Has the COVID-19 Pandemic Worsened Health-Related Quality of Life of Patients with Inflammatory Bowel Disease? A Longitudinal Disease Activity-Controlled Study

The present longitudinal study aimed to investigate the burden of disease activity change on health-related quality of life (HRQoL) of patients with inflammatory bowel disease (IBD) during the two different pandemic waves in 2020 and 2021. A sample of 221 IBD patients (recruited during March–May 2020 for T0 and March–May 2021 for T1) was included. The psychological impact of the COVID-19 pandemic (Impact of Event Scale-Revised (IES-R)) and HRQoL (Inflammatory Bowel Disease Questionnaire (IBDQ)) were assessed. Post-traumatic COVID-19-related symptoms (IES-R) were not significantly different across the disease activity-related groups. Conversely, IBDQ was consistently higher in patients with persistent, quiescent disease activity compared to the other groups, as expected. Even after controlling for baseline IES-R, repeated-measures ANCOVA showed a non-significant main effect of time (p = 0.60) but a significant time-per-group interaction effect with a moderate effect size (η2 = 0.08). During the two different phases of pandemic restrictions, IBD-specific HRQoL was modified by disease-related factors such as disease activity, rather than by the post-traumatic symptoms of COVID-19. This lends further weight to the need for developing an evidence-based, integrated, biopsychosocial model of care for patients with IBD to identify subjective and objective factors that affect the burden of disease

Influence of the COVID-19 Outbreak on Disease Activity and Quality of Life in Inflammatory Bowel Disease Patients

Objective: The present preliminary cross-sectional study aimed to investigate the extent to which health-related quality of life of patients with inflammatory bowel disease (IBD) was influenced by the outbreak of Covid-19 while controlling for disease activity. Methods: Two samples of 195 (recruited before Covid-19 outbreak) and 707 patients (recruited during the Covid-19-related lockdown) were included. Psychological distress (Hospital Anxiety and Depression Scale, HADS), quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), and somatization (Patient Health Questionnaire, PHQ-12) were concurrently assessed. Results: Patients with active IBD were more prevalently affected by ulcerative colitis (60.2%, !2 = 0.12) and, expectedly, showed higher psychological distress (HADS, d = 0.34) and somatization (PHQ-12, d = 0.39), as well as poorer disease-specific health-related quality of life (effect sizes for the total and subscale IBDQ scores in the large range of d > 0.50). Hierarchical regression models revealed that setting (pre-Covid-19 outbreak vs. during lockdown) (p < 0.001) explained only a small portion (8%) of the IBDQ variance. IBD-related factors (ulcerative colitis and disease activity) and psychological factors (psychological distress and somatization) added a significant amount of 25 and 27%, respectively, to the explained IBDQ variance. The final model predicted 59% of the explained IBDQ variance. Conclusion: Clinical and psychological manifestations seem to be major impairments in IBD patients both before and during the Covid-19 outbreak. Furthermore, the quality of life of IBD patients seem to be more influenced by psychological and somatizing distressing symptoms than the pandemic-related living conditions

Gene Expression Profiling in Coeliac Disease Confirmed the Key Role of the Immune System and Revealed a Molecular Overlap with Non-Celiac Gluten Sensitivity

Coeliac disease (CeD) is an immune-mediated disorder triggered by the ingestion of gluten and an as yet unidentified environmental factor in genetically predisposed individuals. The disease involves a major autoimmune component that primarily damages the intestinal mucosa; although, it also has systemic involvement. The Th1 inflammatory response is one of the main events leading to mucosal damage; although, enterocytes and the innate immune response also participate in the pathological mechanism. In this study, we performed an analysis of the gene expression profile of the intestinal mucosa of patients with active disease and compared it with that of patients who do not suffer from gluten-related disorders but report dyspeptic symptoms. This analysis identified 1781 differentially expressed (DE) genes, of which 872 were downregulated and 909 upregulated. Gene Ontology and pathway analysis indicated that the innate and adaptive immune response, in particular the Th1 pathway, are important pathogenetic mechanisms of CeD, while the key cytokines are IL27, IL21, IL2, IL1b, TNF, CSF2 and IL7, as well as type I (IFNA1, IFNA2) and type II (IFNG) interferons. Finally, the comparison between the DE genes identified in this study and those identified in our previous study in the intestinal mucosa of patients with non-celiac gluten sensitivity (NCGS) revealed a high degree of molecular overlap. About 30% of the genes dysregulated in NCGS, most of which are long non-coding RNAs, are also altered in CeD suggesting that these diseases may have a common root (dysregulated long non-coding RNAs) from which they develop towards an inflammatory phenotype of variable degree in the case of CeD and NCGS respectively

Prevalence and clinical characteristics of refractoriness to optimal proton pump inhibitor therapy in non-erosive reflux disease

Background: The real size of the gastro-oesophageal reflux disease (GERD) population not responding to proton pump inhibitor (PPI) therapy has still not been fully elucidated. Causes of PPI refractoriness include incorrect diagnosis and lack of adherence to therapy, in terms of incorrect dosage and timing. Aims: To evaluate the prevalence of refractoriness to optimal PPI therapy and the contribution of non-erosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn, to PPI refractoriness. The association of functional GI symptoms in non-responders was evaluated. Methods: Frequency and severity of GERD symptoms (heartburn, regurgitation, chest pain), dysphagia, belching, epigastric pain, postprandial distress, irritable bowel syndrome (IBS), globus, and ear nose and throat (ENT) symptoms were evaluated in patients previously classified as non-responders. Patients with at least one of the oesophageal symptoms with a frequency 653 /week were treated with esomeprazole 40 mg once daily for 8 weeks and then re-evaluated. Non-responders (patients with oesophageal symptoms 653 times per week) underwent 24 hour multichannel intraluminal impedance-pH monitoring. Results: Of 573 consecutive patients, 92 with oesophageal symptoms and classified as PPI-refractory underwent the esomeprazole trial; 60 did not respond. IBS, epigastric pain, and post-prandial distress episodes were associated with a poor response on multivariate analysis. NERD, reflux hypersensitivity, and functional heartburn patients constituted 32%, 42%, and 26%, respectively of the PPI-refractory group. Conclusions: True refractoriness in patients with GERD symptoms attending a secondary care setting is lower than previously reported. Following a careful history and optimal PPI dosing, the rate of refractoriness was 20%. True NERD constitutes only a third of the PPI-refractory group

An explorative study identifies miRNA signatures for the diagnosis of non-celiac wheat sensitivity.

Non-celiac wheat sensitivity (NCWS), also referred to as non-celiac gluten sensitivity, is a recently described disorder triggered by wheat/gluten ingestion. NCWS elicits a wide range of symptoms including diarrhoea, intestinal discomfort, and fatigue in analogy with other wheat/gluten-related disorders and celiac disease in particular. From the pathological standpoint, NCWS patients only have a slight increase of intraepithelial lymphocytes, while antibodies to tissue transglutaminase (tTG) and villous atrophy, otherwise diagnostic features of celiac disease, are absent. To date, the diagnosis of NCWS relies on symptoms and exclusion of confounding diseases, since biomarkers are not yet available. Here, the expression levels of selected miRNAs were examined in duodenal biopsies and peripheral blood leukocytes collected from newly diagnosed patients with NCWS and, as controls, from patients with celiac disease and gluten-independent gastrointestinal problems. We identified a few miRNAs whose expression is higher in the intestinal mucosa of patients affected by NCWS in comparison to control patients affect by gluten-independent dyspeptic symptoms (Helicobacter pylori-negative) and celiac disease. The present study provided the first evidence that NCWS patients have a characteristic miRNA expression patterns, such peculiarity could be exploited as a biomarker to the diagnosis of this disease

Circulating Extracellular Vesicles Are Increased in Newly Diagnosed Celiac Disease Patients

Extracellular vesicles (EVs) are a class of circulating entities that are involved in intercellular crosstalk mechanisms, participating in homeostasis maintenance, and diseases. Celiac disease is a gluten-triggered immune-mediated disorder, characterized by the inflammatory insult of the enteric mucosa following local lymphocytic infiltration, resulting in villous atrophy. The goal of this research was the assessment and characterization of circulating EVs in celiac disease patients, as well as in patients already on an adequate gluten-free regimen (GFD). For this purpose, a novel and validated technique based on polychromatic flow cytometry that allowed the identification and enumeration of different EV sub-phenotypes was applied. The analysis evidenced that the total, annexin V+, leukocyte (CD45+), and platelet (CD41a+) EV counts were significantly higher in both newly diagnosed celiac disease patients and patients under GFD compared with the healthy controls. Endothelial-derived (CD31+) and epithelial-derived (EpCAM+) EV counts were significantly lower in subjects under gluten exclusion than in celiac disease patients, although EpCAM+ EVs maintained higher counts than healthy subjects. The numbers of EpCAM+ EVs were a statistically significant predictor of intraepithelial leukocytes (IEL). These data demonstrate that EVs could represent novel and potentially powerful disease-specific biomarkers in the context of celiac disease