In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the Wo...In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the World Journal of Gastroen-terology 2023;29(41):5668-5682.Inflammatory bowel diseases(IBD)are emerging as a significant global health concern as their incidence continues to rise on a global scale,with detrimental impacts on quality of life.While many advances have been made regarding the management of the disease,physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD.Chronic pain,fatigue,and fear of exacerbating symptoms promotes physical inactivity among IBD patients,while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity.Physical activity(PA)is accepted to have a positive effect on disease outcomes and quality of life,while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders.The“BE-FIT-IBD”study,focusing on PA levels and barriers in IBD patients of Southern Italy,revealed that a significant proportion(42.9%)were physically inactive.This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease.The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles.Moreover,physical inactivity may also contribute to disability in IBD patients,having a great impact on employment status.Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood,reduce anxiety,and enhance mental health.The“BE-FIT-IBD”study advocated for the integration of PA into IBD management,emphasizing the bidirectional link between PA and IBD.Regular exercise can influence the course of IBD,potentially reducing symptom severity and prolonging remission periods.As such,it is mandatory that healthcare providers actively educate patients,dispel misconceptions,and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.展开更多
Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating a...Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.展开更多
BACKGROUND There is no consensus on the recommended duration of and optimal time to stop azathioprine(AZA)therapy in inflammatory bowel disease(IBD).Determining the optimal duration and cessation time can help to bala...BACKGROUND There is no consensus on the recommended duration of and optimal time to stop azathioprine(AZA)therapy in inflammatory bowel disease(IBD).Determining the optimal duration and cessation time can help to balance the risks of long-term intake with the possibility of relapse after cessation.AIM To describe the events following AZA cessation.METHODS Retrospective analysis was performed to examine data from adult patients affected by IBD who were followed at the University of Padua and had started but then discontinued AZA between 1995 and 2022.Data on therapy duration,reasons for cessation,and type of relapse after cessation were collected.Cox regression models were used to estimate the risk of relapse in different subgroups.RESULTS A total of 133 ulcerative colitis patients and 141 Crohn’s disease patients were included.Therapy with AZA was stopped in the 1st year in approximately 34%of patients but was continued for more than 10 years in approximately 10%of cases.AZA discontinuation was due to primary failure or disease relapse in 30%of patients and due to disease remission in 25.2%of patients.Most of the remaining cases stopped AZA therapy due to side effects(primarily clinical intolerance,cytopenia,and pancreatic disease).Patients who stopped AZA for clinical remission had an 83%lower risk of relapse during the observation time than other groups,with a relapse-free rate of 89%after 1 year and 79%after 2 years.CONCLUSION AZA administration is effective and safe,but it requires careful monitoring for potential minor and major side effects.Only 10%of patients who achieved remission with AZA needed a new treatment within 1 year of drug interruption.展开更多
BACKGROUND Patients with immune-mediated diseases,such as juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)are at increased risk of developing infections,due to disease-related immune dysfunction a...BACKGROUND Patients with immune-mediated diseases,such as juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)are at increased risk of developing infections,due to disease-related immune dysfunction and applying of immunosuppressive drugs.AIM To evaluate vaccine coverage in patients with IBD and JIA,and compare it with healthy children.METHODS In the cross-sectional study we included the data from a questionnaire survey of 190 Legal representatives of children with JIA(n=81),IBD(n=51),and healthy children(HC,n=58).An electronic online questionnaire was created for the survey.RESULTS There were female predominance in JIA patients and younger onset age.Parents of JIA had higher education levels.Employment level and family status were similar in the three studied groups.Patients with JIA and IBD had lower vaccine coverage,without parental rejection of vaccinations in IBD,compare to JIA and healthy controls.The main reason for incomplete vaccination was medical conditions in IBD and JIA.IBD patients had a lower rate of normal vaccine-associated reactions compared to JIA and HC.The encouraging role of physicians for vaccinations was the lowest in JIA patients.IBD patients had more possibilities to check antibodies before immune-suppressive therapy and had more supplementary vaccinations compared to JIA and HC.CONCLUSION JIA and IBD patients had lower vaccine coverage compared to HC.Physicians'encouragement of vaccination and the impossibility of discus about future vaccinations and their outcomes seemed the main factors for patients with immune-mediated diseases,influencing vaccine coverage.Further investigations are required to understand the reasons for incomplete vaccinations and improve vaccine coverage in both groups,especially in rheumatic disease patients.The approaches that stimulate vaccination in healthy children are not always optimal in children with immunemediated diseases.It is necessary to provide personalized vaccine-encouraging strategies for parents of chronically ill children with the following validation of these technics.展开更多
BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IB...BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IBD patients with non-severe disease activity[assessed with partial Mayo score for ulcerative colitis(UC)and Harvey-Bradshaw index for Crohn’s disease]were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire(IPAQ)and to assess disease activity as patient-reported outcomes 2(PRO-2)and finally to assess habits,beliefs and barriers in conducting regular PA.Clinical,anthropometric and demographic data of patients were also collected.PA was expressed as continuous units of resting metabolic rate(Met)in min/wk.Three PA groups were identified:Inactive(<700 Met min/wk),sufficiently active(700-2500 Met min/wk)and health enhancing PA(HEPA)(i.e.,HEPA active,>2500 Met min/wk)patients.RESULTS Included patients(219)showed overall PA levels of 834.5 Met min/wk,with a large proportion(94,42.9%)classified as inactive while only a minority(9,4.1%)as health-enhancing PA.Patients without dyslipidaemia(P<0.0001)or on biologics therapy(P=0.022)showed better IPAQ scores in moderate activities.UC PRO-2 correlated negatively with IPAQ intense activities scores(τ=-0.156,P=0.038).PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity(AUC<0.6).IBD activity did not differ between active and inactive patients(P>0.05).Active patients expressed the need to discuss PA with their gastroenterologist.Some barriers(e.g.,diagnosis of IBD and fear of flare-ups after PA)are significantly more reported by inactive patients.CONCLUSION A significant rate of physical inactivity was recorded in this setting.IPAQ showed good feasibility.PA should be an element of discussion in IBD visits assessed quickly with non-invasive questionnaires.展开更多
Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic th...Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.展开更多
Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow aff...Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.展开更多
Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The...Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The progressive development of information technology has enabled healthcare personnel to deliver care services to patients remotely.Therefore,various applications of telemedicine in IBD management have evolved,including telemonitoring,teleconsulting,teleducation,telenursing,telenutrition,and telepathology.While evidence has been provided for some telemedicine applications,targeted studies are still required.This review summarises the major studies that have evaluated telemedicine and its application in the management of IBD.展开更多
Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,...Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.展开更多
Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease(IBD) and Parkinson's disease(PD). However, the epidemiological fe...Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease(IBD) and Parkinson's disease(PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched Pub Med, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population(adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P < 0.001). A metaanalysis of the temporal relationship revealed that the incidence of IBD was significantly increased before(adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18–1.35, P < 0.001) and after(adjusted RR = 1.40, 95% CI: 1.20–1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis(adjusted HR = 1.25, 95% CI: 1.13–1.38, P < 0.001) or Crohn's disease(adjusted HR = 1.33, 95% CI: 1.21–1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men(adjusted HR = 1.23, 95% CI: 1.10–1.39) and women(adjusted HR = 1.26, 95% CI: 1.10–1.43);however, older(> 65 years old) IBD patients(adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger(≤ 65 years old) patients(adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk(adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.展开更多
Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environment...Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible individuals.Exogenous glucocorticoids(GCs)are widely used as anti-inflammatory therapy in IBDs.In the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission.However,this treatment often results in detrimental side effects.This downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery methods.Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects.The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment.In this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs.This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.展开更多
Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an...Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.展开更多
AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications ad...AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn's disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when necessary to generate a standardized set of data from these studies. From these data, odds ratio (OR) with 95% confidence interval (CI) were calculated.RESULTS: Twenty-five studies of CD were analyzed, 14 of which involved cases of UC. The variant G allele of ATG16L1 was positively associated with CD (OR=1.32, 95% CI: 1.26-1.39, P<0.00001) and UC (OR =1.06, 95% CI:1.01-1.10, P=0.02). For child-onset IBD, a higher G allele frequency was found for cases of CD (OR=1.35, 95% CI: 1.16-1.57, P=0.0001) than for cases of UC (OR = 0.98, 95% CI: 0.81-1.19, P = 0.84) relative to controls.CONCLUSION: The ATG16L1 T300A polymorphism contributes to susceptibility to CD and UC in adults, but different in children, which implicates a role for autophagy in the pathogenesis of IBD.展开更多
The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel di...The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel diseases(IBDs).IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine,and the symptoms of IBDs may include abdominal pain,diarrhea,rectal bleeding,and weight loss.The P2X7 receptor has become a promising therapeutic target for IBDs,especially owing to its wide expression and,in the case of other purinergic receptors,in both human and model animal enteric cells.However,little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine.In this review,an integrated view is provided,correlating the structural organization of the ENS and the effects of IBDs,focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.展开更多
Background:Inflammatory bowel diseases(IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated hosp...Background:Inflammatory bowel diseases(IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated hospitalizations.The study's objectives were to identify the reasons for hospitalization among patients with IBDs,and compare inpatient courses and readmission rates for IBD-related admissions versus non-IBD-related admissions.Methods:A retrospective chart review was performed on all patients with IBD admitted to the Minneapolis Veterans Affairs(VA) Medical Center between September 2010 and September 2012.Results:A total of 111 patients with IBD were admitted during the 2-year study period.IBD flares/complications accounted for 36.9% of the index admissions.Atherothrombotic events comprised the second most common cause of admissions(14.4%) in IBD patients.Patients with an index admission directly related to IBD were significantly younger and had developed IBD more recently.Unsurprisingly,the IBD admission group had significantly more gastrointestinal endoscopies and abdominal surgeries,and was more likely to be started on medication for IBD during the index stay.The median length of stay(LOS) for the index hospitalization for an IBD flare or complication was 4(2–8) days compared with 2(1–4) days for the other patients(P=0.001).A smaller percentage of the group admitted for an IBD flare/complication had a shorter ICU stay compared with the other patients(9.8% vs.15.7%,respectively); however,their ICU LOSs tended to be longer(4.5 vs.2.0 days,respectively,P=0.17).Compared to the other admission types,an insignificantly greater percentage of the group whose index admission was related to an IBD flare or complication had at least one readmission within 6 months of discharge(29% versus 21%; P=0.35).The rate of admission was approximately 80% greater in the group whose index admission was related to an IBD flare or complication compared to the other types of admission(rate ratio 1.8,95% confidence interval 0.96 to 3.4),although this difference did not reach statistical significance(P=0.07).Conclusion:Identifying the reasons for the patients' index admission,IBD flares versus all other causes,may provide valuable information concerning admission care and the subsequent admission history.展开更多
Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinatio...Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations.In addition,the discovery of biomarkers has significantly improved the diagnosis and management of IBD.Several potential genetic,serological,fecal,microbial,histological and immunological biomarkers have been proposed for IBD,and they have been evaluated for clinical routine and clinical trials.Ileocolonoscopy,especially with biopsy collection,has been considered the standard method to diagnose IBD and to assess clinical activity of the disease,but it is limited to the colon and terminal ileum and is considered invasive.For this reason,non-invasive biomarkers are necessary for this type of chronic inflammatory disease,which affects mostly young individuals,as they are expected to have a long follow-up.展开更多
Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic challenge.I...Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic challenge.Immunemediated conditions include primary sclerosing cholangitis(PSC)as the main form,variant forms of PSC(namely small-duct PSC,PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis)and granulomatous hepatitis.PSC is by far the most common,presenting in up to 8%of IBD patients,more frequently in UC.Several genetic foci have been identified,but environmental factors are preponderant on disease pathogenesis.The course of the two diseases is typically independent.PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies.Risk of cholangiocarcinoma is significantly increased in PSC,as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis.No disease-modifying drugs are approved to date.Thus,PSC management is directed against symptoms and complications and includes medical therapies for pruritus,endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease.Other nonimmune-mediated hepatobiliary disorders are gallstone disease,whose incidence is higher in IBD and reported in up to one third of IBD patients,non-alcoholic fatty liver disease,pyogenic liver abscess and portal vein thrombosis.Druginduced liver injury(DILI)is an important issue in IBD,since most IBD therapies may cause liver toxicity;however,the incidence of serious adverse events is low.Thiopurines and methotrexate are the most associated with DILI,while the risk related to anti-tumor necrosis factor-αand anti-integrins is low.Data on hepatotoxicity of newer drugs approved for IBD,like anti-interleukin 12/23 and tofacitinib,are still scarce,but the evidence from other rheumatic diseases is reassuring.Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD,and adequate screening and vaccination is warranted.On the other hand,hepatitis C reactivation does not seem to be a real risk,and hepatitis C antiviral treatment does not influence IBD natural history.The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis,but it is of paramount importance to make a quick and accurate diagnosis,as it may influence the therapeutic management.展开更多
BACKGROUND This is the first study on the epidemiology of inflammatory bowel diseases(IBDs)in Rio Grande do Sul(RS),the southernmost state of Brazil with the country’s fifth largest population.Crohn’s disease(CD)and...BACKGROUND This is the first study on the epidemiology of inflammatory bowel diseases(IBDs)in Rio Grande do Sul(RS),the southernmost state of Brazil with the country’s fifth largest population.Crohn’s disease(CD)and ulcerative colitis(UC)are collectively termed IBDs.They have high incidence and prevalence rates in highincome countries,although in recent years there has been a change in the classic geographical distribution of IBDs,with growing rates in traditionally lowincidence regions.AIM To estimate the incidence and prevalence of IBDs in the RS state,Brazil,between 2014 and 2019.METHODS This is a cross-sectional descriptive observational study.Patients with IBD who had initiated treatment and met the inclusion criteria of the RS state free drug distribution program were included.Data were obtained from registration or renewal records of the RS state specialty pharmacy.The male,female,and total populations were estimated according to mid-year data from the Brazilian Institute of Geography and Statistics,which served as a reference for calculating the incidence and prevalence rates of IBDs during the study period.Results were described using mean,standard deviation,and range.RESULTS We included 1082 patients with IBD,of whom 57.5%were female and 42.5% were male.Patients with CD accounted for 72.45% of the sample,and those with UC accounted for 27.54%.IBD prevalence during the study period was 9.51 per 100000 population,of which 6.89 corresponded to people with CD and 2.62,to people with UC.Incidence rates per 100000 population/year were 2.54 in 2014,2.61 in 2015,1.91 in 2016,0.80 in 2017,0.83 in 2018,and 0.96 in 2019.The mean IBD incidence rate per 100000 population was 1.61,of which 1.17 corresponded to CD and 0.44,to UC.The mean age was 41 years,and patients were mostly aged 30-40 years.Prevalence by region was higher in the state capital metropolitan area:12.69 per 100000 population.CONCLUSION Our results demonstrated an IBD prevalence of 9.51% and incidence of 1.61 per 100000 population.The patients were predominantly female,and CD was more prevalent than UC.展开更多
long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiolog...long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.展开更多
Inflammatory bowel diseases(IBDs) are characterized by inflammation in the gastrointestinal tract and include Ulcerative Colitis and Crohn’s Disease.These diseases are costly to health services,substantially reduce p...Inflammatory bowel diseases(IBDs) are characterized by inflammation in the gastrointestinal tract and include Ulcerative Colitis and Crohn’s Disease.These diseases are costly to health services,substantially reduce patients’ quality of life,and can lead to complications such as cancer and even death.Symptoms include abdominal pain,stool bleeding,diarrhea,and weight loss.The treatment of these diseases is symptomatic,seeking disease remission.The intestine is colonized by several microorganisms,such as fungi,viruses,and bacteria,which constitute the intestinal microbiota(IM).IM bacteria promotes dietary fibers fermentation and produces short-chain fatty acids(SCFAs) that exert several beneficial effects on intestinal health.SCFAs can bind to G protein-coupled receptors,such as GPR41 and GPR43,promoting improvements in the intestinal barrier,anti-inflammatory,and antioxidant effects.Thus,SCFAs could be a therapeutic tool for IBDs.However,the mechanisms involved in these beneficial effects of SCFAs remain poorly understood.Therefore,this paper aims to provide a review addressing the main aspects of IBDs,and a more detailed sight of SCFAs,focusing on the main effects on different aspects of the intestine with an emphasis on IBDs.展开更多
文摘In this editorial we comment on the article titled“Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity:The BE-FIT-IBD study”published in a recent issue of the World Journal of Gastroen-terology 2023;29(41):5668-5682.Inflammatory bowel diseases(IBD)are emerging as a significant global health concern as their incidence continues to rise on a global scale,with detrimental impacts on quality of life.While many advances have been made regarding the management of the disease,physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD.Chronic pain,fatigue,and fear of exacerbating symptoms promotes physical inactivity among IBD patients,while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity.Physical activity(PA)is accepted to have a positive effect on disease outcomes and quality of life,while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders.The“BE-FIT-IBD”study,focusing on PA levels and barriers in IBD patients of Southern Italy,revealed that a significant proportion(42.9%)were physically inactive.This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease.The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles.Moreover,physical inactivity may also contribute to disability in IBD patients,having a great impact on employment status.Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood,reduce anxiety,and enhance mental health.The“BE-FIT-IBD”study advocated for the integration of PA into IBD management,emphasizing the bidirectional link between PA and IBD.Regular exercise can influence the course of IBD,potentially reducing symptom severity and prolonging remission periods.As such,it is mandatory that healthcare providers actively educate patients,dispel misconceptions,and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.
文摘Clostridioides difficile(C.difficile)is progressively colonizing humans and animals living with humans.During this process,hypervirulent strains and mutated toxin A and B of C.difficile(TcdA and TcdB)are originating and developing.While in healthy subjects colonization by C.difficile becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to C.difficile infection and its progression and relapses.TcdB is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled family.Chondroitin sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only necrosis.It is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in apoptosis.Therefore,in subjects with IBD there are the conditions:(1)For greater susceptibility to C.difficile infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than apoptosis.The only therapeutic approach currently possible in IBD patients is monitoring of C.difficile colonization for interventions aimed at reducing tumor necrosis factor-alpha and interferon-gamma levels when the infection begins.The future perspective is to generate bacteriophages against C.difficile for targeted therapy.
文摘BACKGROUND There is no consensus on the recommended duration of and optimal time to stop azathioprine(AZA)therapy in inflammatory bowel disease(IBD).Determining the optimal duration and cessation time can help to balance the risks of long-term intake with the possibility of relapse after cessation.AIM To describe the events following AZA cessation.METHODS Retrospective analysis was performed to examine data from adult patients affected by IBD who were followed at the University of Padua and had started but then discontinued AZA between 1995 and 2022.Data on therapy duration,reasons for cessation,and type of relapse after cessation were collected.Cox regression models were used to estimate the risk of relapse in different subgroups.RESULTS A total of 133 ulcerative colitis patients and 141 Crohn’s disease patients were included.Therapy with AZA was stopped in the 1st year in approximately 34%of patients but was continued for more than 10 years in approximately 10%of cases.AZA discontinuation was due to primary failure or disease relapse in 30%of patients and due to disease remission in 25.2%of patients.Most of the remaining cases stopped AZA therapy due to side effects(primarily clinical intolerance,cytopenia,and pancreatic disease).Patients who stopped AZA for clinical remission had an 83%lower risk of relapse during the observation time than other groups,with a relapse-free rate of 89%after 1 year and 79%after 2 years.CONCLUSION AZA administration is effective and safe,but it requires careful monitoring for potential minor and major side effects.Only 10%of patients who achieved remission with AZA needed a new treatment within 1 year of drug interruption.
文摘BACKGROUND Patients with immune-mediated diseases,such as juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)are at increased risk of developing infections,due to disease-related immune dysfunction and applying of immunosuppressive drugs.AIM To evaluate vaccine coverage in patients with IBD and JIA,and compare it with healthy children.METHODS In the cross-sectional study we included the data from a questionnaire survey of 190 Legal representatives of children with JIA(n=81),IBD(n=51),and healthy children(HC,n=58).An electronic online questionnaire was created for the survey.RESULTS There were female predominance in JIA patients and younger onset age.Parents of JIA had higher education levels.Employment level and family status were similar in the three studied groups.Patients with JIA and IBD had lower vaccine coverage,without parental rejection of vaccinations in IBD,compare to JIA and healthy controls.The main reason for incomplete vaccination was medical conditions in IBD and JIA.IBD patients had a lower rate of normal vaccine-associated reactions compared to JIA and HC.The encouraging role of physicians for vaccinations was the lowest in JIA patients.IBD patients had more possibilities to check antibodies before immune-suppressive therapy and had more supplementary vaccinations compared to JIA and HC.CONCLUSION JIA and IBD patients had lower vaccine coverage compared to HC.Physicians'encouragement of vaccination and the impossibility of discus about future vaccinations and their outcomes seemed the main factors for patients with immune-mediated diseases,influencing vaccine coverage.Further investigations are required to understand the reasons for incomplete vaccinations and improve vaccine coverage in both groups,especially in rheumatic disease patients.The approaches that stimulate vaccination in healthy children are not always optimal in children with immunemediated diseases.It is necessary to provide personalized vaccine-encouraging strategies for parents of chronically ill children with the following validation of these technics.
基金The study was conducted in compliance with the Declaration of Helsinki and received approval from the Ethics Committee of the University of Campania Luigi Vanvitelli(protocol number 7892,15 March 2023).
文摘BACKGROUND The place regular physical activity(PA)should occupy in managing patients with inflammatory bowel diseases(IBD)is unclear.AIM To assess PA levels and barriers in a southern Italian IBD population.METHODS IBD patients with non-severe disease activity[assessed with partial Mayo score for ulcerative colitis(UC)and Harvey-Bradshaw index for Crohn’s disease]were approached to receive an anonymous online questionnaire to assess PA levels using the International Physical Activity Questionnaire(IPAQ)and to assess disease activity as patient-reported outcomes 2(PRO-2)and finally to assess habits,beliefs and barriers in conducting regular PA.Clinical,anthropometric and demographic data of patients were also collected.PA was expressed as continuous units of resting metabolic rate(Met)in min/wk.Three PA groups were identified:Inactive(<700 Met min/wk),sufficiently active(700-2500 Met min/wk)and health enhancing PA(HEPA)(i.e.,HEPA active,>2500 Met min/wk)patients.RESULTS Included patients(219)showed overall PA levels of 834.5 Met min/wk,with a large proportion(94,42.9%)classified as inactive while only a minority(9,4.1%)as health-enhancing PA.Patients without dyslipidaemia(P<0.0001)or on biologics therapy(P=0.022)showed better IPAQ scores in moderate activities.UC PRO-2 correlated negatively with IPAQ intense activities scores(τ=-0.156,P=0.038).PRO-2 did not show notable sensitivity/specificity in predicting IPAQ inactivity(AUC<0.6).IBD activity did not differ between active and inactive patients(P>0.05).Active patients expressed the need to discuss PA with their gastroenterologist.Some barriers(e.g.,diagnosis of IBD and fear of flare-ups after PA)are significantly more reported by inactive patients.CONCLUSION A significant rate of physical inactivity was recorded in this setting.IPAQ showed good feasibility.PA should be an element of discussion in IBD visits assessed quickly with non-invasive questionnaires.
文摘Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.
文摘Many studies point to an association between Helicobacter pylori(H.pylori)infection and inflammatory bowel diseases(IBD).Although controversial,this association indicates that the presence of the bacterium somehow affects the course of IBD.It appears that H.pylori infection influences IBD through changes in the diversity of the gut microbiota,and hence in local chemical characteristics,and alteration in the pattern of gut immune response.The gut immune response appears to be modulated by H.pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair.Therefore,a T helper 2(Th2)/macrophage M2 response is stimulated,while the Th1/macrophage M1 response is suppressed.The immunomodulation appears to be associated with intrinsic factors of the bacteria,such as virulence factors-such oncogenic protein cytotoxin-associated antigen A,proteins such H.pylori neutrophil-activating protein,but also with microenvironmental changes that favor permanence of H.pylori in the stomach.These changes include the increase of gastric mucosal pH by urease activity,and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium.Furthermore,there is a causal relationship between H.pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.
文摘Inflammatory bowel disease(IBD)is a chronic digestive disease that requires continuous monitoring by healthcare professionals to determine the appropriate therapy and monitor short-term and long-term complications.The progressive development of information technology has enabled healthcare personnel to deliver care services to patients remotely.Therefore,various applications of telemedicine in IBD management have evolved,including telemonitoring,teleconsulting,teleducation,telenursing,telenutrition,and telepathology.While evidence has been provided for some telemedicine applications,targeted studies are still required.This review summarises the major studies that have evaluated telemedicine and its application in the management of IBD.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.NRF-2020R1F1A1073595 and 2021R1A2C2006745)。
文摘Polyphenols,including phenolic acids,flavonoids,and procyanidins,are abundant in food and beverage derived from plants.Tea(Camellia sinensis)is particularly rich in polyphenols(e.g.,catechins,theaflavins,thearubigins,gallic acid,and flavonols),which are thought to contribute to the health benefits of tea.High intake of tea polyphenols has been described to prevent and/or attenuate a variety of chronic pathological conditions like cardiovascular diseases,neurodegenerative diseases,diabetes,and cancer.This review focuses on established antioxidant and anti-inflammatory properties of tea polyphenols and underlying mechanisms of their involvement in inflammatory bowel diseases(IBD).Tea polyphenols act as efficient antioxidants by inducing an endogenous antioxidant defense system and maintaining intracellular redox homeostasis.Tea polyphenols also regulate signaling pathways such as nuclear factor-κB,activator protein 1,signal transducer and activator of transcriptions,and nuclear factor E2-related factor 2,which are associated with IBD development.Accumulating pieces of evidence have indicated that tea polyphenols enhance epithelial barrier function and improve gut microbial dysbiosis,contributing to the management of inflammatory colitis.Therefore,this study suggests that supplementation of tea polyphenols could prevent inflammatory conditions and improve the outcome of patients with IBD.
文摘Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease(IBD) and Parkinson's disease(PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched Pub Med, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population(adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P < 0.001). A metaanalysis of the temporal relationship revealed that the incidence of IBD was significantly increased before(adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18–1.35, P < 0.001) and after(adjusted RR = 1.40, 95% CI: 1.20–1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis(adjusted HR = 1.25, 95% CI: 1.13–1.38, P < 0.001) or Crohn's disease(adjusted HR = 1.33, 95% CI: 1.21–1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men(adjusted HR = 1.23, 95% CI: 1.10–1.39) and women(adjusted HR = 1.26, 95% CI: 1.10–1.43);however, older(> 65 years old) IBD patients(adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger(≤ 65 years old) patients(adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk(adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.
基金Supported by National Fund for Scientific and Technological Development No.1170648(MHR)Clínica Las Condes Academic Project PI2013-B002,UApoya No.560959(RQ)National Commission for Scientific and Technological Research scholarship No.21150264(DDJ),No.21120682(MOM),MECESUP Scholarship No.UCH 0714(KDC)
文摘Inflammatory bowel diseases(IBDs),such as ulcerative colitis and Crohn's disease,are chronic pathologies associated with a deregulated immune response in the intestinal mucosa,and they are triggered by environmental factors in genetically susceptible individuals.Exogenous glucocorticoids(GCs)are widely used as anti-inflammatory therapy in IBDs.In the past,patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission.However,this treatment often results in detrimental side effects.This downside drove the development of second generation GCs and more precise(non-systemic)drugdelivery methods.Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects.The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment.A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment.In this review,we examine the clinical characteristics of treatment with GCs,followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs.This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.
文摘Compelling evidence supports the crucial role of the receptor for advanced glycation end-products(RAGE)axis activation in many clinical entities.Since the beginning of the coronavirus disease 2019 pandemic,there is an increasing concern about the risk and handling of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in inflammatory gastrointestinal disorders,such as inflammatory bowel diseases(IBD).However,clinical data raised during pandemic suggests that IBD patients do not have an increased risk of contracting SARS-CoV-2 infection or develop a more severe course of infection.In the present review,we intend to highlight how two potentially important contributors to the inflammatory response to SARS-CoV-2 infection in IBD patients,the RAGE axis activation as well as the cross-talk with the renin-angiotensin system,are dampened by the high expression of soluble forms of both RAGE and the angiotensin-converting enzyme(ACE)2.The soluble form of RAGE functions as a decoy for its ligands,and soluble ACE2 seems to be an additionally attenuating contributor to RAGE axis activation,particularly by avoiding the transactivation of the RAGE axis that can be produced by the virus-mediated imbalance of the ACE/angiotensin II/angiotensin II receptor type 1 pathway.
文摘AIM:To evaluate the association of the autophagy- related 16-like 1 (ATG16L1 ) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis.METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn's disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE data-bases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when necessary to generate a standardized set of data from these studies. From these data, odds ratio (OR) with 95% confidence interval (CI) were calculated.RESULTS: Twenty-five studies of CD were analyzed, 14 of which involved cases of UC. The variant G allele of ATG16L1 was positively associated with CD (OR=1.32, 95% CI: 1.26-1.39, P<0.00001) and UC (OR =1.06, 95% CI:1.01-1.10, P=0.02). For child-onset IBD, a higher G allele frequency was found for cases of CD (OR=1.35, 95% CI: 1.16-1.57, P=0.0001) than for cases of UC (OR = 0.98, 95% CI: 0.81-1.19, P = 0.84) relative to controls.CONCLUSION: The ATG16L1 T300A polymorphism contributes to susceptibility to CD and UC in adults, but different in children, which implicates a role for autophagy in the pathogenesis of IBD.
基金Supported by the Sao Paulo Research (FAPESP, Brazil),No. 2014/25927-2 and No. 2018/07862-1the National Council for Scientific and Technological Development (CNPq, Brazil)
文摘The enteric nervous system(ENS)consists of thousands of small ganglia arranged in the submucosal and myenteric plexuses,which can be negatively affected by Crohn’s disease and ulcerative colitis-inflammatory bowel diseases(IBDs).IBDs are complex and multifactorial disorders characterized by chronic and recurrent inflammation of the intestine,and the symptoms of IBDs may include abdominal pain,diarrhea,rectal bleeding,and weight loss.The P2X7 receptor has become a promising therapeutic target for IBDs,especially owing to its wide expression and,in the case of other purinergic receptors,in both human and model animal enteric cells.However,little is known about the actual involvement between the activation of the P2X7 receptor and the cascade of subsequent events and how all these activities associated with chemical signals interfere with the functionality of the affected or treated intestine.In this review,an integrated view is provided,correlating the structural organization of the ENS and the effects of IBDs,focusing on cellular constituents and how therapeutic approaches through the P2X7 receptor can assist in both protection from damage and tissue preservation.
基金supported by the Department of Veterans Affairs,Veterans Health Administrationthe Health Services Research and Development (HSR & D) Service through the Minneapolis Center of Innovation
文摘Background:Inflammatory bowel diseases(IBDs) are group of chronic inflammatory illnesses with a remitting and relapsing course that may result in appreciable morbidity and high medical costs secondary to repeated hospitalizations.The study's objectives were to identify the reasons for hospitalization among patients with IBDs,and compare inpatient courses and readmission rates for IBD-related admissions versus non-IBD-related admissions.Methods:A retrospective chart review was performed on all patients with IBD admitted to the Minneapolis Veterans Affairs(VA) Medical Center between September 2010 and September 2012.Results:A total of 111 patients with IBD were admitted during the 2-year study period.IBD flares/complications accounted for 36.9% of the index admissions.Atherothrombotic events comprised the second most common cause of admissions(14.4%) in IBD patients.Patients with an index admission directly related to IBD were significantly younger and had developed IBD more recently.Unsurprisingly,the IBD admission group had significantly more gastrointestinal endoscopies and abdominal surgeries,and was more likely to be started on medication for IBD during the index stay.The median length of stay(LOS) for the index hospitalization for an IBD flare or complication was 4(2–8) days compared with 2(1–4) days for the other patients(P=0.001).A smaller percentage of the group admitted for an IBD flare/complication had a shorter ICU stay compared with the other patients(9.8% vs.15.7%,respectively); however,their ICU LOSs tended to be longer(4.5 vs.2.0 days,respectively,P=0.17).Compared to the other admission types,an insignificantly greater percentage of the group whose index admission was related to an IBD flare or complication had at least one readmission within 6 months of discharge(29% versus 21%; P=0.35).The rate of admission was approximately 80% greater in the group whose index admission was related to an IBD flare or complication compared to the other types of admission(rate ratio 1.8,95% confidence interval 0.96 to 3.4),although this difference did not reach statistical significance(P=0.07).Conclusion:Identifying the reasons for the patients' index admission,IBD flares versus all other causes,may provide valuable information concerning admission care and the subsequent admission history.
基金Supported by National Council for Scientific and Technological Development(CNPq),No.301388/2018-0Funding for Education,Research and Extension Support(FAEPEX),University of Campinas.
文摘Inflammatory bowel diseases(IBD)comprise two major forms:Crohn’s disease and ulcerative colitis.The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations.In addition,the discovery of biomarkers has significantly improved the diagnosis and management of IBD.Several potential genetic,serological,fecal,microbial,histological and immunological biomarkers have been proposed for IBD,and they have been evaluated for clinical routine and clinical trials.Ileocolonoscopy,especially with biopsy collection,has been considered the standard method to diagnose IBD and to assess clinical activity of the disease,but it is limited to the colon and terminal ileum and is considered invasive.For this reason,non-invasive biomarkers are necessary for this type of chronic inflammatory disease,which affects mostly young individuals,as they are expected to have a long follow-up.
文摘Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases(IBD),both in Crohn’s disease and ulcerative colitis(UC),and therefore represent a diagnostic challenge.Immunemediated conditions include primary sclerosing cholangitis(PSC)as the main form,variant forms of PSC(namely small-duct PSC,PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis)and granulomatous hepatitis.PSC is by far the most common,presenting in up to 8%of IBD patients,more frequently in UC.Several genetic foci have been identified,but environmental factors are preponderant on disease pathogenesis.The course of the two diseases is typically independent.PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies.Risk of cholangiocarcinoma is significantly increased in PSC,as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis.No disease-modifying drugs are approved to date.Thus,PSC management is directed against symptoms and complications and includes medical therapies for pruritus,endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease.Other nonimmune-mediated hepatobiliary disorders are gallstone disease,whose incidence is higher in IBD and reported in up to one third of IBD patients,non-alcoholic fatty liver disease,pyogenic liver abscess and portal vein thrombosis.Druginduced liver injury(DILI)is an important issue in IBD,since most IBD therapies may cause liver toxicity;however,the incidence of serious adverse events is low.Thiopurines and methotrexate are the most associated with DILI,while the risk related to anti-tumor necrosis factor-αand anti-integrins is low.Data on hepatotoxicity of newer drugs approved for IBD,like anti-interleukin 12/23 and tofacitinib,are still scarce,but the evidence from other rheumatic diseases is reassuring.Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD,and adequate screening and vaccination is warranted.On the other hand,hepatitis C reactivation does not seem to be a real risk,and hepatitis C antiviral treatment does not influence IBD natural history.The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis,but it is of paramount importance to make a quick and accurate diagnosis,as it may influence the therapeutic management.
基金Supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil(CAPES)-Finance Code 001.
文摘BACKGROUND This is the first study on the epidemiology of inflammatory bowel diseases(IBDs)in Rio Grande do Sul(RS),the southernmost state of Brazil with the country’s fifth largest population.Crohn’s disease(CD)and ulcerative colitis(UC)are collectively termed IBDs.They have high incidence and prevalence rates in highincome countries,although in recent years there has been a change in the classic geographical distribution of IBDs,with growing rates in traditionally lowincidence regions.AIM To estimate the incidence and prevalence of IBDs in the RS state,Brazil,between 2014 and 2019.METHODS This is a cross-sectional descriptive observational study.Patients with IBD who had initiated treatment and met the inclusion criteria of the RS state free drug distribution program were included.Data were obtained from registration or renewal records of the RS state specialty pharmacy.The male,female,and total populations were estimated according to mid-year data from the Brazilian Institute of Geography and Statistics,which served as a reference for calculating the incidence and prevalence rates of IBDs during the study period.Results were described using mean,standard deviation,and range.RESULTS We included 1082 patients with IBD,of whom 57.5%were female and 42.5% were male.Patients with CD accounted for 72.45% of the sample,and those with UC accounted for 27.54%.IBD prevalence during the study period was 9.51 per 100000 population,of which 6.89 corresponded to people with CD and 2.62,to people with UC.Incidence rates per 100000 population/year were 2.54 in 2014,2.61 in 2015,1.91 in 2016,0.80 in 2017,0.83 in 2018,and 0.96 in 2019.The mean IBD incidence rate per 100000 population was 1.61,of which 1.17 corresponded to CD and 0.44,to UC.The mean age was 41 years,and patients were mostly aged 30-40 years.Prevalence by region was higher in the state capital metropolitan area:12.69 per 100000 population.CONCLUSION Our results demonstrated an IBD prevalence of 9.51% and incidence of 1.61 per 100000 population.The patients were predominantly female,and CD was more prevalent than UC.
文摘long-term,and relapsing inflammatory disorders.IBD may spontaneously grow in the colon,and in severe cases may result in tumor lesions such as invasive carcinoma in inflamed regions of the intestine.Recent epidemiological reports indicate that old age and underlying diseases such as IBD contribute to severity and mortality in patients with coronavirus disease 2019(COVID-19).Currently,the ongoing COVID-19 pandemic caused serious morbidity and mortality worldwide.It has also been shown that the transmembrane serine protease 2 is an essential factor for viral activation and viral engulfment.Generally,viral entry causes a'cytokine storm'that induces excessive generation of proinflammatory cytokines/chemokines including interleukin(IL)-6,IL-2,IL-7,tumor necrosis factor-α,and interferon-γ.Future research could concentrate on developing inflammatory immunological responses that are efficient to encounter COVID-19.Current analysis elucidates the role of inflammation and immune responses during IBD infection with COVID-19 and provides a list of possible targets for IBD-regulated therapies in particular.Data from clinical,in vitro,and in vivo studies were collected in English from PubMed,Google Scholar,Scopus,and the Cochrane library until May 2021.
基金Supported by the Research Support Foundation of the State of S?o PauloFAPESP+1 种基金Brazil,No.n2014/25927-2 and No.2018/07862-1Higher Education Personnel Improvement Coordination (CAPES,Brazil),No.n88887.506345/2020-00。
文摘Inflammatory bowel diseases(IBDs) are characterized by inflammation in the gastrointestinal tract and include Ulcerative Colitis and Crohn’s Disease.These diseases are costly to health services,substantially reduce patients’ quality of life,and can lead to complications such as cancer and even death.Symptoms include abdominal pain,stool bleeding,diarrhea,and weight loss.The treatment of these diseases is symptomatic,seeking disease remission.The intestine is colonized by several microorganisms,such as fungi,viruses,and bacteria,which constitute the intestinal microbiota(IM).IM bacteria promotes dietary fibers fermentation and produces short-chain fatty acids(SCFAs) that exert several beneficial effects on intestinal health.SCFAs can bind to G protein-coupled receptors,such as GPR41 and GPR43,promoting improvements in the intestinal barrier,anti-inflammatory,and antioxidant effects.Thus,SCFAs could be a therapeutic tool for IBDs.However,the mechanisms involved in these beneficial effects of SCFAs remain poorly understood.Therefore,this paper aims to provide a review addressing the main aspects of IBDs,and a more detailed sight of SCFAs,focusing on the main effects on different aspects of the intestine with an emphasis on IBDs.
