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Background Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD) and may have an unfavorable impact on quality of life (QoL). The IBD-Fatigue scale (with components SCORE1 and SCORE2) is a recently developed disease-specific questionnaire. We sought to validate a Greek version of IBD-F and use it to assess the severity and characteristics of fatigue and its effect on QoL in our study population. Methods The IBD-F scale was validated and used to obtain fatigue-related data from patients with IBD attending a tertiary care hospital. Correlations with other fatigue and QoL instruments were performed. Results The Greek IBD-F showed high internal consistency and test-retest reliability (Cronbach’s alpha = 0.901/0.966 and intraclass correlation coefficient = 0.876/0.895 for SCORE1/SCORE2, respectively). A SCORE1 >7.5 suggested “significant” fatigue. In a cohort of 157 patients (mean age = 35.8 y; male patients = 52.2%; patients with Crohn disease = 65.6%), both SCORE1 and SCORE2 were significantly associated with Crohn disease (odds ratio [OR] = 4.17; 95% confidence interval [CI], 2.05-8.47; b = 8.5; 95% CI, 2.8-14.1, respectively), female sex (OR = 7.27; 95% CI, 3.19-16.6; b = 15.3; 95% CI, 9-21.6), and Harvey-Bradshaw Index/Simple Clinical Colitis Activity Index score (OR = 1.22; 95% CI, 1.06-1.39; b = 1.8; 95% CI, 0.9-2.8). A SCORE1 >7.5 was present in 46% of patients in remission, and 82% of patients with a baseline SCORE1 >7.5 remained fatigued at serial measurements. The SCORE1 was significantly associated with impaired QoL (P < 0.001). Conclusions The validated IBD-F scale is a useful and applicable instrument for use in the IBD population. A large proportion of patients have significant fatigue, which is maintained longitudinally, independent of inflammatory activity. Fatigue impairs QoL, thus necessitating interventions that may lead to its amelioration in the IBD population.

Background Vedolizumab is a monoclonal antibody against the gut-homing integrin α4β7 that is being used for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). An increasing number of studies have reported new onset or reactivation of extra-intestinal manifestations (EIMs), among which arthralgia is the most prominent. Methods We aimed to study the incidence, characteristics and possible predictors of arthralgia development in patients under treatment with Vedolizumab, in a retrospective cohort study in 3 IBD centers in Athens, Greece. UC and CD patients treated with Vedolizumab (n=115, men=50.4%, UC=70.4%, median duration of follow-up=9 months) or Infliximab (n=93, men=69.9%, UC=29%, median duration of follow-up=29.1 months) were recruited. For each participant the entry point for the study was the first day of drug administration while the endpoint was either the day of arthralgia occurrence, the day of drug discontinuation or the day of the last interview if the patient was still receiving the drug. The SPSS-23 statistical program was used for analysis. Results Patients under Vedolizumab were at higher risk for new-onset (HR=4.76, P=0.001) and recurrent (HR=5.41, P=0.003) arthralgia compared to patients under Infliximab. New-onset arthralgia occurred in 20.9% while recurrent in 37.8% of 45 patients with a history of articular EIM. New-onset and recurrent arthralgias differed in certain characteristics. New-onset arthralgia involved peripheral joints in 91.7%, was milder, occurred shortly after Vedolizumab initiation (median drug exposure= 3 months, IQR=5 months) in patients in remission and remitted in 50% of cases. In multivariate Cox’s proportional-hazards model new-onset arthralgia was significantly associated with extensive colitis (HR=2.91, 95%CI=1.04-8.12). Of 15 patients with concomitant treatment of azathioprine no one manifested new-onset arthralgia (X2 P= 0.03, Fisher’s exact test P=0.038). Similarly, no patient with a history of appendectomy manifested new-onset arthralgia (n=12, X2 P= 0.067, Fisher’s exact test P=0.12). No predictors were identified for recurrent arthralgia. No patients discontinued vedolizumab due to arthralgia. Conclusion Vedolizumab treatment may be associated with the temporal manifestation of arthralgias. Patients under Vedolizumab with extensive ulcerative colitis have a higher risk of developing new-onset arthralgia, whereas, concomitant treatment with azathioprine and a history of appendectomy appears to have a prophylactic effect. This effect could be indicative of a distinct pathophysiological lymphocyte-mediated mechanism.

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. Patients with acute hepatitis, active cholestatic disease, or severe heart failure were excluded. The procedures were performed by three adequately trained operators. Standard operating procedures for liver ultrasonography and elastography were followed. RESULTS 2D-SWE was reliable in 98% of 605 patients. SD to mean liver stiffness value ratio greater than 9.14%, which was considered an indicator of reliability, was associated independently with age more than 50 years, obesity, or overweight, and use of statins for hyperlipidemia. 2D-SWE was applicable, requiring a median time of 7 min per examination and exceeding 15 min in only 5.5% of patients. Worse applicability expressed as duration more than 0.7 min per reliable measurement was associated independently with age more than 50 years and obesity. The mean and median liver stiffness values were 11.6 and 7.7 kPa, respectively. Liver stiffness more than 7.7 kPa was associated independently with age more than 50 years and increased waist circumference. CONCLUSION 2D-SWE represents an applicable method of assessment of liver fibrosis that can provide reliable results in the vast majority of patients with chronic liver diseases. Older age and obesity may affect the reliability and applicability of the method as well as the severity of liver fibrosis.

Background Fatigue is common in IBD patients, even in clinical remission and adversely affects the quality of life. For this reason, it has been suggested to use fatigue questionnaires as PROS (patient reported outcomes). We aimed to study the degree of fatigue in IBD patients and identify factors that are positively or negatively related to its presence. Methods Patients with IBD (men: 51.6%, Crohn’s Disease: 65.2%, age: 36.7 years median, 18.1–72 yrs range), with a regular f-up in our Department completed the Fatigue Severity Scale, IBD Fatigue self assessment 1 & 2, short IBDQ and Short Health Scale upon consensus. Two groups of patients were studied: Group A, patients attended the IBD outpatient clinic (121 patients / 144 questionnaires) and Group B, patients attended the infusion centre for biological therapy (55 patients / 414 questionnaires). The SPSS-23 statistical programme was used to identify correlations between fatigue and various clinical-laboratory parameters of patients. Results Problematic fatigue (FSS> 36) was reported by 46.5% of patients. No difference was observed between Crohn’s disease and Ulcerative Colitis or between the two groups of patients. There were statistically significant correlations between fatigue and disease activity (R = 0.428, P Conclusion In the group of IBD patients we studied, a significant correlation with various clinical characteristics was observed. The presence of fatigue is a factor associated with poor quality of life for patients.

Farnesoid x receptor (FXR) belongs to the group of nuclear receptors (NRs), which regulate the expression of various genes by binding to DNA either as a monomer or a heterodimer with retinoid x receptor.FXR affects several metabolic pathways through its specific target genes, regulating bile acid (BA) synthesis and homeostasis, glucose and lipid metabolism, also exhibiting a crucial role in intestinal bacterial growth and liver regeneration. Additionally, FXR is involved in the pathogenesis of different cholestatic diseases, as well as non-alcoholic fatty liver disease, inflammatory bowel disease (IBD) and primary idiopathic BA malabsorption.Analyses of certain FXR polymorphisms revealed associations with clinical phenotypes and susceptibility to various human diseases. FXR single-nucleotide polymorphisms seem to be correlated with differences in glucose homeostasis, gallstone formation, intrahepatic cholestasis of pregnancy, IBD and therapeutic response to hypolipidemic therapy, among studied populations. Unfortunately, little data are still available and more studies remain to be done to determine the contribution of FXR polymorphisms in estimating risk factors and clinical outcomes for several diseases.

UNLABELLED Farnesoid X Receptor (FXR) and its co-partners Retinoid X Receptors (RXRs) are considered to participate in crucial biochemical and cellular processes, being involved in the pathogenesis of several diseases, including cancer. The present study aimed to evaluate the clinical significance of FXR alone and in conjunction with RXRs expression, in pancreatic adenocarcinoma. FXR, RXR-α, -β and -γ protein expression was assessed immunohistochemically on tumoral samples of 55 pancreatic adenocarcinoma cases and was statistically analyzed with clinicopathological characteristics, tumor proliferative capacity and patients' survival. Enhanced FXR expression was borderline associated with earlier histopathological stage (p=0.054). Concomitant elevated FXR/RXR-α expression was significantly associated with decreased tumor histological grade (p=0.017), while concomitant enhanced FXR/RXR-β and FXR/RXR-γ expression with earlier histopathological stage (p=0.017 and p=0.004, respectively) and smaller tumor size (p=0.037 and p=0.005, respectively). Concomitant enhanced FXR/RXR-γ expression was additionally significantly associated with the absence of lymph node metastases (p=0.018). Pancreatic adenocarcinoma patients with enhanced FXR, FXR/RXR-β or -γ expression showed significantly longer survival times compared to those with low expression (p=0.013, p=0.021 and p

Psoriasis is a chronic, immune-mediated and angiogenesis-dependent disease. Activated keratinocytes in psoriatic lesions produce pro-angiogenic cytokines, including vascular endothelial growth factor (VEGF), which binds to vascular endothelial growth factor receptor (VEGFR) and promotes cell proliferation and angiogenesis. Sorafenib (BAY 43-9006) is a molecular multikinase inhibitor of RAF kinase, platelet-derived growth factor (PDGF), VEGFR-1, -2, -3, platelet-derived growth factor receptor (PDGFR)-β and c-Kit. This molecule inhibits tumor cell proliferation and angiogenesis and it is currently approved for the treatment of hepatocellular carcinoma (HCC).We present the complete remission of resistant psoriasis in a hepatitis C virus (HCV)-infected cirrhotic patient who was treated with sorafenib, for recurrent HCC.Several targeted therapies have demonstrated efficacy against psoriasis. More research and well-designed studies, both in novel drugs and those already marketed for other indications, are needed to determine their value as potential novel therapies for psoriasis.

Background Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, −2, −4 and −6 protein expression in pancreatic adenocarcinoma. Methods HDAC-1, −2, −4 and −6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients’ survival. Results Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and −6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634). Conclusions The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

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. Due to the importance of BT in the natural history of cirrhosis, there is intense interest for the discovery of biomarkers of BT. To date, several such candidates have been proposed, which include bacterial DNA, soluble CD14, lipopolysaccharides endotoxin, lipopolysaccharide-binding protein, calprotectin and procalcitonin. Studies on the association of these markers with BT have demonstrated not only promising data but, oftentimes, contradictory results. As a consequence, currently, there is no optimal marker that may be used in clinical practice as a surrogate for the presence of BT.

Objectives Pregnane X receptor (PXR) has been involved in human malignancy, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The present study aimed to assess the clinical significance of PXR in pancreatic adenocarcinoma. Methods Pregnane X receptor and its heterodimers' PXR/retinoid X receptor α (RXR-α), RXR-β, and RXR-γ expression were assessed immunohistochemically on tumoral samples from 55 pancreatic adenocarcinoma patients and were associated with clinicopathologic parameters, tumor proliferative capacity, and patients' survival. Results Enhanced PXR expression was noted in 24 (43.6%) of 55 pancreatic adenocarcinoma cases. Pancreatic adenocarcinoma patients presenting increased histological grade of tumor differentiation showed a significant increased incidence of elevated PXR expression (P = 0.023). Enhanced PXR/RXR-β expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.005 and P = 0.003, respectively). Elevated PXR/RXR-γ expression was significantly associated with smaller tumor size and earlier clinical stage (P = 0.012 and P = 0.014, respectively) and borderline with the absence of lymph node metastases (P = 0.056). In addition, pancreatic adenocarcinoma patients presenting enhanced PXR/RXR-γ expression showed marginally longer survival times compared with those with decreased expression (log-rank test, P = 0.053). Conclusions This study supported evidence that PXR and its copartners' overexpression may be associated with favorable clinicopathologic parameters and better outcome in pancreatic adenocarcinoma.