Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited.

Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.

Immunoglobulin G4-Related Disease of the Intestine: A Clinicopathological Entity to Be Considered.

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated, systemic condition of unknown etiology, associated with fibroinflammatory lesions. Diagnosis is set in the presence of IgG4-positive plasma cell infiltration of the involved tissue and elevated serum IgG4 levels. However, approximately 30% of patients have normal serum IgG4 levels. IgG4-RD may affect several organs, including the pancreas, bile ducts, mesentery, retroperitoneum, and salivary glands, but the involvement of the gastrointestinal tract is uncommon. Materials and Methods: The case series of 4 patients with IgG4-RD involving the intestinal tract was observed in the period of 2017-2022. Colorectal and ileal biopsy specimens were stained with hematoxylin and eosin and immunohistochemical techniques using monoclonal antihuman IgG4 primary antibody. Diagnosis of IgG4-RD was based on the presence of >50 cells/ HPF and IgG4/IgG ratio >40 confirmed by two pathologists. Results: IgG4-RD was set in patients previously diagnosed as affected by Crohn's disease. Conclusions: Systematic IgG4 immunohistochemical staining should be considered in the diagnostic workup of patients with gastrointestinal strictures, mimicking Crohn's disease. The exact prevalence of the condition is likely more frequent than reported and should be defined by a large series of consecutive patients.

COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.

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.

Non-steroidal anti-inflammatory drugs and acetylsalicylic acid increase the risk of complications of diverticular disease: a meta-analysis of case-control and cohort studies.

BACKGROUND: The role of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid in the occurrence of diverticular bleeding (DB), complicated diverticulitis (CD), and acute diverticulitis (AD) is not yet defined. AIM: Update a systematic review and meta-analyses of case-control and cohort studies to evaluate the association between NSAIDs or acetylsalicylic acid with DB, CD, or AD. METHODS: The study included were identified through MEDLINE, Scopus, Web of Science, and Cochrane Library databases. Sizes were pooled across studies to obtain the overall effect size. A random-effects model was used to account for different sources of variation among studies. Odds ratio (OR) with 95% confidence interval (CI) was used as a measure of effect size. RESULTS: Thirteen studies were included in the systematic review and meta-analysis. NSAIDs and acetylsalicylic acid use were associated with an increased risk of DB (OR: 6.90, 95% CI 3.86 to 12.35, P ˂ 0.00001, and OR 2.84, 95% CI 2.19 to 3.67, P < 0.00001, respectively). NSAIDs and acetylsalicylic acid use were also associated with increased risk of CD occurrence (OR 3.13, 95% CI 1.73 to 5.68, P = 0.0002, and OR 1.49, 95% CI 1.02 to 2.17, P = 0.04, respectively). The only study found about AD occurrence showed that NSAIDs use was not associated with AD and acetylsalicylic acid use had a low risk of AD. CONCLUSION: NSAIDs and acetylsalicylic acid significantly increase the risk of DB and CD. Further studies are needed to clarify the role of NSAIDs and acetylsalicylic acid in AD. However, increasing evidence suggests caution in the use of such medications in patients with colonic diverticula.

Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis.

BACKGROUND: It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. METHODS: A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. RESULTS: Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37-3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40-14.00) and delayed PPB (OR 10.80; CI 4.63-25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. CONCLUSIONS: Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role?

INTRODUCTION: The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS: A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS: The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS: None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.

Role of Ulcerative Colitis Endoscopic Index of Severity (UCEIS) versus Mayo Endoscopic Subscore (MES) in Predicting Patients' Response to Biological Therapy and the Need for Colectomy.

BACKGROUND: The main goal in the treatment of ulcerative colitis (UC) is to achieve mucosal healing. Despite being unvalidated, the most widely used scoring system is the Mayo endoscopic subscore (MES). However, the recently established and validated Ulcerative Colitis Endoscopic Index of Severity (UCEIS) represents an interesting alternative method in assessing endoscopic disease activity. OBJECTIVE: Due to a lack of reliable prognostic factors, the aim of this study was to investigate the diagnostic accuracy of the UCEIS and the MES, in predicting response to biological therapy and the need for colectomy. METHODS: We conducted a retrospective, uncontrolled, single-center study on UC patients with endoscopically active disease even with concomitant conventional and/or biological therapy, who had already started or had been changed a biological treatment. RESULTS: Sixty-one UC patients were enrolled. At baseline, 71% were naive to biological therapies and 41% had an extensive colitis. At control time (median time of 11.5 months), MES and UCEIS scores significantly decreased from those at baseline (from 2.6 to 1.8 and 5 to 3.2, respectively, p < 0.001). UCEIS, but not MES, was found to be significantly associated with unresponsiveness to therapy (p = 0.040). Moreover, when UCEIS was ≥7, all patients underwent colectomy after a median time of 5 months (p < 0.001). CONCLUSION: UCEIS may be superior to MES because of its accuracy and predictive role. Therefore, UCEIS should be considered for use in daily clinical practice.

Sleep disorders related to nutrition and digestive diseases: a neglected clinical condition.

Sleep disturbances often result from inappropriate lifestyles, incorrect dietary habits, and/or digestive diseases. This clinical condition, however, has not been sufficiently explored in this area. Several studies have linked the circadian timing system to the physiology of metabolism control mechanisms, energy balance regulation, and nutrition. Sleep disturbances supposedly trigger digestive disorders or conversely represent specific clinical manifestation of gastrointestinal (GI) diseases. Poor sleep may worsen the symptoms of GI disorders, affecting the quality of life. Conversely, short sleep may influence dietary choices, as well as meal timing, and the circadian system drives temporal changes in metabolic patterns. Emerging evidence suggests that patients with inappropriate dietary habits and chronic digestive disorders often sleep less and show lower sleep efficiency, compared with healthy individuals. Sleep disturbances may thus represent a primary symptom of digestive diseases. Further controlled trials are needed to fully understand the relationship between sleep disturbances, dietary habits, and GI disorders. It may be also anticipated that the evaluation of sleep quality may prove useful to drive positive interventions and improve the quality of life in a proportion of patients. This review summarizes data linking sleep disorders with diet and a series of disease including gastro-esophageal reflux disease, peptic disease, functional gastrointestinal disorders, inflammatory bowel diseases, gut microbiota alterations, liver and pancreatic diseases, and obesity. The evidence supporting the complex interplay between sleep dysfunction, nutrition, and digestive diseases is discussed.

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.

Is fecal calprotectin an accurate marker in the management of Crohn's disease?

Although lacking validated cutoff values, fecal calprotectin (FC), besides C-reactive protein, is considered the standard test for assessing disease activity in Crohn's disease (CD). The aim of the present review is to provide a general overview of the literature addressing the role of FC in the clinical and endoscopic assessment of disease activity in CD, seeking correlations with capsule endoscopy, response to therapy, prediction of relapse, and postoperative recurrence. A systematic search of the literature up to September 2019 was performed using Medline, Embase, and the Cochrane Library. Only papers written in English concerning FC in adult patients affected by CD were included. Pediatric studies, in vitro studies, animal studies, studies on blood/serum samples, and studies analyzing FC in ulcerative colitis or in both CD and ulcerative colitis were excluded. Out of 713 citations, 65 eligible studies were identified. FC showed high accuracy in the assessment of intestinal inflammation and response to therapy, in particular in colonic disease, thus proving a good surrogate marker for these aims. FC is useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence, for optimizing or downstage therapy. Unfortunately, FC performs less well in small bowel CD. FC is an effective fecal marker in the management of CD patients, optimizing the use of endoscopic procedures. Owing to its diagnostic accuracy, FC may represent a cornerstone of the "treat-to-target" management strategy of CD patients.

Metabolic Alterations in Celiac Disease Occurring after Following a Gluten-Free Diet.

BACKGROUND AND AIM: Many investigations have demonstrated that changes in body weight are frequent in patients with coeliac disease (CD) after a gluten-free diet (GFD); conversely data on the metabolic syndrome (MS) and hepatic steatosis (HS) are still rare. The aim is to evaluate the prevalence of MS and HS in patients with CD, before and after a GFD. METHODS: One hundred eighty-five coeliac adult patients were enrolled in the study. Diagnosis of MS was made according to the current international criteria including waist circumference (WC), hypertension, reduction of high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, and hyperglycemia. Body mass index (BMI), hypercholesterolemia, and HS were also assessed. RESULTS: CD patients showed an increased risk of developing both MS and HS after following a GFD. MS was reported in 3.24% of the cases at the time of CD diagnosis and in 14.59% after GFD (p < 0.0001). HS was reported in 1.7% at the time of diagnosis and in 11.1% after GFD (p < 0.0001). With regard to metabolic sub-categories, the prevalence of the increase in WC, hypertension, reduction of HDL cholesterol, hyperglycemia, hypercholesterolemia, and BMI > 25 was significantly higher after GFD compared to baseline at CD diagnosis. CONCLUSION: In CD patients, following a GFD maybe can contribute to the development of MS and HS. Patients should be informed about this possible risk.

Vaccine Acceptance in Patients with Inflammatory Bowel Disease: Lessons Learned from the COVID-19 Pandemic.

BACKGROUND: Immunomodulating therapies, which are commonly used in patients with Crohn's disease (CD) and ulcerative colitis (UC), have been linked to an increased risk of contracting opportunistic infectious diseases, the majority of which are preventable through vaccination. Nonetheless, vaccination rates in these patients are suboptimal, and frequently lower than in the general population. The COVID-19 immunization schedule provided a new scenario for investigating vaccine acceptance in patients with inflammatory bowel disease (IBD), with uncertainty and concerns emerging and the number of subjects receiving the third and fourth doses of the vaccine gradually decreasing. This study investigated IBD patients' attitudes towards previous COVID-19 vaccine programs and identified the factors that influence their adherence. It considered demographic and disease-related factors as well as the role of gastroenterologists and primary care physicians (PCPs). METHODS: Data were collected through a self-completed questionnaire administered to all adult IBD patients (age > 18) who visited the Gastroenterology, Hepatology, and Nutrition division at the University of L'Aquila (Italy) for a regular follow-up between November 2021 and December 2022. Non-IBD gastroenterological outpatients who visited during the same period were included as a control group. RESULTS: A total of 178 patients were included in the analysis. The IBD group consisted of 77 patients, 48.1% with CD and 51.9% with UC; the mean age was 49.5 years and 51.9% were female. Overall, 94.8% of IBD patients had undergone at least one vaccine dose and 79.2% had received two doses, versus 8% of the control group (p < 0.0001). A total of 84.4% of IBD patients reported their propensity towards COVID-19 vaccination, with an average agreement score significantly higher than the controls (p = 0.0044). The trust of IBD patients in the effectiveness of the COVID-19 vaccine (p < 0.0001) and its role in hastening pandemic resolution (p < 0.0001) is strongly related to motivation and propensity. Concerns about the safety of the COVID-19 vaccine in IBD (p = 0.0202) and fear of vaccine-induced flare-ups (p = 0.0192) were reported as the main barriers. No correlation was found between COVID-19 vaccine propensity and clinical features like the type of IBD, years of disease, activity, and ongoing treatment. Regarding the recommendations received from physicians to get vaccinated against COVID-19, IBD patients relied heavily on their gastroenterologists for advice, while the control group relied mainly on their PCPs. CONCLUSIONS: The overall positive attitude towards vaccinations reported in our study was better than that observed for other vaccines. The relationship of trust with the gastroenterologist should be used to boost vaccination against other preventable diseases in IBD patients. Our findings add information on the factors influencing vaccine propensity, which can be used to improve current vaccination strategies.

Low Vitamin K and Vitamin D Dietary Intake in Patients with Inflammatory Bowel Diseases.

The inadequate dietary intake of Vitamin D and Vitamin K is an easily reversible factor favoring IBD-associated bone loss, but data on Vitamin K are lacking. A 28-item quantitative food frequency questionnaire was administered to 193 IBD patients (89 Crohn's disease and 104 ulcerative colitis), and 199 controls. Patients' demographics, clinical and laboratory findings were analyzed in relation to recommended daily allowances. VitD intake was inadequate both in the IBD and control patients (8.3 ± 4.5 µg/day in IBD, 53.1% RDA, and 9.7 ± 5.9 µg/day, 63.2% RDA, respectively). Conversely, the mean ViK intake was less than adequate in IBD, at 116.7 ± 116.3 µg/day (78.7% RDA), and high in controls, at 203.1 ± 166.9 µg/day (138.8% RDA). Nonetheless, due to marked inter-individual differences, diets were severely lacking VitK in 40% of UC and 49% of CD patients, more so in females and those with active disease. The intake of Vit D was non-significantly lower in colitis than that in Crohn's disease (7.9 vs. 8.7 µg/day). The opposite was observed for VitK (123.5 vs. 107.0 µg/day). Thus, the diet lacks the micronutrients involved in bone wellbeing in a large proportion of IBD patients. While VitD supplementation is the rule, VitK shortages need proactive nutritional intervention.

Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications.

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged.

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.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

BACKGROUND: The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). METHOD: We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. RESULTS: Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. CONCLUSIONS: This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

This article is a systematic review with meta-analysis of randomized clinical trials involving inflammatory bowel disease patients treated with vitamin D supplementation, compared with placebo. We aim to assess the risk of clinical relapse or disease activity among these patients.

Dietary Factors Modulating Colorectal Carcinogenesis.

The development of colorectal cancer, responsible for 9% of cancer-related deaths, is favored by a combination of genetic and environmental factors. The modification of diet and lifestyle may modify the risk of colorectal cancer (CRC) and prevent neoplasia in up to 50% of cases. The Western diet, characterized by a high intake of fat, red meat and processed meat has emerged as an important contributor. Conversely, a high intake of dietary fiber partially counteracts the unfavorable effects of meat through multiple mechanisms, including reduced intestinal transit time and dilution of carcinogenic compounds. Providing antioxidants (e.g., vitamins C and E) and leading to increased intraluminal production of protective fermentation products, like butyrate, represent other beneficial and useful effects of a fiber-rich diet. Protective effects on the risk of developing colorectal cancer have been also advocated for some specific micronutrients like vitamin D, selenium, and calcium. Diet-induced modifications of the gut microbiota modulate colonic epithelial cell homeostasis and carcinogenesis. This can have, under different conditions, opposite effects on the risk of CRC, through the production of mutagenic and carcinogenic agents or, conversely, of protective compounds. The aim of this review is to summarize the most recent evidence on the role of diet as a potential risk factor for the development of colorectal malignancies, as well as providing possible prevention dietary strategies.

Early hydrogen excretion peaks during breath tests. Small intestinal bacterial overgrowth or accelerated transit?

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) has been reported with varying prevalence, depending upon the criteria used for diagnosis. Lactulose and glucose breath tests are the most used in clinical settings. Early rises of hydrogen excretion during a lactose breath test suggest SIBO, but the finding could result from accelerated mouth-to-caecum transit time. AIMS: Defining the prevalence of early hydrogen peaks during lactose breath tests and assessing the proportion of patients affected by SIBO. METHODS: An early (≤ 60') hydrogen excretion peak was observed in 120/663 patients with positive lactose hydrogen breath test. Eighty-one of them underwent a 50 g-9sample-glucose hydrogen breath test to diagnose SIBO. RESULTS: The glucose breath test proved positive in 11/81 (13.6%) patients. The positivity rate was 18.2% (2/11) in those with the first peak detected at 30' and 12.8% (9/70) in those with the peak occurring at 60'. CONCLUSIONS: Early hydrogen excretion peaks are rarely associated with SIBO. The low positive predictive value indicates that the finding does not help identifying patients at high risk for this condition. Indirectly, the present data support the opinion that the prevalence of SIBO diagnosed by standard lactulose breath tests is much lower than reported, and the reliability of the test is low.