A Combination of Microarray-Based Profiling and Biocomputational Analysis Identified miR331-3p and hsa-let-7d-5p as Potential Biomarkers of Ulcerative Colitis Progression to Colorectal Cancer.

Ulcerative colitis (UC), an inflammatory bowel disease (IBD), may increase the risk of colorectal cancer (CRC) by activating chronic proinflammatory pathways. The goal of this study was to find serum prediction biomarkers in UC to CRC development by combining low-density miRNA microarray and biocomputational approaches. The UC and CRC miRNA expression profiles were compared by low-density miRNA microarray, finding five upregulated miRNAs specific to UC progression to CRC (hsa-let-7d-5p, hsa-miR-16-5p, hsa-miR-145-5p, hsa-miR-223-5p, and hsa-miR-331-3p). The circRNA/miRNA/mRNA competitive endogenous RNA (ceRNA) network analysis showed that the candidate miRNAs were connected to well-known colitis-associated CRC ACVR2A, SOCS1, IGF2BP1, FAM126A, and CCDC85C mRNAs, and circ-SHPRH circRNA. SST and SCARA5 genes regulated by hsa-let-7d-5p, hsa-miR-145-5p, and hsa-miR-331-3p were linked to a poor survival prognosis in a CRC patient dataset from The Cancer Genome Atlas (TCGA). Lastly, our mRNA and miRNA candidates were validated by comparing their expression to differentially expressed mRNAs and miRNAs from colitis-associated CRC tissue databases. A high level of hsa-miR-331-3p and a parallel reduction in SOCS1 mRNA were found in tissue and serum. We propose hsa-miR-331-3p and possibly hsa-let-7d-5p as novel serum biomarkers for predicting UC progression to CRC. More clinical sample analysis is required for further validation.

Profiling the patient with inflammatory bowel disease in the relationship between physical activity and partner/social network status: A post hoc patient-tailored analysis of the "BE-FIT-IBD" study.

INTRODUCTION: Normal quality of life is an ultimate target in the therapeutic approach to inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC) in the context of which regular physical activity (PA) is often a chimeric parameter that is not standardized in terms of quality/quantity. The study aimed to profile a sample of IBD patients about the relationship between PA-partner status and social network support. PATIENTS AND METHODS: A post hoc analysis of the "BE-FIT-IBD" study was set up by stratifying the data of PA with that of partner status and the support that the patient's social network (i.e., relatives, friends) provided in inciting the patient to practice regular PA. RESULTS: In the 219 patients included, there was a greater tendency for patients with stable partners to view the risk of reactivation/worsening of IBD as a barrier to conducting regular PA (p<0.0001). Single patients considered PA more as a protective factor (p=0.045). Patients without a PA-supporting social network retained IBD-related treatment as a PA barrier (p=0.016) and PA as a risk for IBD complications (p=0.01), with less confidence that PA could improve the course of IBD (p<0.001). Rectal syndrome was an IBD-related barrier more represented in patients with PA-deterring social network (p<0.0001). CONCLUSIONS: These factors are potential targets for recovering the IBD patient's adherence to regular PA.

The urotensin-II receptor: A marker for staging and steroid outcome prediction in ulcerative colitis.

BACKGROUND: Urotensin-II receptor- (UTR) related pathway exerts a key-role in promoting inflammation. The aim was to assess the relationship between UTR expression and clinical, endoscopic and biochemical severity of ulcerative colitis (UC), exploring its predictivity of intravenous (iv) steroid administration therapeutic outcome. METHODS: One-hundred patients with first diagnosis of UC and 44 healthy subjects were enrolled. UTR expression was assessed by qPCR, Western Blot (WB) and immunohistochemistry (IHC). Clinical, endoscopic and histological activity of UC were evaluated by using Truelove and Witts (T&W) severity index, Mayo Endoscopic Score (MES), and Truelove and Richards Index (TRI). The partial and full Mayo scores (PMS and FMS) were assessed to stage the disease. RESULTS: The UTR expression, resulted higher in the lesioned mucosa of UC patients in comparison to healthy subjects (p < .0001 all). Direct relationship between UTR (mRNA and protein) expression and disease severity assessment (T&W, PMS, MES and TRI) was highlighted (p < .0001 all). UTR expression resulted also higher in the 72 patients requiring iv steroids administration compared to those who underwent alternative medications, (p < .0001). The 32 steroid-non-responders showed an increased UTR expression (WB, IHC and qPCR from lesioned mucosa), compared to 40 steroid-responders (p: .0002, .0001, p < .0001 respectively). The predictive role of UTR expression (p < .05) on the negative iv steroids administration therapeutic outcome was highlighted and ROC curves identified the thresholds expressing the better predictive performance. CONCLUSIONS: UTR represents a promising inflammatory marker related to clinical, endoscopic, and histological disease activity as well as a predictive marker of steroid administration therapeutic outcome in the UC context.

Dynamic measurement of newly formed carbonyl compounds in vapors from electronic cigarettes.

Recently, the formation of carbonyl compound within e-cigarettes usage has been reported. The aim of this study was to develop a new analytical method for the direct analysis of carbonyl compounds in vaporized liquids. Two different types of e-cigarettes and different puff's duration have been evaluated, using a modified smoking machine for vapor generation. An isotopic dilution approach, based on deuterated internal standard addition to the e-liquid before filling the e-cigarette tank, has been developed. Carbonyl compounds have been sampled in vapors using a direct, simple, solid-phase microextraction technique with on-fiber derivatization. Related oximes have been analyzed by gas chromatography/mass spectrometry technique. Results confirmed that new carbonyl compounds are formed during the vaping process, and that formation depends both from the heating device and from puffing topography.

Depression weights in patients with gastric cancer: Bibliometric analysis as a weapon to chart the future of research.

Bibliometric analyses are increasing in the field of gastric cancer. This letter discusses a recently published analysis that focused on the bidirectional relationship between depression and gastric cancer and evaluated the types of papers published in this field and the changes in the direction of research. There is an increasing need for new, clinically relevant studies of this association.

Machine learning as a tool predicting short-term postoperative complications in Crohn's disease patients undergoing intestinal resection: What frontiers?

The recent study, "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" investigated the predictive efficacy of a machine learning model for major postoperative complications within 30 days of surgery in Crohn's disease (CD) patients. Employing a random forest analysis and Shapley Additive Explanations, the study prioritizes factors such as preoperative nutritional status, operative time, and CD activity index. Despite the retrospective design's limitations, the model's robustness, with area under the curve values surpassing 0.8, highlights its clinical potential. The findings align with literature supporting preoperative nutritional therapy in inflammatory bowel diseases, emphasizing the importance of comprehensive assessment and optimization. While a significant advancement, further research is crucial for refining preoperative strategies in CD patients.

Author's reply: "Assessing ChatGPT and perplexity AI performance".

None.

When the vermiform appendix resembles a polyp: Be cautious of an intussuscepted appendix polypectomy.

This article discusses a recently published case report on a rare instance of type IV appendiceal intussusception with a concurrent mucinous adenocarcinoma of the cecum in a young individual. The report highlights challenges in diagnosing appendiceal intussusception, emphasizing the importance of endoscopic expertise in preventing impulsive decisions such as inappropriate polypectomies. The rarity of the concurrent intussuscepted appendix and mucinous cecal cancer is underscored, prompting consideration of malignancy in appendiceal intussusception cases. Additionally, the report addresses the increasing incidence of early-onset colorectal cancer and the need for a revaluation of diagnostic paradigms in the context of evolving epidemiological trends. The awareness of potential misinterpretations and the imperative for further investigation into this rare condition are emphasized.

Charting new AI education in gastroenterology: Cross-sectional evaluation of ChatGPT and perplexity AI in medical residency exam.

BACKGROUND: Conversational chatbots, fueled by large language models, spark debate over their potential in education and medical career exams. There is debate in the literature about the scientific integrity of the outputs produced by these chatbots. AIMS: This study evaluates ChatGPT 3.5 and Perplexity AI's cross-sectional performance in responding to questions from the 2023 Italian national residency admission exam (SSM23), comparing results and chatbots' concordance with previous years SSMs. METHODS: Gastroenterology-related SSM23 questions were input into ChatGPT 3.5 and Perplexity AI, evaluating their performance in correct responses and total scores. This process was repeated with questions from the three preceding years. Additionally, chatbot concordance was assessed using Cohen's method. RESULTS: In SSM23, ChatGPT 3.5 outperforms Perplexity AI with 94.11% correct responses, demonstrating consistency across years. Concordance weakened in 2023 (κ=0.203, P = 0.148), but ChatGPT consistently maintains a high standard compared to Perplexity AI. CONCLUSION: ChatGPT 3.5 and Perplexity AI exhibit promise in addressing gastroenterological queries, emphasizing potential educational roles. However, their variable performance mandates cautious use as supplementary tools alongside conventional study methods. Clear guidelines are crucial for educators to balance traditional approaches and innovative systems, enhancing educational standards.

Vanek's Tumour as a Rare Cause of Dyspeptic Syndrome in a Patient with Primary Biliary Cholangitis: A Case Report.

BACKGROUND: Inflammatory Fibroid Polyp (IFP), also known as Vanek's tumour, is a rare mesenchymal gastrointestinal tumour, potentially causing a wide range of clinical manifestations (even though it can be completely asymptomatic) primarily related to the location of the formation. The available evidence suggests a fundamentally non-neoplastic behaviour of IFP. CASE PRESENTATION: A 67-year-old female was presented with persistent dyspepsia despite symptomatic therapy. The patient's medical history included primary biliary cholangitis, managed with ursodeoxycholic acid, non-haemorrhagic uterine fibroids, and right knee arthrosis. Clinical examination revealed mild epigastric tenderness, and esophagogastroduodenoscopy identified a sessile mucosal formation. Histological analysis of biopsy samples revealed a gastric hyperplastic polyp, leading to a subsequent esophagogastroduodenoscopy for polypectomy. The excised specimen confirmed the diagnosis of gastric IFP. Post-polypectomy, the patient experienced progressive symptom amelioration, leading to complete resolution within three weeks. DISCUSSION: This case thus describes a rare cause of dyspeptic syndrome associated with the presence of a gastric IFP, promptly managed and resolved after endoscopic removal of the polyp, with no histological signs of neoplasia within the en bloc resected sample. CONCLUSION: IFP is a possible and rare cause of dyspeptic syndrome. There remain significant challenges in diagnosing this rare condition, which lacks pathognomonic or specific signs and symptoms of its presence (especially when it causes symptoms). Endoscopy, when feasible, remains a cornerstone in the resective management of such lesions.

Impact of Helicobacter pylori Eradication on Inflammatory Bowel Disease Onset and Disease Activity: To Eradicate or Not to Eradicate?

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.

Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients' questions? An evidence-controlled 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.

Are Small Molecules Effective in Treating Inflammatory Pouch Disorders Following Ileal Pouch-Anal Anastomosis for Ulcerative Colitis? Here Is Where We Stand.

Ulcerative colitis (UC) management encompasses conventional and advanced treatments, including biological therapy and small molecules. Surgery, particularly in the form of ileal pouch-anal anastomosis (IPAA), is indicated in cases of refractory/severe disease. IPAA can lead to acute complications (e.g., acute pouchitis) as well as late complications, including chronic inflammatory disorders of the pouch. Chronic pouchitis, including the antibiotic-dependent (CADP) and antibiotic-refractory (CARP) forms, represents a significant and current therapeutic challenge due to the substantial need for evidence regarding viable treatment options. Biological therapies have shown promising results, with infliximab, adalimumab, ustekinumab, and vedolizumab demonstrating some efficacy in chronic pouchitis; however, robust randomized clinical trials are only available for vedolizumab. This narrative review focuses on the evidence concerning small molecules in chronic pouchitis, specifically Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P-R) modulators. According to the preliminary studies and reports, Tofacitinib shows a potential effectiveness in CARP. Upadacitinib presents variable outcomes from the case series, necessitating further evaluation. Filgotinib and ozanimod demonstrate anecdotal efficacy. This review underscores the need for high-quality studies and real-world registries to develop robust guidelines for advanced therapies in post-IPAA inflammatory disorders, supported by vigilant clinical monitoring and ongoing education from international IBD specialist societies.

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review.

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8+ T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.

Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients: A matter of disease activity?

BACKGROUND: Melanocortin 3 and 5 receptors (i.e., MC3R and MC5R) belong to the melanocortin family. However, data regarding their role in inflammatory bowel diseases (IBD) are currently unavailable. AIM: This study aims to ascertain their expression profiles in the colonic mucosa of Crohn's disease (CD) and ulcerative colitis (UC), aligning them with IBD disease endoscopic and histologic activity. METHODS: Colonic mucosal biopsies from CD/UC patients were sampled, and immunohistochemical analyses were conducted to evaluate the expression of MC3R and MC5R. Colonic sampling was performed on both traits with endoscopic scores (Mayo endoscopic score and CD endoscopic index of severity) consistent with inflamed mucosa and not consistent with disease activity (i.e., normal appearing mucosa). RESULTS: In both CD and UC inflamed mucosa, MC3R (CD: + 7.7 fold vs normal mucosa, P < 0.01; UC: + 12 fold vs normal mucosa, P < 0.01) and MC5R (CD: + 5.5 fold vs normal mucosa, P < 0.01; UC: + 8.1 fold vs normal mucosa, P < 0.01) were significantly more expressed compared to normal mucosa. CONCLUSION: MC3R and MC5R are expressed in the colon of IBD patients. Furthermore, expression may differ according to disease endoscopic activity, with a higher degree of expression in the traits affected by disease activity in both CD and UC, suggesting a potential use of these receptors in IBD pharmacology.

Lower urinary tract symptoms in patients with inflammatory bowel diseases: A cross-sectional observational study.

BACKGROUND: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AIMS: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). RESULTS: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. CONCLUSION: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.

Emerging space for non-polyethene-glycol bowel preparations in inflammatory bowel disease-related colonoscopy: Veering toward better adherence and palatability.

Patients with inflammatory bowel diseases (IBDs) require repeated endoscopic evaluations over time by colonoscopy to weigh disease activity but also for different and additional indications (e.g., evaluation of postoperative recurrence, colorectal cancer surveillance). Colonoscopy, however, requires adequate bowel preparation to be of quality. The latter is achieved as long as the patient takes a certain amount of product to have a number of bowel movements suitable to clean the colon and allow optimal visualization of the mucosa during endoscopy. However, significant guidelines recommend preparations for patients with IBD not excelling in palatability. This recommendation originates from the fact that most of the studies conducted on bowel preparations in patients with IBD have been done with isosmolar preparations based on polyethylene glycol (PEG), for which, therefore, more safety data exist. As a result, the low-volume non-PEG preparations (e.g., magnesium citrate plus picosulphate, oral sulphate solutions) have been set aside for the whole range of warnings to be heeded because of their hyperosmolarity. New studies, however, are emerging, leaning in overall for a paradigm shift in this matter. Indeed, such non-PEG preparations seem to show a particularly encouraging and engaging safety profile when considering their broad potential for tolerability and patient preference. Indeed, such evidence is insufficient to indicate such preparations in all patients with IBD but may pave the way for those with remission or well-controlled disease. This article summarizes the central studies conducted in IBD settings using non-PEG preparations by discussing their results.

Hericium erinaceus, in combination with natural flavonoid/alkaloid and B3/B8 vitamins, can improve inflammatory burden in Inflammatory bowel diseases tissue: an ex vivo study.

Hericium erinaceus, berberine, and quercetin are effective in experimental colitis. It is unknown whether they can ameliorate inflammatory bowel diseases in humans. This ex vivo study aimed to evaluate the anti-inflammatory potential of a nutraceutical compound of HBQ-Complex® (H. erinaceus, berberine, and quercetin), biotin, and niacin in inflammatory bowel disease patients. Tissue specimens were obtained either from Normal-Appearing Mucosa (NAM) or from Inflamed Mucosa (IM) in 20 patients with inflammatory bowel disease. mRNA and protein expression of COX-2, IL-10, and TNF-α were determined in NAM and IM biopsy samples (T0). IM samples were then incubated in HBQ-Complex® (with the addition of niacin and biotin), and COX-2, IL-10, and TNF-α tissue levels were evaluated at 120 minutes (T1) and 180 minutes (T2). Incubation with this compound resulted in a progressive decrease in gene and protein COX-2 and TNF-α expression at T1/T2 in the IM. IL-10 showed an opposite trend, with a progressive increase of mRNA and protein expression over the same time window. HBQ-Complex® (with the addition of niacin and biotin) decreased the expression of proinflammatory cytokines at the mRNA and protein levels in IBD tissue. On the contrary, mRNA and protein expression of the anti-inflammatory cytokine IL-10 showed a progressive increase.

The use of bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water improves functional gastrointestinal symptoms in patients with non-alcoholic fatty liver disease: A prospective study.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease is increasingly gaining epidemiological ground in liver diseases. Among the proposed non-pharmacologic interventions, dietary interventions have been widely used. Several patients suffering from it complain of gastrointestinal symptoms unrelated to organic gastrointestinal tract disease. However, the role of drinking water quality modifications in this regard has not been investigated in depth. METHODS: Patients with upper or lower functional gastrointestinal symptoms were enrolled and divided into groups based on bright liver ultrasound relief's presence (SP) or absence (NSP). These patients were asked to drink bicarbonate-sulphate-calcium-magnesium and sodium-low drinkable water (Fonte Essenziale ®) for six months. Participants were assessed at baseline (T0), at the end of six months of drinking water intake (T6), and after an additional six months of washout (T12) by questionnaires designed to evaluate lower and upper gastrointestinal symptoms (Leeds dyspepsia score, short form) severity and frequency. RESULTS: A total of 61 patients were enrolled. In the SP population, the severity of lower gastrointestinal symptoms improved between T0-T6 (Z: -2.437; ES: 0.312) and worsened after the water washout (Z: -2.492; ES: 0.319). The same was for the Leeds score severity sub score in T0-T6 (Z: -2.850; ES: 0.364) and T6-T12 (Z: -2.921; ES: 0.374). These improvements seem unrelated to the severity of liver steatosis at baseline. Furthermore, no safety issues were recorded while taking the water nor during the six-month follow-up afterwards. CONCLUSION: Regular six-month intake of 400 mL of Fonte Essenziale® water was associated, in the absence of dietary regimen modifications, with an improvement in some qualitative and quantitative features of upper and lower functional gastrointestinal symptoms in both an SP and NSP sample.