Systematic review: Histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? An IOIBD initiative

Background and aimsAdvances in the medical management of inflammatory bowel disease (IBD) have altered treatment targets. Endoscopic mucosal healing is associated with better outcomes in IBD, though less is known about the significance of achieving histological remission. Our aim was to perform a systematic review to investigate whether histological or ‘complete’ remission constitutes a further therapeutic target in IBD.MethodsA bibliographic search was performed on the 1st of October 2013 and subsequently on the 1st of March 2014 of online databases (OVID SP MEDLINE, OVID EMBASE, National Pubmed Central Medline, Cochrane Library, ISI, conference abstracts), using MeSH terms and key words: (“inflammatory bowel diseases” OR “crohn disease” OR “ulcerative colitis” OR “colitis”) AND (“mucosal healing” OR “histological healing” OR “pathological healing” OR “histological scoring” OR “pathological scoring”).ResultsThe search returned 2951 articles. 120 articles were cited in the final analysis. There is no validated definition of histological remission in IBD. There are 22 different histological scoring systems for IBD, none of which are fully validated. Microscopic inflammation persists in 16–100% of cases of endoscopically quiescent disease. There is evidence that histological remission may predict risk of complications in ulcerative colitis beyond endoscopic mucosal healing, though data are scarce in Crohn's disease.ConclusionsHistological remission in IBD represents a target distinct from endoscopic mucosal healing, not yet routinely sought in clinical trials or practice. There remains a need for a standardized and validated histological scoring system and to confirm the prognostic value of histological remission as a treatment target in IBD.     

Family history of inflammatory bowel disease among patients with ulcerative colitis: A systematic review and meta-analysis

Background and aimsDespite numerous shared susceptibility loci between Crohn's disease and ulcerative colitis, the prevalence of family history among ulcerative colitis patients is not well-established and considered to be less prevalent. A systemic review and meta-analysis were conducted to estimate the prevalence of family history of inflammatory bowel disease in ulcerative colitis patients, and its effect on disease outcomes.MethodsPubMED was searched to identify studies reporting the prevalence of family history of inflammatory bowel disease among ulcerative colitis patients. Definitions of family history, study type, and subtypes of family history prevalence were abstracted, as were disease outcomes including age at ulcerative colitis diagnosis, disease location, surgery and extraintestinal manifestations. Pooled prevalence estimates were calculated using random effects models.ResultsSeventy-one studies (86,824 patients) were included. The prevalence of a family history of inflammatory bowel disease in ulcerative colitis patients was 12% (95% confidence interval [CI] 11 to 13%; range 0–39%). Family history of ulcerative colitis (9%; 22 studies) was more prevalent than Crohn's disease (2%; 18 studies). Patients younger than 18 years of age at time of diagnosis had a greater family history of inflammatory bowel disease (prevalence 15%, 95% CI: 11–20%; 13 studies). There were no differences in disease location, need for surgery, or extraintestinal manifestations among those with a family history, although very few studies reported on these outcomes.ConclusionsOverall, 12% of ulcerative colitis patients have a family history of inflammatory bowel disease, and were more likely to have a family history of ulcerative colitis than Crohn's disease. Pediatric-onset ulcerative colitis patients were more likely to have a family history of inflammatory bowel disease.     

Clinical factors are associated with vitamin D levels in IBD patients: A retrospective analysis

OBJECTIVE

There is growing evidence that vitamin D deficiency plays a role in the development and the course of inflammatory bowel disease (IBD). However, the correlation between vitamin D deficiency and clinical parameters in IBD is still not completely understood.

METHODS

A retrospective study of IBD patients was performed. Vitamin D values were analyzed, regardless of vitamin D substitution administration, and correlated with clinical parameters such as medical therapy, anatomical situation, location of the disease and disease activity. Level of 25‐hydroxyvitamin D [25(OH)D] <50 nmoL/L was regarded as vitamin D deficiency and <75 nmoL/L as insufficiency.

RESULTS

In total, 208 IBD patients were analyzed, including 123 with Crohn's disease (CD) and 85 with ulcerative colitis (UC). Therapy with azathioprine did not affect the vitamin D values of either disease entity. But CD patients benefited from therapy with tumor necrosis factor‐α inhibitor and exhibited significantly higher vitamin D levels than those without. Furthermore, significantly lower vitamin D levels were found if CD was located in the small bowel or if the small bowel had been resected. Moreover, significantly lower levels of vitamin D were detectable for high disease activity (reflected by high simple clinical colitis activity index values) in patients with UC.

CONCLUSIONS

Vitamin D deficiency is common in patients with IBD. However, certain clinical situations lead to significantly lower vitamin D levels and may therefore require close monitoring for vitamin D deficiency.     

Management of inflammatory bowel disease in pregnancy

Background and AimsInflammatory bowel disease (IBD) is a chronic disease affecting mainly young people in their reproductive years. IBD therefore has a major impact on patients’ family planning decisions. Management of IBD in pregnancy requires a challenging balance between optimal disease control and drug safety considerations.This article aims to provide a framework for clinical decision making in IBD based on review of the literature on pregnancy-related topics.MethodsMedline searches with search terms ‘IBD’, ‘Crohn's disease’ or ‘ulcerative colitis’ in combination with keywords for the topics fertility, pregnancy, congenital abnormalities and drugs names of drugs used for treatment of IBD.ResultsIBD patients have normal fertility, except for women after ileal pouch-anal anastomosis (IPAA) and men under sulfasalazine treatment. Achieving and maintaining disease remission is a key factor for successful pregnancy outcomes in this population, as active disease at conception carries an increased risk of preterm delivery and low birth weight.Clinicians should discuss the need for drug therapy to maintain remission with their patients in order to ensure therapy compliance. Most IBD drugs are compatible with pregnancy, except for methotrexate and thalidomide. If possible, anti-TNF therapy should be stopped by the end of the second trimester and the choice of delivery route should be discussed with the patient.ConclusionsDisease control prior to conception and throughout pregnancy is the cornerstone of successful pregnancy management in IBD patients.     

High and increasing prevalence of inflammatory bowel disease in Finland with a clear North–South difference

Background and aimInflammatory bowel disease (IBD) prevalence has increased and a North–South gradient has been reported. We estimated the nationwide prevalence of IBD, ulcerative colitis (UC) and Crohn's disease (CD) in 1993, and prevalence of IBD in 2008, and assessed the geographical distribution of IBD in Finland. In addition, we investigated the vitamin D levels in a study population from a large, nationally representative health examination survey, the Health 2000 Survey.MethodsThe register study for prevalences included all patients who had special reimbursement of medications for IBD in the years 1993 (n = 10,958) and 2008 (31,703). The study for D-vitamin measurement consisted of 6134 persons who had participated in the Health 2000 Survey.ResultsThe nationwide point prevalence of IBD in 1993 was 216 per 100,000 inhabitants, and 595 in 2008. In 1993, the prevalence of UC (177) was fourfold higher than the prevalence of CD (38). The prevalence of IBD and UC in Finland increased from South to North. For CD, no geographical variation could be demonstrated. In the Health 2000 survey, vitamin D levels were lower in Northern than in Southern Finland.ConclusionsFinland belongs to high prevalence area of IBD and this prevalence has increased nearly threefold during the past 15 years. A clear North–South gradient has been shown for IBD and UC, but not for CD. Slightly lower vitamin D levels in Northern Finland may be associated with the observed higher prevalence of IBD there.     

Microscopic colitis in patients with ulcerative colitis or Crohn’s disease: a retrospective observational study and review of the literature

Objectives: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn’s disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.

Methods: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.

Results: We identified 31 patients with onset of MC after a median (range) of 20 (2–52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n?=?16) or lymphocytic colitis (LC) (n?=?5); nine CD patients developed CC (n?=?5) or LC (n?=?4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.

Conclusions: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.     

The use of sirolimus (rapamycin) in the management of refractory inflammatory bowel disease in children

BackgroundManagement of refractory inflammatory bowel disease (IBD) in children is challenging and once response to conventional medical therapy deviates from the expected, options are often limited. Sirolimus is commonly used in post-transplantation management and is used sparsely as rescue therapy in refractory Crohn's disease. In the present study, we report the efficacy of sirolimus as an adjuvant immunosuppressive therapy in a retrospective case review of a selected group of IBD children who were refractory to the conventional treatments.MethodsMedical records of children with refractory IBD unresponsive to conventional therapy and started on sirolimus between 2006 and 2012 were retrospectively reviewed. Clinical response, through Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn's Disease Activity Index (PCDAI), as well as intestinal inflammation, through specific histological scores, was evaluated.ResultsThe records of 14 patients were analyzed. Eleven of them had ulcerative colitis (UC) and 3 Crohn's disease (CD); mean age at diagnosis was 9.1 years (standard deviation 3.8). Of UC patients, 5 (45%) achieved clinical remission and 2 (18%) showed clinical response. All CD patients went into clinical remission. Mucosal healing was achieved by 5 children (45%) with UC and 2 (67%) with CD patients. One child with ulcerative colitis was weaned off adalimumab, while 2 children with CD were weaned off prednisolone and methotrexate successfully.ConclusionOur data provide evidence that sirolimus seems to be effective as rescue therapy in a subgroup of children with severe IBD refractory to conventional therapies by inducing both clinical remission and mucosal healing.     

Nutritional management of inflammatory bowel disease; an overview of the evidences

Background and aimsInflammatory bowel disease (IBD) is a chronic relapsing–remitting systemic disease and one of the most common gastrointestinal diseases that affect many people. This review designed to report the latest findings on the association between some nutrients and IBD.MethodsA review was performed to summarize the effect of various aspects of nutrition and diet on clinical course, the severity of disease, intestinal epithelial inflammation, inflammatory and oxidative stress markers. Literature searches were conducted in PubMed and Google Scholar up to June 27, 2021.ResultsVarious studies have shown that an unhealthy diet and deficiency of some nutrients are involved in the etiology of IBD. It has also been shown that intestinal dysbiosis can increase the risk of developing IBD. The results of some studies have shown that supplementation with some nutrients such as omega-3 polyunsaturated fatty acids and vitamin D and probiotics may have beneficial results in patients with IBD. Adherence to some restrictive diets has also been helpful in some studies.ConclusionsFollowing proper nutritional approaches can play an essential role in managing IBD symptoms. Further studies are needed to substantiate some of these findings.     

Algorithms to facilitate shared decision-making for the management of mild-to-moderate ulcerative colitis

ABSTRACT

Introduction: Nonadherence has been a key barrier to the efficacy of medical treatments in ulcerative colitis (UC). Engaging patients in their IBD care via shared decision-making (SDM) to facilitate self-management may improve adherence to therapy.

Areas covered: This review aims to summarize the most recent trial evidence from 2012 to 2017 for mild-to-moderate UC in order to develop clinical algorithms that guide SDM to facilitate self-management. A structured literature search via multiple electronic databases was performed using the search terms ‘ulcerative colitis,’ ‘treatment,’ ‘management,’ ‘medication,’ ‘maintenance,’ ‘remission,’ ‘5-ASA,’ and ‘inflammatory bowel disease.

Expert commentary: Novel formulations of existing oral and topical medications have expanded the treatment options available for the induction and maintenance therapy for mild-to-moderate UC. Daily dosing of 5-ASA therapy is equivalent to twice daily dosing. The combination therapies of oral plus topical 5-ASA therapy and 5-ASA plus corticosteroid therapy are more effective than monotherapy. Budesonide MMX now plays a role in the management of mild-to-moderate UC. This review collates the evidence on drug efficacy and safety, adherence and tolerability, and noninvasive monitoring of mild-to-moderate UC into SDM-orientated algorithms to facilitate self-management.     

Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon

Background and aimsChanges in intestinal microRNAs have been reported in adult patients with ulcerative colitis or Crohn's disease. The goal of this study was to identify changes in microRNA expression associated with colitis in children with inflammatory bowel disease.MethodsRectal mucosal biopsies (n = 50) and blood samples (n = 47) were collected from patients with known or suspected inflammatory bowel disease undergoing endoscopy. Rectal and serum microRNA levels were profiled using the nCounter® platform and the TaqMan® low-density array platform, respectively. Significantly altered microRNAs were validated in independent sample sets via quantitative RT-PCR. In vitro luciferase reporter assays were performed in the human colorectal Caco-2 cell line to determine the effect of miR-192 on NOD2 expression.ResultsProfiling of rectal RNA identified 21 microRNAs significantly altered between control, UC, and colonic CD sample groups. Nine of the ten microRNAs selected for validation were confirmed as significantly changed. Rectal miR-24 was increased 1.47-fold in UC compared to CD samples (p = 0.0052) and was the only microRNA altered between IBD subtypes. Three colitis-associated microRNAs were significantly altered in sera of disease patients and displayed diagnostic utility. However, no serum microRNAs were found to distinguish ulcerative colitis from Crohn's colitis. Finally, miR-192 inhibition did not affect luciferase reporter activity, suggesting that miR-192 does not regulate human NOD2.ConclusionThis study has demonstrated that rectal and serum microRNAs are perturbed in pediatric inflammatory bowel disease. Future studies identifying targets of inflammatory bowel disease-associated microRNAs may lead to novel therapies.     

Diet and risk of inflammatory bowel disease

BackgroundA better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses.AimTo review current knowledge on dietary risk factors for inflammatory bowel disease.MethodsThe PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease.ResultsEstablished non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case–control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate).ConclusionsA diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects.     

Preoperative use of anti-TNF therapy and postoperative complications in inflammatory bowel diseases: A meta-analysis

Background and aimsAbout one-third of inflammatory bowel disease (IBD) patients still require surgery. A growing number of them receive anti-tumor necrosis factor (TNF) therapy before surgery. The present meta-analysis studied the risk of postoperative complications in IBD patients treated with anti-TNF.MethodsMEDLINE was searched (up to January 2012) to identify observational studies reporting the prevalence of postoperative complications in IBD patients. The prevalence of overall, infectious, and non-infectious postoperative complications was extracted for all studies, and according to preoperative anti-TNF treatment where reported. Pooled prevalence, as well as odds ratios (ORs), with 95% confidence intervals (CIs) was calculated.ResultsThe search identified 86 citations. Twenty-one studies, containing 4251 subjects, reported the prevalence of postoperative complications according to preoperative anti-TNF treatment. Pooled prevalence of any postoperative complication was 21%, 35%, and 26% in Crohn's disease (CD), ulcerative colitis (UC) or inflammatory bowel disease unspecified (IBD-U) and IBD, respectively. The prevalence of any postoperative complication was increased in IBD patients who underwent preoperative anti-TNF therapy (OR: 1.25; 95% CI: 1.02–1.53). Pooled prevalence of infectious postoperative complications was 16%, 17%, and 15% in CD, UC/IBD-U and IBD, respectively. The prevalence of infectious postoperative complications was increased in CD patients who underwent preoperative anti-TNF therapy (OR: 1.45; 95% CI: 1.03–2.05). The confounding effect of concomitant therapies could not be studied.ConclusionsPreoperative anti-TNF use slightly increases the occurrence of overall postoperative complications in IBD patients, and particularly infectious complications in CD patients. Postoperative complications are not increased in UC.     

Medication non-adherence in adult patients affected by inflammatory bowel disease: a critical review and update of the determining factors,consequences and possible interventions

Introduction: Achieving adherence to medications can be a serious challenge for patients affected by inflammatory bowel disease (IBD). Medical treatment is fundamental for inducing and maintaining remission, preventing flares and reducing the risk of colorectal cancer. Non-adherence may affect patients’ quality of life resulting in unfavourable treatment outcomes, more hospitalizations and higher healthcare-related costs. Recognising and improving adherence is therefore a primary aim for the treatment of IBD.

Areas covered: We critically discuss the current knowledge on medication non-adherence in adult patients affected by IBD, also mentioning a few issues concerning the paediatric and adolescent populations. In particular, we reviewed the literature focusing on the definition and detection of non-adherence, on its extent and on the possible non-modifiable and modifiable factors involved (patient-centred, therapy-related, disease-related and physician-related). Furthermore, we analysed the interventional studies performed so far. The literature review was conducted through PubMed addressing medication non-adherence in IBD, using the keywords ‘adherence’ and related terms and ‘IBD, ulcerative colitis or Crohn’s disease’.

Expert commentary: Adherence to therapy for IBD is a complex yet fundamental issue that cannot be solved by addressing a single aspect only. Future studies should focus on patient-tailored and multidimensional interventions.     

Factors affecting vitamin D deficiency in active inflammatory bowel diseases

BackgroundHypovitaminosis D is prevalent in inflammatory bowel disease (IBD) and may be associated with disease activity.AimThis study evaluated vitamin D (VitD) status in an Italian cohort of IBD patients, not taking VitD supplementation. We investigated risk factors for VitD deficiency and its correlation with disease activity.MethodsVitD levels were measured in 300 consecutive outpatients (42% with Crohn’s Disease (CD) and 58% with ulcerative colitis (UC), 56% male) from a tertiary referral center. Data from the IBD cohort were compared with those of 234 healthy controls, matched by sex, age, and the month in which VitD levels were measured.ResultsThe mean VitD level in IBD patients was significantly lower than in controls (18.9 ng/ml vs. 25 ng/ml, p < 0.001) when accounting for gender, age, and season. VitD deficiency was present in 62% of IBD patients. Risk factors for deficiency were: age <40 and ≥60 years, winter, previous surgery, C-reactive protein (CRP) ≥0.5 mg/dl, and erythrocyte sedimentation rate ≥20 mm/h. In multivariate analysis, VitD levels were negatively influenced by disease location and CRP in UC.ConclusionsAlthough VitD deficiency was more prevalent than expected in healthy controls living in a Mediterranean country not at high risk of hypovitaminosis D, it was more common and severe in IBD patients. This study also found an association between VitD status and disease activity     

Perinatal vitamin D levels are not associated with later risk of developing pediatric-onset inflammatory bowel disease: a Danish case-cohort study

Objective Basic and epidemiologic studies on inflammatory bowel disease (IBD) have suggested an association between vitamin D and IBD risk. Though, the literature on IBD – especially pediatric-onset IBD – and vitamin D is still in its cradle. We therefore wanted to examine if levels of 25(OH)D at birth were associated with increased risk of developing pediatric-onset IBD. Material and methods A case-cohort study composed of cases diagnosed with Crohn’s disease, ulcerative colitis or indeterminate/unclassified colitis and healthy controls. Cases and controls were matched on date of birth and were born in the period 1981–2004. Cases were diagnosed before the age of 18 years. The concentration of 25(OH)D was assessed from neonatal dried blood spots using a highly sensitive liquid chromatography tandem mass spectrometry. Odds ratios (OR) were calculated using conditional logistic regression and two-way ANOVA were used to test for season and birth year 25(OH)D variations. A total of 384 matched pairs were included in the statistical analyses. Results No significant association were found between levels of 25(OH)D and IBD risk in the adjusted model (OR [95% CI] (per 25?nmol/L increase), 1.12 [0.88; 1.42], p?=?0.35). 25(OH)D levels were found to fluctuate significantly with season (p?p?Conclusion Our study do not suggest that a window of vulnerability exist around time of birth in regards to 25(OH)D levels and later pediatric-onset IBD risk.     

Familial occurrence and inheritance studies in inflammatory bowel disease

A number of studies have demonstrated aggregation of cases of ulcerative colitis or Crohn's disease in families, and of cases of both diseases within the same families, suggesting that patients share a genetic background. Perhaps because of differences in the selection of patients, study design and diagnostic criteria, different patterns of occurrence of inflammatory bowel disease (IBD) have been found among relatives of patients with these disorders. In recent years, however, several studies have been carried out, aiming by epidemiological methods to reveal (1) the frequency of familial occurrence of IBD among patients with ulcerative colitis and Crohn's disease, and (2) the prevalence of IBD among 1⁰ relatives to patients with these diseases. Results from these studies show a relatively uniform pattern of family occurrence in about 10% of patients with ulcerative colitis and Crohn's disease, and a prevalence among 1⁰ relatives of about 10 times that of the background population. A twin study reported a significantly higher concordance rate for Crohn's disease than for ulcerative colitis in monozygotic twins. By use of complex segregation analyses in 3 different studies, a very similar model of inheritance was found to fit for ulcerative colitis, namely a major dominant or additive gene with a low penetrance. For Crohn's disease the best-fitting model was a major recessive gene, with a high penetrance. This difference strongly supports the concept of ulcerative colitis and Crohn's disease as two separate disease entities. The occurrence of both diseases within the same families in certain members of the affected families is difficult to explain. The search for distinct associations of HLA genes with inflammatory bowel disease has shown a positive correlation between DR2 and ulcerative colitis and a negative association with DR4 and DRw6, compared with ethnically matched controls. In contrast, in Crohn's disease a positive association with the combination of DR1 and DQw5 alleles was revealed, thus indicating genetically different disease susceptibility for the two disorders. In general, however, no consistent pattern has been revealed from studies of association of HLA-A or -B antigens or blood group and serum protein markers. In two French families with several members affected with Crohn's disease no evidence for an HLA haplotype association could be revealed. Possible inherited markers of ulcerative colitis or Crohn's disease have been sought but without convincing success. Increased intestinal permeability, presence of anticolon antibodies and presence of antineutrophil leukocyte antibodies have been proposed, but not proved. Thorough studies are now needed of multimember families with disease for linkage studies to identify loci which contribute to increased liability. Such studies are in progress in different centres.     

Protective links between vitamin D,inflammatory bowel disease and colon cancer

Vitamin D deficiency has been associated with a wide range of diseases and multiple forms of cancer including breast, colon, and prostate cancers. Relatively recent work has demonstrated vitamin D to be critical in immune function and therefore important in inflammatory diseases such as inflammatory bowel disease(IBD). Because vitamin D deficiency or insufficiency is increasingly prevalent around the world, with an estimated 30%-50% of children and adults at risk for vitamin D deficiency worldwide, it could have a significant impact on IBD. Epidemiologic studies suggest that low serum vitamin D levels are a risk factor for IBD and colon cancer, and vitamin D supplementation is associated with decreased colitis disease activity and/or alleviated symptoms. Patients diagnosed with IBD have a higher incidence of colorectal cancer than the general population, which supports the notion that inflammation plays a key role in cancer development and underscores the importance of understanding how vitamin D influences inflammation and its cancer-promoting effects. In addition to human epidemiological data, studies utilizing mouse models of colitis have shown that vitamin D is beneficial in preventing or ameliorating inflammation and clinical disease. The precise role of vitamin D on colitis is unknown; however, vitamin D regulates immune cell trafficking and differentiation, gut barrier function and antimicrobial peptide synthesis, all of which may be protective from IBD and colon cancer. Here we focus on effects of vitamin D on inflammation and inflammation-associated colon cancer and discuss the potential use of vitamin D for protection and treatment of IBD and colon cancer.     

Activation of REG family proteins in colitis

Abstract

Aims. To do a genome-wide gene expression study of active and inactive ulcerative colitis and Crohn's disease (inflammatory bowel disease – IBD) and examine the most differentially expressed genes. As the study showed an extreme upregulation of all regenerating islet-derived genes (REG proteins) in active IBD, we further studied the expression of REGs on protein level in active and inactive IBD, as well as in non-IBD (pseudomembranous) colitis. Methods. Microarray analysis was done on a total of 100 pinch biopsy samples from healthy controls and patients with Crohn's disease or ulcerative colitis. Tissue samples from IBD and pseudomembranous colitis were examined with routine histology and immunohistochemical analysis for REGIα, REGIV, DEFA6, and serotonin. Results. REG mRNAs were up to 83 times overexpressed in diseased mucosa compared with mucosa from healthy individuals. REGIα and REGIV were overexpressed at immunohistochemistry and located to different mucosal cell types. REGIα was expressed in basal half of crypts, REGIV in mid and outer parts of crypts and in surface epithelium and seems to be stored in, and secreted from, goblets. Pseudomembranous colitis samples showed similar staining patterns, and some IBD samples stained REG positive without inflammation on routine histology. Conclusions. All REG family mRNAs are upregulated in IBD. REGIα and REGIV have different cellular localization, possibly reflecting different biological functions. REG protein expression also in pseudomembranous colitis shows that REG family proteins are regulated in inflammatory injury and repair, not specifically for IBD as previously thought.     

Occurrence of inflammatory bowel disease in central Italy: A study based on health information systems

BackgroundThe burden of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, has never been estimated in Italy using administrative data sources.Our objective was to measure the occurrence of inflammatory bowel diseases in the Lazio region (Italy) using administrative data and to test the sensitivity of the Crohn's disease case-finding algorithm with respect to clinical diagnosis.MethodsWe conducted a population-based cross-sectional study identifying prevalent and incident cases. We estimated occurrence rates of inflammatory bowel diseases using hospital discharges or activation of copayment exemptions. Sensitivity was calculated from 2358 subjects with clinical diagnosis of Crohn's disease.ResultsExemptions identified more than 20% of the cases. Prevalence rates (per 100,000) on December 31, 2009 for males and females were 177 and 144 for ulcerative colitis and 91 and 81 for Crohn's disease, respectively. The incidence rates during the years 2008–2009 were 14.5 and 12.2 for ulcerative colitis and 7.4 and 6.5 for Crohn's disease for males and females, respectively. The sensitivity of the administrative sources was 82.2%.ConclusionsHealth and population data sources allow the estimation of inflammatory bowel diseases occurrence. The age-specific peaks of diagnosis were consistent with those reported in other studies. Sensitivity may be affected by temporal changes in the quality of the data sources.     

Vitamin D deficiency in patients with diabetes and COVID- 19 infection

Background and aimsData show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus.MethodsA literature search was carried out by using the key term ‘COVID 19’ combined with ‘Diabetes’, ‘Vitamin D’, ‘Extra skeletal effects’, ‘immunity’, ‘infection’, ‘India’ from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out.ResultsVitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited.ConclusionRobust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.