Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

The many faces of Crohn’s Disease: Latest concepts in etiology

The notion that Crohn’s Disease (CD) occurs as a result of an aberrant reaction to the commensal microbiota in genetically susceptible hosts is widely regarded by physicians and scientists as fact. Yet although it is undisputed that Crohn’s Disease is immune-mediated, an aberrant reaction to one’s own native flora is far from proven. The aim of the current review is to present a summary of the known infectious causes of Crohn’s Disease, whilst highlighting the limitations of using outdated methods to attempt to classify the disease as a single entity. We propose a re-classification of Crohn’s Disease, and suggest that the disease is best conceptualized as a syndrome, an “umbrella-like” term comprising a group of diseases with varying infective etiologies, which clinically, endoscopically and histologically are indistinguishable from CD.

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.

Predicting short-term major postoperative complications in intestinal resection for Crohn’s disease:A machine learning-based study

BACKGROUND Due to the complexity and numerous comorbidities associated with Crohn’s disease(CD),the incidence of postoperative complications is high,significantly impacting the recovery and prognosis of patients.Consequently,additional stu-dies are required to precisely predict short-term major complications following intestinal resection(IR),aiding surgical decision-making and optimizing patient care.AIM To construct novel models based on machine learning(ML)to predict short-term major postoperative complications in patients with CD following IR.METHODS A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022.The study participants were randomly allocated to either a training cohort or a validation cohort.The logistic regression and random forest(RF)were applied to construct models in the training cohort,with model discrimination evaluated using the area under the curves(AUC).The validation cohort assessed the performance of the constructed models.RESULTS Out of the 259 patients encompassed in the study,5.0%encountered major postoperative complications(Clavien-Dindo≥III)within 30 d following IR for CD.The AUC for the logistic model was 0.916,significantly lower than the AUC of 0.965 for the RF model.The logistic model incorporated a preoperative CD activity index(CDAI)of≥220,a diminished preoperative serum albumin level,conversion to laparotomy surgery,and an extended operation time.A nomogram for the logistic model was plotted.Except for the surgical approach,the other three variables ranked among the top four important variables in the novel ML model.CONCLUSION Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complic-ations in patients with CD,with the RF model showing more superiority.A preoperative CDAI of≥220,a di-minished preoperative serum albumin level,and an extended operation time might be the most crucial variables.The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.

Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and fibrosis.AIM To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in CD.METHODS Intestinal tissue and MAT were collected from 12 patients with CD.Histological manifestations and protein expression levels were analyzed to determine lesion characteristics.Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice.The intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.RESULTS Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota structure.Fetal microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD symptoms.Notably,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and adipokines.Furthermore,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.CONCLUSION Gut microbiota play a critical role in the histopathology of CD.Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

Differential diagnosis of Crohn’s disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning

BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

Etiology of inflammatory bowel disease:A unified hypothesis

Inflammatory bowel disease(IBD),including both ulcerative colitis(UC) and Crohn's disease(CD),emerged and dramatically increased for about a century.Despite extensive research,its cause remains regarded as unknown.About a decade ago,a series of findings made me suspect that saccharin may be a key causative factor for IBD,through its inhibition on gut bacteria and the resultant impaired inactivation of digestive proteases and over digestion of the mucus layer and gut barrier(the Bacteria-Protease-Mucus-Barrier hypothesis).It explained many puzzles in IBD such as its emergence and temporal changes in last century.Recently I further found evidence suggesting sucralose may be also linked to IBD through a similar mechanism as saccharin and have contributed to the recent worldwide increase of IBD.This new hypothesis suggests that UC and CD are just two symptoms of the same morbidity,rather than two different diseases.They are both caused by a weakening in gut barrier and only differ in that UC is mainly due to increased infiltration of gut bacteria and the resultant recruitment of neutrophils and formation of crypt abscess,while CD is mainly due to increased infiltration of antigens and particles from gut lumen and the resultant recruitment of macrophages and formation of granulomas.It explained the delayed appearance but accelerated increase of CD over UC and many other phenomena.This paper aims to provide a detailed description of a unified hypothesis regardingthe etiology of IBD,including the cause and mechanism of IBD,as well as the relationship between UC and CD.

Duodenal Crohn’s disease:Case report and systematic review

BACKGROUND Inflammatory bowel disease,including ulcerative colitis,microscopic colitis,and Crohn’s disease(CD),has a global impact.This review focuses on duodenal CD(DCD),a rare subtype affecting the duodenum.DCD’s rarity and asymptomatic nature create diagnostic challenges,impacting prognosis and patient well-being.Delayed diagnosis can worsen DCD outcomes.AIM To report a rare case of DCD and to discuss the diagnostic challenges and its implications on prognosis.METHODS A systematic literature search,following the PRISMA statement,was conducted.Relevant studies were identified and analysed using specific Medical Subject Terms(MeSH)from PubMed/MEDLINE,American Journal of Gastroenterology,and the University of South Wales database.Data collection included information from radiology scans,endoscopy procedures,biopsies,and histopathology results.RESULTS The review considered 8 case reports and 1 observational study,involving 44 participants diagnosed with DCD,some of whom developed complications due to delayed diagnosis.Various diagnostic methods were employed,as there is no gold standard workup for DCD.Radiology scans[magnetic resonance imaging(MRI),computed tomography(CT),and upper gastrointestinal X-ray],endoscopy procedures(colonoscopy and esophagogastroduodenoscopy),biopsies,and clinical suspicions were utilized.CONCLUSION This review discusses DCD diagnosis challenges and the roles of CT,MRI,and fluoroscopy.It notes their limitations and compares findings with endoscopy and histopathology studies.Further research is needed to improve diagnosis,emphasizing scan interpretation,endoscopy procedures,and biopsies,especially in high-risk patients during routine endoscopy.

Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

Inflammatory bowel disease is a chronic,debilitating disorder of the gastrointestinal tract.The etiology of inflammatory bowel disease has not been elucidated,but is thought to be multifactorial with both environmental and genetic influences.A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease.This article reviews this literature,emphasizing the studies of breastfeeding and the studies of genetic factors,particularly NOD2 polymorphisms.

Perianal Crohn’s disease:Still more questions than answers

In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of Gastroenterology.We focus specifically on the burden of illness associated with perianal fistulizing Crohn’s disease(PFCD)and the diagnostic and therapeutic challenges in the management of this condition.Evol-ving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems,to one that is more nuanced and patient-focused to drive ongoing decision making.This editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.

Two-sample Mendelian randomization analysis of causal relationship between eczema and autoimmune diseases

Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.

Physician-dependent diagnosis delay in Crohn's disease:A pseudoproposition or not?

The challenge of diagnosis delay in inflammatory bowel disease(IBD)has emerged as a significant concern for both patients and healthcare professionals.The widely accepted notion that there is an extended time frame from the onset of symptoms to the definitive diagnosis is often attributed to the heterogeneity of IBD and the non-specificity of clinical manifestations.Specific to patients with Crohn’s disease,the issue of delayed diagnosis appears to be more pronounced across different regions globally.The intricate interplay of real-world factors has led to debates regarding the primary contributors to these diagnostic delays.Drawing a comparison solely between patients and physicians and implicating the latter as the predominant influence factor may fall into a simplistic either-or logical trap that may obscure the truth.This letter,grounded in published evidence,explores areas for improvement in a forthcoming paper within the field,hoping to pinpoint the culprit behind the diagnosis delay issue for IBD patients rather than simply attributing it to so-called“physician-dependent factors”.Our objective is to motivate healthcare providers and policymakers in relevant fields to reflect on strategies for addressing this problem to reduce diagnostic delays and enhance patient outcomes.

Navigating the complexities of perianal Crohn’s disease:Diagnostic strategies,treatment approaches,and future perspectives

This article discusses the literature review article by Pacheco et al published in July 2024;the authors provided good reviews of perianal Crohn’s disease(CD),and challenges faced by clinicians in the management.CD,characterized by its chronic and relapsing nature,is an idiopathic condition that can involve any segment of the gastrointestinal tract.Perianal disease impacts up to 40%of patients with CD,with perianal fistulas constituting up to 80%of perianal lesions.Perianal CD can be highly incapacitating and profoundly diminish the overall well-being of patients.The management focuses on controlling the perianal sepsis and treating luminal CD.Biologics are crucial to the treatment approach,and results have been encouraging.The surgery focuses on controlling the sepsis,with more definitive treatments being fistula surgery,fecal diversion,and proctectomy as the last resort.This manuscript briefly describes the burden of CD,the challenges posed by perianal CD,and the role of different treatment modalities from colorectal surgeon’s perspective.

Pediatric stricturing Crohn's disease

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Washed microbiota transplantation for Crohn’s disease:A metagenomic,metatranscriptomic,and metabolomic-based study

BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical phenomena.However,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been reported.AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.METHODS We conducted a prospective,open-label,single-center clinical study.Eleven CD patients underwent WMT.Their clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the procedure.RESULTS Seven of the 11 patients(63.6%)showed an optimal clinical response three months post-WMT.Gut microbiome diversity significantly increased after WMT,consistent with improved clinical symptoms.Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia coli.In addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors.However,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after WMT.CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s microbiome.Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.

Global geoepidemiology of gastrointestinal surgery rates in Crohn’s disease

BACKGROUND Data regarding the worldwide gastrointestinal surgery rates in patients with Crohn’s disease(CD)remains limited.AIM To systematically review the global variation in the rates of surgery in CD.METHODS A comprehensive search analysis was performed using multiple electronic databases from inception through July 1,2020,to identify all full text,randomized controlled trials and cohort studies pertaining to gastrointestinal surgery rates in adult patients with CD.Outcomes included continent based demographic data,CD surgery rates over time,as well as the geoepidemiologic variation in CD surgery rates.Statistical analyses were conducted using R.RESULTS Twenty-three studies spanning four continents were included.The median proportion of persons with CD who underwent gastrointestinal surgery in studies from North America,Europe,Asia,and Oceania were 30%(range:1.7%-62.0%),40%(range:0.6%-74.0%),17%(range:16.0%-43.0%),and 38%respectively.No clear association was found regarding the proportion of patients undergoing gastrointestinal surgery over time in North America(R^(2)=0.035)and Europe(R^(2)=0.100).A moderate,negative association was seen regarding the proportion of patients undergoing gastrointestinal surgery over time(R^(2)=0.520)in Asia.CONCLUSION There appears to be significant inter-continental variation regarding surgery rates in CD.Homogenous evidencebased guidelines accounting for the geographic differences in managing patients with CD is prudent.Moreover,as a paucity of data on surgery rates in CD exists outside the North American and European continents,future studies,particularly in less studied locales,are warranted.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.