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.

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.

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.

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.

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.

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 impact of metabolic health on non-alcoholic fatty liver disease (NAFLD). A single center experience.

BACKGROUND: The role of patients' metabolic clinical and biochemical profile in NAFLD has not been extensively explored. AIMS: The aim of the study was to assess the role of metabolic health in NAFLD patients and to examine liver disease progression in these populations. METHODS: The medical charts of 569 patients diagnosed with fatty liver were thoroughly reviewed; 344 patients were excluded because of other chronic liver diseases. Metabolically healthy people were defined as those who met none of the following criteria: blood pressure ≥ 130/85 mmHg or under hypertension treatment, fasting glucose ≥ 100 mg/dl or under diabetes treatment, serum triglycerides > 150 mg/dl, high density lipoprotein-cholesterol <40/50 mg/dl for men/women. Study participants were followed-up over a median period of 22 months. RESULTS: The present observational case-control study included 225 NAFLD patients; 14 (6.2%) were metabolically healthy. Metabolically healthy participants were younger (p = 0.006), had lower age at diagnosis (p = 0.002), lower levels of γ-GT (p = 0.013), fasting glucose (p <0.001) and triglycerides (p <0.001) and higher HDL-cholesterol (p = 0.005) compared to metabolically non-healthy. By the last follow up assessment, 8 metabolically healthy patients had developed dyslipidemia; 1 patient (14.4%) had presented liver disease progression compared to 8 patients (10.5%) from the unhealthy group (p = 0.567). In multivariate analysis, diabetes mellitus (p = 0.017) and hemoglobin levels (p = 0.009) were the sole independent predictors of disease progression. No significant difference was observed in liver disease progression-free survival rates among the two patient groups (p = 0.503). CONCLUSIONS: Metabolically healthy NAFLD patients presented with a favorable biochemical profile; however, they were diagnosed with NAFLD at a younger age and the liver disease progression risk was similar to that of metabolically unhealthy patients. These findings suggest that metabolically healthy NAFLD may not constitute a benign condition and patients could potentially be at increased risk of metabolic syndrome and liver disease progression.

Combination of Percutaneous Transhepatic Balloon-Assisted Transjugular Intrahepatic Collateral Caval Shunt and Embolization for Successful Hemostasis of Lower Gastrointestinal Bleeding Associated With Extremely Enlarged Anorectal Varicose Veins.

Ectopic varices may frequently occur in the rectum in the context of portal hypertension. Although rectal variceal bleeding is not a frequent bleeding situation, it can be life-threatening unless diagnosed and treated immediately. However, there is no specific treatment strategy established so far. We report a case of a man with extrahepatic portal hypertension and severe hematochezia due to rectal variceal bleeding. The patient was diagnosed in the past with portal vein thrombosis, in the context of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome, with ectopic varices in the small intestine, colon, rectum and anal canal, peritoneum and perisplenic veins, treated with mesorenal shunt placement and an oral beta-blocker. After the initial stabilization with fluid replacement and red blood cell transfusion, he underwent endoscopic injection sclerotherapy, with no effect on bleeding episodes, while the large size of the varices precluded the option of endoscopic band ligation. Due to the presence of large collateral veins next to the inferior vena cava, the patient underwent combination therapy with Percutaneous Transhepatic Balloon-Assisted Transjugular Intrahepatic Collateral Caval shunt placement, to decompress portal pressure, followed by angiographic embolization of the feeding vessels resulting in successful hemostasis. Hematochezia ceased, hemoglobin was stabilized and the patient was safely discharged from the hospital. Controlling and treating rectal varices can be a challenging task indicating the need of a multidisciplinary approach. In the absence of well-established treatment guidelines for rectal varices, we highly recommend treatment of refractory ectopic variceal bleeding, non-responsive to endoscopic treatments, with portocaval shunt placement in combination with embolization.

Olmesartan-Induced Enteropathy: A Report of an Unusual Cause of Chronic Diarrhea.

Olmesartan, an angiotensin II receptor blocker indicated in the treatment of hypertension, has been associ-ated with a seronegative sprue-like enteropathy that should be considered in the differential diagnosis of patients with unexplained chronic diarrhoea. It typically presents with severe chronic diarrhoea, considerable weight loss, and villous atrophy on biopsy and may be difficult to recognize because of its clinical and histological similarities to other clinical entities. Practically, discontinuation of the drug leads to dramatic recovery of the symptoms. We report a 76-year-old Caucasian female who was admitted to our hospital with complaints of chronic diarrhea and significant weight loss. Medical history was notable for hypertension being treated with olmesartan. Initially, investigation for all potential infectious causes and celiac disease was negative. Both upper and lower endoscopy was performed with duodenal biopsies revealing total villous atrophy and colonic biopsies showing lymphocytic colitis. In the presence of negative serology for celiac disease and after a thorough review of the patient's medications, olmesartan in-duced-enteropathy was the most possible diagnosis. Olmesartan was discontinued and the symptoms rapidly resolved. A follow-up done a few months later showed no recurrence of the symptoms. In olmesartan-associated enteropathy, discontinuation of olmesartan results in immediate clinical recovery. Although rare, it is considered an emerging and underdiagnosed enteropathy. This case report illustrates the need for a thorough medication history evaluation and regular review during workup. We aim to increase the awareness of olmesartan-induced enteropathy among clinicians and gastroenterologists. We hope it will add to the current literature and help to understand this rare phenomenon in order to avoid unnecessary testing.

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

Chilaiditi Syndrome With a Large Colonic Loop in a Patient With Autonomic Nervous System Dysfunction.

Chilaiditi syndrome is an unusual condition in which radiographic evidence of a large bowel interposition between the liver and the right hemidiaphragm appears in the chest X-ray. The etiology is unknown and the clinical symptoms vary from case to case. The special characteristics of the syndrome can easily lead to a misdiagnosis and a CT scan is needed to avoid surgical interventions for a suspected pneumoperitoneum. We present a 48-year-old female patient with a medical history of autonomic nervous system dysfunction who referred to the Emergency Department (ED) due to abdominal pain. Chest radiography revealed a radiographic sign of pneumoperitoneum but a CT scan of the abdomen showed interposition of the right colon in the right hemithorax between the diaphragm and the liver without any signs of perforation. The patient was treated with bowel decompression and her symptoms resolved gradually. So far, there is no other case of Chilaiditi syndrome in a patient with autonomic nervous system dysfunction in the published literature. To conclude, Chilaiditi's sign is an unusual radiographic sign presenting as a pneumoperitoneum in the chest X-ray. In order to avoid misdiagnosis and unnecessary surgical interventions, a CT scan should be ordered.

Impact of simple, specific, verbal instructions on the quality of bowel preparation in hospitalized patients undergoing colonoscopy: a multicenter randomized controlled trial.

Background and study aims Bowel preparation for colonoscopy is frequently inadequate in hospitalized patients. We explored the impact of specific verbal instructions on the quality of inpatients bowel preparation and factors associated with preparation failure. Patients and methods Randomized (1:1), two strata (mobilized vs. bedridden; 3:2) trial of consecutive inpatients from four tertiary centers, who received either specific, verbal instructions or the standard of care (SOC) ward instructions about bowel preparation. The rate of adequate bowel preparation (Boston Bowel Preparation Score [BBPS] ≥ 6, no segment < 2) comprised the primary endpoint. Mean BBPS score, good (BBPS score ≥ 7, no segment score < 2) and excellent (BBPS = 9) were among secondary endpoints. Results We randomized 300 inpatients (180 mobile) aged 71.7 ±â€Š15.1 years in the intervention (49.7 %) and SOC (50.3 %) groups, respectively. Overall, more patients in the intervention group achieved adequate bowel preparation, but this difference did not reach statistical significance neither in the intention-to-treat [90/149 (60.4 %) vs. 82/151 (54.3 %); P  = 0.29] nor in the per-protocol analysis [90/129 (69.8 %) vs. 82/132 (62.1 %); P  = 0.19]. Overall BBPS score did not differ statistical significantly in the two groups, but the provision of specific verbal instructions was associated with significant higher rates of good (58.1 % vs. 43.2 %; P  = 0.02) and excellent (31.8 % vs. 16.7 %; P  = 0.004) bowel preparation compared to the SOC group. Administration of same-day bowel preparation and patient American Society of Anesthesiologists score > 2 were identified as risk factors for inadequate bowel preparation. Conclusions Provision of specific verbal instructions did not increase the rate of adequate bowel preparation in a population of mobilized and bedridden hospitalized patients.

Differentially Methylated Ultra-Conserved Regions Uc160 and Uc283 in Adenomas and Adenocarcinomas Are Associated with Overall Survival of Colorectal Cancer Patients.

: Deregulation of the transcribed ultra-conserved regions (T-UCRs) Uc160, Uc283, and Uc346 has been reported in colorectal cancer (CRC) recently. Here, we investigated promoter methylation of these T-UCRs during the adenoma-carcinoma sequence and their clinical significance in CRC patients. Methylation levels were assessed in CRC, adenomas, infiltrated lymph nodes, and metastatic tissue specimens. In situ hybridization was performed in representative tissue specimens. T-UCRs expression levels were also evaluated in HT-29 colon cancer cells before and after the acquired resistance to 5-fluorouracil (5-FU) and oxaliplatin. A gradual increase in T-UCRs methylation levels from hyperplastic polyps to adenomas and to in situ carcinomas (ISC) and a gradual decrease from ISC to infiltrative and metastatic carcinomas was observed (p < 0.001 for Uc160 and Uc283, p = 0.018 for Uc346). Uc160 and Uc283 methylation was associated with the grade of dysplasia in adenoma specimens (p = 0.034 and p = 0.019, respectively). Furthermore, higher Uc160 methylation, mainly in stage III and IV patients, was related to improved overall survival (OS) in univariate (p = 0.009; HR, 0.366) and multivariate analysis (p = 0.005; HR, 0.240). Similarly, higher methylation of Uc283 was associated with longer OS (p = 0.030). Finally, T-UCRs expression was significantly reduced in HT-29 cells after resistance to chemotherapy. This study suggests that promoter methylation of Uc160, Uc283, and Uc346 is altered during CRC development and that Uc160 and Uc283 methylation may have prognostic significance for CRC patients.

Vitamin D-related immunomodulation in patients with liver cirrhosis.

OBJECTIVE(S): Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients' survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients' mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics' mortality. METHODS: One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1ß, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array. RESULTS: 25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients' survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002). CONCLUSION: The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients' mortality, possibly through a proinflammatory immune response.

Polyclonal predominance of concurrently producing OXA-23 and OXA-58 carbapenem-resistant Acinetobacter baumannii strains in a pediatric intensive care unit.

We report a predominance (64.7%) of polyclonal carbapenem-resistant Acinetobacter baumannii (CRAB) strains concurrently producing OXA-23 and OXA-58 carbapenemases in a pediatric intensive care unit in an endemic area. This is the first report of emergence of such double-OXA CRAB strains in a single unit worldwide.

Acute Lower Gastrointestinal Bleeding in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice: Characteristics and Clinical Outcome.

BACKGROUND: Acute lower gastrointestinal bleeding (ALGIB) can occur in patients on anticoagulant therapy (either warfarin or non-vitamin K oral anticoagulants (NOACs)). Use of NOACs has been increasing compared to warfarin in recent years. We analyzed patients with ALGIB on anticoagulation therapy and compared characteristics, management and clinical outcome in patients treated with NOACs versus warfarin. METHODS: All patients with ALGIB on anticoagulation therapy treated in two (affiliated) centers during a 7-year period were evaluated. Characteristics and clinical outcome were compared between patients on warfarin and patients on NOACs. RESULTS: Out of the 587 patients identified with ALGIB during the study period, 43 (7.3%) were on NOACs and 68 (11.6%) on warfarin. Mean age was 75.9 ± 9.5 and 77.1 ± 7.9 years respectively. Site of bleeding was located in the small bowel in 2/43 of NOAC patients and 6/68 of warfarin group. Vascular ectasias (8/43 vs. 6/68, P = 0.010) and polyps/neoplasia (13/43 vs. 6/68, P = 0.025) were more commonly causes of bleeding in patients on NOACs. While endoscopic hemostasis was more commonly needed in patients on NOACs (17/43 vs. 14/68, P = 0.049), they required less hospitalization days (4.5 ± 3.6 vs. 6.1 ± 4.2, P = 0.032). Blood transfusions and need for other interventions (embolization and/or surgery) as well as recurrence of bleeding and mortality were not statistically different. CONCLUSIONS: Although NOAC patients with ALGIB exhibit some differences on certain clinical characteristics when compared to warfarin patients, they share a similar clinical outcome.

Molecular Epidemiology of Endemic Carbapenem-Resistant Gram-Negative Bacteria in an Intensive Care Unit.

The molecular epidemiology of endemic carbapenem-resistant Klebsiella pneumoniae (CRKP), carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB) in an intensive care unit located in an endemic area with high rates of resistance was investigated. A CRPA strain producing VIM and KPC concurrently was detected for the first time in an endemic area. CRKP strains producing K. pneumoniae carbapenemase predominated and were mainly assigned to the "hyperepidemic Greek clone." Predominant OXA-23-like producing CRAB strains were assigned to multiple pulsotypes.

Prognostic significance of vitamin D receptor (VDR) gene polymorphisms in liver cirrhosis.

Several polymorphisms in the vitamin D receptor (VDR) are associated with the occurrence of chronic liver disease. Here, we investigated the association between BsmI, ApaI, TaqI and FokI VDR polymorphisms and the severity of liver cirrhosis in relation to serum cytokine and lipopolysaccharide binding protein (LBP) levels and their role on survival in cirrhotic patients. We found that patients harboring the BB genotype had higher MELD score, and they were mainly at CP stage C; patients harboring the AA genotype had increased LBP, IL-1ß and IL-8 levels, and they were mostly at CP stage C; TT genotype carriers had higher MELD score and they were mainly at CP stage C and FF genotype carriers had lower IL-1ß levels when compared to Bb/bb, Aa/aa, Tt/tt and Ff/ff genotypes respectively. In the multivariate analysis ApaI, BsmI and TaqI polymorphisms were independently associated with liver cirrhosis severity. In the survival analysis, the independent prognostic factors were CP score, MELD and the FF genotype. Our results indicate that the ApaI, TaqI and BsmI polymorphisms are associated with the severity of liver cirrhosis, through the immunoregulatory process. Survival is related to the FF genotype of FokI polymorphism, imparting a possible protective role in liver cirrhosis.

Quality of life in patients with nonalcoholic fatty liver disease: A systematic review.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent medical condition, which may lead to severe complications including cirrhosis and hepatocellular carcinoma. Its chronic course and its association with obesity and diabetes mellitus augment the long-term impact of NAFLD on patients' health and quality of life (QoL) and put great strain on healthcare systems worldwide. Research is growingly focusing on NAFLD patients' QoL in an attempt to describe the full spectrum of disease burden and tackle its future consequences. Relevant studies are characterized by sample heterogeneity and provide conflicting findings which should be interpreted with the use of a systematic and integrative approach. In this context, our aim was to conduct a systematic literature review on the topic of NAFLD patients' QoL. METHODS: We performed a systematic search of PubMed, ScienceDirect and GoogleScholar databases according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. RESULTS: Our search yielded 14 suitable articles reporting data from almost 5000 patients. All authors agree that NAFLD patients' QoL is impaired especially in the physical sub-domain. In addition, several demographic, clinical and histopathological parameters have emerged as major determinants of patients' QoL. However, future studies are needed to further clarify these issues. CONCLUSIONS: NAFLD patients report poor physical QoL. QoL impairment is associated with a variety of disease-related parameters, mostly the presence of fatigue and cirrhosis.