Wall Thickness Ratio-A New Magnetic Resonance Parameter-Is Associated With the Outcome of Biological Therapy in Patients With Ileal and Ileocolonic Crohn's Disease.

GOALS: The present study was aimed at identifying a new magnetic resonance enterography (MRE) parameter assessing the clinical outcome of biological therapy in patients with active ileal/ileocolonic Crohn's disease (CD). BACKGROUND: Transmural healing (TH) has been associated with improved outcomes in CD. However, some patients with clinical remission and inactive disease at endoscopy do not achieve TH. MATERIALS AND METHODS: Ileal/ileocolonic CD patients scheduled for biological therapy were prospectively evaluated, at baseline (T0) and after 1 year of treatment (T1), with Harvey Bradshaw Index score, blood tests, ileocolonscopy, and MRE. Clinical activity was assessed after 2 years of treatment (T2). Wall thickness ratio (WTR) was calculated in the same affected ileal segment, as the ratio between the ileum wall thickness value at T1 and the ileum wall thickness value at T0. RESULTS: A total of 103 patients were included. Mean WTR at T1 in nonresponders was significantly higher than in responders. At receiver operating characteristic analysis, WTR values were significantly associated to biological therapy responsiveness. A WTR cutoff value of 0.77 mm was identified to discriminate responders from nonresponders (sensitivity: 79%; specificity: 67%). In responders, the proportion of patients with a WTR<0.77 was significantly higher than the proportion of patients achieving TH at T1. Among patients achieving endoscopic remission, 11/29 (37.9%) presented TH, while 20/29 (68.9%) presented WTR<0.77 ( P : 0.035). At multivariate logistic regression analysis, WTR<0.77 was significantly associated to biological therapy response. CONCLUSION: WTR index represents an easy-to-calculate MRE parameter and seems to be a promising tool for monitoring therapeutic response in CD patients during biological therapy.

Colonic Epithelial Permeability to Ions Is Restored after Vedolizumab Treatment and May Predict Clinical Response in Inflammatory Bowel Disease Patients.

Vedolizumab (VDZ) is used for treating inflammatory bowel disease (IBD) patients. A study investigating colonic epithelial barrier function ex vivo following VDZ is lacking. This work aims to evaluate ex vivo the colonic epithelial barrier function in IBD patients at baseline and during VDZ treatment, and to investigate the relationships between barrier function and clinical parameters. Colonic specimens were obtained from 23 IBD patients before, and at 24 and 52 weeks after VDZ treatment, and from 26 healthy volunteers (HV). Transepithelial electrical resistance (TEER, permeability to ions) and paracellular permeability were measured in Ussing chambers. IBD patients showed increased epithelial permeability to ions (TEER, 13.80 ± 1.04 Ω × cm2 vs. HV 20.70 ± 1.52 Ω × cm2, p < 0.001) without changes in paracellular permeability of a 4 kDa probe. VDZ increased TEER (18.09 ± 1.44 Ω × cm2, p < 0.001) after 52 weeks. A clinical response was observed in 58% and 25% of patients at week 24, and in 62% and 50% at week 52, in ulcerative colitis and Crohn's disease, respectively. Clinical and endoscopic scores were strongly associated with TEER. TEER < 14.65 Ω × cm2 predicted response to VDZ (OR 11; CI 2-59). VDZ reduces the increased permeability to ions observed in the colonic epithelium of IBD patients before treatment, in parallel to a clinical, histological (inflammatory infiltrate), and endoscopic improvement. A low TEER predicts clinical response to VDZ therapy.

SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves.

BACKGROUND: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. METHODS: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. RESULTS: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). CONCLUSION: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves.

Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

The Results From Up-Front Esophageal Testing Predict Proton Pump Inhibitor Response in Patients With Chronic Cough.

INTRODUCTION: The clinical management of chronic cough patients is challenging, and their response to proton pump inhibitors (PPIs) is considered as unsatisfactory. Few data concerning the association between impedance-pH variables and PPI response in these patients are available. Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index increase the diagnostic yield of impedance-pH in gastroesophageal reflux disease. METHODS: Demographic, clinical, and endoscopy findings; impedance-pH; and high-resolution manometry tracings from consecutive patients assessed for cough were evaluated. Univariable and multivariable regression models were generated to evaluate the association between impedance-pH and high-resolution manometry findings, endoscopic and clinical characteristics, and PPI response. RESULTS: A total of 178 patients were included. Eighty-four of 178 cough patients (47.2%) displayed grade C-D erosive esophagitis or were characterized by a pathological acid exposure time (AET) and/or positive symptom association probability/symptom index. When also considering MNBI and PSPW, 135 of 178 patients (75.8%) were characterized by the evidence of reflux disease (P < 0.001). Eighty patients (44.9%) had cough responding to PPIs, whereas 98 (55.1%) were nonresponders (P = 0.071). At the receiver operating characteristic analysis, both PSPW index and MNBI were associated to PPI responsiveness. MNBI and PSPW index showed higher sensitivity in predicting PPI response compared with AET and symptom association probability/symptom index. The area under the curves of MNBI and PSPW index were significantly higher than that of AET (P < 0.01 for both comparisons). When patients were stratified according to AET and excluding those with erosive esophagitis, pathological MNBI or PSPW index, hiatal hernia, and hypomotility features were associated to PPI response in all groups. DISCUSSION: Our results demonstrate the usefulness of an up-front esophageal testing in discriminating reflux-related cough patients and predicting PPI response.

Role of Esophageal Motility, Acid Reflux, and of Acid Suppression in Nonobstructive Dysphagia.

GOALS: The present study was aimed at evaluating, in dysphagic patients, the role of high-resolution manometry (HRM) findings, presence of gastroesophageal reflux disease (GERD), and proton-pump inhibitor (PPI) therapy on dysphagia perception. BACKGROUND: A relevant proportion of patients with nonobstructive dysphagia present normal esophageal HRM findings. Patients with GERD often complain of dysphagia and factors, such as hypersensitivity, might be involved in its occurrence. STUDY: In total, 37 nonerosive reflux disease (NERD) patients with only dysphagia (group 1) and 52 patients with both dysphagia and typical GERD symptoms (group 2) were evaluated with symptom scores, HRM combined with impedance and 24 hours impedance-pH monitoring. In total, 44 NERD patients, not presenting dysphagia, underwent the same protocol. A total of 22/37 group 1 patients [11 with pathologic acid exposure time (AET)] were treated with esomeprazole 40 mg oid for 4 weeks and were reassessed during the last week of therapy. RESULTS: A total of 15/37 group 1 patients (40%), 27/52 group 2 patients (52%), and 19/44 (43%) NERD patients presented pathologic AET [P=not significant (NS)]. Group 1 patients with a pathologic AET showed a significantly lower mean distal contractile integral (DCI) and a significant correlation (ρ=-0.71) between individual DCI and total bolus transit time values. During PPI therapy, in group 1 patients with pathologic AET, the mean dysphagia score value decreased significantly [7.5 (range, 3 to 9) before, 4 (range, 2 to 6) during PPI; P<0.01)] and mean DCI value increased significantly. CONCLUSIONS: In total, 40% of dysphagic patients show a pathologic AET and reduced peristaltic vigor. In these patients, an adequate PPI therapy significantly decreases dysphagia frequency and severity and improves the esophageal peristaltic force.

Impedance-high resolution manometry analysis of patients with nonerosive reflux disease.

BACKGROUND & AIMS: Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals. METHODS: We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test. RESULTS: The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05). CONCLUSIONS: In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects.

Weak peristalsis with large breaks is associated with higher acid exposure and delayed reflux clearance in the supine position in GERD patients.

OBJECTIVES: Ineffective esophageal motility is frequently observed in gastroesophageal reflux disease (GERD) patients but its clinical relevance remains controversial. In healthy subjects and in patients with nonobstructive dysphagia, it has been demonstrated, by means of high-resolution manometry (HRM), that long breaks of esophageal peristalsis predict delayed bolus clearance. METHODS: HRM and 24-h multichannel impedance-pH (MI-pH) monitoring were performed in 40 GERD patients with no evidence of hiatal hernia. Total bolus clearing time (BCT) in upright and supine position and acid exposure time (AET) were calculated. RESULTS: Of the 40 patients, 23 showed a pathological AET and 15 erosive reflux disease (ERD). Patients with a pathological number of large breaks were characterized by a significantly lower BCT value in the supine position and higher AET. In all, 10/15 ERD patients (67%) and 5/25 nonerosive reflux disease patients (20%) were characterized by an abnormal number of small or large breaks (P<0.05). ERD patients were characterized by significantly higher AET and BCT in the supine position. CONCLUSIONS: GERD patients with a pathological number of large breaks, assessed by HRM, are characterized by a significantly prolonged reflux clearance in the supine position and higher AET. ERD patients display a higher number of esophageal breaks that might explain the development of erosions.

Psychological distress in inflammatory bowel disease.

INTRODUCTION: Mental health disorders are common in inflammatory bowel disease (IBD) and affect patients' quality of life, impacting on disease outcomes and health care-related costs. AREAS COVERED: Even if psychological issues in IBD patients are highly burdened in terms of quality of life, psychiatric comorbidities still receive less attention into routine care than the physical symptoms of the disease. The present review provides an overview of recent literature, focusing on the association between perceived stress and IBD outcomes. For this purpose, the epidemiology of more common psychological comorbidities in IBD and their potential effect on the onset and disease course have been examined. Moreover, therapeutic interventions in the management of these patients have also been evaluated. EXPERT OPINION: Screening of patients at high risk of psychological issues is currently an unmet, clinical need in the management of IBD. Under-diagnosed and under-treated mental health disorders in IBD patients may impact outcomes, leading to increased disability and health-care utilization and associated costs. A patient-tailored, integrated model of care in the management of IBD is required to optimize disease outcomes and improve patients' quality of life.

Comparison of two strategies for the management of postoperative recurrence in Crohn's disease patients with one clinical risk factor: A multicentre IG-IBD study.

BACKGROUND: The management of postoperative recurrence (POR) in Crohn's disease (CD) after ileo-colonic resection is a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in the presence of at least one clinical risk factor. OBJECTIVE: Our aim was to determine whether early immunosuppression can be avoided and guided by endoscopy in CD patients with only one risk factor. METHODS: CD patients with only one risk factor for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, and active smoking, were retrospectively included. Two groups were formed based on whether immunosuppression was started immediately after surgery ("prophylaxis group") or guided by endoscopy ("endoscopy-driven group"). Primary endpoints were rates of any endoscopic recurrence (Rutgeerts ≥ i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence rates at 6, 12 and 24 months after surgery. RESULTS: A total of 195 patients were enroled, of whom 61 (31.3%) received immunoprophylaxis. No differences between immunoprophylaxis and the endoscopy-driven approach were found regarding any endoscopic recurrence (36.1% vs. 45.5%, respectively, p = 0.10) and severe endoscopic recurrence (9.8% vs. 15.7%, respectively, p = 0.15) at the first endoscopic evaluation. Clinical recurrence rates were also not statistically different (p = 0.43, p = 0.09, and p = 0.63 at 6, 12, and 24 months, respectively). CONCLUSIONS: In operated CD patients with only one risk factor for POR, immediate immunoprophylaxis does not decrease the rate of early clinical and endoscopic recurrence. Prospective studies are needed to confirm our results.

Impedance baseline and reflux perception in responder and non-responder non-erosive reflux disease patients.

BACKGROUND: It was recently shown that GERD patients have lower impedance baseline (IB) values than healthy controls and, that the esophageal acid exposure time (AET) correlates with IB levels. GOALS: To explore the sensitivity of IB measurements in NERD patients, responders and non-responders to PPIs, when compared with pH-impedance (MII-pH) variables, and to evaluate whether this variable could represent a marker of GERD symptoms. Reproducibility and inter-observer agreement of IB measurement were also assessed. Study. MII-pH tracings from 44 NERD responders and 22 non-responders were analysed. Ten healthy volunteers underwent the same protocol. IB values were measured at the distal and proximal esophagus. IB was also analysed in a subgroup of patients and in controls with two methods and by two blinded operators. RESULTS: Mean IB values at the distal esophagus were significantly lower in NERD patients than in controls. IB values did not differ between responders and non-responders. Of the 8 responders with negative AET and symptom association probability (SAP), 3 (37.5%) showed IB values lower than controls. IB values in responders with positive and negative SAP were similar (1832 (1596-2068) Ω vs 1667 (1361-1973) Ω, p: n.s.). No differences were found between the IB values measured with the two methods and the inter-observer agreement was good. CONCLUSIONS: IB is a promising and easy to calculate MII-pH variable and appears to increase the sensitivity of MII-pH monitoring. IB values cannot predict PPI response and are not associated with reflux perception in NERD patients.

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

BACKGROUND: The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD. METHODS: All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey-Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values. RESULTS: Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08-0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events). CONCLUSION: Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

Non-infectious uveitis burden on quality of life and work impairment assessed through different psychometric questionnaires.

BACKGROUND: The purpose of this study was to evaluate the association between a novel psychometric 12-item questionnaire (U-qest) and other validated questionnaires to assess quality of life and work impairment in patients with non-infectious uveitis. METHODS: Data were collected at baseline and 3 months postbaseline using U-qest and two other validated questionnaires: The National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and the 12-Item Short-Form Health Survey (SF-12). RESULTS: A total of 136 patients (52.2% female) aged 47.9 ± 14.8 years (mean ± SD) were enrolled in 14 uveitis referral centres. U-qest correlated moderately with VFQ-25 and SF-12 at baseline and at 3 months. Both U-qest and VFQ-25 scores improved as disease improved; however, U-qest also detected improvement in patients for whom VFQ-25 scores did not improve. Disease activity was shown to significantly affect activity impairment. Patients and physicians expressed positive perceptions regarding the use and benefit of this instrument. U-qest showed very good reliability in terms of internal consistency (Cronbach's alpha = 0.91). CONCLUSIONS: U-qest can be considered a useful tool to assess the burden of uveitis on quality of life.

Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study.

BACKGROUND: Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. AIMS: We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. METHODS: The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (≥65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. RESULTS: The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age ≥65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-α agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. CONCLUSION: Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD.

Novel impedance-pH parameters are associated with proton pump inhibitor response in patients with inconclusive diagnosis of gastro-oesophageal reflux disease according to Lyon Consensus.

BACKGROUND: The Lyon Consensus delineates impedance-pH parameters that can demonstrate/exclude gastro-oesophageal reflux disease (GERD). In patients with acid exposure time between 4% and 6%, GERD diagnosis has been considered inconclusive. In these cases, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave (PSPW) index may either confirm or refute GERD diagnosis and represent predictors of proton pump inhibitor (PPI) response. AIMS: To investigate the diagnostic yield of MNBI and PSPW index and their relationship with PPI response in patients with inconclusive GERD diagnosis. METHODS: Review of impedance-pH tracings from PPI responder/non-responder patients with typical reflux symptoms. Multivariate regression analysis was performed to determine the association of MNBI and PSPW index to PPI response. RESULTS: Among 233 patients evaluated, 145/233 (62.2%) were PPI responders; 62 had conclusive and 65 inconclusive evidence of GERD, 46 had reflux hypersensitivity, and 60 functional heartburn. Abnormal MNBI and PSPW index were significantly more frequent in inconclusive GERD as compared to the functional heartburn group (P < 0.001). Within the inconclusive GERD group, 35/65 (54%) patients were PPI responders and displayed a significantly higher proportion of cases with pathological MNBI or PSPW index as compared to non-responders (32/35 [91.4%] and 30/35 [85.7%] vs 9/30 [30%] and 7/30 [23.3%], P < 0.001). By multivariate analysis, pathological PSPW index and/or MNBI values were significantly associated with PPI response in all groups. CONCLUSIONS: The present study highlights the value of MNBI and PSPW index as adjunctive metrics in characterising patients with inconclusive evidence of GERD and identifying those responsive to PPI treatment.

Inflammatory bowel disease course in liver transplant versus non-liver transplant patients for primary sclerosing cholangitis: LIVIBD, an IG-IBD study.

BACKGROUND: Data regarding the effect of orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD) course are scarce and conflicting. AIMS: To compare the incidence of refractory IBD in two groups (OLT and non-OLT) of patients affected by IBD and PSC. METHODS: An observational, multicentre, cohort retrospective study was conducted by the Italian Group for the study of IBD in Italy. The primary outcome was the need for biologic therapy or bowel resection for medically refractory IBD or hospitalization due to IBD relapse during the follow-up. Secondary outcomes were rate of colonic dysplasia, colorectal cancer, other solid tumours, lymphoma. RESULTS: Eighty-four patients were included in the study. The primary outcome was not different between OLT and non-OLT groups (11/27, 40.7%, versus 20/57, 35.1%, respectively, p = 0.62). The lymphoma and other tumours (thyroid cancer, kidney cancer, ileal tumour, ovarian cancer, cervical cancer) rates were significantly higher in the OLT group (p = 0.04 and p = 0.005, respectively), at the limit of statistical significance for high-grade colonic dysplasia (p = 0.06). CONCLUSION: OLT in patients affected by IBD and PSC is not a risk factor for a more severe IBD course, but it is associated with a higher occurrence of cancer.

Therapies for inflammatory bowel disease do not pose additional risks for adverse outcomes of SARS-CoV-2 infection: an IG-IBD study.

BACKGROUND: Older age and comorbidities are the main risk factors for adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD). The impact of IBD medications is still under investigation. AIMS: To assess risk factors for adverse outcomes of COVID-19 in IBD patients and use the identified risk factors to build risk indices. METHODS: Observational cohort study. Univariable and multivariable logistic regression was used to identify risk factors associated with pneumonia, hospitalisation, need for ventilatory support, and death. RESULTS: Of the 937 patients (446 with ulcerative colitis [UC]) evaluated, 128 (13.7%) had asymptomatic SARS-CoV-2 infection, 664 (70.8%) had a favourable course, and 135 (15.5%) had moderate or severe COVID-19. In UC patients, obesity, active disease and comorbidities were significantly associated with adverse outcomes. In patients with Crohn's disease (CD), age, obesity, comorbidities and an additional immune-mediated inflammatory disease were identified as risk factors. These risk factors were incorporated into two indices to identify patients with UC or CD with a higher risk of adverse COVID-19 outcomes. In multivariable analyses, no single IBD medication was associated with poor COVID-19 outcomes, but anti-TNF agents were associated with a lower risk of pneumonia in UC, and lower risks of hospitalisation and severe COVID-19 in CD. CONCLUSION: The course of COVID-19 in patients with IBD is similar to that in the general population. IBD patients with active disease and comorbidities are at greater risk of adverse COVID-19 outcomes. IBD medications do not pose additional risks. The risk indices may help to identify patients who should be prioritised for COVID-19 re-vaccination or for therapies for SARS-CoV-2 infection.

Understanding the relationship between esophageal motor disorders and reflux disease.

INTRODUCTION: The management of gastro-esophageal reflux disease (GERD) patients is often complex as the clinical presentation is heterogeneous and the mechanisms underlying symptoms are multifactorial. In the past decades, investigations conducted with conventional manometry and, above all, the more accurate high resolution manometry (HRM), helped us in exploring the field of esophageal motility and in understanding the link between motor features and GERD pathogenesis. AREAS COVERED: Several studies carried out with conventional manometry and HRM have confirmed a relevant role of esophageal motor function in GERD pathogenesis. In particular, HRM studies have shown a direct correlation between impaired esophageal body motility, disruption of the esophagogastric junction and reflux burden. These findings impact the clinical and therapeutical management of GERD patients. Moreover, HRM findings might be helpful in evaluating patients with proton pump inhibitor (PPI) resistance and inconclusive evidences of GERD. EXPERT OPINION: The relationship between esophageal motility and GERD pathogenesis needs to be further evaluated by multicenter outcome studies involving a large number of GERD patients and healthy controls. However, other more promising areas could be progressed.

Nutritional Aspects in Inflammatory Bowel Diseases.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing, inflammatory disorders of the digestive tract that characteristically develop in adolescence and early adulthood. The reported prevalence of malnutrition in inflammatory bowel disease (IBD) patients ranges between 20% and 85%. Several factors, including reduced oral food intake, malabsorption, chronic blood and proteins loss, and intestinal bacterial overgrowth, contribute to malnutrition in IBD patients. Poor nutritional status, as well as selective malnutrition or sarcopenia, is associated with poor clinical outcomes, response to therapy and, therefore, quality of life. The nutritional assessment should include a dietetic evaluation with the assessment of daily caloric intake and energy expenditure, radiological assessment, and measurement of functional capacity.

Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults.

In recent years, research has focused on the use of dietary fibers and prebiotics, since many of these polysaccharides can be metabolized by intestinal microbiota, leading to the production of short-chain fatty acids. The metabolites of prebiotic fermentation also show anti-inflammatory and immunomodulatory capabilities, suggesting an interesting role in the treatment of several pathological conditions. Galacto-oligosaccharide and short- and long-chain fructans (Fructo-oligosaccharides and inulin) are the most studied prebiotics, even if other dietary compounds seem to show the same features. There is an increasing interest in dietary strategies to modulate microbiota. The aim of this review is to explore the mechanisms of action of prebiotics and their effects on the principal gastro-intestinal disorders in adults, with a special focus on Galacto-oligosaccharides, Fructo-oligosaccharides, lactulose and new emerging substances which currently have evidence of prebiotics effects, such as xilooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, lactobionic acid, resistant starch and polyphenols.