Safety and Potential Role of Lactobacillus rhamnosus GG Administration as Monotherapy in Ulcerative Colitis Patients with Mild-Moderate Clinical Activity.

Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 1010 CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy (n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition (p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).

Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients. RESEARCH DESIGN AND METHODS: A retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF. RESULTS: We enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded. CONCLUSIONS: Our RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Application of validated bleeding risk scores for atrial fibrillation in obscure gastrointestinal bleeding patients increases videocapsule endoscopy's diagnostic yield: a retrospective monocentric study.

BACKGROUND: Videocapsule endoscopy (VCE) is considered the gold standard for overt and obscure gastrointestinal bleeding (OGIB), after negative upper and lower endoscopy. Nonetheless, VCE's diagnostic yield is suboptimal, and it represents a costly, time-consuming, and often not easily available technique. In order to evaluate bleeding risk in patients with atrial fibrillation, several scoring systems have been proposed, but their utilization outside the original clinical setting has rarely been explored. The aim of the study is to evaluate potential role of bleeding risk scoring systems in predicting the occurrence of positive findings at VCE examination, and therefore in increasing VCE diagnostic yield. METHODS: Data from consecutive patients undergoing VCE between April 2015 and June 2020 were retrospectively retrieved, and clinical and demographic characteristics were collected. HAS-BLED, ATRIA, and ORBIT scores were calculated, and patients were considered at low or high risk of bleeding accordingly. Discriminative ability of the scores for positive VCE findings has been evaluated by area under receiver operator characteristic curve (AUC) calculation. Diagnostic yield of scores in high- and low-risk patients was calculated. RESULTS: A total of 413 patients underwent VCE examination, among which 368 (89%) for OGIB. Positive findings were observed in 246 patients (67%), with angiodysplasias being the most frequent lesion (92%). The three scores displayed similar consistent discriminative ability for positive VCE findings (mean AUC = 0.69), and identified high-risk group of patients in which VCE has a higher diagnostic yield. CONCLUSIONS: In the present retrospective study, bleeding scores accurately discriminated patients with higher probability of positive findings at VCE examination. Bleeding scores utilization may help in the management of patients with OGIB, with a potential consistent resource optimization and cost-saving.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

BACKGROUND: Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn's disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. RESEARCH DESIGN AND METHODS: Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. RESULTS: 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). CONCLUSION: We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug's longterm efficacy.

Probiotics and Vitamin D/Vitamin D Receptor Pathway Interaction: Potential Therapeutic Implications in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) are chronic conditions of unknown etiology and immunomediated pathogenesis. In the last years, the comprehension of the complex mechanisms involved in the intestinal mucosal homeostasis, and the analysis of the alterations potentially leading to inflammatory pathologic states, has consistently increased. Specifically, the extraordinary impulse in the field of research of the intestinal microbiome has opened the door to the investigation of possible novel approaches to the diagnosis, management and therapeutic applications in IBD. In line with that, administration of probiotic bacteria has been intensely evaluated, leading to much more exciting results in experimental models than in clinical practice. Considering the consistent heterogeneity of the available studies on probiotics, the increased knowledge of the properties of the single bacterial species would ideally lead to unravel potential mechanisms of action that may bring therapeutic applications in specific pathologic condition. Among the relevant molecular pathways for mucosal homeostasis maintenance, the vitamin D/vitamin D receptor (VDR) pathway has been intensely studied in the very last years. In fact, besides osteometabolic functions, the vitamin D exerts important homeostatic effects in the organism at multiple levels, such as immunomodulation, inflammation control, and microbiota regulation, which are likely to play a relevant role in intestinal mucosa protection. In the present review, recent findings about probiotic applications in IBD and mechanisms of action linking vitamin D/VDR pathway to IBD are reported. Available evidence for probiotic effect on vitamin D/VDR are reviewed and potential future application in IBD patients are discussed. At present, many aspects of IBD pathogenesis are still obscure, and current therapeutic options for IBD treatment are at best suboptimal. The increasing comprehension of the different pathways involved in IBD pathogenesis will lead to novel findings ideally leading to potential clinical applications. Microbiota manipulation and vitamin/VDR pathway appear a promising field for future research and therapeutic developments.

Corticosteroids in Inflammatory Bowel Disease Patients: A Practical Guide for Physicians.

Inflammatory Bowel Diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the '50s, are still the mainstay of treatment for moderate to severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on the long-term natural history of the disease, the steroid-sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so-called "low bioavailability" steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and a more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding.

BACKGROUND: Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. AIMS: To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. METHODS: In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. RESULTS: Overall, 602 patients underwent early upper endoscopy, and 472 presented with non-variceal bleeding. High risk endoscopic stigmata were detected in 145 (30.7%) cases. T-score sensitivity and specificity for high risk endoscopic stigmata and bleeding-related mortality was 96% and 30%, and 80% and 71%, respectively. No statistically difference in predicting high risk endoscopic stigmata between T-score and Glasgow Blatchford risk score was observed (ROC curve: 0.72 vs. 0.69, p=0.11). The two scores were also similar in predicting re-bleeding (ROC curve: 0.64 vs. 0.63, p=0.4) and 30-day bleeding-related mortality (ROC curve: 0.78 vs. 0.76, p=0.3). CONCLUSIONS: The T-score appeared to predict high risk endoscopic stigmata, re-bleeding and mortality with similar accuracy to Glasgow Blatchford risk score. Such a score may be helpful for the prediction of high-risk patients who need a very early therapeutic endoscopy.

Regional variations in the use of complementary and alternative medicines (CAM) for inflammatory bowel disease patients in Italy: an IG-IBD study.

BACKGROUND AND AIM: Complementary and alternative medicines (CAM) are being used increasingly by patients with Crohn's disease (CD) and ulcerative colitis (UC). We aimed to assess the prevalence and usage of CAM in different geographical areas of Italy and possible predictors of their use. METHODS AND MATERIALS: A structured questionnaire, administered to outpatients, attending 8 general hospitals and 9 tertiary referral centres, was completed by 2011 patients (909 CD, 1087 UC and 15 indeterminate colitis). 583 patients lived in the North, 659 in Central Italy and 769 in the South. RESULTS: CAM users were 475 (23.6%) with no regional differences in their distribution. Usage correlated significantly with female gender (p=0.030), higher education (p=0.021), hospitalization rates (p=0.000), extra-intestinal complications (p=0.000), non-adherence to conventional treatments (p=0.054), adverse reactions to conventional treatments (p=0.000), and active disease (p=0.007); 5-ASA usage was associated with a more limited use of CAM (p=0.005). Dietary changes or supplements and prayer were significantly more frequently reported in South, while Northern Italian patients more frequently used homeopathy, herbal medicines and physical exercises. Patients in Central Italy adopted an intermediate behavior. CAM use ameliorated the patient's general well-being according to two thirds of the users. Costs were higher for Northern patients than in Central or Southern Italy. CONCLUSION: One in four IBD patients in Italy use CAM. More money is spent on CAM in Northern Italy. Regional differences emerged as regards the type of CAM but not in terms of disease features, frequency of and reasons for CAM use, or perceived effects.

Endoscopic findings in patients with upper gastrointestinal bleeding clinically classified into three risk groups prior to endoscopy.

AIM: To investigate in a prospective study whether a simplified clinical score prior to endoscopy in upper gastrointestinal bleeding (UGIB) patients was able to predict endoscopic findings at urgent endoscopy. METHODS: All consecutive UGIB patients referred to a single endoscopic center during a 16 mo period were enrolled. Before endoscopy patients were stratified according to a simple clinical score (T-score), including T1 (high-risk), T2 (intermediate-risk) and T3 (low-risk). Endoscopy was performed in all cases within 2 h, and high-risk stigmata were considered for further analysis. RESULTS: Out of the 436 patients included into the study, 126 (29%) resulted to be T1, 135 (31%) T2, and 175 (40%) T3. Overall, stigmata of recent haemorrhage (SRH) were detected in 118 cases (27%). SRH occurred more frequently in T1 patients than in T2/T3 cases (85% vs 3.2%; c2 = 304.5309, P < 0.001). Older age (t = 3.311; P < 0.01) and presence of comorbidities (c2 = 14.7458; P < 0.01) were more frequently detected in T1 than in T2/T3 patients. CONCLUSION: Our simplified clinical score appeared to be associated with the detection of endoscopic findings which may deserve urgent endoscopy. A further, randomised study is needed to assess its accuracy in safely scheduling endoscopy in UGIB patients.