianidis / Athanasios Siampanos / Garyphalia Poulakou / George Adamis / Aggeliki Rapti / Haralampos Milionis / George N. Dalekos / Vasileios Petrakis / Styliani Sympardi / Symeon Metallidis / Zoi Alexiou / Theologia Gkavogianni / Evangelos J. Giamarellos-Bourboulis / Theoharis C. Theoharides

International Journal of Molecular Sciences, Vol 23, Iss 4894, p

2022 Volume 4894

Abstract: The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of ... ...

Abstract	The trajectory from moderate and severe COVID-19 into acute respiratory distress syndrome (ARDS) necessitating mechanical ventilation (MV) is a field of active research. We determined serum levels within 24 h of presentation of 20 different sets of mediators (calprotectin, pro- and anti-inflammatory cytokines, interferons) of patients with COVID-19 at different stages of severity (asymptomatic, moderate, severe and ARDS/MV). The primary endpoint was to define associations with critical illness, and the secondary endpoint was to identify the pathways associated with mortality. Results were validated in serial measurements of mediators among participants of the SAVE-MORE trial. Levels of the proinflammatory interleukin (IL)-8, IL-18, matrix metalloproteinase-9, platelet-derived growth factor (PDGF)-B and calprotectin (S100A8/A9) were significantly higher in patients with ARDS and MV. Levels of the anti-inflammatory IL-1ra and IL-33r were also increased; IL-38 was increased only in asymptomatic patients but significantly decreased in the more severe cases. Multivariate ordinal regression showed that pathways of IL-6, IL-33 and calprotectin were associated with significant probability for worse outcome. Calprotectin was serially increased from baseline among patients who progressed to ARDS and MV. Further research is needed to decipher the significance of these findings compared to other acute-phase reactants, such as C-reactive protein (CRP) or ferritin, for the prognosis and development of effective treatments.
Keywords	ARDS ; COVID-19 ; cytokines ; IL-18 ; IL33r ; IL-38 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spontaneous Cirrhosis Regression in an IFN-beta-induced AIH-like Syndrome Following Drug Withdrawal

Maria Kalafateli / Christos Triantos / Athanasios Tsamandas / George N Dalekos

European Journal of Case Reports in Internal Medicine, Vol 3, Iss

Art of Facts or Artifacts?

2016 Volume 4

Abstract: Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) ... ...

Abstract	Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) administration for multiple sclerosis (MS). Based on liver autoimmune serology, histology and appropriate exclusion of other liver diseases, a diagnosis of AIH-related cirrhosis was established. Following discontinuation of IFNβ-1b, a complete resolution of biochemical activity indices was observed and the patient remained untreated on her own decision. However, 3 years later, after a course of intravenous methylprednisolone for MS, a new acute transaminase flare was recorded which subsided again spontaneously after 3 weeks. Liver biopsy and elastography showed significant fibrosis regression (F2 fibrosis). To our knowledge, this is the first report showing spontaneous cirrhosis regression in an IFNβ-1b-induced AIH-like syndrome following drug withdrawal, suggesting that cirrhosis might be reversible if the offending fibrogenic stimulus is withdrawn.
Keywords	Autoimmune hepatitis ; cirrhosis ; drug-induced liver injury ; interferon-beta ; multiple sclerosis ; Medicine ; R
Subject code	610
Language	English
Publishing date	2016-06-01T00:00:00Z
Publisher	SMC MEDIA SRL
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece

Katerina Tsilipounidaki / Zoi Athanasakopoulou / Elke Müller / Sindy Burgold-Voigt / Zoi Florou / Sascha D. Braun / Stefan Monecke / Nikolaos K. Gatselis / Kalliopi Zachou / Aggelos Stefos / Ilias Tsagalas / Marina Sofia / Vassiliki Spyrou / Charalambos Billinis / George N. Dalekos / Ralf Ehricht / Efthymia Petinaki

Microorganisms, Vol 10, Iss 159, p

No End to a Continuous Genetic Evolution

2022 Volume 159

Abstract: Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. ...

Abstract	Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca . This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.
Keywords	carbapenem resistance ; antimicrobial resistance genes ; Klebsiella pneumoniae ; Acinetobacter baumannii ; Pseudomonas aeruginosa ; Greece ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Epigenetic Modifications in Generalized Autoimmune Epithelitis

Pinelopi Arvaniti / Kalliopi Zachou / Aggeliki Lyberopoulou / Nikolaos K. Gatselis / Wesley H. Brooks / George N. Dalekos / Yves Renaudineau

Epigenomes, Vol 3, Iss 3, p

Sjögren’s Syndrome and Primary Biliary Cholangitis

2019 Volume 15

Abstract: Sjögren’s syndrome (SjS) and primary biliary cholangitis (PBC) can be classified as a model of generalized autoimmune epithelitis based on their frequent coexistence in clinical practice and the highly specific immune mediated injury of target epithelial ...

Abstract	Sjögren’s syndrome (SjS) and primary biliary cholangitis (PBC) can be classified as a model of generalized autoimmune epithelitis based on their frequent coexistence in clinical practice and the highly specific immune mediated injury of target epithelial cells. Both of these autoimmune diseases are characterized by female predominance, highly specific circulating autoantibodies, and immune-mediated destruction of the salivary and lachrymal glands and the biliary epithelial cells, respectively. Although the genetic predisposition has been well described for both diseases, genetic studies have failed to completely elucidate their pathogenesis. The recent integration of epigenetic data, analyzing the different cellular partners, opens new perspectives and allows for better understanding of these complex and still incurable diseases. Epigenetic studies on SjS have elucidated the role of DNA methylation alterations in disease pathogenesis, while epigenetic changes that influence expression of genes on the X chromosome have been implicated in the geo-variability and occurrence of PBC. The aim of this review is to describe the advances in epigenetics in the field of autoimmune epithelitis as well as to highlight how epigenetic changes could contribute to better understanding of disease pathogenesis and progression. These advances could yield insights on novel therapeutic interventions.
Keywords	Sjögren Syndrome ; sicca complex ; primary biliary cholangitis ; epithelitis ; epigenetics ; DNA methylation ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Early Primary Biliary Cirrhosis

Nikolaos K. Gatselis / Kalliopi Zachou / George N. Dalekos

Gastroenterology Research and Practice, Vol

A New Association with Erythema Nodosum of Unknown Origin

2010 Volume 2010

Abstract: Primary biliary cirrhosis (PBC) is associated with immune-mediated dermatologic disorders. The association of PBC with erythema nodosum (EN) seems rare. We report two females (42 and 44 years old) with low-grade fever, arthralgias, and elevated ... ...

Abstract	Primary biliary cirrhosis (PBC) is associated with immune-mediated dermatologic disorders. The association of PBC with erythema nodosum (EN) seems rare. We report two females (42 and 44 years old) with low-grade fever, arthralgias, and elevated cholestatic enzymes in the first and fatigue in the second. Patients were also suffering from typical EN lesions characterized by multiple erythematous, painful nodules over the anterior portions of their lower extremities. Clinical and extensive laboratory work up excluded all known EN causes. PBC diagnosis was established according to the cholestatic biochemical profile, anti-mitochondrial antibodies (AMA) positivity and liver histology (first), and AMA and antinuclear (ANA) PBC-specific antibodies (second). Our report may suggest that PBC could be kept in mind in EN patients of unknown aetiology and particularly, when middle-aged female patients are affected. In such cases a thorough evaluation for AMA and/or ANA PBC-specific antibodies could be helpful to achieve a correct and timely diagnosis.
Keywords	Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2010-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoimmune hepatitis in patients with chronic HBV and HCV infections

Eirini I. Rigopoulou / Kalliopi Zachou / Nikolaos Gatselis / George K. Koukoulis / George N. Dalekos

Annals of Hepatology, Vol 13, Iss 1, Pp 127-

patterns of clinical characteristics, disease progression and outcome

2014 Volume 135

Abstract: We retrospectively investigated the characteristics, patterns of disease progression, outcome and difficulties in the management in 11 patients with concurrent autoimmune hepatitis (AIH) and HBV or HCV infections (5 HCV and 6 HBV including 2 with HDV co- ... ...

Abstract	We retrospectively investigated the characteristics, patterns of disease progression, outcome and difficulties in the management in 11 patients with concurrent autoimmune hepatitis (AIH) and HBV or HCV infections (5 HCV and 6 HBV including 2 with HDV co-infection) since there are scarce data on this issue. HCV or HBV diagnosis preceded that of AIH in all patients by many years. At initial clinical and histological assessment almost half of patients had cirrhosis (45.5%) with the group of AIH and HCV carrying the highest frequency (4/5; 80%). In two thirds of patients, mostly with HCV and HBV/HDV, AIH was assumed to be IFNalpha-induced and experienced difficulties in achieving sustained virological response. On the contrary, the outcome of patients with HBV and AIH was better compared to those with AIH and HCV or HDV. In conclusion, chronic viral hepatitis infections concomitant with AIH are often very difficult to recognize and therefore, a significant delay in AIH diagnosis in this specific group of patients is usual. HBV patients with concomitant AIH seem to carry the most favorable outcome compared to those with HCV probably because of the use of nucleos(t)ide analogues which contrary to IFN-alpha can control HBV replication with no adjacent effect, related to exacerbation of autoimmune phenomena.
Keywords	Autoimmune hepatitis ; Hepatitis B ; Hepatitis C ; Hepatitis D ; Specialties of internal medicine ; RC581-951
Subject code	610
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Autoimmune hepatitis type-2 and Epstein-Barr virus infection in a toddler

Aglaia Zellos / Vana Spoulou / Eleftheria Roma-Giannikou / Ourania Karentzou / George N. Dalekos / Maria Theodoridou

Annals of Hepatology, Vol 12, Iss 1, Pp 147-

art of facts or an artifact?

2013 Volume 151

Abstract: Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) ... ...

Abstract	Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.
Keywords	Autoimmune liver diseases ; Children ; Cholestasis ; Epstein-Barr infection ; Liver kidney microsome antibodies ; Specialties of internal medicine ; RC581-951
Subject code	610
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Transcriptomic similarities and differences in host response between SARS-CoV-2 and other viral infections

Simone A. Thair / Yudong D. He / Yehudit Hasin-Brumshtein / Suraj Sakaram / Rushika Pandya / Jiaying Toh / David Rawling / Melissa Remmel / Sabrina Coyle / George N. Dalekos / Ioannis Koutsodimitropoulos / Glykeria Vlachogianni / Eleni Gkeka / Eleni Karakike / Georgia Damoraki / Nikolaos Antonakos / Purvesh Khatri / Evangelos J. Giamarellos-Bourboulis / Timothy E. Sweeney

iScience, Vol 24, Iss 1, Pp 101947- (2021)

2021

Abstract: Summary: The pandemic 2019 novel coronavirus disease (COVID-19) shares certain clinical characteristics with other acute viral infections. We studied the whole-blood transcriptomic host response to severe acute respiratory syndrome coronavirus 2 (SARS- ... ...

Abstract	Summary: The pandemic 2019 novel coronavirus disease (COVID-19) shares certain clinical characteristics with other acute viral infections. We studied the whole-blood transcriptomic host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using RNAseq from 24 healthy controls and 62 prospectively enrolled patients with COVID-19. We then compared these data to non-COVID-19 viral infections, curated from 23 independent studies profiling 1,855 blood samples covering six viruses (influenza, respiratory syncytial virus (RSV), human rhinovirus (HRV), severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), Ebola, dengue). We show gene expression changes in COVID-19 versus non-COVID-19 viral infections are highly correlated (r = 0.74, p < 0.001). However, we also found 416 genes specific to COVID-19. Inspection of top genes revealed dynamic immune evasion and counter host responses specific to COVID-19. Statistical deconvolution of cell proportions maps many cell type proportions concordantly shifting. Discordantly increased in COVID-19 were CD56bright natural killer cells and M2 macrophages. The concordant and discordant responses mapped out here provide a window to explore the pathophysiology of the host response to SARS-CoV-2.
Keywords	Molecular Biology ; Immunology: Bioinformatics ; Transcriptomics ; Science ; Q
Subject code	610 ; 572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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