Gut Microbiota Profile Changes in Patients with Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease: A Metagenomic Study.

Gut microbiota imbalances have a significant role in the pathogenesis of Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD). Herein, we compared gut microbial composition in patients diagnosed with either IBD or NAFLD or a combination of both. Seventy-four participants were stratified into four groups: IBD-NAFLD, IBD-only, NAFLD-only patients, and healthy controls (CTRLs). The 16S rRNA was sequenced by Next-Generation Sequencing. Bioinformatics and statistical analysis were performed. Bacterial α-diversity showed a significant lower value when the IBD-only group was compared to the other groups and particularly against the IBD-NAFLD group. ß-diversity also showed a significant difference among groups. The higher Bacteroidetes/Firmicutes ratio was found only when comparing IBD groups and CTRLs. Comparing the IBD-only group with the IBD-NAFLD group, a decrease in differential abundance of Subdoligranulum, Parabacteroides, and Fusicatenibacter was found. Comparing the NAFLD-only with the IBD-NAFLD groups, there was a higher abundance of Alistipes, Odoribacter, Sutterella, and Lachnospira. An inverse relationship in the comparison between the IBD-only group and the other groups was shown. For the first time, the singularity of the gut microbial composition in IBD and NAFLD patients has been shown, implying a potential microbial signature mainly influenced by gut inflammation.

COVID-19 Vaccine Booster Shot Preserves T Cells Immune Response Based on Interferon-Gamma Release Assay in Inflammatory Bowel Disease (IBD) Patients on Anti-TNFα Treatment.

Immune-modifying treatment in inflammatory bowel disease (IBD) impairs the humoral response. The role of T lymphocytes in this setting is still unclear. This study aims to assess if a booster shot (third dose) of BNT162b2 mRNA COVID-19 vaccine enhanced the humoral response and elicited cellular immunity in IBD patients on different immuno-therapy regimens compared to healthy controls (HCs). Five months after a booster dose, serological and T-cell responses were assessed. The measurements were described using geometric means with 95% confidence intervals. The differences between study groups were assessed by Mann-Whitney tests. Seventy-seven subjects (n = 53 IBD patients and n = 24 HCs), who were fully vaccinated and not previously SARS-CoV-2 infected, were recruited. Regarding the IBD patients, 19 were affected by Crohn's disease and 34 by ulcerative colitis. During the vaccination cycle, half of the patients (53%) were on stable treatment with aminosalicylates, and 32% were on biological therapy. No differences in antibody concentrations between IBD patients and HCs, nor T-cell responses, were found. Stratifying IBD patients based on the type of treatment (anti-TNFα agents vs. other treatment regimens), a decrease only in antibody titer (p = 0.008), but not in cellular response, was observed. Even after the COVID-19 vaccine booster dose, the TNFα inhibitors selectively decreased the humoral immune response compared to patients on other treatment regimens. The T-cell response was preserved in all study groups. These findings highlight the importance of evaluating T-cell immune responses following COVID-19 vaccination in a routine diagnostic setting, particularly for immunocompromised cohorts.

Enacted Stigma in Inflammatory Bowel Disease: An Italian Phenomenological Study.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract that has a profound impact on the quality of life of those afflicted with it. The scientific literature shows how the quality of life of people with IBD influences and is influenced by the clinical manifestations of the disease. Strongly connected with excretory functions, which have always been taboo in society, these clinical manifestations can lead to stigmatizing behaviours. The purpose of this study was to understand the lived experiences of the enacted stigma of people with IBD through Cohen's phenomenological method. Two main themes (stigma in the workplace and stigma in social life) and one subtheme (stigma in love life) emerged from the data analysis. The data analysis revealed that stigma is associated with a multitude of negative health outcomes for the people targeted by it and can add to the already complex physical, psychological and social burdens endured by people with IBD. Having a better understanding of the stigma attached to IBD will facilitate the development of care and training interventions that can improve the quality of life of people suffering from IBD.

Satisfaction in Social Roles and Physical Function in Immune-mediated Inflammatory Diseases: A Cross-Sectional Study.

BACKGROUND: Although mood disorders have been well characterized in Immune-mediated inflammatory diseases, physical function and satisfaction in social roles have not yet been defined as independent domains. OBJECTIVE: The study aims to assess satisfaction in social roles and physical function alterations in an Immune-mediated inflammatory diseases population and identify associated characteristics. METHODS: Physical function and social roles satisfaction were evaluated through the Patient-Reported Outcomes Measurement System. Besides comparisons between groups, univariate and multivariable logistic regression were performed to identify independent predictors. RESULTS: Two hundred sixty-five Immune-mediated Inflammatory Diseases patients and 206 controls were recruited. Compared with controls, Inflammatory Bowel Diseases patients had impaired physical function (p<0.001), while Inflammatory Arthritis patients reported impairment in both domains (p<0.001, each). In the univariate logistic regression, gender, high school educational level, physical activity and occupation were positively associated with physical function and social role satisfaction (p<0.001; p=0.001; p<0.001; p=0.001 and p<0.001; p=0.012; p=0.008; p=0.004, respectively). Active disease and steroids were inversely associated with physical function and social roles satisfaction (p=0.033; p=0.022 and p=0.002; p=0.038, respectively). Further associations were found between age and physical function (p=0.002); biological treatment and ESR with social roles satisfaction (p<0.001; p=0.043; respectively). In the multivariable regression, gender remained associated with physical function (p<0.001) and social roles satisfaction (p=0.003). Negatively associated factors were biological treatment for satisfaction in social roles (p<0.001) and steroids for physical function (p=0.021) and social roles satisfaction (p=0.018). CONCLUSION: Immune-mediated Inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independent associated factors. Patient-Reported Outcomes should be considered in clinical management to define patients' real needs.

Fatigue and Associated Factors in an Immune-Mediated Inflammatory Disease Population: A Cross-Sectional Study.

Fatigue is a main symptom of chronic diseases, including immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel disease (IBD) and inflammatory arthritis (IA); however, the pathophysiological mechanisms are not completely understood. The aim of this study was to assess the prevalence of fatigue and the associated factors in an IMIDs population. A control group, IBD, and IA patients, were enrolled. The PROMIS® fatigue questionnaire was used to evaluate the symptoms. Information on demographics, anthropometrics, disease characteristics, and medications was collected for each participant. A total of 471 subjects (137 with IBD, 103 with IA, and 206 controls) were enrolled. IBD and IA patients reported greater fatigue than controls (p < 0.001, each). In univariate regression, patients with anxiety and depression were more likely to report fatigue (p = 1.40 × 10−9 and p = 3.80 × 10−11, respectively). Males, holding a high school diploma, and being employed were inversely correlated to the domain (p = 1.3 × 10−5; p = 0.003 and p = 0.005, respectively). The use of steroids and disease activity determined increased fatigue (p = 0.014 and p = 0.019; respectively). In the multivariate analysis, anxiety and depression remained associated (p = 0.002 and p = 1.3 × 10−5, respectively). IMIDs patients present increased fatigue compared with healthy subjects. Anxiety and depression are the main associated factors, suggesting a psychological component of the symptom; thus, a holistic management should be established.

Autoimmune colitis and neutropenia in adjuvant anti-PD-1 therapy for malignant melanoma: efficacy of Vedolizumab, a case report.

Immune checkpoint inhibitors (ICIs) represent an important advance in the adjuvant treatment of patients with high-risk melanoma. Although the safety profile of anti-programmed cell death protein-1 (PD-1) is fairly acceptable, different immune-related adverse events (irAEs) are described. Herein we report for the first time a notably multidisciplinary combined approach on a malignant melanoma (MM) patient treated with anti-PD-1 antibody in adjuvant setting. In this novel approach, corticosteroid-refractory immune-mediated colitis (IMC) was effectively treated with Vedolizumab, a selective blockade of the α4ß7 integrin and corticosteroids were successfully administered for autoimmune neutropenia. Notably, our patient also express HLA-B*35, a potential biomarker for predicting a genetic basis of autoimmune susceptibility. Our experience offers a possible future perspective about the use of Vedolizumab together with immunotherapy in a strategic early approach for high-risk patients genotyped for HLA.

Psychometric evaluation of an Italian custom 4-item short form of the PROMIS anxiety item bank in immune-mediated inflammatory diseases: an item response theory analysis.

BACKGROUND: There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)'s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons' responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs. METHODS: We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease (n = 246), rheumatological (n = 100) and dermatological (n = 43) diseases, and healthy volunteers (n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form. RESULTS: Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach's α = 0.93, McDonald's ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs. control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group (ps < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves (p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson's r = 0.98) and led to similar results. DISCUSSION: The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients.

Effects of listening to music in digestive endoscopy: A prospective intervention study led by nursing.

AIMS: To explore whether music can reduce anxiety and pain in patients who underwent diagnostic endoscopic examinations in conscious and deep sedation and to assess degree of satisfaction and willingness to repeat the procedure. DESIGN: Prospective study led by nursing. METHODS: Between March 2019-June 2019, consecutive outpatients undergoing endoscopic examinations were simple matched into four groups: Group 1: conscious sedation with music; Group 2: conscious sedation without music; Group 3: deep sedation with music and Group 4: deep sedation without music. Ten minutes before the procedure, two trainee nurses applied music. State-Trait Anxiety Inventory was used to evaluate anxiety. RESULTS: Before and at the end of the procedure, patients who listened to music had a lower level anxiety than those who did not listen and, also, reported lower pain intensity during procedure. Only within Group 1 median anxiety, measured after the procedure, is lower than that measured before. In the bivariate logistic regression model, pain and listening to music were independent factors for satisfaction and willingness to repeat procedure. CONCLUSION: music in digestive endoscopy reduce pain and anxiety in conscious sedation, thus could be used to reduce anxiety in support to conscious sedation leading to lower usage of deep sedation and consequently reduction of costs and adverse events. IMPACT: Anxiety in digestive endoscopy limits patients' satisfaction. Music in digestive endoscopy as a specific nursing intervention could reduce anxiety of patients. This nursing intervention study confirms positive effect of music in digestive endoscopy. As part of nursing management, the addition of music to daily care practice in digestive endoscopy may reduce anxiety and increase the patient's degree of satisfaction. Use of music could limit deep sedation use in digestive endoscopy with consequent reduction of risks for patients, execution times, and costs of procedures.

COVID-19 and Inflammatory Bowel Disease: Patient Knowledge and Perceptions in a Single Center Survey.

Background and objectives: Spreading of SARS-CoV-2 infection from China to countries with a higher prevalence of inflammatory bowel disease (IBD) has generated concern among gastroenterologists and patients. The aim of this survey is to evaluate knowledge about clinical importance of COVID-19, disease management, prevention measures, and anxiety level during pandemic among patients with IBD. Material and methods: From 15th March to 15th April 2020, a questionnaire survey was administered to 200 patients with IBD by email or phone application. The questionnaire consisted of five sections: (1) anthropometric, demographic and clinical characteristics, (2) knowledge about clinical importance of COVID-19, (3) IBD management, (4) prevention measures, (5) anxiety level during pandemic. Results: One hundred forty two questionnaires were completed. Ninety-seven patients (68.3%) were males with a mean age of 46 years (SD 13; range 17-76). Fifty-four individuals (38%) were affected by Crohn disease and 88 (62%) by Ulcerative Colitis. Most patients reported high knowledge about clinical importance of COVID-19 (80%), IBD management (72%), and prevention measures (97%). Sixty-two percent of them showed moderate-high level of anxiety. High education level was independently associated with high knowledge about clinical importance of COVID-19 (odds ratio [OR] 5, 95% confidence interval [CI] 1.49-16.6, p = 0.009) and older age (OR 1, 95%, CI 1.01-1.1, p = 0.01), while the receipt of e-format educational material with low knowledge about clinical importance of COVID-19 (OR 3, 95%, CI 1.08-9.3, p = 0.03). Displaying an active disease appeared to be independently associated with low knowledge of IBD management (OR 5.8, 95% CI 1.4-22.8, p = 0.01) and no variables other than an older age was independently associated with higher level of anxiety (OR 1.04, 95% CI 1.009-1.09, p = 0.01). Conclusions: High educational level and aging promote knowledge about clinical importance of COVID-19, while e-format educational material does not. Taken together with findings that an active disease status compromises knowledge of IBD management and the high level of anxiety related to increasing age, these data suggest the need of further supporting patient-oriented strategies in IBD during Covid-19 pandemic.

Ulcerative Colitis as an Independent Risk Factor for Hepatic Steatosis.

Inflammatory bowel disease (IBD) is an inflammatory condition of the gastrointestinal tract encompassing Crohn disease and ulcerative colitis, often associated with extraintestinal manifestations. Nonalcoholic fatty liver disease represents one of the described inflammatory bowel disease-related liver diseases. To understand the IBD contribution to nonalcoholic fatty liver disease onset, we compared liver fat content and fibrosis between IBD patients and healthy controls integrating medical and nursing expertise (integrated nursing approach). A total of 95 patients and 53 healthy volunteers were recruited. Only nondiabetic and nonobese individuals were included in the study. Liver evaluation was performed by an experienced nurse using transient elastography. We found that IBD patients had higher liver fat content than the control group (p = .003). Bonferroni post hoc analyses revealed that patients with Crohn disease or ulcerative colitis had higher liver fat than the control group. We also found that ulcerative colitis was associated with more than a 4-fold increased risk for mild steatosis and 7-fold increased risk for moderate/severe steatosis independently from other risk factors such as glucose and body mass index. In conclusion, we showed for the first time that ulcerative colitis is an independent risk factor for hepatic steatosis measured by transient elastography.

Weight Gain and Liver Steatosis in Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIM: Most studies focused on the benefits of weight loss on hepatic steatosis and no studies have been specifically designed to assess the role of weight gain on the development of liver steatosis in patients affected by inflammatory bowel diseases. The aim of this study was to analyse the relation between weight change over time and liver steatosis in patients with inflammatory bowel diseases. METHODS: We retrospectively evaluated a population of 89 ambulatory patients in clinical remission or affected by mild disease, as determined from disease activity indices, with at least one follow-up visit. Transient elastography was used to quantify liver steatosis. RESULTS: A total of 49 individuals (55%) were overweight/obese at baseline. A significant difference in weight change was found between participants that improved, were stable and worsened, over a mean follow-up of four years. (-1.0 kg ± 4; 2.5 kg ± 6; and 5.4 kg ± 5; respectively, p = 0.009). We found a greater probability of worsening in the hepatic fat content in individuals who gained more than 6% of body weight than in those gaining less than this value (log⁻rank (Mantel⁻Cox) χ² test = 9.85; df = 1; p = 0.002). CONCLUSIONS: A body weight gain of 6% increases the probability of deterioration in liver steatosis over a period of four years in patients with inflammatory bowel diseases. Weight gain prevention with lifestyle interventions may be the cornerstone treatment of these patients.

Deregulation of SGK1 in Ulcerative Colitis: A Paradoxical Relationship Between Immune Cells and Colonic Epithelial Cells.

BACKGROUND: Inflammatory bowel disease (IBD) is due to the interaction of genetic and environmental factors that trigger an unbalanced immune response ultimately resulting in the peculiar inflammatory reaction. Experimental models of IBD point to a role of T-cell-derived cytokines (Th17) and to SGK1 as mediator of the Th17 switch. We hypothesize that SGK1, a salt inducible kinase, directs lymphocytic behavior and tissue damage. METHODS: Eleven controls and 32 ulcerative colitis (UC) patients were randomized according to endoscopic Mayo score. Mucosal biopsies from different intestinal tracts were analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction to check the expression of disease markers including SGK1. Peripheral blood mononuclear cells (PBMCs) from patients and controls were analyzed by fluorescence-activated cell sorting. Finally, an in vitro cell model was developed to test the hypothesis. RESULTS: SGK1 mRNA and protein expression in lesional areas of UC patients were lower than in normal peri-lesional areas of the same patients and in normal tissues of healthy controls. SGK1 expression was increased in PBMCs from UC patients, particularly in the CD4+ cell population, enriched in Th17 cells. IL17/IL13 was increased in patients and correlated with SGK1 expression. Genetically engineered Jurkat cells confirmed the effect of SGK1 overexpression on viability of RKO cells. CONCLUSIONS: These observations suggest a pathogenic mechanism whereby SGK1 overexpression in CD4+ T cells induces the secretion of the inflammatory cytokines IL17 and IL13, which downregulate the expression of SGK1 in target tissues. Our data suggest a novel hypothesis in the pathogenesis of UC, integrating colonic epithelial cells and lymphocytes.

PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS: The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS: Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS: Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.