Intussuscepted Polypoid Meckel's Diverticulum Presenting With Gastrointestinal Bleeding in a Young Adult.

A 22-year-old female patient with a recent hospitalization for gastrointestinal bleeding presented with recurrent hematochezia and a positive shock index. Previous investigations, including endoscopy and wireless small bowel capsule, were non-diagnostic. CT angiography revealed extravasation in the ileum. Initial tests like technetium-99m scintigraphy and ileocolonoscopy were negative. Repeat wireless small bowel capsule identified a partially ulcerated polypoid mass in the distal ileum. At surgical exploration, an intussuscepted Meckel's diverticulum was identified and resected. A histopathologic examination confirmed the diagnosis. Meckel's diverticulum is a rare cause of gastrointestinal bleeding in adults. Preoperative diagnosis can be challenging. Reports of a polypoid morphology are very scarce in indexed literature and mostly derive from investigation with device-assisted enteroscopy. We report this extremely rare finding at capsule endoscopy to raise clinician awareness and to discuss diagnostic difficulties associated with similar cases, such as the negative scintigraphy result and the optimal timing of repeat capsule endoscopy.

Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

BACKGROUND: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. METHODS: Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. RESULTS: Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. CONCLUSION: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.

Low Urinary Free Cortisol as a Risk Factor for Patients with Variceal Bleeding.

Background and Objectives: Specificity and reliability issues of the current cortisol assessment methods lead to limitations on the accurate assessment of relative adrenal insufficiency. Although free cortisol provides a more accurate evaluation of adrenal cortisol production, the expense and time-consuming nature of these assays make them impractical for routine use. Research has, thus, focused on alternative methods, such as indirectly measuring free cortisol using Coolens' equation or directly assessing salivary cortisol concentration, which is considered a more favorable approach despite associated challenges like sampling issues and infection risks. The aim of this study was to explore correlations between 24 h urinary free cortisol (UFC), free plasma cortisol, serum total cortisol, and salivary cortisol as potential reliable indices of free cortisol in the setting of variceal bleeding. Additionally, we assessed the predictive value of UFC for 6-week mortality and 5-day treatment failure in patients with liver cirrhosis and variceal bleeding. Materials and Methods: A total of 40 outpatients with liver cirrhosis and variceal bleeding were enrolled. Free cortisol levels in serum, saliva, and urine were assessed using the electrochemiluminescence immunoassay method. For the measurement of plasma-free cortisol, a single quadrupole mass spectrometer was employed. The quantification of free cortisol was fulfilled by analyzing the signal response in the negative ESI-MS mode. Results: UFC was significantly correlated to free plasma cortisol. Negative correlations were demonstrated between UFC, the Child-Pugh (CP) score, and C reactive protein (CRP) levels. In the multivariate analysis, CP stage C was associated with 6-week mortality risk and portal vein thrombosis with 5-day treatment failure using Cox regression and binary logistic regression analyses, respectively. Patients who experienced rebleeding, infection, or death (or any combination of these events) presented with lower levels of UFC. Conclusions: This study suggests that low levels of UFC may impose a risk factor for patients with liver cirrhosis and variceal bleeding. The use of UFC as an index of adrenal cortisol production in variceal bleeding warrants further investigation.

The Role of the Pancreatic Stone Protein in Predicting Intra-Abdominal Infection-Related Complications: A Prospective Observational Single-Center Cohort Study.

BACKGROUND: The Pancreatic Stone Protein (PSP) is an acute-phase protein that is mainly secreted by pancreatic cells in response to stress. The current literature supports its use as a predictor of sepsis. Its prognostic role has recently been evaluated in a point-of-care setting, mostly in high-risk patients. We conducted a prospective observational cohort study to evaluate its utility in the prognosis of patients admitted to the hospital with a diagnosis of intra-abdominal infection. METHODS: Adult patients consecutively admitted to the Internal Medicine Department of the University Hospital of Patras, Greece, with a diagnosis of intra-abdominal infection were enrolled. PSP levels were measured within 24 h of admission in whole blood. RESULTS: a total of 40 patients were included after being diagnosed with IAI. PSP was used as an independent predictive factor for sepsis after adjusting for age with OR = 7.888 (95% CI: 1.247-49.890). PSP also predicted readmission and the need for treatment escalation (p: <0.01) and was an excellent prognostic factor regarding these outcomes (AUC = 0.899, 95% CI: 0.794-1.0, and AUC = 0.862, 95% CI: 0.748-0.976, respectively). PSP also proved superior to CRP, ferritin, and fibrinogen in sepsis diagnosis, treatment escalation, and readmission prediction with an AUC of 0.862, 0.698, and 0.899, respectively. CONCLUSIONS: PSP can predict unfavorable outcomes, such as sepsis development, readmission, and the need for treatment escalation among patients with intra-abdominal infections.

Alexithymic characteristics and interoceptive abilities are associated with disease severity and levels of C-reactive protein and cytokines in patients with inflammatory bowel disease.

Background: Alexithymia and atypical gut-brain signaling have been linked to the pathophysiology of inflammatory bowel disease (IBD). We herein assessed IBD patients' alexithymia levels and interoceptive abilities, and detected potential correlations with psychological distress, symptom severity and disease activity, and inflammation indices. Methods: Adult IBD outpatients and healthy controls were recruited. Alexithymia was assessed using the Toronto Alexithymia Scale, interoceptive accuracy using the Heartbeat Counting Test (cardiac interoception) and the Water Load Test-II (gastric interoception), and interoceptive sensibility using the Multidimensional Assessment of Interoceptive Awareness (MAIA). Results: Forty-one patients with Crohn's disease (CD), 16 with ulcerative colitis (UC), and 50 healthy controls were included. In CD patients, the level of externally oriented thinking and total alexithymia score were correlated with disease activity (P=0.027 and P=0.047, respectively), while in UC patients difficulties in identifying emotions were linked to disease activity (P=0.007). In CD patients, the Noticing, Not-Worrying and Emotional Awareness MAIA subscale score were correlated with C-reactive protein levels (P=0.005, P=0.048 and P=0.005), the Noticing subscale score with interleukin (IL)-1ß levels (r=-0.350, P=0.039), the Not-Distracting subscale score with IL-6 levels (r=-0.402, P=0.017), and the Emotional Awareness subscale score with IL-1ß (r=-0.367, P=0.030) and IL-6 (r=-0.379, P=0.025) levels. Finally, in UC patients, the Not-Worrying subscale score was significantly associated with IL-6 levels (r=-0.532, P=0.049), while difficulties in identifying emotions were linked to IL-8 levels (r=0.604, P=0.022). Conclusion: Emotional and interoceptive processing is associated with IBD disease activity, suggesting a potential implication for IBD pathophysiology.

The Influence of Single Nucleotide Polymorphisms on Vitamin D Receptor Protein Levels and Function in Chronic Liver Disease.

Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been associated with chronic liver disease. We investigated the role of VDR SNPs on VDR protein levels and function in patients with chronic liver disease. VDR expression levels were determined in peripheral T lymphocytes (CD3+VDR+), monocytes (CD14+VDR+), and plasma from patients (n = 66) and healthy controls (n = 38). Genotyping of SNPs and the determination of expression of VDR/vitamin D-related genes were performed by using qPCR. The effect of FokI SNP on vitamin D-binding to VDR was investigated by molecular dynamics simulations. CD14+VDR+ cells were correlated with the MELD score. The ApaI SNP was associated with decreased CD3+VDR+ levels in cirrhotic patients and with higher liver stiffness in HCV patients. The BsmI and TaqI SNPs were associated with increased VDR plasma concentrations in cirrhotic patients and decreased CD14+VDR+ levels in HCV patients. The FokI SNP was associated with increased CD3+VDR+ levels in cirrhotic patients and controls. VDR polymorphisms were significantly related to the expression of genes critical for normal hepatocyte function and immune homeostasis. VDR expression levels were related to the clinical severity of liver disease. VDR SNPs may be related to the progression of chronic liver disease by affecting VDR expression levels.

HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

Sedation during endoscopic procedures: a Hellenic Society of Gastroenterology Position Statement.

Administration of sedation by non-anesthesiologists during gastrointestinal endoscopy remains highly controversial in Greece. The aim of this set of 16 position statements prepared by experts in the field on behalf of the Hellenic Society of Gastroenterology is to aid gastroenterologists in their everyday clinical practice and provide evidence for the best use of drugs for the sedation of patients who undergo an endoscopy. The statements address issues such as the level of sedation required, the best drugs used, their mode of action, their side-effects and possible ways to counter their action, and were adopted if at least 80% of all participants agreed upon them.

Gastrointestinal bleeding in athletes.

Gastrointestinal (GI) bleeding (GIB) in athletes has previously been reported in several studies, as an important factor of underperformance in competitive sports events. Yet it is still underreported, partly because it is usually occult and self-limited soon after the effort. It can originate in either the upper or the lower GI tract and can be proportionally related to the amount and duration of effort. Key pathophysiological factors seem to include splanchnic hypoperfusion, mechanical trauma of the GI wall, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Appropriate nutrition, hydration and regulation of exercise, along with substances such as arginine and citrulline can relieve upper and lower GI symptoms, including nausea, vomiting, cramping, diarrhea, and possibly hemorrhage. Cessation of NSAIDs, use of proton pump inhibitors and H2-receptor-antagonists, as well as "training" the gut, also seem to be effective in reducing the incidence of GIB in athletes. Maintenance of hemodynamic stability and identification of the source of bleeding are key elements in the management of this condition. Endoscopy might be necessary for both. GIB should not be immediately attributed to endurance exercise, and endoscopy should always be performed to rule out other existing pathology.

Treatment of portal vein thrombosis in cirrhosis: a multicenter real life cοhort study.

BACKGROUND: Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics. METHODS: This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used. RESULTS: Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047). CONCLUSIONS: In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Vitamin D and Microbiome: Molecular Interaction in Inflammatory Bowel Disease Pathogenesis.

Studies of systemic autoimmune diseases point to characteristic microbial patterns in various diseases, including inflammatory bowel disease (IBD). Autoimmune diseases, and IBD in particular, show a predisposition to vitamin D deficiency, leading to alterations in the microbiome and disruption of intestinal epithelial barrier integrity. This review examines the role of the gut microbiome in IBD and discusses how vitamin D-vitamin D receptor (VDR)-associated molecular signaling pathways contribute to the development and progression of IBD through their effects on gut barrier function, the microbial community, and immune system function. The present data demonstrate that vitamin D promotes the proper function of the innate immune system by acting as an immunomodulator, exerting anti-inflammatory effects, and critically contributing to the maintenance of gut barrier integrity and modulation of the gut microbiota, mechanisms that may influence the IBD development and progression. VDR regulates the biological effects of vitamin D and is related to environmental, genetic, immunologic, and microbial aspects of IBD. Vitamin D influences the distribution of the fecal microbiota, with high vitamin D levels associated with increased levels of beneficial bacterial species and lower levels of pathogenic bacteria. Understanding the cellular functions of vitamin D-VDR signaling in intestinal epithelial cells may pave the way for the development of new treatment strategies for the therapeutic armamentarium of IBD in the near future.

Small Extracellular Vesicles (sEVs) Biogenesis Molecular Players Are Associated with Clinical Outcome of Colorectal Cancer Patients.

A growing number of studies have shed light on the role of small extracellular vesicles (sEVs), including exosomes, in colorectal cancer (CRC). Available data regarding the clinical significance of molecular players in CRC, implicated in sEVs biogenesis, is limited. In this study, we assessed the expression of the most important genes which are implicated in sEVs biogenesis and their association with sEVs plasma levels, investigated with a double sandwich ELISA assay, as well as with the clinical outcome of patients with CRC. Our study shows that RAB27A, RAB27B, RAB2B, and RAB3B mRNA levels were lower in tumor tissues compared to tumor adjacent, non-malignant tissues (p < 0.001, p = 0.009, p = 0.011, and p < 0.001, respectively). In addition, high tumor expression of RAB27A, RAB27B, RAB9A, RAB11B, and STX1A was favorable of a 5-year survival (p = 0.038, p = 0.015, p = 0.008, p = 0.002, and p = 0.028, respectively). Furthermore, patients with adenomas had lower overall plasma sEVs concentrations, compared to healthy volunteers (p = 0.026), while no statistically significant differences were observed in the overall or tumor-derived plasma sEVs concentration (p = 0.885 and p = 0.330, respectively) of CRC patients. In conclusion, sEVs biogenesis has a potentially significant role in CRC, with RAB27A, RAB27B, RAB9A, RAB11B, and STX1A having a promising role in survival outcomes.

miRNA Molecules-Late Breaking Treatment for Inflammatory Bowel Diseases?

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a critical role in regulating epigenetic mechanisms in inflammation-related diseases. Inflammatory bowel diseases (IBDs), which primarily include ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic recurrent inflammation of intestinal tissues. Due to the multifactorial etiology of these diseases, the development of innovative treatment strategies that can effectively maintain remission and alleviate disease symptoms is a major challenge. In recent years, evidence for the regulatory role of miRNAs in the pathogenetic mechanisms of various diseases, including IBD, has been accumulating. In light of these findings, miRNAs represent potential innovative candidates for therapeutic application in IBD. In this review, we discuss recent findings on the role of miRNAs in regulating inflammatory responses, maintaining intestinal barrier integrity, and developing fibrosis in clinical and experimental IBD. The focus is on the existing literature, indicating potential therapeutic application of miRNAs in both preclinical experimental IBD models and translational data in the context of clinical IBD. To date, a large and diverse data set, which is growing rapidly, supports the potential use of miRNA-based therapies in clinical practice, although many questions remain unanswered.

Comparative performance and external validation of three different scores in predicting inadequate bowel preparation among Greek inpatients undergoing colonoscopy.

Background: Predictive scores aim to predict bowel preparation adequacy among hospitalized patients undergoing colonoscopy. We evaluated the comparative efficacy of these scores in predicting inadequate bowel cleansing in a cohort of Greek inpatients. Methods: We performed a post hoc analysis of data generated from a cohort of inpatients undergoing colonoscopy in 4 tertiary Greek centers to validate the 3 models currently available (models A, B and C). We used the Akaike information criterion to quantify the performance of each model, while Harrell's C-index, as the area under the receiver operating characteristics curve (AUC), verified the discriminative ability to predict inadequate bowel prep. Primary endpoint was the comparison of performance among models for predicting inadequate bowel cleansing. Results: Overall, 261 patients-121 (46.4%) female, 100 (38.3%) bedridden, mean age 70.7±15.4 years-were included in the analysis. Model B showed the highest performance (Harrell's C-index: AUC 77.2% vs. 72.6% and 57.5%, compared to models A and C, respectively). It also achieved higher performance for the subgroup of mobilized inpatients (Harrell's C-index: AUC 72.21% vs. 64.97% and 59.66%, compared to models A and C, respectively). Model B also performed better in predicting patients with incomplete colonoscopy due to inadequate bowel preparation (Harrell's C-index: AUC 74.23% vs. 69.07% and 52.76%, compared to models A and C, respectively). Conclusions: Predictive model B outperforms its comparators in the prediction of inpatients with inadequate bowel preparation. This model is particularly advantageous when used to evaluate mobilized inpatients.

NAFLD and HBV interplay - related mechanisms underlying liver disease progression.

Non-alcoholic fatty liver disease (NAFLD) and Hepatitis B virus infection (HBV) constitute common chronic liver diseases with worldwide distribution. NAFLD burden is expected to grow in the coming decade, especially in western countries, considering the increased incidence of diabetes and obesity. Despite the organized HBV vaccinations and use of anti-viral therapies globally, HBV infection remains endemic and challenging public health issue. As both NAFLD and HBV have been associated with the development of progressive fibrosis, cirrhosis and hepatocellular carcinoma (HCC), the co-occurrence of both diseases has gained great research and clinical interest. The causative relationship between NAFLD and HBV infection has not been elucidated so far. Dysregulated fatty acid metabolism and lipotoxicity in NAFLD disease seems to initiate activation of signaling pathways that enhance pro-inflammatory responses and disrupt hepatocyte cell homeostasis, promoting progression of NAFLD disease to NASH, fibrosis and HCC and can affect HBV replication and immune encountering of HBV virus, which may further have impact on liver disease progression. Chronic HBV infection is suggested to have an influence on metabolic changes, which could lead to NAFLD development and the HBV-induced inflammatory responses and molecular pathways may constitute an aggravating factor in hepatic steatosis development. The observed altered immune homeostasis in both HBV infection and NAFLD could be associated with progression to HCC development. Elucidation of the possible mechanisms beyond HBV chronic infection and NAFLD diseases, which could lead to advanced liver disease or increase the risk for severe complications, in the case of HBV-NAFLD co-existence is of high clinical significance in the context of designing effective therapeutic targets.

Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases.

There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D-VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D-VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.

Acute Upper Gastrointestinal Bleeding: Less Severe Bleeding in More Frail and Older Patients, Comparison Between Two Time Periods Fifteen Years Apart.

Background: Acute upper gastrointestinal bleeding (AUGIB) remains a common medical emergency with considerable morbidity and mortality. The aim of this study was to describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with AUGIB nowadays and compare these with those of patients 15 years ago. Methods: This was a single-center survey of adults (> 16 years) presenting with AUGIB to a tertiary hospital. Data from 401 patients presenting with AUGIB in a tertiary hospital between January 1, 2019 and December 31, 2020 were analyzed and compared with data from 434 patients presenting with AUGIB at the same hospital between January 1, 2004 and December 31, 2005. Results: Nowadays, patients were older, mean age was 69.5 (± 15.4) vs. 66.2 (± 16.0) years, they had more frequently coexisting diseases (83.5% vs. 72.8%), especially cardiovascular diseases (62.3% vs. 52.5%), and more individuals were inpatients at onset of bleeding (8.2% vs. 4.1%). In addition, more patients were under anticoagulants (18.5% vs. 6.2%), but less were under acetylsalicylic acid ± clopidogrel (36.9% vs. 33.9%). Carlson Comorbidity Index was higher nowadays (5.6 ± 6.4 vs. 3.4 ± 2.3). Moreover, a peptic ulcer was less frequently found as the cause of bleeding (38.4% vs. 56.9%), while more often nowadays endoscopy was negative (12.7% vs. 3.5%). In patients with peptic ulcer, active bleeding on endoscopy was less frequent (7.1% vs. 14.2%). Also, bleeding spots requiring hemostasis were less common on endoscopy (39.6% vs. 49.4%) and more patients were without spots of recent bleeding (49.4% vs. 38.9%). Finally, the rate of rebleeding statistically decreased (7.8% vs. 4.2%), while overall mortality remained relatively unchanged (5.0% vs. 6.2%). Conclusions: AUGIB episodes nowadays are less severe with less peptic ulcer bleeding, but the patients are older and with more comorbidities.

Urinary free cortisol is a reliable index of adrenal cortisol production in patients with liver cirrhosis.

BACKGROUND: The measurement of total and free cortisol has been studied as a clinical index of adrenal cortisol production in patients with liver cirrhosis. Correlations between free plasma and salivary cortisol have previously been reported in stable cirrhotic patients. Urinary free cortisol constitutes an index of adrenal cortisol production; however, it has never been used in assessing adrenal function in patients with liver cirrhosis. AIMS: The aim of this observational study was to determine associations between urinary free cortisol, serum total, salivary, measured and calculated plasma free cortisol levels in cirrhotics, determining which of them can be used as an indirect index of free cortisol levels. Moreover, we investigated the potential use of 24 h urinary free cortisol as a prognostic factor for mortality. METHODS: Seventy-eight outpatients with liver cirrhosis were included. Serum, salivary and urinary free cortisol were measured using the electrochemiluminenscence immunoassay. Plasma free cortisol determination was conducted using a single quadrupole mass spectrometer. The quantification of free cortisol was achieved by determining the signal response on negative ESI-MS mode. RESULTS: Twenty-four hour urinary free cortisol levels correlated with free cortisol determined by mass spectrometer, total cortisol and calculated free cortisol levels. Patients with low levels of urinary free cortisol presented a significantly higher mortality rate compared to those with high levels. The factors associated with death risk were determined by Cox regression. In the multivariate analysis, two models were applied; in the first model, CP score, PVT and urinary free cortisol were found to be significantly related to patients' survival, whereas in the second, MELD score, ascites and urinary free cortisol were independently related to survival. CONCLUSIONS: This study suggests that 24 h urinary free cortisol could be considered as a potential index of adrenal cortisol production in patients with liver cirrhosis and it potentially detects patients with a high mortality risk.

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection.

Background: Vitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC). Methods: A total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data. Results: The cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression. Conclusions: In patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.