OBJECTIVE: Renal involvement in inflammatory bowel disease is rather uncommon. This study aims to describe the spectrum of renal involvement in pediatric patients with IBD and reduce delay in detection and management.
METHODS: This is a retrospective study of the renal function of all patients, aged <18 years, who have been followed for IBD in our pediatric gastroenterology department from January 2019 till January 2023.
RESULTS: From the 75 IBD patients included in this study 16 % had renal manifestations. The urinalysis revealed proteinuria in 7 patients, proteinuria and hematuria in 3 and proteinuria and glycosuria in 2 patients. All 12 patients with abnormal urinalysis underwent further investigation in order to determine the cause of renal damage and the results are as follows: 2 patients had glomerulonephritis and in other 2 patients renal damage was due to medication adverse effect, 1 had pyelonephritis in combination with chronic active tubulointerstitial nephritis and another 1 had thin basement membrane disease. Three patients had IBD-related dependent renal involvement and 1 resulted in chronic renal failure due to amyloidosis.
CONCLUSIONS: It is important for all clinicians to be aware of the possibility of renal manifestations in IBD patients for the early diagnosis and prevention of these manifestations and complications.

Background/Objectives: The treatment of patients with mild-to-moderate ulcerative colitis (UC) is challenging. Although there are commonly used guidelines, therapy optimization is not standardized. We conducted a survey to investigate the management and treatment of patients with mild-to-moderate UC. Methods: Physicians with experience in treating inflammatory bowel diseases (IBD) were invited to participate in an anonymous, multiple-choice survey between June and July 2023. The survey addressed various issues of patient care such as patient monitoring, treatment optimization, follow-up, treatment decision making, and therapy de-escalation. Results: The survey included 222 physicians (59.9% men; mean age = 50.4 years) from 66 countries worldwide. Gastroenterologists were the most represented specialists (89.6%), followed by surgeons (3.2%), and internal medicine doctors (2.7%). Two-thirds of the participants (66.7%) had >10 years of experience in the field of IBD. The combination of oral (≥4 g/day) and rectal 5-aminosalicylic acid (5-ASA) was the preferred choice when optimizing therapy. Budesonide MMX (41.8%) and systemic steroids (39.9%) were preferred in patients who failed 5-ASA. Treatment decisions were predominantly based on endoscopic (99.0%) or clinical (59.8%) activity. A significant percentage of clinicians did not optimize therapy in the case of increased fecal calprotectin alone (45.1%) or radiological/ultrasound activity (39.8%) alone. Conclusions: The guidelines for the management of mild-to-moderate UC are well accepted in clinical practice. Endoscopic remission remains the main therapeutic target, followed by clinical remission. Fecal calprotectin and intestinal ultrasound still elicit complaints from physicians.

Medical therapy is the cornerstone of ulcerative colitis (UC) management and aims to induce and maintain remission. In case of mild-to-moderate UC, mesalamine (5-ASA) is the first-line option. 5-ASA requires local release at the level of the inflamed mucosa to exert its therapeutic action. While rectal preparations are useful in distal colitis, in cases of UC of at least rectosigmoid extent, guidelines suggest the association of oral and rectal 5-ASA. Mesalamine with Multi Matrix System® technology (MMX mesalamine) is an oral, high-strength (1.2 g/tablet), once-daily formulation of 5-ASA, designed to provide delayed and prolonged release throughout the entire colon. Clinical trials demonstrated a strong efficacy in inducing and maintaining clinical and endoscopic remission in active mild-to-moderate UC. The efficacy is related to specific colonic drug-delivery, to its high-dosage and once-daily administration, thus improving patients\' adherence and outcomes. The specific colonic-delivery is also associated with very low rates of systemic absorption and adverse events (AEs). With this comprehensive review we aimed to summarize current knowledge on MMX mesalamine in mild-to-moderate UC, in terms of clinical pharmacology, efficacy and safety, also compared to other 5-ASA products. In addition we provided an expert opinion on the topic, examining the implications on clinical practice.

Inflammatory bowel disease (IBD) is associated with various immune mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis and uveitis. Chronic kidney disease (CKD) is defined by a reduction in kidney function (eGFR less than 60ml/min/1.73m2) and/ or damage markers that are present for at least three months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, utilizing a random effect model. The systematic review was registered in PROSPERO (RD42023381927). Fifty-four articles were included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients (n = 102,230) vs. healthy populations (n = 762,430). Of these, diagnosis of CKD was based on ICD codes in five studies vs. on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59 (95%CI 1.31-1.93), without any difference between studies using diagnostic coding (OR 1.70 95%CI 1.33-2.19) vs. diagnosis based on eGFR (OR 1.36 95%CI 1.33-1.64). IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.

Ulcerative colitis (UC) is an idiopathic disease characterized by colonic mucosal tissue destruction secondary to an excessive immune response. We synthesized pH-sensitive cross-linked chitosan/Eudragit® S100 nanoparticles (EU S100/CS NPs) as carriers for 5-aminosalicylic acid (5-ASA) and hesperidin (HSP), then conducted in-vitro and in-vivo studies and evaluated the therapeutic effects. In-vitro analysis revealed that the 5-ASA-loaded EU S100/CS NPs and the HSP-loaded EU S100/CS NPs had smooth and curved surfaces and ranged in size between 250 and 300 nm, with a zeta potential of 32 to 34 mV. FTIR analysis demonstrated that the drugs were loaded on the nanoparticles without significant alterations. The loading capacity and encapsulation efficiency of loading 5-ASA onto EU S100/CS NPs were 25.13 % and 60.81 %, respectively. Regarding HSP, these values were 38.34 % and 77.84 %, respectively. Drug release did not occur in simulated gastric fluid (SGF), while a slow-release pattern was recorded for both drugs in simulated intestinal fluid (SIF). In-vivo macroscopic and histopathological examinations revealed that both NPs containing drugs significantly relieved the symptoms of acetic acid (AA)-induced UC in Wistar rats. We conclude that the synthesized pH-sensitive 5-ASA/EU S100/CS NPs and HSP/EU S100/CS NPs offer promise in treating UC.

UNASSIGNED: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a significant health-care burden worldwide. While medical therapy aims to induce and maintain remission, optimal management of mild to moderate UC remains challenging due to heterogeneity in severity classifications and non-standardized approaches. This comprehensive review summarizes current evidence and knowledge gaps to optimize clinical decision-making in patients with mild to moderate UC.
UNASSIGNED: After an extensive literature search of PubMed, Medline, and Embase through August 2023, we provide an overview of definitions utilized to characterize mild to moderate UC severity and established therapeutic targets. Current medical treatments including mesalazine formulations, corticosteroids, and their combinations are surveyed. The role of emerging intestinal ultrasound, telemedicine, and home testing is explored. Individualized, patient-centered paradigms aiming to streamline care delivery through proactive identification of relapses are also examined.
UNASSIGNED: Addressing inconsistencies in disease activity stratification will better align tailored regimens with each patient\'s profile. Advancing noninvasive technologies like ultrasound criteria and home testing could improve UC management by enabling personalized models. Realizing individualized plans through informed shared-decision making between health-care providers and fully engaged patients holds promise to maximize quality of life outcomes. Continuous improvement relies on innovation bridging different domains to overcome current limitations and push the field toward more predictive and tailored care.

UNASSIGNED: 5-aminosalicylates (5-ASA) are used to treat mild to moderate ulcerative colitis. Despite their lack of efficacy in Crohn disease (CD), they are still used in real-world practice. Additionally, when patients have progressive disease, they may escalate to biologic therapy, at which time 5-ASA may or may not be discontinued.
UNASSIGNED: The aim of this study is to assess the clinical outcomes of patients started on 5-ASA for the treatment of pediatric CD. The secondary aims were to evaluate the outcomes of those who continue 5-ASA to those who discontinue 5-ASA upon biologic escalation.
UNASSIGNED: We performed a single-center retrospective chart review of pediatric CD patients from 2010 to 2019 who were initially treated with 5-ASA. Demographics, medication and laboratory data, and clinical disease activity were collected.
UNASSIGNED: Sixty-one patients were included in the study; the majority had inflammatory CD with ileocolonic involvement. Twenty-four patients were on a concomitant immunomodulator. The majority of patients (85.2%) required escalation to biologics. Thirty-two patients (61.5%) who escalated to biologic therapy continued on 5-ASA. Eighty percent of patients achieved clinical remission at 1 year, and there was no difference between those who continued 5-ASA at time of biologic initiation compared to those who did not continue the medication. Patients who discontinued 5-ASA had an average annual cost savings of $6741.
UNASSIGNED: 5-ASA is not a durable monotherapy for the treatment of pediatric CD. Patients who require escalation from 5-ASA to biologic therapy do not benefit from concomitant 5-ASA therapy. Further prospective studies are needed to confirm these findings.

The prevalence of ulcerative colitis (UC) in the Middle East is increasing, impacting the economic and healthcare burden. The management of patients with mild to moderate UC is still a challenge as several factors can affect optimal care, including drug choice, induction and maintenance dose, treatment optimization and de-escalation, therapy duration, monitoring, and safety profile. We conducted an expert consensus to standardize the management of patients with mild to moderate UC. Sixteen experts in inflammatory bowel diseases, through a well-established and accepted Delphi methodology, voted and approved eight statements in order to provide practical guidance to clinicians in the Middle East.

Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.