Abstract: Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH), characterized by liver inflammation, fibrosis, and fat accumulation, can develop into cirrhosis and liver cancer. Despite its increasing prevalence worldwide, there are few established therapies for advanced MASH. We previously demonstrated that stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) exerted therapeutic effects in a MASH mouse model. The gut-liver axis is thought to be associated with liver disease progression, and soluble Siglec-9 (sSiglec-9), an immunoinhibitory receptor, is a key protein in SHED-CM that induces anti-inflammatory macrophages and has intestinal epithelial protective effects. Therefore, we evaluated sSiglec-9’s role in intestinal barrier protection in MASH mice. Methods: We evaluated sSiglec-9 effects on intestinal barrier function using in vitro Caco-2 cell monolayers injured by TNF-α and IFN-γ. For the MASH mouse model, male C57BL/6J mice were given a Western diet and high-sugar solution orally; to induce liver injury, CCl4 was intraperitoneally administered for 12 weeks. Mice were treated weekly with 10 ng/g sSiglec-9 or vehicle. Intestinal permeability was assessed by blood 4 kDa FITC-dextran concentration, and intestinal transcriptomes and liver histology were analyzed. Results: sSiglec-9 decreased intestinal permeability and liver inflammation in MASH mice. sSiglec-9 and SHED-CM reduced 4 kDa FITC-dextran permeability in injured Caco-2 cells, and sSiglec-9 significantly reduced intestinal permeability and modulated expression of 34 intestinal genes. NAFLD Activity Score indicated significantly reduced inflammation following sSiglec-9 treatment. Conclusions: sSiglec-9 may protect intestinal barrier function by mitigating mucosal inflammation. sSiglec-9 treatment may represent a novel therapeutic approach for MASH via gut-liver axis modulation.

Abstract: Background/Objectives: Inflammatory Bowel Diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), are chronic disorders with complex pathophysiology involving immune dysregulation, gut microbiota alterations, and environmental triggers. Diet plays a critical role in disease onset and management. This review examines current evidence on dietary interventions and oral nutritional supplementation (ONS) in IBD management, assessing impacts on disease activity and clinical outcomes. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science databases, analyzing studies on various dietary approaches and ONS in IBD. Results: Exclusive Enteral Nutrition (EEN) remains firmly established as first-line therapy for pediatric CD, achieving remission rates comparable to corticosteroids while promoting mucosal healing and avoiding steroid-related adverse effects. The Crohn's Disease Exclusion Diet with Partial Enteral Nutrition demonstrates efficacy comparable to EEN with superior long-term adherence. The Mediterranean Diet represents a sustainable anti-inflammatory approach particularly suited for maintenance therapy. Emerging evidence supports other targeted interventions including low-FODMAP diet for functional symptoms and low-emulsifier diets for active CD. ONS effectively addresses malnutrition in IBD, with formulations ranging from elemental to specialized immunomodulating products tailored to specific clinical scenarios. Conclusions: Dietary interventions and ONS are valuable components of IBD management, offering benefits for inflammation reduction and nutritional optimization. Future research should focus on personalized nutrition approaches, standardized trials, and integration with pharmacological management to enhance evidence-based recommendations for IBD patients.

Abstract: Background/Objectives: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a rare and poorly understood condition that primarily affects infants and young children. This study aimed to evaluate the clinical characteristics and outcomes of oral food challenge (OFC) tests in patients diagnosed with FPIES. Methods: A retrospective cohort study was conducted on pediatric patients who underwent OFCs for FPIES at a tertiary health service from January 16, 2018, to June 20, 2024. Both accidental and scheduled in-hospital OFC results were considered. Results: Five patients were included, and 19 OFCs were evaluated. Four patients underwent 4 OFCs each, and one patient underwent 3 OFCs. The mean age of the first symptom onset was 35 days (ranging from 3 days to 2 months). Before the first OFC, the mean duration of the elimination diet was 7 months, and for patients who required additional OFCs, was 11.6 months. Four patients were admitted to the intensive care unit. Two patients were being fed on formula, and three were having mixed feeding. Two patients had a personal and family history of atopy, and one had only a family history of atopy. Two patients had genetic syndromes. All patients developed tolerance to cow’s milk protein within a mean time of 44 months, ranging from 17 to 103 months. The two patients with genetic syndromes had a longer time to develop tolerance. Conclusions: FPIES may require multiple OFCs for diagnosis and management. The time to develop tolerance was longer in patients with genetic syndromes.

Abstract: The COVID-19 vaccine is a significant technological advancement with widespread global use. However, its effect on cancer immunity, particularly with repeated vac-cinations, remains unclear. We aimed to investigate the relationship between repeated vaccinations and pancreatic cancer (PC) prognosis. Additionally, we examined serum IgG4 levels, known to be an immune suppressor and increased with repeated vac-cinations. Methods: We retrospectively examined the effect of vaccination on survival in 272 PC patients diagnosed at our hospital from January 2018 to November 2023 and analyzed prognostic factors, including IgG4 levels in 96 PC patients. Immunohisto-chemistry for Foxp3 in the tumor tissue was performed and serum IgG4 level was measured. Serum samples from 79 patients with benign and malignant diseases, in-cluding PC, were collected between September and November 2023, and spike-specific IgG4 level was determined using enzyme-linked immunosorbent assay. Results: The overall survival (OS) of PC patients was shortened in those vaccinated three times or more, and the total serum IgG4 levels increased with the number of vaccinations. Of note, OS was significantly shorter in the high IgG4 group, and Foxp3-positive cells in the tumor tissues were increased. Repeated vaccinations in-creased spike-specific IgG4 levels, and a positive correlation was observed between spike-specific IgG4 and total IgG4. Conclusions: These findings highlight repeated vaccination as a poor prognostic factor in PC patients and suggest that IgG4 is induced by repeated vaccination and may be associated with a poor prognosis in these pa-tients.

Abstract: Small intestinal bacterial overgrowth (SIBO) has recently garnered significant attention from both medical professionals and the general public, likely due to its increasing prevalence and advancements in testing technology. However, the accuracy of breath tests in clinical practice for diagnosing SIBO still requires thorough validation. This review compiles the definition, etiology, influencing factors, novel testing methods, and the determination and interpretation of SIBO results. We particularly discuss the various controversies and limitations associated with these tests. By comparing and evaluating the advantages and disadvantages of different diagnostic methods fo rSIBO, we aim to enhance the understanding of its clinical diagnosis and promote future research focused on accurate detection methods.

Abstract: Oxidative stress as well as endoplasmic reticulum (ER) stress are the major underlying factors that promote non-alcoholic steatohepatitis (NASH), which eventually leads to hepatocarcinogenesis. Knockout (KO) of superoxide dismutase 1 (Sod1) causes impaired lipid metabolism and an increase in hepatocarcinogenesis in aged mice whereas lipid overload alone neither induces NASH nor increases the incidence of tumor development in them. The double knockout (DKO) of Sod1 and peroxiredoxin 4 (Prdx4), a thiol oxidase that resides in the ER, causes NASH-mimicking symptoms even at younger ages. We found that in addition to high mortality, any surviving DKO mice develop hepatocellular carcinoma within the first year of life. The administration of a physiological dose of L-ascorbate (1.5 mg/ml) in drinking water decreased the rates of mortality and effectively prevented tumor development. Precancerous lesions showed higher reactivity to a ferroptosis-specific antibody compared with tumor lesions. Analyses of liver tissues from 8-month-old DKO mice revealed that upregulation in the metabolic pathways of amino acids were robustly suppressed by supplementation with L-ascorbate, which suggested a possible role in hepatocarcinogenesis. Iron-regulatory protein and aconitase activity were decreased in the DKO mice regardless of their ascorbate status. Given the dominant occurrence of ferroptosis in precancerous cells, it is conceivable that supplementation with ascorbate along with aberrant iron metabolism selectively induces the death of cells destined for tumorigenic proliferation at the precancerous stage. An adequate intake of ascorbate in daily life could ameliorate the tumorigenic processes that are promoted by the hepatic steatosis elicited by oxidative insult

Abstract: Background/Objectives: Inflammatory bowel diseases (IBD) include Crohn’s disease (CD) and ulcerative colitis (UC). The availability of an increasing number of new mol-ecules approved for IBD treatment has increased our ability and aspirations to change their natural history. The STRIDE II consensus is the current established suggested strategy for IBD management. Primary objective of this study is to describe the clinical history of IBD in post-STRIDE era, and to quantify the burden of IBD in terms of hos-pitalization rate. Secondary objective is to estimate the 5-years risk of intestinal resec-tion among IBD patiesnts. Methods: Observational time series analysis was conducted on population data; retrospective data from Jan 2011 was collected for Local Health Authority “Roma 1” population (circa 1.5 million residents). Prospective data from hospitalizations among residents since Jan 2018 was also collected. Hospitalization and surgery events among newly diagnosed patients (n= 556) were collected and pro-spectively followed since Jan 2018. Kaplan-Mayer survivor functions were proposed, considering surgical intervention as primary outcome. Results: Current IBD preva-lence is estimated to be 218 (77.2 CD, 141.1 UC) cases/100,000ppl. Incidence trend slowly increased during the last decade up to 5.3 (CD) and 9.4 (UC) cas-es/100,000ppl/year. Yearly hospitalization remained constant near 16.5%, while 6-years risk of surgery is 36% for CD, and 20% for UC. Conclusions: Incidence of IBD increased in the last decades, with substantial stability in the incidence of surgeries and hospitalizations. Thus, current IBD management has only a small effect on changing the natural history of the disease.

Abstract: Background: Postoperative fluid collections (POFCs) after abdominal surgeries, particularly pancreatic surgeries, are associated with high morbidity and mortality rates and they were historically managed with surgical re-exploration and drainage. In particular, postoperative pancreatic fluid collections (PPFCs) are the most common complications after pancreatic surgery resulting from pancreatic leak. It occours in up to 50% of cases and apporximately 10% of them need to be drained to avoid further sequelae. Endoscopic UltraSonography (EUS)-guided drainage of PPFCs represents nowadays the first-line treatment, but many aspects are still beated. Methods: We describe a retrospective case series of patients from multiple italian centers who underwent EUS-guided drainage (EUS-D) of POFC, aiming to provide data on efficacy and safety of this procedure, supported by a review of the existing literature on this topic. The primary outcomes were technical and clinical success, and the secondary outcomes were the type and rate of adverse events (AE) and rate of recurrence. Results: A total of 47 patients were included. The procedure demonstrated a technical success of 98% (46/47) and a clinical success of 96% (45/47). The rate of AEs was 11% (5/47), represented by bleeding (3/5), stent occlusion (1/5) and buried syndrome (1/5). Conclusion: Management of POFC has over time shifted towards an endoscopic approach with optimal efficacy and safety.

Abstract: Frailty is increasingly recognized as a critical predictor of adverse outcomes in older adults, particularly those with cancer. However, the role of frailty—distinct from comorbidity burden—has not been fully characterized in older adults hospitalized with cholangiocarcinoma (CCA), a rare but aggressive malignancy with rising incidence in the aging population. A retrospective cross-sectional analysis of the Nationwide Inpatient Sample (NIS) 2019–2022 was performed. Adult inpatients aged ≥65 with CCA-related ICD-10 codes were identified. Patients were stratified into frailty categories based on the Hospital Frailty Risk Score (HFRS). Multivariable regression models were used to assess associations with in-hospital mortality, length of stay (LOS), and hospital charges. Among 18,785 hospitalizations, the in-hospital mortality rate was 7.18%. High frailty conferred an eight-fold increased risk of mortality, a 70% longer LOS, and 52% higher charges com-pared to low frailty. Elixhauser comorbidity scores were not significantly associated with outcomes. These findings support the use of frailty screening to guide inpatient care planning and optimize outcomes in older adults with CCA.

Abstract: Background and aims: The role of coffee consumption in upper gastrointestinal (GI) diseases has been a topic of ongoing debate. While some studies suggest a potential association, the causal relationship remains unclear. This critical review evaluated the evidence linking coffee consumption to upper GI diseases via Hill’s criteria for causation.Methods: By performing a comprehensive literature search across many databases, such as PubMed, Scopus, and Google Scholar, the author was able to find relevant papers. Once the article had been downloaded, it was imported into the reference manager. The author then manually screens the article for duplicate references by using author names, journals, and publication years. Studies were identified and critically reviewed using Hill’s criteria to assess the causality of this relationship.Results: The findings remain inconclusive. The strength of the associations between coffee consumption and specific upper GI conditions, such as gastroesophageal reflux disease (GERD), peptic ulcers, and esophageal cancer, varied significantly across studies. Temporality was challenging to establish because of the observational nature of most studies. Biological plausibility exists, supported by evidence of the effect of coffee on gastric acid secretion and motility. However, dose‒response relationships and experimental evidence are inconsistent. Overall, the review concluded that the evidence supports a correlation, but the causal nature of the relationship remains inconclusive.Conclusion: The evidence reviewed suggests a weak correlation between coffee consumption and upper GI diseases, with insufficient support for a direct causal link. While coffee may influence certain GI parameters, confounding factors and study design limitations preclude definitive conclusions.

Abstract: Background and aims: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis-tests in patients with metabolic liver disease (MASLD). An unmet need is to reduce the uncertainty of biomarkers for the diagnosis of the early stage of clinically significant fibrosis (eF). This can be achieved if three essential but neglected STARD methods (3M) are used—a more sensitive histological score than the standard comparator (five-tiers), the weighted area under the characteristic-curve (wAUROC) instead of the binary-AUROC, and biopsy length. We applied 3M to FibroTest-T2D to demonstrate this reduction of uncertainty, and constructed proxies predicting eF in large populations. Methods: For uncertainty, seven subsets were analyzed, four included biopsies (n=1,903), and to assess eF incidence, three MASLD-populations (n=299,098). FibroTest-T2D classification-rates after BS and in out-patients-T2D (n=402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding-factors used hazard-ratios.Results: After BS (110 biopsies), reversal of eF was observed in 16/29 patients (84%) using seven-tier scores vs. 3/20 patients (47%) using five-tier scores (P=.005). When biopsy length was above the median, FibroTest-T2D wAUROC was .90 (SD=.01), and the wAUROC was .88 (SD=.1) when the length was below the median (P<.001). For the first time, obesity was associated with eF, before T2D (P<.001), and perimenopausal age with apoA1 and haptoglobin increases (P<.0001).Conclusion: Validations of circulating biomarkers need to assess their uncertainty. FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance.

Abstract: Vonoprazan is a potassium competitive acid blocker, has shown potential used to treat acid reflux and eliminating Helicobacter pylori. Its enhanced anti-secretory action, quick action, and reduced anti-secretory variability make it a more suitable option than PPIs. However, many research is needed to fully understand the effects and its safety and tolerability profiles. The drug's effectiveness in treating reflux esophagitis is also reviewed. Due to the limits and unfulfilled therapeutic needs of proton pump inhibitors (PPIs), new medications also developed to address acid-related disorders and the elimination of H. pylori. Vonoprazan, a recently developed potassium-competitive acid blocker (P-CAB), demonstrated greater inhibition of stomach acid secretion. The effectiveness of vonoprazan in treating illnesses linked to acid reflux is reviewed in this paper, with an emphasis on its application in the elimination of Helicobacter pylori. Professional judgement: Vonoprazan demonstrated a few benefits over PPIs for the pharmacokinetic and pharmacodynamic characteristics of the drug: more powerful and extended suppression of acid secretion, quick commencement of action without the need for acid activation and precise dosing time, includes reduced anti-secretory variability and improved acid regulation at night. According to recent research, vonoprazan's enhanced anti-secretory action may make it a more suitable option than PPIs for treating reflux esophagitis and eliminating Helicobacter pylori. Furthermore, vonoprazan has good safety and tolerability profiles, albeit more extensive research is needed to fully understand its effects.

Abstract: This case report discusses the successful management of a 75-year-old woman with recurrent Clostridiumdifficile infection (rCDI), complicated by multiple comorbidities including cardiovascular disease, diabetes,and marked anxiety. The treatment included butyrate supplementation, probiotic therapy with Clostridium butyricum CBM588®, and low-dose amitriptyline to address both the gastrointestinal and psychological components of her condition. The combination therapy resulted in a significant reduction in gastrointestinal symptoms, prevention of further CDI recurrences, and improved mentalwell-being. The discussion highlights how restoring the gut microbiota positively impacts the reduction of inflammation, intestinal permeability, andthe gut-brain axis, as well as the importance of a multidisciplinary approach in rCDI. Further research is recommended to validate the efficacy of these therapies in broader populations.

Abstract: EUS-BD, including EUS-CDS and EUS-HGS, is an efficacious alternative to ERCP and its common complications are bile leak, infection, stent migration and bleeding. Here, we report an atypical case of a patient who developed dark green urine after receiving EUS-HGS, which we suspected to be caused by an abnormal biliary-vascular fistula. A 76-year-old woman diagnosed with pancreatic adenocarcinoma received EUS-HGS for relieving jaundice. The patient reported abdominal pain and chest tightness after the operation, with difficulty in urinating. X-ray suggested right-sided pleural effusion and dark green pleural effusion was drained out. However, the patient also developed dark green urine, which appeared everyday afternoon and disappeared automatically after intravenous treatment. The phenomenon was rare and interesting ,and also called for more alert on post-operative complication detection after EUS-BD operation.

Abstract: Indigo naturalis (IN) is a traditional Chinese medicine concocted from medicinal plants such as Baphicacanthus cusia (Nees) Bremek. IN has multifaceted pharmacological activities. Recent research highlights the remarkable efficacy of IN in treating ulcerative colitis (UC). We has developed a new IN processing technology without use of lime. Correspondingly, the content of active ingredients has relatively increased in Indigo Naturalis prepared using a novel method (NIN). In this study, the protective effects of NIN on UC was verified in dextran sulfate sodium salt (DSS) induced mouse UC models. NIN could significantly improve weight loss, diarrhoea and prolapse, bloody stools, elevated Disease activity index (DAI) and alleviate the colitis symptoms of mice; it could also improve the shortening of colon, disappearance of intestinal crypts, epithelial cell destruction and inflammatory infiltration caused by UC; and it could also significantly reduce the Histological index (HI); Besides, NIN relieved the inflammatory response by decreasing the content of pro-inflammatory cytokines TNF-α and IL-1β, and elevating the content of anti-inflammatory cytokines IL-10 and IL-22; and restores the intestinal mucosal barrier by increasing the level of MUC2 protein expression at the site of colonic injury. The significant effects of NIN on UC were verified for the first time, suggesting that NIN was worth further developing into a novel therapeutic drug. And necessarily, further safety evaluation and comparison with traditional IN will help in the application of NIN.

Abstract: Hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis presents significant treatment challenges due to the impaired liver function, altered pharmacokinetics, and systemic inflammation associated with advanced liver disease. This review explores the complexities of managing HCC in this high-risk population, focusing on the pharmacological considerations and the impact of cirrhosis on drug metabolism, treatment efficacy, and adverse effects. Studies indicate that drugs metabolized by the liver, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), accumulate in patients with decompensated cirrhosis, increasing the risk of toxicity. Additionally, portal hypertension and systemic inflammation further complicate treatment, limiting the effectiveness of both systemic therapies and immunotherapy. This article discusses potential strategies, including dose adjustments, pharmacokinetic monitoring, and combination therapies, to optimize treatment outcomes.

Abstract: Portal vein thrombosis (PVT) is a partial or complete obstruction of blood flow through the portal vein (PV) due to an intraluminal thrombus. Neoplastic portal vein thrombosis is a common complication in cases of hepatocellular carcinoma (HCC), and it is a sign of a poor prognosis. Diagnosing HCC and tumor PVT is usually performed using non-invasive radiological imaging and measuring tumor marker blood levels. Sometimes, a PVT is present without any detectable liver tumor mass or conclusive findings. In cases like these, a tumor PVT biopsy is performed for confirmation. In the available literature, tumor PVT biopsy is performed either percutaneous or endoscopic, as fine-needle aspiration biopsy (FNAB). Only a single publication was regarding PVT CORE needle biopsy (CNB). At this moment, we present three cases of percutaneous transhepatic ultrasound-guided biopsy. For the patients in question, the single method remained for diagnostic, staging, and pathohistological verification due to the insufficient sensitivity of the performed radiological imaging. In all three cases, the diagnosis of HCC was confirmed. All three procedures have been carried out without any complications.

Abstract: Hepatocellular carcinoma remains one of the leading contributors to global cancer mortality, frequently stemming from chronic liver conditions, such as viral hepatitis, non-alcoholic fatty liver disease, and alcohol-induced cirrhosis. While antiviral treatments have made significant strides, the rising prevalence of hepatocellular carcinoma linked to non-infectious causes underscores the pressing demand for more effective diagnostic tools and therapeutic interventions. Advances in imaging and liquid biopsy technologies have facilitated early detection and diagnosis, and treatment strategies are diversifying: immune checkpoint inhibitors, tyrosine kinase inhibitors, and interventional therapies. Translational therapies for advanced hepatocellular carcinoma have improved surgical opportunities and patient survival. Artificial intelligence has played a transformative role in the diagnosis and treatment of hepatocellular carcinoma, in terms of image analysis, histopathologic classification, drug development, and targeted therapy. The future of hepatocellular carcinoma lies in precision oncology and the collaboration of multidisciplinary teams as well as in early detection. The ultimate goal is to keep patients alive longer and reduce the global burden of this complex malignancy.

Abstract: Colonoscopy is an essential diagnostic and therapeutic tool in gastroenterology, significantly impacting colorectal cancer (CRC) detection and management. Effective bowel preparation is critical for optimal visualization, directly influencing colonoscopy accuracy and patient outcomes. However, diabetic patients frequently encounter challenges achieving adequate bowel preparation, primarily due to gastroparesis, autonomic neuropathy, altered colonic motility, fluid-electrolyte imbalances, and complexities related to antihyperglycemic medication adjustments. This review aims to evaluate current literature on bowel preparation efficacy in diabetic patients undergoing colonoscopy, assess existing guidelines from leading gastroenterological societies, and highlight the necessity for detailed, diabetes-specific recommendations. We conducted a comprehensive PubMed search identifying 20 pertinent studies, including randomized controlled trials, meta-analyses, multicenter studies, cohort studies, and reviews. The findings consistently indicate diabetes as an independent predictor of inadequate bowel preparation. Furthermore, an evaluation of guidelines from the European Society of Gastrointestinal Endoscopy (ESGE), the US Multi-Society Task Force, and the Canadian Association of Gastroenterology revealed either absent or insufficiently detailed diabetes-specific recommendations. Given the rising global prevalence of diabetes and CRC, inadequate bowel preparation significantly impacts the quality of colonoscopy, adenoma detection rates, patient safety, and healthcare costs. This review underscores the urgent need for additional research focusing on tailored bowel preparation strategies for diabetic patients. Ultimately, the implementation of standardized, evidence-based protocols designed explicitly for this high-risk group is essential to enhance diagnostic efficacy, improve patient outcomes, and reduce CRC-related morbidity and mortality.

Abstract:

Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within one year if left untreated. The pathophysiology of POR is multifactorial, involving dysregulated immune responses, gut microbiota alterations, and mucosal healing impairment, highlighting the need for targeted therapeutic strategies. This review aims to explore the current landscape of POR management, focusing on biologic therapies and emerging advanced treatments. Conventional management relies on early prophylactic therapy with anti-TNF agents such as infliximab and adalimumab, which have demonstrated efficacy in reducing endoscopic and clinical recurrence. However, newer biologics, including IL-23 inhibitors (risankizumab) and Janus kinase (JAK) inhibitors (upadacitinib), have shown promise in CD management, though their role in POR remains underexplored. The lack of direct clinical evidence for advanced biologics in POR prevention, combined with inter-individual variability in treatment response, underscores the need for further research. Future directions should focus on optimizing therapeutic strategies through personalized medicine, identifying predictive biomarkers, and conducting robust trials to establish the efficacy of novel agents in POR prevention. A tailored, evidence-driven approach is essential to improving long-term outcomes and minimizing disease recurrence in post-operative CD patients.