Search Results (97)

Background: Ulcerative colitis (UC) is increasing in incidence, including among pediatric populations. Treatment aims primarily to induce and maintain remission. For those inadequately responding to 5-aminosalicylic acid, remission may be induced via oral steroids or, in severe instances, intravenous methylprednisolone. This retrospective case series aims to evaluate the efficacy of high-dose intravenous methylprednisolone pulses (30 mg/kg, max 1 g per day for 3–5 days) in inducing remission in moderate and severe pediatric UC cases. Methods: From a cohort of pediatric patients (<18 years) hospitalized in 2018–2021 due to an acute flare of UC, those treated with high doses of methylprednisolone to induce remission were identified. The Pediatric Ulcerative Colitis Activity Index (PUCAI) was used to determine the response to treatment, considering a 20-point reduction or a score below 10 as significant improvement and indicative of remission induction. Results: Disease activity was severe in most patients (12/15), with 3/15 having moderate but refractory disease. We observed a clinically significant response in 9/15 patients (60%) with a mean PUCAI decrease of 39.4 ± 14.7 points. The median duration to clinical remission was 4 (IQR 3–4) days. For the 6/15 non-responders to methylprednisolone pulses, treatment was escalated. Adverse effects were not observed during the treatment period. Conclusions: High-dose methylprednisolone may be a viable alternative for inducing remission in pediatric UC. However, the small sample size and retrospective design warrant further prospective studies to validate these findings. Full article

Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy due to their low cost-effectiveness. Additionally, the concomitant use of xanthine oxidase inhibitors and 5-aminosalicylates may slow the metabolism of 6-mercaptopurine. Case Description: We describe a case of a 26-year-old Caucasian man with Crohn’s disease and psoriatic arthritis treated with mesalazine and AZA (100 mg daily) who developed prolonged bone marrow aplasia and neutropenic fever after increasing the daily dose of AZA from 100 to 150 mg (from 44 to 66 mg/m²), without frequent total blood count monitoring. Discontinuation of AZA, multiple transfusions of red blood cells and platelet concentrate, filgrastim, empirical antibiotic therapy, and antiviral and antifungal prophylaxis were obtained after 11 days complete recovery of bone marrow aplasia. Methods: Genomic DNA genotyping of coding regions of TPMT (exons 2–9) and NUDT15 (exons 1–3). Results: Heterozygous alleles in the untranslated region (c.460G>A and c.719A>G) associated with TPMT deficiency and a benign variant (c.*7G>A) in the 3′-UTR of NUDT15 with no effect on enzyme activity were found. Conclusions: This case highlights the importance of monitoring the total blood count frequently during the first weeks of treatment with moderate-to-high doses of AZA. Furthermore, the interaction between AZA and mesalazine may play a significant role in the development of prolonged bone marrow aplasia. Full article

Smart packaging materials (SPMs) combine the properties of intelligent and active packaging into a single system, enabling for the monitoring of the packaged product while enhancing its desired conditions. In this study, poly(lactic acid) (PLA) was used as the base polymer and functionalized with in situ synthesized gold nanoparticles (AuNPs) and methyl red (MR) as a pH-sensitive dye. Various additives, including poly(amic) acid (PAA), bromothymol blue (BB), 5-aminosalicylic acid (5AS), glutaraldehyde (GA), and silver and gold nanoparticles (AgNPs, Au NPs), were tested to optimize the SPMs. To evaluate their performance, the synthesized SPMs were characterized using UV-Vis spectroscopy, IR spectroscopy, SEM, microbiological assays, and mechanical tests. Our results revealed that PLA films containing AuNPs and MR exhibited excellent mechanical, chemical, and antimicrobial properties, making them highly suitable for smart packaging applications. In contrast, the addition of PAA disrupted film formation, while AgNPs and blueberry extracts increased the brittleness of the films, thereby limiting their practical use. Furthermore, BB was found to inhibit the in situ synthesis of AuNPs. A real-world application study demonstrated that cheddar cheese wrapped in the optimized PLA films remained unspoiled after 12 months of refrigeration. IR spectroscopy confirmed that no film components migrated into the cheese during the storage period. GA was identified as a critical component for maintaining the structural integrity of the films over the 12-month storage period. This is the first study to report on the development of PLA-based SPMs that incorporate AuNPs, MR, and GA, offering a promising solution for sustainable and intelligent food packaging. Full article

Background/Objectives: The burden of ulcerative colitis (UC) is increasing in Saudi Arabia (KSA), and patients with UC often suffer from delays in diagnosis and appropriate management. This study investigates the current UC patient journey in KSA from the healthcare professionals’ (HCPs) perspective. It aims to evaluate treatment patterns, identify critical gaps, and provide insights to guide interventions that enhance the quality of life for UC patients in KSA. Methods: Quantitative interviews were conducted with 60 HCPs (45 gastroenterologists and 15 internal medicine specialists) from different regions in Saudi Arabia (KSA) using a Computer-Assisted Personal Interview (CAPI) system. The survey domains included clinical symptoms, diagnostic testing, endoscopic scoring, treatment goals, and medication sequencing. Results: Data were collected from 60 HCPs with an average of 17 ± 12.5 years of experience. Most patients with UC were referred by general practitioners (28%), internal medicine physicians (25%), followed by surgeons (16%). The first-ranked treatment goals were clinical remission (53.3%), endoscopic remission (35%), and improvement of quality of life (33.3%). For outpatient moderate-to-severe UC, the most common first-line treatments are oral systemic steroids (34%), 5-aminosalicylates (5-ASAs) (26%), and TNF-α inhibitors (21%). While second-line treatment rankings were TNF-α inhibitors (23%), followed by Interleukin 12/23 inhibitors (19%), and Janus kinase (JAK) inhibitors (14%). Sphingosine 1-phosphate (S1P) receptor modulators are not well-utilized due to a lack of availability (88%), unfamiliarity with the treatment (24%), and formulary exclusion (12%). Conclusions: In conclusion, most UC patients are referred by general practitioners. Treating gastroenterologists prioritize clinical remission as a treatment goal. Corticosteroids remain overutilized as reflected by treating physicians’ responses. The underutilization of advanced therapies underscores the need for enhanced education and improved access to integrate emerging therapies effectively. Full article

Background/Objectives: Elderly populations are under-represented in inflammatory bowel disease (IBD) clinical trials, with limited data on phenotype, treatment patterns, outcomes, and comorbidities. The main objective of this study was to evaluate, in an elderly cohort with IBD, demographic and disease characteristics, comorbidity, polypharmacy, and treatment patterns according to the development of IBD at or before old age. Secondarily, the same analysis was performed based on the type of IBD: ulcerative colitis (UC) or Crohn’s disease (CD). Materials and Methods: Observational, single-center, retrospective study including patients diagnosed with IBD and aged 65 years or older seen at the IBD office of the Regional University Hospital of Malaga between September and November 2022. Data were recorded on demographic, disease-related, and IBD treatment-related variables, comorbidities, and polypharmacy. A descriptive and analytical study was undertaken according to the age of IBD onset and type of IBD. Results: Of the patients included, 50.8% were male, 55.1% had CD, and 44.9% UC. IBD onset was before age 65 years in 69.5% and ≥65 years in 30.5%. Elderly with IBD who debuted <65 presented longer disease duration (19.67 ± 9.82 years) and required more IBD-related surgeries (37.8%); elderly with IBD who debuted ≥65 were older (77.69 ± 6.26 years), with no differences in the other variables. According to the type of IBD, elderly UC patients were older (74.55 ± 6.9 years), used more aminosalicylates (77.4%), and had higher rates of polypharmacy (90.6%). Elderly patients with CD had higher IBD activity (moderate/severe in 72.3%), used more biologic drugs (58.5%), and required more IBD-related surgeries (44.6%). Conclusions: Elderly patients who develop IBD before or after the age of 65 years are overall very similar in baseline and disease-related characteristics. Elderly with CD have higher IBD activity and require more biologic drugs and IBD-related surgeries. Elderly with UC are older and have higher rates of polypharmacy and aminosalicylate use. Full article

Background: 5-Aminosalicylic acid (5-ASA), the first-line therapy for ulcerative colitis, is a poorly soluble zwitterionic drug. Unformulated 5-ASA is thought to be extensively absorbed in the small intestine. Methods: The pH-dependent solubility of 5-ASA in vitro and the intestinal membrane distribution of 5-ASA and its N-acetyl metabolite (AC-5-ASA) after the oral administration of 5-ASA were examined in fed rats. 5-ASA was administered as a suspension in water, 0.1 M HCl, or 0.1 M NaOH to untreated rats or as a solution in 5% NaHCO₃ to lansoprazole-pretreated rats. Results: 5-ASA solubility in vitro was higher at pH < 2 and pH > 7. In rats, the 5-ASA and AC-5-ASA were detected mostly in the small intestine at 3 h and in the colonic region at 8 h after administration. The dosing vehicle (suspension or solution) and lansoprazole pretreatment did not significantly affect the pH of the luminal fluid in rats or the 5-ASA distribution in membranes. Conclusions: The 5-ASA distribution in membranes in the proximal intestine was found to be restricted by the intrinsic regional luminal pH, low solubility, and saturable membrane permeability. Unabsorbed 5-ASA in the proximal intestine was delivered to the distal intestine. The higher the oral dose of 5-ASA, the more 5-ASA may be delivered to the distal intestine due to the restricted absorption in the small intestine. Full article

Background: Biologics are a cornerstone in the treatment of severe cases of inflammatory bowel disease (IBD) and aim to control the disease and improve quality of life. This study investigated changes in nonbiologic medication prescriptions for IBD patients initiating biologic therapy in Germany. Methods: This study used data from anonymized pharmacy records in the German longitudinal prescription (LRx) database and included biologic-naive IBD patients who received their first biologic therapy prescription between 2016 and 2022. Changes in prescription rates and pill counts for nonbiologic medications (corticosteroids, 5-aminosalicylates (5-ASA), proton pump inhibitors, analgesics, immunosuppressants, Vitamin D, iron, and antibiotics) before and after the initiation of biologic therapy were assessed using descriptive statistics, McNemar’s tests, and Poisson regression models, adjusting for age and sex. Results: A total of 29,559 biologic-naive IBD patients were included. Prior to index, 91.2% received at least one nonbiologic medication prescription, where corticosteroids and 5-ASA were the most common. Postindex, the overall prescription rate decreased to 87.7%, with significant reductions in prescriptions observed for corticosteroids, 5-ASA, and immunosuppressants (p-values < 0.001). The mean (SD) pill count dropped from 704 (1712) to 514 (1651), with the largest mean differences (95% CI) having been for corticosteroids (−77.9 [−80.3 to −75.5]), 5-ASA (−61.6 [−65.2 to −58.1]), and immunosuppressants (−55.0 [−57.5 to −52.6]). Older patients tended to have greater decreases in pill counts for corticosteroids and 5-ASA, while males showed statistically significant reductions in pill count for immunosuppressants compared with females. Conclusions: This study demonstrates that the prescription of nonbiologic medications significantly decreased after biologic therapy initiation. The use of biologics may therefore lead to improved disease management and potentially better patient outcomes. Full article

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria. Full article

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disorder with two main subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis involves genetic predisposition, dysbiosis, and immune dysregulation. Complications include perianal lesions, strictures, fistulas, perforations, and an increased risk of colon cancer. Clinical classification ranges from mild to fulminant and recurrent disease, with common symptoms such as abdominal discomfort, rectal bleeding, diarrhea, and weight loss. Extraintestinal manifestations include arthritis, erythema nodosum, pyoderma gangrenosum, and uveitis. Conventional treatments using aminosalicylates, corticosteroids, and immunomodulators have limitations. Biologics, introduced in the 1990s, offer improved efficacy and specificity, targeting factors like TNF-α, integrins, and cytokines. Monoclonal antibodies play a crucial role in IBD management, aiming to reduce relapses, hospitalizations, and surgeries. In conclusion, this review is aimed at summarizing the latest knowledge, advantages, and drawbacks of IBD therapies, such as small molecules, biologics, and monoclonal antibodies, to provide a basis for further research in the IBD field. Full article

Biliverdin IXβ reductase (BLVRB) has emerged as a promising therapeutic target for thrombocytopenia due to its involvement in reactive oxygen species (ROS) mechanisms. During the pursuit of inhibitors targeting BLVRB, olsalazine (OSA) became apparent as one of the most potent candidates. However, the direct application of OSA as a BLVRB inhibitor faces challenges, as it is prone to degradation into 5-aminosalicylic acid through cleavage of the diazenyl bond by abundant azoreductase (AzoR) enzymes in gut microbiota and eukaryotic cells. To overcome this obstacle, we devised olsalkene (OSK), an inhibitor where the diazenyl bond in OSA has been substituted with an alkene bond. OSK not only matches the efficacy of OSA but also demonstrates improved stability against degradation by AzoR, presenting a promising solution to this limitation. Furthermore, we have found that both OSK and OSA inhibit BLVRB, regardless of the presence of nicotinamide adenine dinucleotide phosphate, unlike other known inhibitors. This discovery opens new avenues for investigating the roles of BLVRB in blood disorders, including thrombocytopenia. Full article

Background: Current management of mild-to-moderate ulcerative colitis (UC) involves monitoring clinical markers of disease activity, such as stool frequency (SF) and rectal bleeding (RB), and adjusting treatment accordingly. Our aim was to assess whether targeting treatment based on faecal calprotectin (FC) levels (treat-to-target; T2T) provides greater UC disease control versus a symptom-based approach. Methods: This was a pragmatic, randomised (1:1) controlled study of patients with mild-to-moderate UC (global Mayo score 2–6) treated with ≤2.4 g/day 5-aminosalicylic acid that compared the effectiveness of two management strategies with (interventional arm) and without (reference arm) FC home monitoring over 12 months of follow-up. Treatment was optimised in the interventional arm using FC values and clinical symptoms (PRO-2), while the reference arm used only PRO-2. Results: 193 patients completed the study. No significant difference was found for the primary endpoint (Mayo Endoscopic Subscore [MES] = 0 at 12 months). A numerical advantage for the interventional arm over the reference arm for the primary endpoint (37.0% vs. 33.4%, respectively) and for MES ≤ 1, RB = 0, and SF ≤ 1 at 12 months was found following imputation for missing data. The composite endpoint of MES = 0, RB = 0, and SF ≤ 1 at 12 months was achieved at a significantly higher rate in the interventional arm than the reference arm (effect size [ES]: 0.17, 95% CI 0.02–0.32; p < 0.05). A similar result was obtained for MES ≤ 1, RB = 0 and SF ≤ 1 (ES: 0.22; 95% CI 0.07–0.37; p < 0.05). Conclusions: T2T using FC monitoring was effective in patients with mild-to-moderate UC at 12 months. Further longer-term studies are required to confirm the results. Full article

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. Full article

Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients. Full article

Diabetic wounds (DWs) are considered chronic complications observed in patients suffering from type 2 diabetes mellitus (DM). Usually, DWs originate from the interplay of inflammation, oxidation, impaired tissue re-epithelialization, vasculopathy, nephropathy, and neuropathy, all of which are related to insulin resistance and sensitivity. The conventional approaches available for the treatment of DWs are mainly confined to the relief of wound pressure, debridement of the wound, and management of infection. In this paper, we speculate that treatment of DWs with 5-aminosalicylic acid (5-ASA) and subsequent activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) and transforming growth factor beta (TGF-β) via the AhR pathway might be highly beneficial for DW patients. This estimation is based on several lines of evidence showing that 5-ASA and PPAR-γ activation are involved in the restoration of insulin sensitivity, re-epithelialization, and microcirculation. Additionally, 5-ASA and TGF-β activate inflammation and the production of pro-inflammatory mediators. Suitable stabilized formulations of 5-ASA with high absorption rates are indispensable for scrutinizing its probable pharmacological benefits since 5-ASA is known to possess lower solubility profiles because of its reduced permeability through skin tissue. In vitro and in vivo studies with stabilized formulations and a control (placebo) are mandatory to determine whether 5-ASA indeed holds promise for the curative treatment of DWs. Full article

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 μL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC. Full article