Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease.

During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.

Is mastocytic colitis a specific clinical-pathological entity?

The number of intestinal mast cells (MC) is increased in several types of colitis, but the mucosa of patients with chronic non-bloody diarrhea has not been studied. The current study sought to determine the relationship between MC counts and degranulation and the severity of symptoms in patients with chronic loose stools. Following a negative laboratory workup for the most common causes of chronic diarrhea, patients with chronic non-bloody loose stools were included in the study. Patients with macroscopic evidence of inflammation or organic disease were excluded after endoscopy with biopsies. Biopsies from the 179 patients in the study were stained with hematoxylin and eosin and anti-CD117 c-kit antibodies. Immunohistochemistry was used to assess the degree of MC degranulation. Out of the 179 patients, 128 had normal histologic findings suggestive of irritable bowel syndrome and were used as controls. Twenty-four presented with abnormally high MC counts (≥40 MC x HPF), 23 with ≥20 intraepithelial lymphocytes x HPF suggesting lymphocytic colitis, and 4 had both (≥40 MC and ≥20 intraepithelial lymphocytes x HPF). In the patients with high MC counts, figures were significantly higher in the right colon versus the left colon (p=0.016), but degranulation did not differ in the right versus the left colon (p=0.125). No age or sex-related difference was observed (p=0.527 and p=0.859 respectively). The prevalence of abdominal pain and bloating did not differ in the three groups (p=0.959 and p=0.140, respectively). Patients with lymphocytic colitis (p=0.008) and those with high MC counts (p=0.025) had significantly higher evacuation rates compared to controls. There was no difference between these two groups (p=0.831). Mast cell degranulation was not associated with the number of evacuations, abdominal pain, or bloating (p=0.51; p=0.41; p=0.42, respectively). The finding that a significantly higher number of evacuations was linked to increased MC in the colonic mucosa of a subset of patients with otherwise normal laboratory and endoscopic findings suggests that "mastocytic colitis" may be a new clinical-pathological entity responsible for chronic non-bloody diarrhea. Prospective studies with a larger number of patients, as well as endoscopic and histological follow-up, are needed to confirm this hypothesis.

Systematic review and meta-analysis: the advantage of endoscopic Mayo score 0 over 1 in patients with ulcerative colitis.

BACKGROUND: Mucosal healing (MH) evaluated by endoscopy is a novel target of therapy in UC as it is associated with improved long-term outcomes. It is defined based on the Mayo endoscopic score (MES), but it is still to define whether a value of MES 0 or 1 should be the target. The purpose of this paper is to present the results of a systematic review with meta-analysis which compares long-term outcomes of patients in steroid-free clinical remission with MES 0 with those with MES 1. METHODS: A systematic electronic search of the literature was performed using Medline, Scopus, and CENTRAL through December 2020 (PROSPERO n:CRD42020179333). The studies concerned UC patients, in steroid-free clinical remission, with MES of 0 or 1, and with at least 12-months of follow-up. RESULTS: Out of 4611 citations, 15 eligible studies were identified. Increases in clinical relapse among patients with MES 1 were observed in all the studies included in this review, suggesting that MES of 1 have a higher risk of relapse than a score of 0. MES 0 patients displayed a lower risk of clinical relapse (OR 0.33; 95% CI 0.26-0.43; I2 13%) irrespective of the follow-up time (12-months or longer). On the other hand, no differences were found comparing MES 0 versus MES 1 about the risk of hospitalization or colectomy. CONCLUSIONS: MES 0 is associated with a lower rate of clinical relapse than is MES 1. For this reason, MES 0, rather than MES 0-1, should be considered the therapeutic target for patients with UC.

Association of Colonic Diverticula with Colorectal Adenomas and Cancer.

Background and Objectives: Conflicting evidence is reported regarding any association between colonic diverticula with colorectal adenomas or cancer. The present study aimed to evaluate, in a cohort of Caucasian patients, the association between colonic diverticula and colorectal polyps and cancer. Materials and Methods: All consecutive patients undergoing colonoscopy at our institution were included in the study. The presence and location of diverticula, polyps, and cancers were recorded. Histologically, polyps were classified as adenoma (with low or high dysplasia), hyperplastic, or inflammatory. The relative risk of the association of polyps and cancer with diverticula was assessed. Multiple logistic regression analyses, including age, sex, family history for colorectal cancer (CRC), and family history for diverticula, were carried out. Results: During the study period, 1490 patients were enrolled; 37.2% (n = 555) showed colonic diverticula or polyps or CRC (308 males, mean age 66 years). Particularly, 12.3% (n = 183) patients presented only diverticula, 13.7% (n = 204) only polyps or cancer, 11.3% (n = 168) both diseases, and 62.7% (n = 935) neither diverticula nor polyps and cancer. A total of 38 patients presented colorectal cancer, 17 of which had also diverticula. A significant increase in relative risk (RR 2.81, 95% CI 2.27-3.47, p < 0.0001) of colorectal adenoma and cancer in patients with colonic diverticula was found. At multivariate analysis, only diverticula resulted to be significantly associated with colorectal adenomas and cancer (Odds Ratio, OR 3.86, 95% CI 2.90-5.14, p < 0.0001). Conclusions: A significant association of colonic diverticula with colorectal adenoma or cancer was found. This implies that patients with colonic diverticula require a vigilant follow-up procedure for the prevention of colorectal cancer from those applicable to the general population.

Association between Corrected QT Interval and C-Reactive Protein in Patients with Inflammatory Bowel Diseases.

Background and objectives: Electrocardiograph abnormalities (i.e., QT interval prolongation) have been described in inflammatory bowel diseases (IBD). We aimed to measure the QT interval in a cohort of patients with IBD and to analyze its relationship with clinical and inflammatory activity. Materials and Methods: We performed a cross-sectional study that included 38 IBD outpatients and 38 "age- and sex-matched" healthy controls. Nine patients had active IBD, and 29 were in clinical remission. Among the latter, 10 patients had sustained (lasting >1 year) and 19 had short-term remission (≤1 year). Corrected QT (QTc) interval was measured on standard 12-lead electrocardiograph. A systematic review of the literature on studies investigating the QT interval in patients with IBD was also performed. Results: QTc interval values were similar between IBD patients and healthy controls (417.58 ± 22.05 ms vs. 409.13 ± 19.61 ms, respectively; p: 0.479). Patients with active IBD had significantly higher QTc values (435.11 ± 27.31 ms) than both controls (409.13 ± 19.61 ms) and patients in remission (412.14 ± 17.33 ms) (p: 0.031). Post hoc analysis showed that the difference in QTc values between active IBD and remission was attributable to the group of patients with sustained remission (p < 0.05). Lastly, a significant correlation between QTc interval and C-reactive protein (CRP) values was observed (Spearman test: r = 0.563; p: 0.0005). Conclusions: Our study demonstrates an association between QTc duration and both clinical and inflammatory activity in patients with IBD. The higher the CRP value, the longer is the QTc duration. For practical purposes, all patients with active IBD should undergo a standard ECG. Prescription of drugs able to modify the QT interval should be avoided in patients with active IBD. The systematic review of the literature indicated that this is the first published study demonstrating an association between the QTc duration and CRP values in patients with IBD.

Duodenal lymphocytosis in functional dyspepsia.

BACKGROUND AND STUDY AIMS: Functional dyspepsia is an exclusion diagnosis requiring different tests, including endoscopy, often repeated over time. Duodenal biopsies are frequently resorted to, not rarely revealing duodenal microscopic inflammation. Aim of the study is to confirm a previously supposed role of antro-duodenal low-grade inflammation in functional dyspepsia, evaluating the frequency of duodenal lymphocytosis, H. pylori infection and their association in a group of patients with functional dyspepsia compared to asymptomatic control subjects. PATIENTS AND METHODS: A cross-sectional, observational study has been conducted screening all the patients who underwent duodenal biopsies during upper endoscopy, in a 30 months period. All the patients without endoscopic lesions were analysed. The study group consisted of patients compatible with the diagnosis of functional dyspepsia (Rome III criteria). The control group consisted of healthy asymptomatic subjects in the population subjected to endoscopy. The presence of duodenal lymphocytosis and of H. pylori infection in the two groups was evaluated. RESULTS: 216 patients were enrolled: 161 in the functional dyspepsia group and 55 as asymptomatic control group. The frequency of duodenal lymphocytosis was similar between cases and control groups (25.47% vs 25.45%; p = 0.99), as well as H. pylori infection (26.71% vs 23.64%; p = 0.78). Duodenal lymphocytosis was significantly associated with functional dyspepsia only in H. pylori positive dyspeptic patients (p = 0.047). 94% of the subjects with both lymphocytosis and H. pylori infection suffer from dyspepsia. Duodenal intraepithelial lymphocytosis is significantly associated with bloating (p = 0.0082). CONCLUSIONS: In our cohort of dyspeptic patients, duodenal lymphocytosis is significantly associated with bloating and the simultaneous presence of duodenal lymphocytosis and H. pylori infection is significantly more prevalent than in control subjects.

Mastocytic Enterocolits and the Role of Mast Cells in Functional and Inflammatory Intestinal Disorders: A Systematic Review.

BACKGROUND: Chronic diarrhoea affects 5-10% of the adult population. Histologic lesions of possible diagnostic significance are found under normal colonoscopy in approximately 30% of patients affected by chronic diarrhoea. Mastocytic enterocolitis is characterized by an increase in the number of mucosal mast cells (MC) in the gut of patients with chronic intractable diarrhoea, detected by immunohistochemical staining, responding to mast-cell targeted drugs. The question arises whether to search for MC infiltration in specific subsets of patients as a matter of routine clinical practice. SUMMARY: A systematic electronic search of the English literature up to December 2017 was performed, using Medline, EMBASE, Web of Science, Scopus, and the Cochrane Library. This revealed 9 studies reporting an increased number of MC in the gut mucosa of patients with chronic diarrhoea. No consensus was found, however, on the actual cutoff point, the overlap in range between patients and controls being too great to be of clinical significance. The available evidence does not therefore justify the routine evaluation of MC count. Key Messages: More studies are needed to better define MC count and the significance of MC degranulation in normal and pathological settings. Until these become available, the search for MC infiltration in specific subsets of patients should be restricted to research settings.

Subtypes of chronic gastritis in patients with celiac disease before and after gluten-free diet.

BACKGROUND: Celiac disease (CD) often manifests with dyspeptic symptoms and chronic gastritis is a common finding. AIM: To evaluate the frequency of lymphocytic gastritis (LG), chronic active gastritis (CAG), and chronic inactive gastritis (CIG) in patients with CD, before and after gluten-free diet (GFD). METHODS: A five-year prospective study including all consecutive patients with a new diagnosis of CD was conducted. Gastric and duodenal biopsy specimens taken both at the time of the CD diagnosis and at the first endoscopic control after 18-24 months on GFD were evaluated. RESULTS: 213 patients with CD were enrolled. At the time of the diagnosis, 42 patients (19.7%) showed normal gastric mucosa, 34 (15.9%) LG, 67 (31.5%) CAG, and 70 (32.9%) CIG. Out of the 34 patients with LG, all were Helicobacter pylori negative and the majority of them showed an improvement both of gastritis (94.1%) and duodenal lesions (82.3%) after GFD. GFD did not show significant effects on CAG and CIG. CONCLUSIONS: LG is present in 16% of CD patients, it is not associated with H. pylori infection, and it improves after GFD. Both CAG and CIG are also frequently associated with CD, but fail to respond to a GFD.

The prognostic value of histology in ulcerative colitis in clinical remission with mesalazine.

BACKGROUND: The aim of the study was to compare the prognostic value of histological and endoscopic activity in patients with ulcerative colitis (UC). METHODS: Patients in clinical remission for 1 year under treatment with mesalazine underwent a planned colonoscopy with biopsies. Histological activity was scored using the histological activity index (HAI). Endoscopic activity was scored using the Mayo endoscopic subscore (MES). The clinical course was evaluated measuring relapses needing steroids during a follow up of 3 years. RESULTS: A total of 52 patients were enrolled into the study and followed up for 3 years. At baseline 29 patients (55.77%) had no endoscopic lesions, and 17 patients (32.69%) showed no histological alteration. At 3 years of follow up, overall, 26 patients (50%) were still in steroid-free remission. Using univariate logistic regression analysis, both histological (HAI ⩾ 1) and endoscopic activity (MES ⩾ 1) were significantly associated with outcome, showing, respectively, a relapse risk (odds ratio [OR]) 16.4 times higher than histological remission (HAI 0) (96% confidence interval [CI]: 3.2-84.3) and 6.3 times higher with respect to endoscopic remission (MES 0) (96% CI: 1.9-21.3). After multivariate logistic regression analysis, histological activity was the only factor significantly associated with outcome (OR 10.2; 95% CI: 1.7-59.4). CONCLUSIONS: Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

Mastocytic enterocolitis: Increase of mast cells in the gastrointestinal tract of patients with chronic diarrhea / Enterocolitis mastocítica: aumento de los mastocitos en el tracto gastrointestinal de pacientes con diarrea crónica

No disponible

Non-Celiac Gluten Sensitivity among Patients Perceiving Gluten-Related Symptoms.

BACKGROUND: Non-celiac gluten sensitivity (NCGS) is a recently recognized disorder, characterized by the occurrence of symptoms following gluten ingestion. It is often self-diagnosed by the patient, but should be confirmed by the response to a gluten-free diet, followed by a gluten challenge. Celiac disease (CD) and wheat allergy (WA) must first be ruled out. AIMS: (1) to determine the frequency of visits performed for symptoms self-perceived as gluten-related; (2) to assess in this cohort, the proportion of patients satisfying the diagnostic criteria for NCGS. METHODS: A two-year prospective study including all consecutive patients complaining of gluten-related symptoms. NCGS was diagnosed on the basis of the disappearance of the symptoms within 6 months of a gluten-free diet, followed by their reappearance with the reintroduction of gluten in the diet for 1 month. RESULTS: Three hundred and ninety two patients complaining of gluten-related symptoms were enrolled; 26 of these (6.63%) were affected by CD, 2 (0.51%) by WA and 27 were diagnosed with NCGS (6.88%). The remaining 337 patients (85.96%) did not experience any change of symptoms with a gluten-free diet. The PPV of the gluten-related symptom was found to be 7%. CONCLUSION: Eighty six percent of patients reporting gluten-related symptoms have neither NCGS, nor CD, nor WA. Self-perceived gluten-related symptoms are rarely indicative of the presence of NCGS.

Nanotechnology in the treatment of inflammatory bowel diseases.

BACKGROUND AND AIMS: Treatment of inflammatory bowel diseases (IBD) is only aimed to block or inhibit the pathogenetic steps of the inflammatory cascade. Side effects of systemic therapies, poor targeting of orally administered topical drug and low adherence to prescription represent frequent therapeutic challenges. Recent observations suggest that nanotechnology could provide amazing advantage in this field since particles having dimension in the nanometer scale (nanoparticles) can modify pharmacokinetic step of biologic and conventional therapeutic agents with a better delivery of drugs within the intestinal inflammatory cells. The aim of this review was to provide the clinician with an insight into the potential role of nanotechnology in the treatment of IBD. METHODS: A systematic search (PubMed) for experimental studies on the treatment of intestinal inflammation using nanotechnology for the delivery of drugs. RESULTS AND CONCLUSIONS: The size of the pharmaceutical formulation is inversely related to specificity for inflammation. Nanoparticles can penetrate epithelial and inflammatory cells resulting in much higher, effective and long-acting concentrations than can be obtained using conventional delivery systems. From a practical point of view, this should lead to improvements in both efficacy and adherence to treatment, providing patients with the prospect of stable and prolonged remissions with reduced drug loadings. Reduced systemic side effects could also be expected.