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Introduction: Rates of elderly patients with inflammatory bowel diseases (IBDs) are increasing, and biomarkers are needed to optimise their therapies. Serum triiodothyronine-to-thyroxine (T3/T4) ratio has been correlated with geriatric patient frailty., Aim: To assess the suitability of T3/T4 ratio as a response marker to biologics in elderly patients with IBD., Methods: Patients with IBD over 60 years old were enrolled, when starting biological therapy. Therapeutic outcome was assessed after 54 weeks of treatment as mucosal healing (Mayo endoscopic score < 2 for ulcerative colitis; ulcer disappearance for Crohn's disease) and clinical remission (Partial Mayo Score < 2 for ulcerative colitis; Harvey-Bradshaw Index < 5 for Crohn's disease). T3/T4 ratio was evaluated at baseline, and its association with therapeutic outcomes was tested by multivariable logistic regression and receiver operating characteristic (ROC)., Results: We enrolled 80 patients; 44 achieved clinical remission and 36 mucosal healing. Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9-14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79-0.94]; positive and negative likelihood ratios 6.8 [2.9-15.9] and 0.3 [0.1-0.5] respectively)., Conclusions: T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD. If validated, the assessment of this parameter before starting biological treatment might be suggested., (© 2020 John Wiley & Sons Ltd.)

Background: Alcohol abuse represents the most common cause of liver disease in the Western countries. Pre-clinical and clinical studies showed that alcohol consumption affects amount and composition of gut microbiota. Moreover, gut flora plays an important role in the pathogenesis of alcoholic liver injury., Aim: To review the relationship between alcohol administration and changes on gut microbiota, its involvement in the pathogenesis of alcoholic liver disease, and how gut microbiota modulation could be a target for the treatment of alcoholic liver disease., Methods: Articles were identified using the PubMed database with the search terms 'Alcohol', 'Gut Microbiota', 'Alcoholic liver disease', 'Probiotic', 'Prebiotic', 'Symbiotic' and 'Antibiotic'. English-language articles were screened for relevance. Full review of publications for the relevant studies was conducted, including additional publications that were identified from individual article reference lists., Results: Alcohol abuse induces changes in the composition of gut microbiota, although the exact mechanism for this alteration is not well known. The translocation of bacterial products into the portal blood appears to play a key role in alcohol-induced liver damage. Several studies show that the modulation of gut microbiota seem to be a promising strategy to reduce alcohol-induced liver injury., Conclusions: Further studies are needed to better understand the relationship between alcohol administration and changes in gut microbiota, and its involvement in alcoholic liver disease. Moreover larger studies are needed to confirm the preliminary results on the therapeutic effects of gut microbiota modulation., (© 2015 John Wiley & Sons Ltd.)

Background: Aminosalicylates are the mainstay of therapy to prevent relapse of quiescent ulcerative colitis. The rationale for using probiotics is based on the evidence implicating intestinal bacteria in the pathogenesis of this disorder., Aim: To evaluate the efficacy of Lactobacillus GG alone or in combination with mesalazine vs. mesalazine as maintenance treatment in ulcerative colitis., Patients and Methods: 187 ulcerative colitis patients with quiescent disease were randomized to receive Lactobacillus GG 18 x 10(9) viable bacteria/day (65 patients), mesalazine 2400 mg/day (60 patients) or Lactobacillus GG + mesalazine (62 patients). Disease activity index, endoscopic and histological scores were determined at 0, 6 and 12 months and in case of relapse. The primary end point was to evaluate sustained remission., Results: Overall analysis showed no difference in relapse rate at 6 (P = 0.44) and 12 months (P = 0.77) among the three treatment groups. However, the treatment with Lactobacillus GG seems to be more effective than standard treatment with mesalazine in prolonging the relapse-free time (P < 0.05)., Conclusions: Lactobacillus GG seems to be effective and safe for maintaining remission in patients with ulcerative colitis, and it could represent a good therapeutic option for preventing relapse in this group of patients.

Background: Patients with inflammatory bowel disease have an increased risk of thrombotic complications; moreover, mesenteric microvascular thrombosis has been hypothesized as a contributing factor in the pathogenesis of inflammatory bowel disease., Aim: To assess the extent of subclinical atherosclerosis in inflammatory bowel disease by measuring the intima-media thickness of the common carotid artery., Methods: Fifty-two patients were enrolled in the study. Patients aged >45 years, with a history of cardiovascular disease and known risk factors for atherosclerosis were excluded from the study. Twenty healthy subjects were studied as controls. Carotid ultrasonography was performed in all patients and controls. intima-media thickness was measured proximal to the carotid bifurcation over both right and left common carotid arteries. The clinical characteristics and the laboratory parameters relevant to disease activity were recorded for all inflammatory bowel disease patients. In particular, plasma homocysteine, a well-known risk factor for thrombosis, was assessed., Results: Common carotid artery intima-media thickness was significantly higher in inflammatory bowel disease patients (0.63 +/- 0.15 mm) compared with controls (0.53 +/- 0.08 mm). Multiple regression analysis revealed a significant association of carotid intima-media thickness with homocysteine levels and age., Conclusions: Inflammatory bowel disease patients have an increased risk of early atherosclerosis than healthy controls as showed by greater values of carotid intima-media thickness. Homocysteine levels and age resulted independently associated with the increased arterial wall thickness.

Background: Anxiety and depression are common features of coeliac disease. Depression is cause of non-compliance to treatment in chronic illness., Aim: To evaluate the useful of psychological support counselling to improve affective disorders and gluten-free diet adherence in coeliac disease with anxiety and depression., Methods: A total of 66 coeliac disease patients with state anxiety and current depression were enrolled. Patients were randomized in two groups: in group A psychological support was started at the beginning of gluten-free diet, while group B was free of psychological support. Both groups were followed every 2 weeks for 6 months. State and Trait Anxiety Inventory test Y-1 and the modified Zung self-rating depression scale were administered before (T0) and after 6 months of gluten-free diet (T1)., Results: At T1 no difference was found between groups in the percentage of state anxiety, while a significant lower percentage of depressed subjects was found in group A with respect to group B (15.1% vs. 78.8%; P=0.001). In the follow-up period, a significant lower compliance to gluten-free diet was found in group B with respect to group A (39.4% vs. 9.1%; P=0.02)., Conclusions: In coeliac disease patients with affective disorders psychological support seems to be able to reduce depression and to increase gluten-free diet compliance.

Background: Helicobacter pylori infection may persist after both first- and second-line current treatments., Aim: To assess the efficacy of a third-line, culture-guided treatment approach for the eradication of H. pylori., Methods: Patterns of resistance were analysed in H. pylori isolates from 94 consecutive patients in whom H. pylori infection had persisted after two eradication attempts. Using the epsilometer test, susceptibility analysis was performed for amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin. Patients were then treated with a culture-guided, third-line regimen: 89 patients with a 1-week quadruple regimen including omeprazole, bismuth, doxycycline and amoxicillin, and five patients with a 1-week triple regimen containing omeprazole, amoxicillin and levofloxacin or clarithromycin., Results: Ninety-four subjects (100%) were resistant to metronidazole, 89 (95%) to clarithromycin, 29 (31%) to levofloxacin and five (5%) to tetracycline. No resistance to amoxicillin was found in any patient. Overall, H. pylori eradication was obtained in 90% of subjects. The quadruple regimen was effective in 81 patients (92% by per protocol and 91% by intention-to-treat analysis). Four patients (80%, both per protocol and intention-to-treat analysis) were H. pylori-negative after the triple regimen., Conclusions: A culture-guided, third-line therapeutic approach is effective for the eradication of H. pylori. Furthermore, the 1-week doxycycline- and amoxicillin-based quadruple regimen is a good third-line 'rescue' treatment option.

Cell-based therapies, comprising isolated hepatocyte transplantation, ex vivo gene therapy and bioartificial liver devices, may actually design a new scenario in the treatment of patients with liver failure. Recent advances in the liver repopulation field and the considerable excitement surrounding the use of haematopoietic stem cells for a 'regenerative medicine', allow us to see under a new light the alternative cell sources actually under investigation. In particular, the major drawbacks and the most important advantages of xenogenic primary cells, tumour-derived cell lines, immortalised hepatocytes and stem cells in the wide range of experimental and clinical applications are presented. Even if up to now none of them represent a 'gold standard' in the clinical practice, the intersecting advances in the development of mechanical components of artificial devices and in the liver biology and bioengineering will open tantalising possibilities to treat patients with liver failure, by tailoring the therapeutic choice on the basis of the aetiology and the stage of liver disease.

Background: Acid suppression plus two antibiotics is considered the reference anti-Helicobacter pylori treatment. Reported eradication rates are around 65-80%. Human Lactobacillus acidophilus shows an in vitro inhibitory effect on the attachment of H. pylori to gastric epithelial cell lines. Culture supernatant of this bacillus seems to decrease the in vitro viability of H. pylori., Aim: To evaluate whether the supplementation with an inactivated preparation of L. acidophilus could improve the efficacy of a standard anti-H. pylori therapy., Methods: One-hundred and twenty H. pylori-positive patients were randomly assigned to a 7-day triple therapy based on rabeprazole (20 mg b.d.), clarithromycin (250 mg t.d.s.) and amoxicillin (500 mg t.d.s.) (RCA group: 60 subjects), or to the same regimen supplemented with a lyophilized and inactivated culture of Lactobacillus acidophilus (t.d.s.) (RCAL group: 60 subjects)., Results: In the RCA group, eradication was successful in 72% (42 out of 58 patients) from a per protocol (PP) analysis, or 70% (42 out of 60 patients) using an intention-to treat (ITT) analysis. In the RCAL group a significant increase in the eradication rate was observed: 88% (52 out of 59 patients) from PP analysis (P=0.03), 87% (52 out of 60 patients) from ITT analysis (P=0.02)., Conclusions: These results seem to confirm the in vitro anti-H. pylori effect of L. acidophilus, suggesting that the inactivated L. acidophilus could be effective in increasing eradication rates of a standard anti-H. pylori therapy.

Unfractioned heparin was recently reported to be beneficial in the treatment of inflammatory bowel disease. The available uncontrolled data show that it may be effective in steroid-resistant ulcerative colitis with a percentage of complete clinical remission of over 70% after an average of 4-6 weeks of therapy. The administration of unfractioned heparin is not currently justified by the very limited available data. The worsening of rectal bleeding is infrequent in treated ulcerative colitis patients and only rarely does it require blood transfusion or a colectomy. Low molecular weight heparin was used in a single trial in patients with steroid-refractory ulcerative colitis, with results similar to those observed with unfractioned heparin. Since a prothrombotic state has been described in inflammatory bowel disease, and microvascular intestinal occlusion seems to play a role in the pathogenesis of inflammatory bowel disease, it is reasonable that part of the beneficial effects of unfractioned heparin in inflammatory bowel disease may result from its anticoagulant properties. However, beyond its well-known anticoagulant activity, unfractioned heparin also exhibits a broad spectrum of immunomodulating and anti-inflammatory properties, by inhibiting the recruitment of neutrophils and reducing pro-inflammatory cytokines. Moreover, it can restore the high-affinity receptor binding of basic fibroblast growth factor and this would aid healing of the ulcerated mucosa. In conclusion, unfractioned heparin may represent a safe therapeutic option for severe, steroid-resistant ulcerative colitis, although randomized, controlled trials are needed to confirm these data.

Background: One-week low-dose proton pump inhibitor-based triple therapies have usually proved to be effective treatments for Helicobacter pylori infection., Aim: To investigate the eradication efficacy, safety profile and patient compliance of two triple therapies containing a standard dose of rabeprazole and a new fluoroquinolone, levofloxacin., Methods: One hundred patients referred to us for gastroscopy, who were H. pylori-positive, were consecutively recruited in a prospective, open-label study. The enrolled patients were randomised to receive a seven-day course of rabeprazole 20 mg o.d. plus levofloxacin 500 mg o.d. and either amoxycillin 1 g b.d. (RLA group) or tinidazole 500 mg b.d. (RLT group). Their H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the end of treatment., Results: All 100 enrolled patients completed the study. Forty-six of 50 patients treated with RLA (both PP and ITT analysis: 92%; 95% CI: 81-98%) and 45 of 50 with RLT (both PP and ITT analysis: 90%: 95% CI: 78-97%), became H. pylori-negative. Slight or mild side-effects occurred in 4 (8%) patients of the RLA group and in 5 (10%) of the RLT group., Conclusions: This study demonstrates the efficacy of two 1-week rabeprazole-based triple therapies including levofloxacin to eradicate H. pylori. These regimens prove to be safe, well-tolerated, and achieved good eradication rates. Levofloxacin may be an effective alternative to clarithromycin in triple therapy regimens.

Background: Ranitidine bismuth citrate (RBC)-based triple therapies for a period of 7 days have proved to be an effective treatment for Helicobacter pylori., Aim: To investigate the eradication efficacy, safety profile and patient compliance of two RBC-based triple therapies given for 5 days., Methods: Eighty H. pylori-positive patients with dyspeptic symptoms, referred to us for gastroscopy, were consecutively enrolled in this prospective, randomized, open-label study. These patients were randomly assigned to receive a 5-day course of RBC 400 mg b.d. plus clarithromycin 500 mg b.d. and either tinidazole 500 mg b.d. (RBCCT group) or amoxycillin 1 g b.d. (RBCCA group). The H. pylori status was assessed by means of histology and rapid urease test at entry, and by 13C-urea breath test 8 weeks after the completion of treatment., Results: All enrolled patients completed the study. Thirty-seven of 40 patients treated with RBCCT (both PP and ITT analysis: 93%; 95% CI: 80-98%) and 35 of 40 in the RBCCA group (both PP and ITT analysis: 88%; 95% CI: 73-96%) returned H. pylori-negative. Slight or mild side-effects occurred in 4/40 patients (10%) in the RBCCT group and in 5/40 (12%) in the RBCCA group., Conclusions: This is the first study demonstrating the efficacy of RBC-based triple therapies given for only 5 days. RBC regimens containing high-dose clarithromycin and either amoxycillin or tinidazole prove to be well tolerated, safe and preserve good eradication rates even when administered for a shorter than conventional duration.

Background: Helicobacter pylori eradication therapies do not achieve 100% success rates. Antibiotic resistant strains are among the major causes of failure. Current recommendations concerning the management of treatment failures are not fully clear., Aim: To evaluate the efficacy of a multi-step therapeutic strategy in a large group of infected patients., Methods: A total of 2606 H. pylori-positive patients were administered tinidazole, clarithromycin and a proton pump inhibitor for 1 week. Patients with continuing infection were then given a second 1-week course of amoxycillin, clarithromycin and ranitidine bismuth citrate. Patients still infected after the second course underwent upper gastrointestinal endoscopy with H. pylori culture, and then received a 1-week quadruple proton pump inhibitor-bismuth based scheme established on H. pylori antibiotic sensitivity., Results: After the first step, eradication was achieved in 2063 out of 2413 patients [86% per protocol analysis (PP); 79% intention-to-treat analysis (ITT)]. First-step failures (350 out of 2413; 14.5% PP) showed second-step eradication rates of 82% (271 out of 329 patients, PP; 77% ITT). The specific quadruple therapy for second-step failures (58 out of 329, 18% PP) achieved 77% (30 out of 39 patients, PP) or 52% (ITT) success. This algorithm led to overall eradication rates of 99% (PP) or 91% (ITT)., Conclusions: This multi-step strategy succeeded in a high percentage of H. pylori infected patients. Given the lack of precise guidelines on treatment failures, assessing H. pylori sensitivity to antibiotics only after failure of the second treatment could be suggested in clinical practice.