Bridging the gap:Unveiling the crisis of physical inactivity in inflammatory bowel diseases

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.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

AIM To perform a systematic review and meta-analysis on proton pump inhibitors(PPIs) therapy and the risk of Clostridium difficile infection(CDI). METHODS We conducted a systematic search of MEDLINE/Pub Med and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios(ORs) estimates with 95% confidence intervals(CIs) were calculated using the random effect. Heterogeneity was assessed by I^2 test and Cochran's Q statistic.Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale(NOS). RESULTS Fifty-six studies(40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI(pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control(OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort(OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted(OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted(OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter(OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter(OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years(OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years(OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses(test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies(I^2 = 85.4%, P < 0.001) as well as evidence of publication bias(funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Update on adrenal insufficiency in patients with liver cirrhosis

Liver cirrhosis is a major cause of mortality worldwide,often with severe sepsis as the terminal event.Over the last two decades,several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation,and that the treatment with corticosteroids decreases mortality in such patients.Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure,decreased peripheral vascular resistance,increased cardiac output,hypo-responsiveness to vasopressors,increased levels of proinflammatory cytokines [interleukine(IL)-1,IL-6,tumor necrosis factor-alpha] and it has,consequently,been reported that adrenal insufficiency(AI) is common in critically ill cirrhotic patients.AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation.The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications,and it suggests that it could be a feature of liver disease per se,with a dif-ferent pathogenesis from that of septic shock.Relative AI is the term given to inadequate cortisol response to stress.More recently,another term is used,namely "critical illness related corticosteroid insufficiency" to define "an inadequate cellular corticosteroid activity for the severity of the patient's illness".The mechanisms of AI in liver cirrhosis are not completely understood,although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested.The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease(compensated or decompensated,with or without sepsis),the diagnostic criteria defining AI and the methodology used.The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial.This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis.

Capsule endoscopy:the road ahead

Since its introduction into clinical practice 15 years ago,capsule endoscopy(CE)has become the first-line investigation procedure in some small bowel pathologies,and more recently,dedicated esophageal and colon CE have expanded the fields of application to include the upper and lower gastrointestinal disorders.During this time,CE has become increasingly popular among gastroenterologists,with more than 2 million capsule examinations performed worldwide,and nearly 3000Pub Med-listed studies on its different aspects published.This huge interest in CE may be explained by its noninvasive nature,patient comfort,safety,and access to anatomical regions unattainable via conventional endoscopy.However,CE has several limitations which impede its wider clinical applications,including the lack of therapeutic capabilities,inability to obtain biopsies and control its locomotion.Several research groups are currently working to overcome these limitations,while novel devices able to control capsule movement,obtain high quality images,insufflate the gut lumen,perform chromoendoscopy,biopsy of suspect lesions,or even deliver targeted drugs directly to specific sites are under development.Overlooking current limitations,especially as some of them have already been successfully surmounted,and based on the tremendous progress in technology,it is expected that,by the end of next 15years,CE able to perform both diagnostic and therapeutic procedures will remain the major form of digestive endoscopy.This review summarizes the literature that prognosticates about the future developments of CE.

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.

Impact of Clostridium difficile infection on inflammatory bowel disease outcome: A review

Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection (CDI) in inflammatory bowel disease (IBD), only few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn&#x02019;s disease. However, studies reported variable results in both short- and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some North-American and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients&#x02019; outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.

Portal vein thrombosis in cirrhotic patients-it is always the small pieces that make the big picture

Portal vein thrombosis(PVT) is a frequent and serious complication in patients with liver cirrhosis(LC). Recently, a new classification of PVT was proposed, although the functional component was not completed included. The status of liver disease(compensated/decompensated) should be added to this classification. Reduced portal flow velocity and the acquired hypercoagulable status associated with LC are the main risk factors for PVT development, although endothelial dysfunction may play an important role that needs to be further evaluated. The European Association for the Study of the Liver and the American Association for the Study of Liver Disease recommend that the anticoagulant treatment should be consider in cirrhotic patients with PVT. Low molecular weight heparin and vitamin K antagonists proved their efficacy and relatively safety in PVT treatment, although in addition to recanalization rates, more complex endpoints such as mortality and decompensation rate should be evaluated. The new oral anticoagulant therapies offers the advantage of oral administration in the absence of laboratory monitoring, however, there are a few reports regarding their use in cirrhotic patients, most of them referring to compensated isolated cases. Transjugular intrahepatic portosystemic shunt could be an alternative if thrombosis progresses despite anticoagulatant therapy and/or when PVT is associated with portal hypertension complications. The aim of this editorial is to discuss the different aspects of pathophysiology, clinical relevance, diagnosis and management of PVT in patients with LC.

FibroSURE^(TM) and FibroScan~ in relation to treatment response in chronic hepatitis C virus

AIM:To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus(HCV)cohort.METHODS:Patients with chronic HCV were randomized to receive interferon-based therapy for 24(genotypes 2/3)or 48(genotype 1)wk.FibroSURE～TM(FS)was assessed at baseline and at week-12 post-treatment follow-up.Baseline biopsy for METAVIR was assessed by a single pathologist.FibroScan～ transient elastogra-phy(TE)was performed during treatment in a patient subset.RESULTS:Two thousand and sixty patients(n = 253 in Asia)were classif ied as METAVIR F0-1(n = 1682)or F2-4(n = 378).For F2-4,FS(n = 2055)had sensitiv-ity and specif icity of 0.87 and 0.61,respectively,with area under the receiver-operating curve of 0.82;corre-sponding values for TE(n = 214)and combined FS/TE(n = 209)were 0.77,0.88 and 0.88,and 0.93,0.68 and 0.88.Overall FS/TE agreement for F2-4 was 71%(κ = 0.41)and higher in Asians vs non-Asians(κ = 0.86 vs 0.35;P < 0.001).Combined FS/TE had 97% accuracy in Asians(n = 33).Baseline FS(0.38 vs 0.51,P < 0.001)and TE(8.0 kPa vs 11.9 kPa,P = 0.006)scores were lower in patients with sustained virological response than in nonresponders,and were maintained through follow-up.CONCLUSION:FS and TE may reliably differentiate mild from moderate-advanced disease,with a potential for high diagnostic accuracy in Asians with chronic HCV.

Checkmate to liver biopsy in chronic hepatitis C?

Liver biopsy (LB) has traditionally been considered the gold standard for pretreatment evaluation of liver fibrosis in patients with chronic hepatitis C (CHC). However, LB is an invasive procedure with several shortcomings (intra-and interobserver variability of histopathological interpretation, sampling errors, high cost) and the risk of rare but potentially life-threatening complications. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Further-more, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of non-invasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. Despite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial improvement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.

Ulcerated intussuscepted jejunal lipoma-uncommon cause of obscure gastrointestinal bleeding: A case report

BACKGROUND Intestinal lipomas are rare benign gastrointestinal(GI)tumors,usually asymptomatic,but may become symptomatic as the result of some complications such as intussusception,intestinal obstruction,volvulus or bleeding.They can occur at any site along the entire GI tract,more frequent in colon and rarely in small intestine.The patient reported here is a very rare case of jejunal lipoma,ulcerated and intussuscepted,diagnosed in an adult investigated for a chronic iron deficiency anemia(IDA),and successfully managed by segmental jejunal resection.CASE SUMMARY A 63-year-old male was referred to“St.Spiridon”Hospital,Institute of Gastroenterology and Hepatology,Iasi,to investigate an obscure GI bleeding with an IDA.After upper GI endoscopy and colonoscopy were performed,excluding potentially bleeding lesions,videocapsule endoscopy was then carried out,revealing fresh blood and a protruding lesion in proximal jejunum,findings confirmed by a single-balloon enteroscopy.Multiple biopsies were taken from the lesion,but histological results were inconclusive.Then,contrast-enhanced computed tomography was performed showing jejunal polypoid mass with homogenous fat density,suggestive for lipoma.A week later a laparotomy was performed revealing the intussuscepted jejunal segment which was resected enbloc,and sent for further histopathologic analysis.The patient made an uneventful recovery and was discharged seven days later,and at six months follow-up he had no complains and his hemoglobin returned to normal value.CONCLUSION Lipomas are very rarely located in the jejunum,usually asymptomatic,but they may lead to complications such as intussusception and bleeding.Surgical resection remains the treatment of choice.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Role of ammonia in predicting the outcome of patients with acuteon- chronic liver failure

BACKGROUND High venous ammonia(VA)values have been proven to be a part of the mechanism of hepatic encephalopathy in patients with liver cirrhosis(LC)as well as acute hepatitis.Moreover,VA has been associated with poor prognosis and high mortality in these clinical settings.However,the role of ammonia in acuteon-chronic liver failure(ACLF)has not yet been clearly established.AIM To assess the role of VA in predicting the outcome of cirrhotic patients with ACLF in a tertiary care center.METHODS We performed a retrospective observational study including consecutive patients with LC hospitalized for acute non-elective indications such as ascites,hepatic encephalopathy(HE),upper gastrointestinal bleeding,or bacterial infections that fulfilled the Asian Pacific Association for the Study of the Liver(APASL)criteria for ACLF.The study was conducted in“St.Spiridon”University Hospital,Iasi,Romania,a tertiary care center,between January 2017 and January 2019.The APASL ACLF Research Consortium(AARC)score was calculated and ACLF grade was established accordingly.West-haven classification was used for HE.Statistical analysis was performed using IBM SPSS version 22.0.RESULTS Four hundred and forty-six patients were included,aged 59(50-65)years,57.4%men.Child-Pugh,model for end-stage liver disease(MELD)and AARC scores were 11(10-12),19.13±6.79,and 7(6-8),respectively.66.4%had ACLF grade I,31.2%ACLF grade II,and 2.5%ACLF grade III.HE was diagnosed in 83.9%,34%grade I,37.2%grade II,23.5%grade III,and 5.3%grade IV.Overall mortality was 7.8%.VA was 103(78-148)μmol/L.Receiver operating characteristic analysis showed good accuracy for the prediction of in-hospital mortality for the AARC score[Area under the curve(AUC)=0.886],MELD score(AUC=0.816),VA(AUC=0.812)and a fair accuracy for the Child-Pugh score(AUC=0.799).Subsequently,a cut-off value for the prediction of mortality was identified for VA(152.5μmol/L,sensitivity=0.706,1-specificity=0.190).Univariate analysis found acute kidney injury,severe HE(grade III or IV),VA≥152.5μmol/L,MELD score≥22.5,Child-Pugh score≥12.5,and AARC score≥8.5 to be associated with inhospital mortality.Multivariate analysis identified AARC score≥8.5 and venous ammonia≥152μmol/L to be independent predictors of in-hospital mortality.CONCLUSION VA could be used as an inexpensive predictor of in-hospital mortality in patients with ACLF.Patients with both ACLF and VA>152.5μmol/L have a high risk for a poor outcome.

Did the severe acute respiratory syndrome-coronavirus 2 pandemic cause an endemic Clostridium difficile infection?

BACKGROUND Clostridium difficile infection(CDI)has increased in prevalence during the last years.The coronavirus disease 2019(COVID-19)pandemic has negatively influenced patient outcomes.The majority of the severe acute respiratory syndrome-coronavirus 2(SARS-CoV-2)-infected patients received antibiotics during hospitalization.AIM To analyze the factors that influenced CDI development after SARS-CoV-2 infection.METHODS Between March 2020 to December 2020,we performed a prospective observational study including 447 patients diagnosed with CDI who were admitted to our tertiary referral university hospital.The diagnosis of CDI was based on the presence of diarrhea(≥3 watery stools within 24 h)associated with Clostridium difficile toxins A or B.We excluded patients with other etiology of acute diarrhea.RESULTS Among the total 447(12.5%)patients with CDI,most were male(54.3%)and mean age was 59.7±10.8 years.Seventy-six(17.0%)had history of COVID-19,most being elderly(COVID-19:62.6±14.6 years vs non-COVID-19:56.8±17.6 years,P=0.007),with history of alcohol consumption(43.4%vs 29.4%,P=0.017),previous hospitalizations(81.6%vs 54.9%,P<0.001)and antibiotic treatments(60.5%vs 35.5%,P<0.001),requiring higher doses of vancomycin and prone to recurrent disease(25.0%vs 13.1%,P=0.011).Age over 60 years[odds ratio(OR):2.591,95%confidence interval(CI):1.452-4.624,P=0.001],urban residence(OR:2.330,95%CI:1.286-4.221,P=0.005),previous antibiotic treatments(OR:1.909,95%CI:1.083-3.365,P=0.025),previous hospitalizations(OR:2.509,95%CI:1.263-4.986,P=0.009)and alcohol consumption(OR:2.550,95%CI:1.459-4.459,P=0.001)were risk factors of CDI in COVID-19.CONCLUSION CDI risk is unrelated to history of SARS-CoV-2 infection.However,previous COVID-19 may necessitate higher doses of vancomycin for CDI.