Gastrointestinal Motility Disorders and Their Clinical Implications in Cirrhosis

Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis

Sol-Gel Derived Mg-Based Ceramic Scaffolds Doped with Zinc or Copper Ions: Preliminary Results on Their Synthesis, Characterization, and Biocompatibility

Glass-ceramic scaffolds containing Mg have shown recently the potential to enhance the proliferation, differentiation, and biomineralization of stem cells in vitro, property that makes them promising candidates for dental tissue regeneration. An additional property of a scaffold aimed at dental tissue regeneration is to protect the regeneration process against oral bacteria penetration. In this respect, novel bioactive scaffolds containing Mg2+ and Cu2+ or Zn2+, ions known for their antimicrobial properties, were synthesized by the foam replica technique and tested regarding their bioactive response in SBF, mechanical properties, degradation, and porosity. Finally their ability to support the attachment and long-term proliferation of Dental Pulp Stem Cells (DPSCs) was also evaluated. The results showed that conversely to their bioactive response in SBF solution, Zn-doped scaffolds proved to respond adequately regarding their mechanical strength and to be efficient regarding their biological response, in comparison to Cu-doped scaffolds, which makes them promising candidates for targeted dental stem cell odontogenic differentiation and calcified dental tissue engineering

Prognosis of cirrhotic patients admitted to intensive care unit: a meta-analysis

and METAREACIR GroupInternational audienceBackgroundThe best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown.MethodsWe conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores).ResultsIn-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36–0.59; p 19 at baseline (OR 8.54; 95% CI 2.09–34.91; p 26 (OR 3.97; 95% CI 1.92–8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24–17.64; p = 0.022; PPV = 0.88).ConclusionsPrognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child–Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality

Inflammatory bowel diseases and markers of primary atherosclerosis

Atherosclerosis is an inflammatory process of the arterial wall, and inflammation is an independent risk factor for cardiovascular disease (CVD). The association between inflammatory bowel diseases (IBD) and CVD remains equivocal. The aim of this study was to assess non-invasive markers of CV risk, carotid intima-media thickness (cIMT), arterial stiffness as assessed by pulse wave velocity (cfPWV), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, as well as the levels of the adipokines resistin and adiponectin that play a role in both inflammation and likely atherosclerosis, in patients with IBD without history of CVD compared to a group of matched controls for traditional CVD risk factors. We included 44 patients with IBD, 29 with Crohn’s disease (CD) and 15 with ulcerative colitis (UC), and 44 controls matched for age, gender, body mass index (BMI) and smoking habits. Established CVD risk factors and IBD characteristics (disease duration, extent of bowel involvement, disease activity and treatment) were recorded. IBD patients had lower haemoglobin, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and folic acid levels, and higher platelet count. cIMT was significantly higher in IBD patients compared to controls (0.62 vs. 0.52 mm; p<0.0005). There was no difference in cIMT between patients with CD and UC. Factors associated with cIMT were age, BMI and presence of IBD, with the latter making the greater unique contribution. There was no difference in cfPWV between patients and controls (6.8 vs. 6.4 m/s), but patients with CD had higher cfPWV compared to those with UC (7 vs. 6.3 m/s; p=0.044), and to controls. Smoking rates were significantly higher among CD patients. Factors associated with cfPWV were age, mean arterial pressure and smoking. Lp-PLA2 activity was significantly lower in patients with IBD (46.8 vs. 53.9 nmol/ml/min; p=0.011), but there was no difference in Lp-PLA2 to LDL-C ratio between the two groups. There was no difference in Lp-PLA2 between CD and UC patient. LDL-C was the only significant predictor of Lp-PLA2 activity. Resistin levels were significantly higher in IBD patients (13.7 vs. 10 ng/mL; p=0.022), but there was no difference in adiponectin levels. Resistin levels were significantly higher in patients with active disease (18.9 vs. 11.3 ng/mL; p=0.014). Adiponectin levels correlated inversely with both cIMT (rho=-0.255; p=0.021) and cfPWV (rho=-0.434; p<0.0005). This study showed increased cIMT in patients with IBD, and that IBD is a significant predictor of increased cIMT even when other CVD risk factors are taken into consideration. These findings are highly suggestive of an association between early arterial wall alterations and inflammation in IBD. Arterial stiffness and Lp-PLA2/LDL-C ratio are likely less sensitive markers. Adiponectin is inversely associated with arterial changes and might play a protective role.Η αθηροσκλήρωση αποτελεί φλεγμονώδη διεργασία του αρτηριακού τοιχώματος και η φλεγμονή αποτελεί ανεξάρτητο παράγοντα κινδύνου για καρδιαγγειακή νόσο (ΚΑΝ). Η συσχέτιση μεταξύ φλεγμονωδών νοσημάτων του εντέρου (ΦΝΕ) και ΚΑΝ παραμένει αμφιλεγόμενη. Σκοπός της παρούσας μελέτης ήταν η εκτίμηση μη-επεμβατικών δεικτών ΚΑ κινδύνου, του πάχους του έσω-μέσου χιτώνα των καρωτίδων (cIMT), της αρτηριακής σκληρία όπως εκτιμάται με την ταχύτητα διάδοσης του σφυγμικού κύματος (cfPWV) και της ενεργότητας της λιποπρωτεϊνικής φωσφολιπάσης A2 (Lp-PLA2), καθώς και των επιπέδων των αντιποκινών ρεζιστίνης και αντιπονεκτίνης, οι οποίες παίζουν ρόλο τόσο στη φλεγμονή όσο πιθανώς και στην αθηροσκλήρωση, σε μια ομάδα ασθενών με ΦΝΕ χωρίς ιστορικό ΚΑΝ σε σύγκριση με μια ομάδα μαρτύρων με παρόμοιους κλασικούς παράγοντες ΚΑ κινδύνου. Συμπεριλήφθηκαν 44 ασθενείς με ΦΝΕ, 29 με Crohn (ΝC) και 15 με ελκώδη κολίτιδα (ΕΚ), και 44 μάρτυρες matched ως προς την ηλικία, το φύλο, τον δείκτη μάζας σώματος και τις καπνιστικές συνήθειες. Έγινε καταγραφή των καθιερωμένων παραγόντων ΚΑ κινδύνου και των χαρακτηριστικών των ΦΝΕ (διάρκεια νόσου, έκταση εντερικής προσβολής, ενεργότητα νόσου και θεραπευτική αγωγή). Οι ασθενείς με ΦΝΕ είχαν χαμηλότερα επίπεδα αιμοσφαιρίνης, ολικής χοληστερόλης, χαμηλής πυκνότητας λιποπρωτεΐνης (LDL-C) και φυλλικού οξέος, και υψηλότερο αριθμό αιμοπεταλίων. Το cIMT ήταν σημαντικά υψηλότερο στους ασθενείς με ΦΝΕ σε σύγκριση με τους μάρτυρες (0.62 έναντι 0.52 mm, p<0.0005). Δεν βρέθηκε διαφορά στο cIMT μεταξύ των ασθενών με NC και ΕΚ. Παράμετροι που συσχετίσθηκαν με το cIMT ήταν η ηλικία, ο δείκτης μάζας σώματος και η παρουσία ΦΝΕ, με την τελευταία να παρουσιάζει την ισχυρότερη συσχέτιση. Δεν διαπιστώθηκε διαφορά στο cfPWV μεταξύ ασθενών και μαρτύρων (6.8 έναντι 6.4 m/s), ενώ οι ασθενείς με NC είχαν υψηλότερη cfPWV σε σύγκριση με αυτούς με ΕΚ (7 έναντι 6.3 m/s, p = 0.044) και με τους μάρτυρες. Το κάπνισμα ήταν συχνότερο στην ομάδα των ασθενών με NC. Παράμετροι που συσχετίσθηκαν με την cfPWV ήταν η ηλικία, η μέση αρτηριακή πίεση και το κάπνισμα. Η ενεργότητα της Lp-PLA2 ήταν σημαντικά χαμηλότερη στους ασθενείς με ΦΝΕ (46.8 έναντι 53.9 nmol/ml/min, p=0.011), ωστόσο δεν υπήρχε διαφορά στον λόγο Lp-PLA2 προς LDL-C μεταξύ των δύο ομάδων. Δεν διαπιστώθηκε διαφορά στην Lp-PLA2 μεταξύ ασθενών με ΝC και ΕΚ. Η LDL-C ήταν ο μόνος προγνωστικός παράγοντας της Lp-PLA2. Τα επίπεδα της ρεζιστίνης ήταν σημαντικά υψηλότερα στους ασθενείς με ΦΝΕ (13.7 έναντι 10 ng/mL, p=0.022), ενώ δεν υπήρχε διαφορά στα επίπεδα της αντιπονεκτίνης. Τα επίπεδα της ρεζιστίνης ήταν σημαντικά υψηλότερα στους ασθενείς με ενεργό νόσο (18.9 έναντι 11.3 ng/mL, p=0.014). Τα επίπεδα της αντιπονεκτίνης συσχετίσθηκαν αντιστρόφως τόσο με το cIMT (rho=-0.255, p=0.021) όσο και με το cfPWV (rho=-0.434, p<0.0005). Η παρούσα μελέτη έδειξε αυξημένο cIMT στους ασθενείς με ΦΝΕ, και ότι τα ΦΝΕ αποτελούν σημαντικό προγνωστικό παράγοντα της αύξησης του cIMT ακόμα και όταν ληφθούν υπόψιν οι υπόλοιποι παράγοντες ΚΑ κινδύνου. Τα ευρήματα αυτά υποστηρίζουν μια πιθανή συσχέτιση μεταξύ πρώιμων αλλαγών του αρτηριακού τοιχώματος και της φλεγμονής στα ΦΝΕ. Η αρτηριακή σκληρία και ο λόγος Lp-PLA2/LDL-C είναι πιθανώς λιγότερο ευαίσθητοι δείκτες. Η αντιπονεκτίνη συσχετίσθηκε αντιστρόφως με τις αρτηριακές αλλαγές και παίζει πιθανώς προστατευτικό ρόλο

The Role of RASs /RVs in the Current Management of HCV

The approval of combination therapies with direct-acting antiviral (DAA) regimens has led to significant progress in the field of hepatitis C virus (HCV) treatment. Although most patients treated with these agents achieve a virological cure, resistance to DAAs is a major issue. The rapid emergence of resistance-associated substitutions (RASs), in particular in the context of incomplete drug pressure, has an impact on sustained virological response (SVR) rates. Several RASs in NS3, NS5A and NS5B have been linked with reduced susceptibility to DAAs. RAS vary based on HCV characteristics and the different drug classes. DAA-resistant HCV variant haplotypes (RVs) are dominant in cases of virological failure. Viruses with resistance to NS3-4A protease inhibitors are only detected in the peripheral blood in a time frame ranging from weeks to months following completion of treatment, whereas NS5A inhibitor-resistant viruses may persist for years. Novel agents have been developed that demonstrate promising results in DAA-experienced patients. The recent approval of broad-spectrum drug combinations with a high genetic barrier to resistance and antiviral potency may overcome the problem of resistance

Cardiac dysfunction in cirrhosis - does adrenal function play a role? A hypothesis

Cirrhotic cardiomyopathy (CCM), a condition of unknown pathogenesis, is characterized by suboptimal ventricular contractile response to stress, diastolic dysfunction and QT interval prolongation. It is most often found in patients with advanced cirrhosis. It is clinically relevant during stressful conditions, such as sepsis, bleeding and surgery. CCM reverses after liver transplantation and potentially has a role in the pathogenesis of hepatorenal syndrome. In adrenal insufficiency (AI), cardiac dysfunction is a feature with low ejection fraction, decreased left ventricular chamber size and electrocardiographic abnormalities, including QT interval prolongation. With optimal diagnostic tests, AI is present in approximately 10% of patients with cirrhosis, particularly in those with advanced disease. Down-regulation and decreased number of beta-adrenergic receptors, and high catecholamine levels are common to both cardiac conditions. Thus, AI may play a role in CCM. Steroid replacement therapy reverses cardiac changes in AI, and may do so for CCM, with important therapeutic implications; this needs formal evaluation. © 2012 John Wiley & Sons A/S