Patients'perspectives on smoking and inflammatory bowel disease:An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations

BACKGROUNDSmoking has detrimental effects on Crohn’s disease (CD) activity while data onulcerative colitis (UC) are conflicting. Little is known about the use and impact ofalternative smoking products in inflammatory bowel diseases (IBD).AIMTo understand the patients’ perceptions of the impact of smoking on their IBDand to assess differences between CD and UC patients.METHODSThe questionnaire was developed by Philip Morris Products SA in cooperationwith European Federation of Crohn's and Ulcerative Colitis Associations. Thefinal survey questionnaire consisted of 41 questions divided in 8 categories: (1)Subject screener;(2) Smoking history;(3) Background information;(4) IBD diseasebackground;(5) Current disease status;(6) Current therapeutics and medications;and (7) Current nicotine/cigarettes use and awareness of the impacts of smokingon IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative ColitisAssociations website to IBD patients who were current smokers or had a historyof smoking.RESULTSIn total 1050 IBD patients speaking nine languages participated to the survey.Among them, 807 (76.9%) patients declared to have ever smoked or consumed analternative smoking product, with a higher proportion of current cigarettesmokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About twothirdsof the participants declared to have ever stopped cigarette smoking andrestarted (67.0%), with a significantly higher proportion among UC patientscompared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significantdifferences between CD and UC patients in the awareness of the healthconsequences of smoking in their disease and in the perceived impact of smokingon disease activity, for both cigarettes and alternative smoking products.CONCLUSIONThis survey found significant differences between CD and UC patients in bothawareness and perception of the impact of smoking on their disease. Furtherefforts should be done to encourage smoking cessation for all IBD patients,including UC patients.

Disease clearance in ulcerative colitis:A new therapeutic target for the future

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and progression.This has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic armamentarium.Subsequently,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal healing.While the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic measures.Current recommendations lack consideration of histological healing.The simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully investigated.This has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

Evaluation of inflammatory activity in Crohn's disease and ulcerative colitis

Crohn's disease and ulcerative colitis evolve with a relapsing and remitting course.Determination of inflammatory state is crucial for the assessment of disease activity and for tailoring therapy.However,no simple diagnostic test for monitoring intestinal inflammation is available.Noninvasive markers give only indirect assessments of disease activity.Histopathological or endoscopical examinations accurately assess inflammatory activity,but they are invasive,time consuming and expensive and therefore are unsuitable for routine use.Imaging procedures are not applicable for ulcerative colitis.The usefulness of ultrasound and Doppler imag-ing in assessing disease activity is still a matter of discussion for Crohn's disease,and an increased interest in computed tomography enterograph (CTE) has been seen,mainly because it can delineate the extent and severity of bowel wall inflammation,besides detecting extraluminal findings.Until now,the available data concerning the accuracy of magnetic resonance enterography in detecting disease activity is less than CTE.Due to this,clinical activity indices are still commonly used for both diseases.

Systemic interleukin-9 in inflammatory bowel disease: Association with mucosal healing in ulcerative colitis

To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP® technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.

Clinical value of the Toronto inflammatory bowel disease global endoscopic reporting score in ulcerative colitis

BACKGROUND Endoscopic evaluation in diagnosing and managing ulcerative colitis(UC)is becoming increasingly important.Several endoscopic scoring systems have been established,including the Ulcerative Colitis Endoscopic Index of Severity(UCEIS)score and Mayo Endoscopic Subscore(MES).Furthermore,the Toronto Inflammatory Bowel Disease Global Endoscopic Reporting(TIGER)score for UC has recently been proposed;however,its clinical value remains unclear.AIM To investigate the clinical value of the TIGER score in UC by comparing it with the UCEIS score and MES.METHODS This retrospective study included 166 patients with UC who underwent total colonoscopy between January 2017 and March 2023 at the Affiliated Hospital of Qingdao University(Qingdao,China).We retrospectively analysed endoscopic scores,laboratory and clinical data,treatment,and readmissions within 1 year.Spearman’s rank correlation coefficient,receiver operating characteristic curve,and univariate and multivariable logistic regression analyses were performed using IBM SPSS Statistics for Windows,version 26.0(IBM Corp.,Armonk,NY,United States)and GraphPad Prism version 9.0.0 for Windows(GraphPad Software,Boston,Massachusetts,United States).RESULTS The TIGER score significantly correlated with the UCEIS score and MES(r=0.721,0.626,both P<0.001),showed good differentiating values for clinical severity among mild,moderate,and severe UC[8(4-112.75)vs 210(109–219)vs 328(219–426),all P<0.001],and exhibited predictive value in diagnosing patients with severe UC[area under the curve(AUC)=0.897,P<0.001].Additionally,the TIGER(r=0.639,0,551,0.488,0.376,all P<0.001)and UCEIS scores(r=0.622,0,540,0.494,and 0.375,all P<0.001)showed stronger correlations with laboratory and clinical parameters,including C-reactive protein,erythrocyte sedimentation rate,length of hospitalisation,and hospitalisation costs,than MES(r=0.509,0,351,0.339,and 0.270,all P<0.001).The TIGER score showed the best predictability for patients'recent advanced treatment,including systemic corticosteroids,biologics,or immunomodulators(AUC=0.848,P<0.001)and 1-year readmission(AUC=0.700,P<0.001)compared with the UCEIS score(AUC=0.762,P<0.001;0.627,P<0.05)and MES(AUC=0.684,P<0.001;0.578,P=0.132).Furthermore,a TIGER score of≥317 was identified as an independent risk factor for advanced UC treatment(P=0.011).CONCLUSION The TIGER score may be superior to the UCIES score and MES in improving the accuracy of clinical disease severity assessment,guiding therapeutic decision-making,and predicting short-term prognosis.

Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease

In 2018,the pan-Janus kinase(JAK)inhibitor tofacitinib was launched for the treatment of ulcerative colitis(UC).Although tofacitinib has proven efficacious in patients with active UC,it failed in patients with Crohn’s disease(CD).This finding strongly hints at a different contribution of JAK signaling in both entities.Here,we review the current knowledge on the interplay between the JAK/signal transducer and activator of transcription(STAT)pathway and inflammatory bowel diseases(IBD).In particular,we provide a detailed overview of the differences and similarities of JAK/STAT-signaling in UC and CD,highlight the impact of the JAK/STAT pathway in experimental colitis models and summarize the published evidence on JAK/STAT-signaling in immune cells of IBD as well as the genetic association between the JAK/STAT pathway and IBD.Finally,we describe novel treatment strategies targeting JAK/STAT inhibition in UC and CD and comment on the limitations and challenges of the new drug class.

Identification of pathologic features associated with “ulcerative colitis-like” Crohn's disease

AIM: To identify pathologic features associated with this &#x0201c;ulcerative colitis (UC)-like&#x0201d; subgroup of Crohn&#x02019;s disease (CD).

MicroRNAs expression influence in ulcerative colitis and Crohn's disease:A pilot study for the identification of diagnostic biomarkers

BACKGROUND Inflammatory bowel disease(IBD)comprises two distinct diseases,Crohn’s disease(CD)and ulcerative colitis(UC),both of which are chronic,relapsing inflammatory disorders of the gastrointestinal tract with a mostly unknown etiology.The incidence and prevalence of IBD are continually increasing,indicating the need for further studies to investigate the genetic determinants of these diseases.Since microRNAs(miRNAs)regulate protein translation via complementary binding to mRNA,discovering differentially expressed miRNAs(DE)in UC or CD patients could be important for diagnostic biomarker identification,assisting in the appropriate disease differentiation progressing the understanding of IBD pathogenesis.AIM To determine the miRNA expression profile in UC and CD patients and the potential pathophysiological contributions of differentially expressed miRNA.METHODS A total of 20 formalin-fixed paraffin-embedded colonic samples were collected from the Pathology Department of Botucatu Medical School at São Paulo State University(Unesp).The diagnosis of UC or CD was based on clinical,endoscopic,radiologic,and histological criteria and confirmed by histopathological analysis at the time of selection.The TaqMan™Array Human MicroRNA A+B Cards Set v3.0(Applied Biosystems™)platform was used to analyze 754 miRNAs.Targets of DE-miRNAs were predicted using miRNA Data Integration Portal(mirDIP)and the miRNA Target Interaction database(MiRTarBase).All statistical analyses were conducted using GraphPad Prism software.Parametric and nonparametric data were analyzed using t-tests and Mann-Whitney U tests,respectively.RESULTS The results showed that of the 754 miRNAs that were initially evaluated,643 miRNAs were found to be expressed in at least five of the patients who were diagnosed with either CD or UC;the remaining 111 miRNAs were not considered to be expressed in these patients.The expression levels of 28 miRNAs were significantly different between the CD and UC patients(P≤0.05);13 miRNAs demonstrated a fold-change in expression level greater than 1.Five miRNAs with a downregulated expression were selected for enrichment analysis.The miRNAs whose expression levels were significantly lower in UC patients than in CD patients were enriched in certain signaling pathways that were mostly correlated with cancer-related processes and respective biomarkers.CONCLUSION MiRNAs could be used to differentiate UC from CD,and differently expressed miRNAs could help explain the distinct pathophysiology of each disease.

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples

AIM： The goal of the current work was to analyse the prevalence of the ＋49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene （CTLA4） in Hungarian patients with Crohn＇s disease （CD） and ulcerative colitis （UC）. METHODS： A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism （SNP）. The genotypes were determined by using PCR/RFLP test. RESULTS： The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION： The results of the current study show that carriage of the ＋49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn's disease?

It has been a big puzzle as why the inflammation of ulcerative colitis (UC) is limited to the mucosa, while in Crohn's disease (CD) the inflammation is transmural and can be seen in all layers of the gut. Here, I give a tentative explanation extended from the unified hypothesis I proposed on the etiology of inflammatory bowel disease. This hypothesis suggested that both UC and CD are caused by weakening of the gut barrier due to damage of the protective mucus layer and the underlying tissue by the poorly inactivated digestive proteases resulting from a reduction of gut bacteria by dietary chemicals like saccharin and sucralose. However, the large amounts of bacteria in the colon make the recruitment of neutrophils and formation of crypt abscess the main manifestation of UC, while the infiltration of antigens and dietary particles in the small and large intestine mainly cause the recruitment of macrophages and formation of granulomas as the main manifestations in CD. The fast reacting and short life span of neutrophils make the fight and damage limited to the surface of the mucosa. In contrast, the long life span and constant movement of macrophages may bring the harmful agents deep into the tissue. Therefore, the pathogenesis of UC may be more like bacterial pneumonia, while CD may be more like pneumoconiosis or tuberculosis of the lung.

Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

BACKGROUND The healthcare burden of inflammatory bowel disease(IBD)is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis.AIM To understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODS We performed serological profiling of 100 Crohn’s disease(CD)patients,100 ulcerative colitis(UC)patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays.The study subjects were randomly divided into discovery(n=150)and validation(n=150)sets.Statistical analysis was performed using R packages.RESULTS Anti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses.We identified novel antibodies against the antigens of Bacteroidetes vulgatus(BVU_0562)and Streptococcus pneumoniae(SP_1992)showing higher prevalence in CD patients relative to healthy controls.We also identified antibodies against the antigen of Streptococcus pyogenes(SPy_2009)showing higher prevalence in healthy controls relative to UC patients.Using these novel antibodies,we built biomarker panels with area under the curve(AUC)of 0.81,0.87,and 0.82 distinguishing CD vs control,UC vs control,and CD vs UC,respectively.Subgroup analysis revealed that penetrating CD behavior,colonic CD location,CD patients with a history of surgery,and extensive UC exhibited highest antibody prevalence among all patients.We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSION We have identified antibody signatures for CD and UC using a comprehensive analysis of antimicrobial antibody response in IBD.These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and,after future validation,should aid early and accurate diagnosis of IBD.

Use of blood based biomarkers in the evaluation of Crohn's disease and ulcerative colitis

Despite significant improvements in our understanding of Crohn's disease(CD) and ulcerative colitis(UC) in recent years, questions remain regarding the best approaches to assessment and management of these chronic diseases during periods of both relapse and remission. Various serologic biomarkers have been used in the evaluation of patients with both suspected and documented inflammatory bowel disease(IBD), and while each has potential utility in the assessment of patients with IBD, potential limitation remain with each method of assessment. Given these potential shortcomings, there has been increased interest in other means of evaluation of patients with IBD, including an expanding interest in the role of gene expression profiling. Among patients with IBD, gene expression profiles obtained from whole blood have been used to differentiate active from inactive CD, as well as to differentiate between CD, UC, and non-inflammatory diarrheal conditions. There are many opportunities for a non-invasive, blood based test to aid in the assessment of patients with IBD, particularly when considering more invasive means of evaluation including endoscopy with biopsy. Furthermore, as the emphasis on personalized medicine continues to increase, the potential ability of gene expression analysis to predict patient response to individual therapies offers great promise. While whole blood gene expression analysis may not completely replace more traditional means of evaluating patients with suspected or known IBD, it does offer significant potential to expand our knowledge of the underlying genes involved in the development of these diseases.

Increasing thirty-day readmissions of Crohn’s disease and ulcerative colitis in the United States:A national dilemma

BACKGROUND The prevalence of Crohn’s disease(CD)and ulcerative colitis(UC)is on the rise worldwide.This rising prevalence is concerning as patients with CD and UC may frequently relapse leading to recurrent hospitalizations and increased healthcare utilization.AIM To identify trends and adverse outcomes for 30 d readmissions for CD and UC.METHODS This was a retrospective,interrupted trends study involving all adult(≥18 years)30 d readmissions of CD and UC from the National Readmission Database(NRD)between 2008 and 2018.Patients<18 years,elective,and traumatic hospitalizations were excluded from this study.We identified hospitalization characteristics and readmission rates for each calendar year.Trends of inpatient mortality,mean length of hospital stay(LOS)and mean total hospital cost(THC)were calculated using a multivariate logistic trend analysis adjusting for age,gender,insurance status,comorbidity burden and hospital factors.Furthermore,trends between CD and UC readmissions were compared using regression of the interaction coefficient after adjusting for age and gender to determine relative trends between the two populations.Stata®Version 16 software(StataCorp,TX,United States)was used for statistical analysis and P value≤0.05 were considered statistically significant.RESULTS Total number of 30 d readmissions increased from 6202 in 2010 to 7672 in 2018 for CD and from 3272 in 2010 to 4234 in 2018 for UC.We noted increasing trends for 30-day all-cause readmission rate of CD from 14.9%in 2010 to 17.6%in 2018(P-trend<0.001),CD specific readmission rate from 7.1%in 2010 to 8.2%in 2018(P-trend<0.001),30-day all-cause readmission rate of UC from 14.1%in 2010 to 15.7%in 2018(P-trend=0.003),and UC specific readmission rate from 5.2%in 2010 to 5.6%in 2018(P-trend=0.029).There was no change in the risk adjusted trends of inpatient mortality and mean LOS for CD and UC readmissions.However,we found an increasing trend of mean THC for UC readmissions.After comparison,there was no statistical difference in the trends for 30 d all-cause readmission rate,inpatient mortality,and mean LOS between CD and UC readmissions.CONCLUSION There was an increase in total number of 30 d readmissions for CD and UC with a trend towards increasing 30 d all-cause readmission rates.

Diagnostic delay in inflammatory bowel diseases in a German population

BACKGROUND Early diagnosis is key to prevent bowel damage in inflammatory bowel disease(IBD).Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists.AIM To identify risk factors leading to prolonged diagnostic time in a German IBD cohort.METHODS Between 2012 and 2022,430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis.Total diagnostic time was defined as the time from symptom onset to consulting a physician(patient waiting time)and from first consultation to IBD diagnosis(physician diagnostic time).Univariate and multivariate analyses were performed to identify risk factors for each time period.RESULTS The total diagnostic time was significantly longer in Crohn’s disease(CD)compared to ulcerative colitis(UC)patients(12.0 vs 4.0 mo;P<0.001),mainly due to increased physician diagnostic time(5.5 vs 1.0 mo;P<0.001).In a multivariate analysis,the predominant symptoms diarrhea(P=0.012)and skin lesions(P=0.028)as well as performed gastroscopy(P=0.042)were associated with longer physician diagnostic time in CD patients.In UC,fever was correlated(P=0.020)with shorter physician diagnostic time,while fatigue(P=0.011)and positive family history(P=0.046)were correlated with longer physician diagnostic time.CONCLUSION We demonstrated that CD patients compared to UC are at risk of long diagnostic delay.Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic disrupted healthcare in the United States.AIM To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease(IBD)decedents.METHODS We performed a register-based study using data from the National Vital Statistics System,which reports death data from over 99%of the United States population,from January 1,2006 through December 31,2021.IBD-related deaths among adults 25 years and older were stratified by age,sex,race/ethnicity,place of death,and primary cause of death.Predicted and actual age-standardized mortality rates(ASMRs)per 100000 persons were compared.RESULTS 49782 IBD-related deaths occurred during the study period.Non-COVID-19-related deaths increased by 13.14%in 2020 and 18.12%in 2021[2020 ASMR:1.55 actual vs 1.37 predicted,95%confidence interval(CI):1.26-1.49;2021 ASMR:1.63 actual vs 1.38 predicted,95%CI:1.26-1.49].In 2020,non-COVID-19-related mortality increased by 17.65%in ulcerative colitis(UC)patients between the ages of 25 and 65 and 36.36%in non-Hispanic black(NHB)Crohn’s disease(CD)patients.During the pandemic,deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased.CONCLUSION IBD patients suffered excess non-COVID-19-related death during the pandemic.Excess death was associated with younger age among UC patients,and with NHB race among CD patients.Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the East.The epidemiology of IBD in Asia differs significantly from the patterns in the West.AIM To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and outcomes.METHODS We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South Korea.Patients with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to 2018.RESULTS In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and 2018.The annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) person-years.Since 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in 2018.The CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and UC.The clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study period.CONCLUSION The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and 2018.IBD clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

More on the interplay between gut microbiota,autophagy,and inflammatory bowel disease is needed

The concept of inflammatory bowel disease(IBD),which encompasses Crohn’s disease and ulcerative colitis,represents a complex and growing global health concern resulting from a multifactorial etiology.Both dysfunctional autophagy and dysbiosis contribute to IBD,with their combined effects exacerbating the related inflammatory condition.As a result,the existing interconnection between gut microbiota,autophagy,and the host’s immune system is a decisive factor in the occurrence of IBD.The factors that influence the gut microbiota and their impact are another important point in this regard.Based on this initial perspective,this manuscript briefly highlighted the intricate interplay between the gut microbiota,autophagy,and IBD pathogenesis.In addition,it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context.Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms,which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.