Publications by authors named "Spyros I Siakavellas"

Article Synopsis
  • Hepatocellular carcinoma (HCC) is the leading type of primary liver cancer, with increasing incidence and high mortality rates, and there are currently limited curative treatment options available despite advances in diagnosis and therapy.
  • Recent advances in understanding the tumor microenvironment have brought attention to immunotherapy as a promising approach for treating advanced HCC, although only a small number of patients benefit from existing solutions.
  • The glucocorticoid-induced TNFR-related protein (GITR) shows potential as a therapeutic target for HCC due to its role in enhancing T-cell function and inhibiting regulatory T-cells, along with evidence suggesting it may aid in anti-tumor effects and liver regeneration.
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Background: The UNITI trial reports efficacy of ustekinumab (UST) dose intensification in Crohn's disease (CD) from 12- to 8-weekly, but not 4-weekly. We aimed 1) to assess the cumulative incidence of UST dose intensification to 4- or 6-weekly, 2) to identify factors associated with dose intensification, and 3) to assess the effectiveness of this strategy.

Methods: We performed a retrospective, observational cohort study in NHS Lothian including all UST treated CD patients (2015-2020).

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Article Synopsis
  • The study aimed to evaluate the long-term effectiveness and safety of the adalimumab biosimilar SB5 in patients with inflammatory bowel disease (IBD), comparing those who switched from the ADA originator and those who started directly on SB5.
  • A total of 481 IBD patients were analyzed, with 70.8% of those who switched to SB5 remaining on the treatment after a year, while 60.3% of new users also persisted beyond that timeframe.
  • Overall, no significant changes in clinical outcomes were observed post-switch, suggesting that switching to SB5 is both effective and safe for long-term use in IBD patients.
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Background: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy.

Aims: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes.

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Background & Aims: The level of fecal calprotectin (FC) correlates with endoscopic evidence of inflammation in Crohn's disease (CD). A treat-to-target algorithm for patients with CD, that incorporates FC, outperforms a treatment strategy based on symptoms alone in the induction of mucosal healing at 12 months. We investigated whether normalization of FC within 12 months of diagnosis of CD is associated with a reduction in disease progression.

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Purpose Of Review: Immune checkpoint inhibitors are monoclonal antibodies against the inhibitory, co-stimulatory molecules CTLA-4 and PD-1/PD-L1. Their use in oncology has been associated with frequent and diverse immune-related adverse events. In the digestive tract, such toxicity presents primarily as colonic inflammation, resembling inflammatory bowel disease (IBD).

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Background And Aim: Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract with the potential to progress to a severe debilitating state. Treatment with biological agents is highly efficient, improving both short-term outcomes and long-term prognosis. Nonetheless, up to 60% of patients receiving biological therapy will exhibit nonresponse at some point.

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Aim: To examine the impact of liver cirrhosis on QT interval and cardiac autonomic neuropathy (CAN).

Methods: A total of 51 patients with cirrhosis and 51 controls were examined. Standard 12-lead electrocardiogram recordings were obtained and QT as well as corrected QT interval (QTc) and their dispersions (dQT, dQTc) were measured and calculated using a computer-based program.

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Aim: To evaluate the utility of fecal calprotectin (FC) in predicting relapse and endoscopic activity during follow-up in an inflammatory bowel disease (IBD) cohort.

Methods: All FC measurements that were obtained during a 3-year period from patients with inflammatory bowel disease in clinical remission were identified. Data regarding the short-term (6 mo) course of the disease were extracted from the medical files.

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Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs).

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Article Synopsis
  • DcR3 is a protein with antiapoptotic and immune-modulating functions, and its serum levels (sDcR3) have not been studied in the context of chronic liver diseases like hepatitis and cirrhosis.
  • Research found that sDcR3 levels were significantly higher in patients with chronic viral hepatitis, decompensated cirrhosis, and hepatocellular carcinoma compared to healthy controls, indicating a potential marker for liver disease severity.
  • Elevated sDcR3 levels correlated with liver damage severity, suggesting that it could be used to assess liver fibrosis and monitor progression to more severe stages of liver disease.
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Background/aim: Two-dimensional shear-wave elastography (2D-SWE) is a new elastographic technique that is increasingly being used across several indications. We assessed the reliability and applicability of 2D-SWE in patients with various chronic liver diseases and attempted to identify parameters potentially affecting liver stiffness.

Methods: We included all patients with chronic liver disease who underwent 2D-SWE examination over a 15-month period.

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Background: Bacterial translocation (BT) commonly occurs in cirrhosis. Reliable biomarkers for BT are currently lacking. Human beta defensin-1 (hBD-1) is a member of the family of natural antimicrobial peptides produced by epithelial cells and participates in the mucosal defensive mechanisms that prevent BT.

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Bacterial translocation (BT) refers to the passage of viable bacteria or bacterial products from the intestinal lumen, through the intestinal epithelium, into the systemic circulation and extraintestinal locations. The three principal mechanisms that are thought to be involved in BT include bacterial overgrowth, disruption of the gut mucosal barrier and an impaired host defence. BT is commonly observed in liver cirrhosis and has been shown to play an important role in the pathogenesis of the complications of end stage liver disease, including infections as well as hepatic encephalopathy and hepatorenal syndrome.

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Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) is a member of the TNF superfamily of proteins (TNFSF15), which signals through association with death domain receptor 3 (DR3). Decoy receptor 3 (DcR3) competes with DR3 for TL1A binding and inhibits functional signaling. These proteins are significantly upregulated in inflamed intestinal tissues, and their pathogenetic importance for inflammatory bowel disease (IBD) is suggested by accumulating evidence.

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Importance: TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases.

Objectives: This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA).

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Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants.

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Background: Mucosal expression of immunological mediators is modified in inflammatory bowel disease (IBD). Quantification of target gene messenger RNA (mRNA) transcripts depends on the normalization to a housekeeping or reference gene. Stability of housekeeping gene expression is critical for the accurate measurement of transcripts of the target gene.

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Crohn's disease is an immune-mediated disease that is characterized by chronic intestinal inflammation. Effector CD4+ T-lymphocytes are expanded in Crohn's disease-associated inflammatory lesions and play a critical role in the pathogenesis of this condition. Recently, a novel population of effector T-lymphocytes has been identified, which is clearly separated from the traditional Th1 and Th2 lineages and is characterized by the secretion of IL-17, hence its designation as Th17.

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Immunosuppressive drugs are commonly used for the treatment of inflammatory bowel disease. Patients receiving immunosuppressants are susceptible to a variety of infections with opportunistic pathogens. We present a case of skin infection with Mycobacterium chelonae in a 60-year-old Caucasian woman with ulcerative colitis who had been treated with corticosteroids and azathioprine.

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Background: TNF-like cytokine 1A provides co-stimulatory signals to activated lymphocytes through binding to death-domain receptor-3. Decoy receptor-3 inhibits death-domain receptor-3 signalling, rendering immunocytes resistant to apoptosis. These functions may be important for the pathogenesis of Crohn's disease.

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Aim: To investigate the significance of ileocolonoscopy with histology in the evaluation of post-transplantation persistent diarrhea (PD).

Methods: We retrospectively reviewed all records of renal transplant patients with PD, over a 3-year period. All patients were referred for ileocolonoscopy with biopsy, following a negative initial diagnostic work up.

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Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls.

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Background/aims: The incidence of celiac disease (CD) has increased in recent years due to the recognition of atypical forms and the identification of silent cases through serological screening. Our aim was to detect temporal trends in the presentation of pediatric CD in Greece.

Methods: We reviewed the medical files of all children diagnosed with CD between 1978 and 2007 at a single academic pediatric center.

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