Associations between immune biomarkers and symptoms of anxiety, depression, and insomnia in paediatric inflammatory bowel disease: A preliminary longitudinal analysis.

Innate immunity may influence the onset of affective symptoms and alter sleep patterns in chronic inflammatory conditions. Here, we tested the prospective associations between baseline serum C-reactive protein (CRP), albumin, and CRP/albumin ratio (CAR, i.e., an emerging biomarker of disease activity), and self-reported symptoms of anxiety, depression, and insomnia at 1-year follow up in paediatric inflammatory bowel disease (n = 17). After controlling for baseline values, CAR (ρ = 0.591, p = 0.026) predicted anxiety symptoms, while albumin predicted both anxiety (ρ = -0.687, p = 0.007) and insomnia symptoms (ρ = -0.648, p = 0.012). Current findings preliminarily suggest that inflammation may influence anxiety and sleep disturbance in paediatric IBD.

Inflammation as an aetiological trigger for depressive symptoms in a prospective cohort of patients with inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is often comorbid with mood disorders and depressive symptoms. The aetiology of depressive symptoms in IBD, however, remains largely unknown. Consistent with the inflammatory hypothesis of depression, the aim of this study was to explore the prospective associations between inflammatory biomarkers and depressive symptoms in a cohort of IBD patients with and without a previous clinical diagnosis of mood disorder. METHOD: IBD clinical activity was determined using the Harvey-Bradshaw Index for CD and the Partial Mayo score for UC; serum C-reactive protein (CRP) and faecal calprotectin (fCAL) were used as biomarkers of systemic and intestinal inflammation, respectively. Participants were administered the Hospital Anxiety and Depression Scale-depression (HADS-D) at baseline and 1-year follow-up. RESULTS: Eighty-four participants (50 ± 16 years; 75% UC and 25% CD) were included in the main analyses. Longitudinal moderated regression models showed that baseline CRP significantly predicted follow-up HADS-D scores among individuals with a previous mood disorder diagnosis (ß = 0.843, p < .001), but not among individuals without (ß = -0.013, p = .896), after controlling for baseline HADS-D scores, body mass index, IBD phenotype, sex, and perceived stress. Likely due to lower power, results on FCAL (n = 31) were not statistically significant. CONCLUSION: This study suggests that IBD patients with previous diagnosis of mood disorder may be at higher risk of inflammation-related depressive symptoms.

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.

BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.

Magnetic-Assisted Capsule Endoscopy in Children With Crohn Disease: Feasibility and Impact on Gastric Transit Time.

OBJECTIVES: Standard capsule endoscopy (CE) is ineffective for upper gastrointestinal (GI) tract examination because it does not allow operator-controlled navigation of the capsule. Magnetically assisted capsule endoscopy (MACE) may offer a solution to these problems. This pilot study is aimed to evaluate the feasibility of MACE system in pediatric Crohn disease (CD) and if magnetic steering could enhance capsule gastric emptying when compared with standard CE. METHODS: Pediatric CD patients already studied by standard small bowel CE were enrolled. All participants swallowed a magnetically assisted CE and an external magnetic field navigator was used to guide the capsule through the upper GI tract. Maneuverability, completeness of the MACE examination, differences in the esophageal transit time (ETT), gastric transit time (GTT), and pyloric transit time (PTT) between standard CE and MACE were assessed. RESULTS: Ten patients [mean age 11.4 years (range 6-15); 60% male] were enrolled. Maneuverability was defined as good and fair in 60% and 40% of participants, respectively. Completeness of MACE examination was 95%, 65%, and 92.5% in the esophagus, proximal, and distal stomach, respectively. Transpyloric passage of the capsule under magnetic control was successfully performed in 80% of patients. Magnetic intervention significantly increased ETT ( P < 0.001) and reduced GTT and PTT ( P = 0.002). No significant adverse events occurred. CONCLUSIONS: MACE is a safe and feasible technique in children. Magnetic steering enhances capsule gastric emptying and facilitates capsule transpyloric passage when compared with standard CE.

A meta-analysis on sleep quality in inflammatory bowel disease.

Evidence of poor sleep quality in inflammatory bowel disease (IBD, i.e., Crohn's disease and ulcerative colitis) has been reported but never systematically reviewed or meta-analysed. We conducted a systematic review and meta-analysis of pairwise comparisons that included 1) IBD patients/controls, 2) Crohn's disease/ulcerative colitis, 3) active/inactive IBD on standardised measures of sleep quality. PubMed, Medline, PsycINFO, Scopus, and CINAHL were searched up to March 2021. Forty-two studies met the inclusion criteria. Results showed poorer subjective sleep quality in IBD patients than in controls, with moderate effect sizes (g = .49, [95% CI = .32 - .66], p < .001). No differences within IBD subtypes were found (g = -.07, [95% CI = -.17-.05], p = .208). Individuals with an active IBD reported poorer sleep quality than those in remission, with a large effect size (g = .66, [95% CI = .35 - .98], p < .001). Results on objectively recorded sleep were mixed, with no clear evidence of objective sleep impairments in individuals with IBD. Results support the view of subjective poor sleep quality as a relevant comorbidity in IBD. As a potential factor affecting immune and inflammatory responses as well as patients' quality of life, sleep quality should be taken into account in the treatment of IBD.

Enteroscopy in children and adults with inflammatory bowel disease.

Inflammatory bowel disease (IBD) includes Crohn's disease (CD), ulcerative colitis and unclassified entities. CD commonly involves the terminal ileum and colon but at the time of diagnosis it can be confined to the small bowel (SB) in about 30% of the patients, especially in the young ones. Management of isolated SB-CD can be challenging and objective evaluation of the SB mucosa is essential in differentiating CD from other enteropathies to achieve therapeutic decisions and to plan the follow-up. The introduction of cross-sectional imaging techniques and capsule endoscopy (CE) have significantly expanded the ability to diagnose SB diseases providing a non-invasive test for the visualization of the entire SB mucosa. The main CE limitations are the low specificity, the lack of therapeutic capabilities and the impossibility to take biopsies. Device assisted enteroscopy (DAE) enables histological confirmation when traditional endoscopy, capsule endoscopy and cross-sectional imaging are inconclusive and also allows therapeutic interventions such as balloon stricture dilation, intralesional steroid injection, capsule retrieval and more recently stent insertion. In the current review we will discuss technical aspect, indications and safety profile of DAE in children and adults with IBD.

Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: How to maintain standards of care.

BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Acute fulminant hepatitis E virus genotype 3e infection: description of the first case in Europe.

Hepatitis E virus (HEV) is the most important causative agent of acute hepatitis in developing countries. The disease is usually characterized by a self-limiting, benign course. However, when particular conditions coexist (pregnancy, old age, pre-existing liver disease) it may run an unfavourable course. To date, 4 HEV genotypes have been described. Historically, in the Western world, HEV infection was considered a travel-related disease, however in the last 2 decades a great number of non-travel-related autochthonous cases have been described, more often related to genotype 3 or 4 and in the context of zoonosis. We report the case of an elderly Italian man with an acute fulminant HEV infection genotype 3e that developed in the context of pre-existing liver disease; this is the first case of an unfavourable outcome associated with subgenotype 3e. The potential pathogenicity of this subgenotype together with the influence of host-related risk factors are discussed.

Repeated transabdominal ultrasonography is a simple and accurate strategy to diagnose a biliary etiology of acute pancreatitis.

OBJECTIVES: Transabdominal ultrasonography (US) usually reveals diagnosis of biliary acute pancreatitis (AP). Guidelines suggest repeating US in AP patients without cause at first examination. This approach has been poorly investigated, as well as the accuracy of repeated US as compared with that of magnetic resonance cholangiopancreatography. This study aims at evaluating the diagnostic accuracy of repeated US for biliary AP. METHODS: The accuracy of each test for diagnosis of biliary AP was evaluated according to the final diagnosis. Comparison between tests was obtained by examining the areas under the receiver operating characteristic curves. RESULTS: Among 155 patients, the etiology was biliary in 52% and alcoholic in 20%. The accuracy of the first US alone and of the 2 combined examinations for a biliary etiology were 66% and 83%, respectively. Comparison of receiver operating characteristic curves showed a better performance of repeated US (difference between areas under the curve, 0.135; 95% confidence interval, 0.02-0.24; P = 0.021). Magnetic resonance cholangiopancreatography had high specificity (93%) but low sensitivity (62%), with 76% accuracy. The accuracy of the combination of the 2 US examinations and of elevated alanine transferase was 87%. CONCLUSIONS: Repeated US is effective for biliary AP diagnosis. The combination of repeated US examinations and biochemical tests seems an effective approach, whereas magnetic resonance cholangiopancreatography might be restricted to selected cases.

Liver biopsy: Analysis of results of two specialist teams.

AIM: To analyze the safety and the adequacy of a sample of liver biopsies (LB) obtained by gastroenterologist (G) and interventional radiologist (IR) teams. METHODS: Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to 31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease, both in the setting of day hospital and regular admission (RA) care, were retrieved and the data entered in a database. Patients were divided into two groups: one undergoing an ultrasonography (US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team. For the first group, an intercostal approach (US-assisted) and a Menghini modified type needle 16 G (length 90 mm) were used. The IR team used a subcostal approach (US-guided) and a semiautomatic modified Menghini type needle 18 G (length 150 mm). All the biopsies were evaluated for appropriateness according to the current guidelines. The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report. Clinical, laboratory and demographic patient characteristics, the adverse events rate and the diagnostic adequacy of LB were analyzed. RESULTS: During the study period, 226 patients, 126 males (56%) and 100 females (44%), underwent LB: 167 (74%) were carried out by the G team, whereas 59 (26%) by the IR team. LB was mostly performed in a day hospital setting by the G team, while IR completed more procedures on inpatients (P < 0.0001). The groups did not differ in median age, body mass index (BMI), presence of comorbidities and coagulation parameters. Complications occurred in 26 patients (16 G team vs 10 IR team, P = 0.15). Most gross samples obtained were considered suitable for basal histological evaluation, with no difference among the two teams (96.4% G team vs 91.5% IR, P = 0.16). However, the samples obtained by the G team had a higher mean number of portal tracts (G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20) (P = 0.0192) and a longer mean length (G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm) (P = 0.0001). CONCLUSION: LB can be performed with similar outcomes both by G and IR. Use of larger dimension needles allows obtaining better samples, with a similar rate of adverse events.

Effectiveness of entecavir in the management of acute hepatitis B developing in a patient with Hodgkin's lymphoma: a case report.

We describe a case of severe acute hepatitis B developing in a patient with Hodgkin's lymphoma after chemotherapy and before radiotherapy. Entecavir was administered leading to virological and biochemical response, which allowed the scheduled treatment to be completed. The patient had complete haematological remission and made a complete recovery from hepatitis B.

Nasogastric or nasointestinal feeding in severe acute pancreatitis.

AIM: To assess the rate of spontaneous tube migration and to compare the effects of naso-gastric and naso-intestinal (NI) (beyond the ligament of Treitz) feeding in severe acute pancreatitis (SAP). METHODS: After bedside intragastric insertion, tube position was assessed, and enteral nutrition (EN) started at day 4, irrespective of tube localization. Patients were monitored daily and clinical and laboratory parameters evaluated to compare the outcome of patients with nasogastric (NG) or NI tube. RESULTS: Spontaneous tube migration to a NI site occurred in 10/25 (40%) prospectively enrolled SAP patients, while in 15 (60%) nutrition was started with a NG tube. Groups were similar for demographics and pancreatitis aetiology but computed tomography (CT) severity index was higher in NG tube patients than in NI (mean 6.2 vs 4.7, P = 0.04). The CT index seemed a risk factor for failed obtainment of spontaneous distal migration. EN trough NG or NI tube were similar in terms of tolerability, safety, clinical goals, complications and hospital stay. CONCLUSION: Spontaneous distal tube migration is successful in 40% of SAP patients, with higher CT severity index predicting intragastric retention; in such cases EN by NG tubes seems to provide a pragmatic alternative opportunity with similar outcomes.

Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis.

AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori (H pylori) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r = 0.2216, P = 0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.

Can patient characteristics predict the outcome of endoscopic evaluation of iron deficiency anemia: a multiple logistic regression analysis.

BACKGROUND: The purpose of this study was to identify clinical and biochemical variables that predict the outcome of upper/lower endoscopy in outpatients with iron deficiency anemia and to determine which endoscopic procedure should be performed first. METHODS: Ninety-eight patients (74 women, 24 men; mean age 55 years) with iron deficiency anemia referred from the hematology department were interviewed and responded to a questionnaire that included clinical and biochemical variables, and underwent EGD (with biopsies) and colonoscopy. The endoscopic findings were recorded as presence/absence of GI cancer, upper/lower GI tract lesions and bleeding/non-bleeding-associated GI lesions. A multiple logistic regression analysis was applied to identify variables significantly related with the outcome of the investigations. Multiple analyses were performed so that a Bonferroni correction for multiple testing removed significance except where p<0.01. RESULTS: A likely cause of iron deficiency anemia was found in 86.7% of patients. The risk factors for GI malignancies were: male gender (OR 7.5: 95% CI[1.7, 31.9]; p<0.01), advanced age (OR 1.1/y: 95% CI[1, 1.2]; p<0.01), and lower mean corpuscular volume (OR 1.1/unit: 95% CI[1, 1.2]; p<0.002). The risk factors for bleeding-related diseases were the following: greater age (OR 1.1/y: 95% CI[1.1, 1.2]; p<0.001), absence of lower-GI tract symptoms (OR 4.7: 95% CI[1.3, 16.6]; p<0.05), and a positive fecal occult blood test (OR 4.1: 95% CI[1.2, 14.3]; p<0.05). The risk factors for non-bleeding-related GI tract diseases were the following: negative fecal occult blood test (OR 4.5: 95% CI[1.16, 20]; p<0.05) and higher Hb level (OR 1.4/unit: 95% CI[1.1, 1.8]; p<0.05). CONCLUSIONS: For non-hospitalized patients with iron deficiency anemia, colonoscopy should be the initial investigation in those greater than 50 years of age, particularly men, and those without upper-GI tract symptoms and with lower values for mean corpuscular volume and Hb. EGD should be performed first in younger patients, particularly those with a mild decrease in Hb and a negative fecal occult blood test.

Intragastric ascorbic but not uric acid is depleted in relation with the increased pH in patients with atrophic body gastritis and H. pylori gastritis.

BACKGROUND: Helicobacter pylori gastritis induces reversible lowering of Ascorbic Acid (AA) intragastric concentrations. No studies have been aimed at determining the gastric juice AA concentration of atrophic body gastritis (ABG) patients. Uric Acid (UA), is another potent hydro-soluble scavenger of ROS and its possible modification in the gastric juice of patients with H. pylori gastritis have never been investigated. This study was aimed at investigating the levels of AA and UA in the plasma and gastric juice of ABG patients, compared with H. pylori positive patients without corporal atrophy, and with healthy individuals. MATERIALS AND METHODS: Thirteen ABG patients (Group 1); 32 Chronic non-atrophic H. pylori gastritis patients (Group 2); and 13 healthy stomach controls (Group 3) attending gastroscopy with gastric biopsies (antrum=3, corpus=3) had plasma and intragastric levels of AA and UA measured. RESULTS: Intragastric AA concentration was significantly lower in group 1 (median 0.21 microg/ml, range 0.1-24) compared both with groups 2 (median 5.5 microg/ml, range 0.1-33.2) (p=0.043) and 3 (median 14.9 microg/ml, range 0.34-44.8) (p=0.0028). Intragastric UA was not different between the three groups. Intragastric AA concentration resulted negatively correlated with the intragastric pH (Spearman r=-0.47, p=0.0003). In patients with gastritis (groups 1 and 2) there was a significant negative correlation between the sum of the Sydney Score variables in the body mucosa, and AA in the gastric juice (Spearman r=-0.55; p=0.0001). CONCLUSION: The study shows that intragastric pH is the key factor for the depletion of gastric juice AA observed in patients with corporal atrophy and to a lower extent with nonatrophic H. pylori gastritis.