Non-celiac gluten or wheat sensitivity (NCWS) is a "clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing ...foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded". This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords "non-celiac gluten sensitivity", "non-celiac wheat sensitivity", and "diagnosis". We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Treatment of inflammatory bowel disease (IBD) is traditionally based on several drugs, including salicylates, corticosteroids, and antibiotics; in addition, the therapeutic armamentarium has ...considerably evolved with the advent of newer, effective therapeutic measures (such as the biological agents) that are able to improve in a considerable manner both the clinical and endoscopic variables. Thus, mucosal healing, at least considered from an endoscopic point of view, is today regarded as the ultimate endpoint for treatment of these conditions. However, it is also increasingly clear that endoscopic healing is not necessarily paralleled by histological healing; There are few doubts that the latter should be considered as a true, objective healing and the ultimate goal to reach when treating patients with IBD. Unfortunately, and surprisingly, only a few, incomplete, and somewhat conflicting data exist on this topic, especially because there is still the need to standardize both histological assessment and the severity grading of these disorders; Issues that have not been yet been resolved for clinical practice and therapeutic trials. Hopefully, with the help of an increased awareness on the clinical researchers' side, and the availability of dedicated pathologists on the other side, this matter will be effectively faced and resolved in the near future.
Background and Aims Endoscopic inflammation and healing are important therapeutic endpoints in ulcerative colitis (UC). We developed and validated a new electronic virtual chromoendoscopy (EVC) score ...that could reflect the full spectrum of mucosal and vascular changes including mucosal healing in UC. Methods Eight participants reviewed a 60-minute training module outlining 3 different i-SCAN modes demonstrating the entire spectrum of inflammatory mucosal and vascular changes in UC. Performance characteristics in endoscopic scoring and predicting the histologic inflammation with EVC (i-SCAN) by using 20 video clips before (pre-test) and after (post-test) were evaluated. Exploratory univariate factor analysis was performed on Paddington International Virtual Chromoendoscopy Score (PICaSSO) covariates for mucosal and vascular score separately. Subsequently, a proportional odds logistic regression model for the prediction of histologic scores was analyzed. Results The interobserver agreement for Mayo endoscopic score in the pre-test (κ = .85; 95% CI, .78-.90) and the post-test (κ = .85; 95% CI, .77-.90) evaluation were very good. This was also true for the Ulcerative Colitis Endoscopic Index of Severity in the pre-test and post-test score interobserver agreement (κ = .86; 95% CI, .77-.92; and κ = .84; 95% CI, .75-.91, respectively). The interobserver agreement of the PICaSSO endoscopic score was very good in the pre-test and post-test evaluations (κ = .92; 95% CI, .87-.96; and κ = .89; 95% CI, .84-.94, respectively). The accuracy of the overall PICaSSO in assessing histologic abnormalities and inflammation by Harpaz score was 57% (95% CI, 48%-65%), by Robarts Histological Index 72% (95% CI, 64%-79%), and by the extent, chronicity, activity, plus system (full spectrum of histologic changes) 83% (95% CI, 76%-88%). Conclusions The EVC score “PICaSSO” showed very good interobserver agreement. The new EVC score may be used to define the endoscopic findings of mucosal and vascular healing in UC and reflected the full spectrum of histologic changes.
Abstract
Currently, the main targets of drug therapy for ulcerative colitis UC are endoscopic and clinical remission. However, there is active discussion about the additional advantages of including ...histological remission as a target. Accumulating evidence indicates that microscopic activity persists in endoscopically quiescent UC, that histological changes may lag behind clinical remission after treatment, and that absence of histological activity predicts lower rates of relapse, hospitalization, surgery and subsequent neoplasia.
Obtaining useful information from mucosal biopsies in this setting depends on accurate and consistent evaluation of histological features. However, there is no standardization of biopsy procedures, histological sample processing technique or histological scoring systems, and there is no agreement on the definitions of histological remission, response or activity. Accordingly, a consensus expert panel convened by the European Crohn’s and Colitis Organisation ECCO reviewed the literature and agreed a number of position statements regarding harmonization of UC histopathology. The objective was to provide evidence-based guidance for the standardization and harmonization of procedures, definitions and scoring systems for histology in UC, and to reach expert consensus where possible.
We propose the absence of intraepithelial neutrophils, erosion and ulceration as a minimum requirement for the definition of histological remission. For randomized control trials we recommend the use of the Robarts histopathology index RHI or the Nancy index NI. For observational studies or in clinical practice we recommend the use of the NI. To predict the risk of future neoplasia in UC, cumulative histological scores over time are more useful than single scores.
Endoscopic and histologic remission are important goals in the treatment of ulcerative colitis (UC). We investigated the correlation of the recently developed Paddington International Virtual ...ChromoendoScopy ScOre (PICaSSO) and other established endoscopic scores against multiple histological indices and prospectively assessed outcomes.
In this prospective multicenter international study, inflammatory activity was assessed with high-definition and virtual chromoendoscopy in the rectum and sigmoid using the Mayo Endoscopic Score (MES), UC Endoscopic Index of Severity (UCEIS), and PICaSSO. Targeted biopsies were taken for assessment using Robarts Histological Index (RHI), Nancy Histological index (NHI), ECAP (Extent, Chronicity, Activity, Plus score), Geboes, and Villanacci. Follow-up data were obtained at 6 and 12 months after colonoscopy.
A total of 307 patients were recruited. There was strong correlation between PICaSSO and histology scores, significantly superior to correlation coefficients of MES and UCEIS with histology scores. A PICaSSO score of ≤3 detected histologic remission by RHI (≤3 + absence of neutrophils) with area under the receiver operating characteristic curve (AUROC) 0.90 (95% confidence interval CI 0.86–0.94) and NHI (≤1) AUROC 0.82 (95% CI 0.77–0.87). The interobserver agreement for PICaSSO was 0.88 (95% CI 0.83–0.92). At 6- and 12-months follow-up, PICaSSO score ≤3 predicted better outcomes than PICaSSO >3 (hazard ratio HR 0.19 0.11–0.33 and 0.22 0.13–0.34, respectively),} as well as PICaSSO 4–8 (HR 0.25 0.12–0.53 and 0.22 (0.12–0.39), respectively) and similar to histologic remission.
In this first real-life multicenter study, the PICaSSO score correlated strongly with multiple histological indices. Furthermore, PICaSSO score predicted specified clinical outcomes at 6 and 12 months, similar to histology. Thus, PICaSSO can be a useful endoscopic tool in the therapeutic management of UC.
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A number of epidemiological studies have evaluated the potential association between
and cardiovascular disease, but with contrasting results. We have previously shown that
infection is able to ...induce in mice and humans autoantibodies cross-reacting with histo-blood group Lewis antigens, expressed in different organs and in plasma glycoproteins and glycolipids. The aim of this study was to assess whether immunization of animals with
might induce myocardial histopathological changes. We have retrospectively examined, in detail, the histology of archived organs from mice and rabbits immunized with
in our previous studies. Human sera and cross-reacting monoclonal antibodies were also tested against bacterial preparations and tissue sections. Areas of myocardial necrosis, associated with coronary thrombotic occlusion, were found in 5 of 20 mice and 2 of 5 rabbits previously immunized with suspensions of
. No similar lesions were found in control animals, suggesting a causal link with
immunization. The animals bearing myocardial lesions had not been infected but only immunized months earlier with parenteral injections of dead
cells. This strongly suggests that immunization, by itself, might play a causative role. We propose that the cross-reactive autoimmune response induced by
could promote thrombotic occlusion through direct endothelial damage or by perturbing the coagulation process.
The relationship between motility and inflammatory gastrointestinal disorders is at the same time complex and intriguing since these conditions might share some genetic,environmental,immunological ...and microbial predisposing factors.In addition,significant symptom overlapping may occur,muddling the waters within the clinical context.Although on one hand this represents a challenge for the clinician for a potential under-or over-treatment and diagnostic delay,on the other hand it possibly represents an opportunity for the researcher to better disclose the intimate relationship between chronic(often low-grade)inflammation,motor disorders and deranged sensory function.The best example is probably represented by Crohn’s disease and ulcerative colitis.In fact,a number of gastrointestinal motor disorders have been described in association with these diseases,disorders which span from the esophagus to the anorectum,and which will be extensively covered in this review.It is conceivable that at least part of this derangement is strictly related to inflammatory cytokine trafficking and neuromuscular changes;however,given the high prevalence of functional gastrointestinal disorders in the general population,this overlap might also be serendipitous.However,it is worth noting that literature data on this topic are relatively scarce,sometimes quite outdated,and mostly focused on the interplay between irritable bowel syndrome and inflammatory bowel disease.Nevertheless,both researchers and clinicians must be aware that symptoms related to gastrointestinal motility disorders may be highly prevalent in both active and inactive inflammatory bowel disease,correlate with greater psychological comorbidity and poorer quality of life,and may negatively influence the therapeutic approaches.
Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the ...motility alterations in STC might be considered of neuropathic type.In addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.
A structural weakness of the mucus barrier (MB) is thought to be a cause of ulcerative colitis (UC). This study aims to investigate the mucin (MUC) composition of MB in normal mucosa and UC. ...Ileocolonic biopsies were taken at disease onset and after treatment in 40 patients, including 20 with relapsing and 20 with remitting UC. Ileocolonic biopsies from 10 non-IBD patients were included as controls. Gut-specific MUC1, MUC2, MUC4, MUC5B, MUC12, MUC13, MUC15, and MUC17 were evaluated immunohistochemically. The promoters of mucin genes were also examined. Normal mucosa showed MUC2, MUC5B, and MUC13 in terminal ileum and colon, MUC17 in ileum, and MUC1, MUC4, MUC12, and MUC15 in colon. Membranous, cytoplasmic and vacuolar expressions were highlighted. Overall, the mucin expression was abnormal in UC. Derangements in MUC1, MUC4, and MUC5B were detected both at onset and after treatment. MUC2 and MUC13 were unaffected. Sequence analysis revealed glucocorticoid-responsive elements in the
promoter, retinoic-acid-responsive elements in the
promoter, and butyrate-responsive elements in the
promoter. In conclusion, MUCs exhibited distinct expression patterns in the gut. Their expression was disrupted in UC, regardless of the treatment protocols. Abnormal MUC1, MUC4, and MUC5B expression marked the barrier dysfunction in UC.
Despite great progress in pharmaceutical research, the medical treatment of chronic idiopathic constipation is far from ideal. The aim of the present article was to review literature data, focusing ...on poorly studied or commercially unavailable/unapproved drugs potentially useful for the treatment of chronic idiopathic constipation in adults. An extensive online literature search was conducted using the keywords "chronic constipation", "colon", "constipation", "drugs", "laxatives", and "treatment", in various combinations between January 1960 and December 2022. The literature search showed the presence of some drugs whose efficacy has only recently been demonstrated by modern investigations, and which are likely to be incorporated into future guidelines, of others that are proven effective and potentially effective on constipated patients but limited by small or relatively old studies, or by side effects which could be used in experienced hands, and of others that might be useful but lack a solid scientific background. Looking into the future for patients with chronic constipation might add some more tools to the therapeutic portfolio, especially for certain subgroups of these patients.
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