Inflammatory Bowel Disease and Dementia:Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study

Objective Observational studies have found associations between inflammatory bowel disease(IBD)and the risk of dementia,including Alzheimer’s dementia(AD)and vascular dementia(VD);however,these findings are inconsistent.It remains unclear whether these associations are causal.Methods We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia.Mendelian randomization(MR)analysis based on summary genome-wide association studies(GWASs)was performed.Genetic correlation and Bayesian colocalization analyses were used to provide robust genetic evidence.Results Ten observational studies involving 80,565,688 participants were included in this metaanalysis.IBD was significantly associated with dementia(risk ratio[RR]=1.36,95%CI=1.04-1.78;I2=84.8%)and VD(RR=2.60,95%CI=1.18-5.70;only one study),but not with AD(RR=2.00,95%CI=0.96-4.13;I^(2)=99.8%).MR analyses did not supported significant causal associations of IBD with dementia(dementia:odds ratio[OR]=1.01,95%CI=0.98-1.03;AD:OR=0.98,95%CI=0.95-1.01;VD:OR=1.02,95%CI=0.97-1.07).In addition,genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.Conclusion Our study did not provide genetic evidence for a causal association between IBD and dementia risk.The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.

Therapeutic advances in non-alcoholic fatty liver disease:A microbiota-centered view

Non-alcoholic fatty liver disease(NAFLD)is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide,especially in the West.There are no drugs available at present to treat NAFLD,and the primary therapeutic options include weight loss and the combination of healthy diet and exercise.Therefore,novel interventions are required that can target the underlying risk factors.Gut microbiota is an“invisible organ”of the human body and vital for normal metabolism and immuno-modulation.The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus,and is most abundant in the intestine.Since dysregulated gut microbiota is an underlying pathological factor of NAFLD,it is a viable therapeutic target that can be modulated by antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation,and microbial metabolites.In this review,we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies,and critically evaluate novel targets and strategies for treating NAFLD.

Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases:Prospective multicenter study in Japan

AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy(SOCPS) using the Spy Glass system in widespread clinical application for biliary and pancreatic diseases.METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2%(135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5%(84/89) and 88.2%(15/17), respectively. Diagnosis: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS(bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7%(53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5%(14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2%(23/31) and 42.9%(3/7) of the patients, respectively. Others: SOCPS using the Spy Glass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4%(8/148). CONCLUSION: SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Quantitative assessment of self-management in patients with nonalcoholic fatty liver disease: An unmet clinical need

In this editorial we comment on the article titled“Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease”by Zeng et al published in a recent issue of the World Journal of Gastroenterology.Non-alcoholic fatty liver disease(NAFLD)represents one of the current challenges in hepatology and public health,due to its continuous growing prevalence and the rising incidence of NAFLD-related fibrosis,non-alcoholic steatohepatitis and cirrhosis.The only effective therapeutic strategy for this dis-ease is represented by encouraging patients to improve their lifestyle through the modification of dietary intake and increased physical exercise,but the effective application of such modifications is often limited by various factors such as lack of information,psychological barriers or poor social support.While poor adherence to a healthy lifestyle can be decisive in determining the clinical outcome,in daily practice there is a lack of quantitative instruments aimed at identifying patients with the lowest adherence to lifestyle changes and higher risk of disease progre-ssion in the course of follow-up.In this article,Zeng et al propose a quantitative scale to assess the grade of adherence of patients with NAFLD to hea-lthy lifestyle intervention,called the Exercise and Diet Adherence Scale(EDAS).This scale,consisting of 33 items divided into 6 dimensions which relates to six subjective aspects in the self-management of NAFLD,has shown a good correlation with the identification of the sub-cohort of patients with the highest reduction in caloric intake,increase in physical exercise,probability of a reduction in liver stiffness measurement and alanine aminotransferase levels.The cor-relation among clinical outcomes and specific dimensions of this scale also highlights the pivotal role of a good and confidential doctor-patient relationship and of an effective communication.There is an urgent need for practical and effective instruments to assess the grade of self-management of NAFLD patients,together with the development of multidisciplinary teams with the aim of applying structured behavioral interventions.

Efficacy and safety of rebamipide/nizatidine in patients with erosive gastritis: A randomized, multicenter, phase 4 study

BACKGROUND For the treatment of gastritis,rebamipide,a mucoprotective agent,and nizatidine,a gastric acid suppressant,are commonly employed individually.AIM To compare the efficacy of Mucotra®SR(rebamipide 150 mg)and Axid®(nizatidine 150 mg)combination therapy with the sole administration of Axid®in managing erosive gastritis.METHODS A total of 260 patients diagnosed with endoscopically confirmed erosive gastritis were enrolled in this open-label,multicenter,randomized,phase 4 clinical trial,allocating them into two groups:Rebamipide/nizatidine combination twice daily vs nizatidine twice daily for 2 weeks.The full-analysis set analysis encompassed 239 patients(rebamipide/nizatidine,n=121;nizatidine,n=118),while the per-protocol analysis included 218 patients(n=110 vs 108).Post-treatment assessments comprised primary(erosion improvement rate)and secondary(erosion and edema cure rates,erythema improvement rates,hemorrhage,and gastrointestinal symptoms)endpoints.Furthermore,drug-related adverse effects were evaluated.RESULTS Primary efficacy assessment showed a statistically significant improvement rate in mucosal erosions in the combination group compared to the control group in the full-analysis set(rebamipide/nizatidine 62.0%,nizatidine 49.2%,P=0.046),with a similar trend noted in the per-protocol analysis(62.7%vs 50.0%,P=0.058).Both groups were effective in curing erosion and edema and improvement of bleeding,erythema,and gastrointestinal symptoms,whereas no inter-group differences were noted.When confined to the participants with gastritis symptoms,improvement of erosion was more optimal in the combination group(63.0%vs 49.5%,P=0.046).No adverse events related to the drugs were observed.CONCLUSION Rebamipide/nizatidine combination is effective in treatment of erosive gastritis.

Acute abdominal pain complicated by cecal perforation caused by an unnoticed swallowed toothpick:A case report

BACKGROUND Acute abdominal pain is one of the most common gastrointestinal symptoms.The etiology of acute abdomen can be challenging for gastroenterologists to establish.Cecal foreign body is a rare cause of cecal perforation.CASE SUMMARY We report a 35-year-old male from China who initially exhibited symptoms suggestive of acute appendicitis.However,during a minimally invasive colonoscopy procedure,the authors found that a wooden toothpick caused the perforation.The patient presented to our emergency department with a 2 days history of right lower abdominal pain and low grade fever.The patient was in good health and had eaten fish 2 days earlier.Physical examination revealed mild pain with positive rebound tenderness in the right lower abdomen.However,computed tomography of the abdomen confirmed a strip of high-density shadows protruding beyond the intestinal cavity outline,with a small amount of peritoneal seepage in the ileocecal area.Combined with the medical history,the possibility of foreign body perforation by a fishbone and peripheral peritonitis were considered.However,the high-density shadow was identified as a wooden toothpick,which was removed via a minimally invasive procedure using a foreign body forceps under colonoscopy.The patient's condition improved significantly within 5 days after treatment.CONCLUSION We emphasize the importance of a detailed patient history,accurate diagnosis and proper treatment in patients with acute abdomen.

Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases

The introduction of biologics such as anti-tumor necrosis factor(TNF)monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases(IBD).Furthermore,a newly developed anti-p40 subunit of interleukin(IL)-12 and IL-23(ustekinumab)has been recently approved in the United States for patients with moderate to severe Crohn’s disease who have failed treatment with anti-TNFs.However,these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant percentage of patients.This strongly underlines the need to identify novel treatment targets beyond immune suppression to treat IBD.Recent studies have revealed the critical role of intestinal epithelial cells(IECs)in the pathogenesis of IBD.Physical,biochemical and immunologic driven barrier dysfunctions of epithelial cells contribute to the development of IBD.In addition,the recent establishment of adult stem cell-derived intestinal enteroid/organoid culture technology has allowed an exciting opportunity to study human IECs comprising all normal epithelial cells.This long-term epithelial culture model can be generated from endoscopic biopsies or surgical resections and recapitulates the tissue of origin,representing a promising platform for novel drug discovery in IBD.This review describes the advantages of intestinal enteroids/organoids as a research tool for intestinal diseases,introduces studies with these models in IBD,and gives a description of the current status of therapeutic approaches in IBD.Finally,we provide an overview of the current endeavors to identify a novel drug target for IBD therapy based on studies with human enteroids/organoids and describe the challenges in using enteroids/organoids as an IBD model.

Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

Recent advancement of therapeutic endoscopy in the esophageal benign diseases

Over the past 30 years, the field of endoscopy has witnessed several advances. With the advent of endoscopic mucosal resection, removal of large mucosal lesions have become possible. Thereafter, endoscopic submucosal resection was refined, permitting en bloc removal of large superficial neoplasms. Such techniques have facilitated the development of antireflux mucosectomy, a promising novel treatment for gastroesophageal reflux. The introduction and use of over the scope clips has allowed for endoscopic closure of defects in the gastrointestinal tract, which were traditionally treated with surgical intervention. With the development of per-oral endoscopic myotomy(POEM), the treatment of achalasia and spastic disorders of the esophagus have been revolutionized. From the submucosal tunnelling technique developed for POEM, Per oral endoscopic tumor resection of subepithelial tumors was made possible. Simultaneously, advances in biotechnology have expanded esophageal stenting capabilities with the introduction of fully covered metal and plastic stents, as well as biodegradable stents. Once deemed a primarily diagnostic tool, endoscopy has quickly transcended to a minimally invasive intervention and therapeutic tool. These techniques are reviewed with regards to their application to benign disease of the esophagus.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH).

The effect of NAFLD (non-alcoholic fatty liver disease) on long-term outcome of chronic hepatitis B in Iranian patients

Background: The influence of Non-Alcoholic Fatty Liver Disease on the outcome of chronic hepatitis B disease, including viral, biochemical and histologic characteristics, in Iranian patients is not yet fully un- derstood. Aim: To evaluate the effect of Non-Alcoholic Fatty Liver Disease (NAFLD) on long-term histology- cal, biochemical and viral outcome of chronic he- pa-tictis B in Iranian patients. Methods: We retro- spec-tively evaluated 94 “e Ag” negative chronic hepatitis B patients (with NAFLD: 44, without NAFLD: 50). Non-Alcoholic Fatty Liver Disease was diagnosed based on liver biopsy according to Kleiner classifica-tion. Liver biopsy was done for all patients. Serologi-cal and biochemical variables were evaluated with repeated measure analysis. Results: Non-Alcoholic Fat- ty Liver Disease (NAFLD) was present in 47% of the patients (44 out of 94 patients). In the NAFLD group, increase in AST, ALT, stage (P = 0.002), grade, and total score of liver biopsy were independently related to non-alcoholic fatty liver disease, while HBV-DNA viral load did not correlate with the presence of a fatty liver. Conclusion: Abnormalities of liver enzymes and liver histopathology are more prevalent in concurrent chronic hepatitis B and Non-Alcoholic Fatty Liver Disease (NAFLD).

Non-alcoholic fatty liver disease later diagnosed as myotonic dystrophy

BACKGROUND Myotonic dystrophy(MD)is sometimes accompanied by metabolic/endocrine disorders,including dyslipidemia,central obesity,and hypogonadism.Due to considerable individual differences in the severity and progression of myopathy,MD patients with minimal-to-mild muscle symptoms might be followed as having other diseases,such as non-alcoholic fatty liver disease(NAFLD).CASE SUMMARY A 40-year-old non-obese man without a history of regular ethanol consumption was referred to our hospital due to persistent liver dysfunction and hyperlipidemia.His body mass index was 23.4 kg/m2.Liver histology demonstrated macrovesicular steatosis,ballooned hepatocytes with eosinophilic inclusion bodies,and perisinusoidal fibrosis,leading to the diagnosis of nonalcoholic steatohepatitis(NASH).Although he had no discernable muscle pain or weakness,persistently high serum creatine kinase(CK)and myoglobin levels as well as the presence of frontal baldness,a hatched face,history of cataract surgery,and grip myotonia indicated the possibility of MD.Southern blotting of the patient’s DNA revealed the presence of CTG repeats,confirming the diagnosis.CONCLUSION When gastroenterologists encounter NAFLD/NASH patients,serum CK should be verified.If hyperCKemia,frontal baldness,a hatched face,history of cataract surgery,and grip myotonia are noted,the possibility of MD may be considered.

Case of Fitz-Hugh-Curtis syndrome in male without presentation of sexually transmitted disease

Fitz-Hugh-Curtis syndrome is a type of perihepatitis that causes liver capsular infection without infecting the hepatic parenchyma or pelvis. Fitz-Hugh-Curtis syndrome is known to occur commonly in women of childbearing age who do not use oral contraceptives and have sexual partners older than 25 years of age. However, the syndrome has been reported to occur rarely in males. The clinical symptoms are right upper quadrant pain and tenderness, and pleuritic right sided chest pain. The clinical presentation is similar in male and female. We experienced a case of Fitz-HughCurtis syndrome in a 60-year-old man with the chief complaint of right upper quadrant abdominal pain. Despite a previous history of gonorrhea, we have also described our experiences of improved symptoms and recovery with allopathic medicines and have thereby reported the present case with a literature review.

Short health scale: A valid measure of health-related quality of life in Korean-speaking patients with inflammatory bowel disease

AIM To evaluate the short health scale(SHS),a new,simple,four-part visual analogue scale questionnaire that is designed to assess the impact of inflammatory bowel disease(IBD)on health-related quality of life(HRQOL),in Korean-speaking patients with IBD.METHODS The SHS was completed by 256 patients with Crohn’s disease(CD)and ulcerative colitis(UC).Individual SHS items were correlated with inflammatory bowel disease questionnaire(IBDQ)dimensions and with disease activity to assess validity.Test-retest reliability,responsiveness and patient or disease characteristics with probable association with high SHS scores were analyzed.RESULTS Of 256 patients with IBD,139(54.3%)had UC and 117(45.7%)had CD.The correlation coefficients between SHS questions about"symptom burden","activities of daily living",and"disease-related worry"and their corresponding dimensions in the IBDQ ranged from0.62 to 0.71,compared with correlation coefficients ranging from-0.45 to-0.61 for their non-corresponding dimensions.There was a stepwise increase in SHS scores,with increasing disease activity in both CD and UC(all P values<0.001).Reliability was confirmed with test-retest correlations ranging from 0.68 to 0.90(all P values<0.001).Responsiveness was confirmed with the patients who remained in remission.Their SHS scores remained unchanged,except for the SHS dimension"disease-related worry".In the multivariate analysis,female sex was associated with worse"general well-being"(OR=2.28,95%CI:1.02-5.08)along with worse disease activity.CONCLUSION The SHS is a valid and reliable measure of HRQOL in Korean-speaking patients with IBD.

Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A large single center experience

BACKGROUND Establishing a diagnosis of pancreatic cystic lesions(PCLs)preoperatively still remains challenging.Recently,endoscopic ultrasound(EUS)-through-the-needle biopsy(EUS-TTNB)using microforceps in PCLs has been made available.AIM To assess the efficacy and safety of EUS-TTNB in the diagnosis of PCLs.METHODS We retrospectively collected data of patients with PCLs who underwent both EUS-fine-needle aspiration(FNA)for cytology and EUS-TTNB at our institution since 2016.EUS-FNA for cytology was followed by EUS-TTNB in the same session.Evaluation of the cyst location,primary diagnosis,adverse events,and comparison between the cytologic fluid analyses and histopathology was performed.Technical success of EUS-TTNB was defined as visible tissue present after biopsy.Clinical success was defined as the presence of a specimen adequate to make a histologic or cytologic diagnosis.RESULTS A total of 56 patients(mean age 66.9±11.7,53.6%females)with PCLs were enrolled over the study period.The mean cyst size was 28.8 mm(12-85 mm).The EUS-TTNB procedure was technically successful in all patients(100%).The clinical success rate using EUS-TTNB was much higher than standard EUS-FNA,respectively 80.4%(45/56)vs 25%(14/56).Adverse events occurred in 2 patients(3.6%)who developed mild pancreatitis that resolved with medical therapy.Using TTNB specimens,23 of 32 cases(71.9%)with intraductal papillary mucinous neoplasm were further differentiated into gastric type(19 patients)and pancreaticobiliary type(4 patients)based on immunochemical staining.CONCLUSION EUS-TTNB for PCLs was technically feasible and had a favorable safety profile.Furthermore,the diagnostic yield for PCLs was much higher with EUS-TTNB than standard EUS-FNA cytology and fluid carcinoembryonic antigen.EUSTTNB should be considered as an adjunct to EUS-FNA and cytologic analysis in the diagnosis and management of PCLs.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases:A current trend or an indispensable tool?

Contrast enhanced ultrasound(CEUS)has been widely implemented in clinical practice because of the enormous quantity of information it provides,along with its low cost,reproducibility,minimal invasiveness,and safety of the secondgeneration ultrasound contrast agents.To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour,quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years.The quantification of perfusion parameters[named as dynamic-CEUS(D-CEUS)]has several applications in gastrointestinal neoplastic and inflammatory disorders.However,the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS,which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases.In this article,we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases,with a special focus on liver,pancreas,and inflammatory bowel diseases.

Impact of COVID-19 in individuals with and without pre-existent digestive disorders with a particular focus on elderly patients

Coronavirus disease 2019(COVID-19)has several extrapulmonary symptoms.Gastrointestinal(GI)symptoms are among the most frequent clinical manifestations of COVID-19,with severe consequences reported in elderly patients.Furthermore,the impact of COVID-19 on patients with pre-existing digestive diseases still needs to be fully elucidated,particularly in the older population.This review aimed to investigate the impact of COVID-19 on the GI tract,liver,and pancreas in individuals with and without previous digestive diseases,with a particular focus on the elderly,highlighting the distinctive characteristics observed in this population.Finally,the effectiveness and adverse events of the anti-COVID-19 vaccination in patients with digestive disorders and the peculiarities found in the elderly are discussed.

Predictive proteomic biomarkers for inflammatory bowel disease-associated cancer:Where are we now in the era of the next generation proteomics?

Recent advances in genomic medicine have opened up the possibility of tailored medicine that may eventually replace traditional &#x0201c;one-size-fits all&#x0201d; approaches to the treatment of inflammatory bowel disease (IBD). In addition to exploring the interactions between hosts and microbes, referred to as the microbiome, a variety of strategies that can be tailored to an individual in the coming era of personalized medicine in the treatment of IBD are being investigated. These include prompt genomic screening of patients at risk of developing IBD, the utility of molecular discrimination of IBD subtypes among patients diagnosed with IBD, and the discovery of proteome biomarkers to diagnose or predict cancer risks. Host genetic factors influence the etiology of IBD, as do microbial ecosystems in the human bowel, which are not uniform, but instead represent many different microhabitats that can be influenced by diet and might affect processes essential to bowel metabolism. Further advances in basic research regarding intestinal inflammation may reveal new insights into the role of inflammatory mediators, referred to as the inflammasome, and the macromolecular complex of metabolites formed by intestinal bacteria. Collectively, knowledge of the inflammasome and metagenomics will lead to the development of biomarkers for IBD that target specific pathogenic mechanisms involved in the spontaneous progress of IBD. In this review article, our recent results regarding the discovery of potential proteomic biomarkers using a label-free quantification technique are introduced and on-going projects contributing to either the discrimination of IBD subtypes or to the prediction of cancer risks are accompanied by updated information from IBD biomarker research.

Heart failure as an adverse effect of infliximab for Crohn's disease: A case report and review of the literature

BACKGROUND Anti-tumor necrosis factor agents were the first biologic therapy approved for the management of Crohn's disease(CD).Heart failure(HF)is a rare but potential adverse effect of these medications.The objective of this report is to describe a patient with CD who developed HF after the use of infliximab.CASE SUMMARY A 50-year-old woman with a history of hypertension and diabetes presented with abdominal pain,diarrhea,and weight loss.Colonoscopy and enterotomography showed ulcerations,areas of stenosis and dilation in the terminal ileum,and thickening of the intestinal wall.The patient underwent ileocolectomy and the surgical specimen confirmed the diagnosis of stenosing CD.The patient started infliximab and azathioprine treatment to prevent post-surgical recurrence.At 6 mo after initiating infliximab therapy,the patient complained of dyspnea,orthopnea,and paroxysmal nocturnal dyspnea that gradually worsened.Echocardiography revealed biventricular dysfunction,moderate cardiac insufficiency,an ejection fraction of 36%,and moderate pericardial effusion,consistent with HF.The cardiac disease was considered an infliximab adverse effect and the drug was discontinued.The patient received treatment with diuretics for HF and showed improvement of symptoms and cardiac function.Currently,the patient is using anti-interleukin for CD and is asymptomatic.CONCLUSION This reported case supports the need to investigate risk factors for HF in inflammatory bowel disease patients and to consider the risk-benefit of introducing infliximab therapy in such patients presenting with HF risk factors.