Comparison of hypersensitivity rates to intravenous and intramuscular PEG-asparaginase in children with acute lymphoblastic leukemia: A meta-analysis and systematic review.

BACKGROUND: Pegylated-asparaginase (PEG-ASP) is a critical treatment for pediatric acute lymphoblastic leukemia (ALL) and has traditionally been delivered via intramuscular (IM) injection. In an attempt to reduce pain and anxiety, PEG-ASP has increasingly been delivered via intravenous (IV) administration. The study objective was to perform a meta-analysis and systematic review to compare and generate pooled hypersensitivity rates for IM and IV PEG-ASP. METHODS: A systematic literature search was conducted for all epidemiological studies that investigated IV and IM hypersensitivity rates for pediatric ALL. Included studies were critically appraised using the GRACE checklist. Pooled estimates and odds ratios with 95% confidence intervals (CIs) for IM and IV hypersensitivity rates were derived based on either a random or fixed effects model. RESULTS: Four studies satisfied the inclusion criteria and were of adequate quality. The random effects pooled hypersensitivity rates were 23.5% (95% CI 14.7-33.7) and 8.7% (95% CI 5.4-12.8) for IV and IM, respectively. The fixed effects pooled odds ratio after adjusting for publication bias was 2.49 (95% CI 1.62-3.83), indicating a significantly higher risk of hypersensitivity for IV over IM PEG-ASP. This risk is far more pronounced for high-risk (HR) patients compared with standard-risk (SR) patients (IV vs. IM: HR ↑35.2% and SR ↓2.9%). CONCLUSIONS: Although administering PEG-ASP through IV is preferable for patients, it poses a significantly higher risk of hypersensitivity when compared with IM administration, especially for HR patients. We recommend pediatric oncologists consider treating patients with HR pediatric ALL with IM PEG-ASP to reduce the risk of hypersensitivity.

Risk Stratification in Cardiac Sarcoidosis With Cardiac Positron Emission Tomography: A Systematic Review and Meta-Analysis.

BACKGROUND: Although positron emission tomography (PET) imaging is well established for its diagnostic role in cardiac sarcoidosis, less is known about the prognostic value of PET and its use in risk stratification for major adverse cardiac events (MACE). OBJECTIVES: The goal of this study was to perform a systematic review and meta-analysis looking at the prognostic value of PET imaging in patients with cardiac sarcoidosis. METHODS: Study investigators systematically searched EMBASE (Excerpta Medica dataBASE), MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ClinicalTrials.gov, and the European Union Clinical Trial Registry for cardiac sarcoidosis and PET imaging. The primary outcome of interest was MACE. RESULTS: The search revealed 3,010 records, of which 55 studies were included. This represented 5,250 patients. Factors associated with MACE included the following: the combination of abnormal fluorodeoxyglucose (FDG) uptake and perfusion defect, which had an OR of 2.86 (95% CI: 1.74-4.71; P < 0.0001); abnormal perfusion or FDG uptake, which had an OR of 2.69 (95% CI: 1.67-4.33); abnormal FDG uptake, which had an OR of 2.61 (95% CI: 1.51-4.50); focal abnormal right ventricular uptake, which had an OR of 6.27 (95% CI: 3.19-12.32; P < 0.00001); and a lack of response to immunosuppression on serial PET, which had an OR of 8.43 (95% CI: 3.25-21.85; P < 0.0001). A QUIPS (Quality in Prognostic Studies) tool analysis found a low to moderate risk of bias, particularly given the small sample sizes in the individual studies. CONCLUSIONS: Multiple cardiac PET parameters provide risk stratification value in cardiac sarcoidosis. Focal right ventricular uptake and a lack of response to immunosuppressive therapy on serial PET imaging were particularly predictive of MACE.

Quality, Reliability, Technical Quality, and Readability of Google Online Information on Childhood Glaucoma.

PURPOSE: To evaluate the quality, reliability, technical quality, and readability of online information related to childhood glaucoma. METHODS: In this cross-sectional study, no human subjects were studied. Analysis was done for online websites on childhood glaucoma. The terms "childhood glaucoma," "pediatric glaucoma," "congenital glaucoma," "buphthalmos," and "big eyes" were entered into the Google search engine and the first 100 search results were assessed for quality, reliability, technical quality, and readability. Peer-reviewed articles, patient forum posts, dictionary definitions, and websites that appeared as targeted ads, were not in English, or were not focused on humans were excluded. Each website was evaluated for (1) quality and reliability using the DISCERN, HONcode, and JAMA criteria; (2) technical quality assessing 11 technical aspects; and (3) readability using six separate criteria (Flesch-Kincaid Reading Ease Score and Grade Level, Gunning Fog Index score, the Simple Measure of Gobbledygook Index, Coleman-Liau Index, and Automated Readability Index). RESULTS: The median scores for the DISCERN, HONcode, and JAMA criteria were 2.6 (range = 1 to 4.75; 1 = worst, 5 = best), 10 (range = 0 to 16; 0 = worst, 16 = best), and 2 (range = 0 to 4; 0 = worst, 4 = best), respectively. The median technical quality score was 0.7. Readability was poor among most websites, with a median Flesch-Kincaid grade Grade Level Score of 9.3. The median Gunning Fog Index score was 9.8. There was a statistically significantly higher JAMA score and Gunning Fog Index score among the private websites compared to the institutional websites. However, institutional websites had higher technical quality. CONCLUSIONS: Online information on childhood glaucoma had poor to moderate quality and reliability. The technical quality is good; however, most websites' readability was above the recommended 5th to 6th grade reading level. [J Pediatr Ophthalmol Strabismus. 2024;61(3):198-203.].

Alleviation of carbendazim toxicity effect by Moringa oleifera oil and Linum usitatissimum L. oil on testes of male rats: Physiological, histological and in silico study.

Carbendazim (CBZ) is a widely used fungicide that is used to control the unwanted growth of fungi on fruits and vegetables. Sixty male rats were divided into six groups, each having ten. Group one served as control, animals belonging to group two were exposed to CBZ in the measure of 200 mg/kg body weight (BW). In the third and fourth groups, rats were administered 800 mg/kg BW of Moringa oleifera (moringa oil) and Linum usitatissimum L. (flaxseed oil), plus CBZ with the same dose given to group two. Groups five and six were administered with moringa and flaxseed oils respectively for six weeks. A marked decline was seen in oxidative stress markers, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and a rise in malondialdehyde (MDA) level in group two with severe histological disruptions. Moringa oil and flaxseed oil were used to alleviate these changes. In addition, a biocomputational molecular docking analysis of three proteins found in male rats was performed. In relation to CBZ (CID:10584007) the screened proteins namely testis-expressed protein (TX101_RAT), EPPI_RAT, and glutathione peroxidase 5 (GPX5_RAT) were docked, and their docking score were obtained (-5.9 kcal/mol), (-5.8 kcal/mol) and (-5.6 kcal/mol) respectively. By examining these interactions in 2D and 3D structures, a detailed understanding of the unique and specific binding affinity, hydrogen bonds, hydrophobic interactions, ionic bonds, and water bonds were obtained. Structure-based virtual screening (SBVS) molecular docking analysis showed that protein interaction with CBZ causes reproductive complications in protein expression and functions by hampering their normal function and blocking active sites.

The BLISTER Score: A Novel, Externally Validated Tool for Predicting Cardiac Implantable Electronic Device Infections, and Its Cost-Utility Implications for Antimicrobial Envelope Use.

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P<0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P=0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P<0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P=0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P=0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P=0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P=0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P=0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator_876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients.

Concurrent Pacemaker Lead Perforation and Subacute Coronary Stent Thrombosis: A Case Report.

Stent thrombosis and lead perforation are important differentials for patients presenting with chest pain following recent coronary stent insertion and pacemaker insertion. In this report, we describe an unusual case of a 78-year-old male who presented with sharp chest pain one week after admission for posterior ST-elevation myocardial infarction (STEMI) and subsequent Mobitz type II block, for which he received primary percutaneous coronary intervention (PPCI) to the left circumflex artery (LCx) and dual chamber permanent pacemaker (PPM) insertion. Computed tomography (CT) chest and CT coronary angiogram (CTCA), respectively, showed he had concurrent lead perforation and stent thrombosis. On balance, the cause of chest pain was likely lead perforation. This diagnosis was reached by having a high index of suspicion for both of these important post-procedure complications and investigating appropriately.

A Detailed Correlation of Oral-Health-Related Quality of Life of Patients Undergoing Fixed Orthodontic Therapy.

Malocclusion is a dental condition that can affect both children's and adolescents' oral-health-related quality of life (OHRQoL), and the seriousness of the condition is indicated by the patient's requirement for orthodontic therapy. The patient or his or her caretaker may personally report the necessity for orthodontic therapy, or the doctor or orthodontist may quantify it objectively. However, discrepancies in the requirement for either objective orthodontic therapy or subjective orthodontic therapy have been noted. The OHRQoL measurements should be used in conjunction with the indicator of orthodontic therapy requirement to represent the patient's anticipated treatment requirement. Some systematic reviews have revealed evidence that malocclusion has a detrimental effect on OHRQoL. In addition to the effects of malocclusion, the impact of orthodontic therapy on OHRQoL has also been documented. There is a dearth of related follow-up studies, particularly those documenting OHRQoL improvements in adolescents both before the beginning of treatment and termination of orthodontics treatment. Additionally, it has been hypothesized that self-esteem affects OHRQoL, albeit there is insufficient data to support either its specific function or its connection to perceptions of oral health. As a result, the purpose of this literature review is to determine whether patients receiving fixed orthodontic therapy report any changes in their reported OHRQoL. There was an extensive review of available original research, case reports, systematic reviews, literature reviews, etc., available in reliable sources of information like PubMed, Scopus, Web of Science, etc. The review found that the process of receiving orthodontic therapy might be unpleasant, affecting OHRQoL. The discomfort caused by orthodontic equipment, which are foreign things put into a delicate portion of the body, is both psychological and physical. Such discomfort may have a detrimental effect on the patient's willingness to receive therapy, their participation, and the treatment's effectiveness. The main sources of discomfort that patients undergoing fixed orthodontic treatment report are the appliance's design, amount of force used in the early stages of their therapy, prior painful memories, emotional variables, cognitive variables, and environmental factors such as age, sex, and culture. As a result, orthodontic treatment may have negative effects on a person's QoL that, in most situations, are temporary.

Rectal roflumilast improves trinitrobenzenesulfonic acid-induced chronic colitis in rats.

Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.

NeuroCartography: Scalable Automatic Visual Summarization of Concepts in Deep Neural Networks.

Existing research on making sense of deep neural networks often focuses on neuron-level interpretation, which may not adequately capture the bigger picture of how concepts are collectively encoded by multiple neurons. We present Neurocartography, an interactive system that scalably summarizes and visualizes concepts learned by neural networks. It automatically discovers and groups neurons that detect the same concepts, and describes how such neuron groups interact to form higher-level concepts and the subsequent predictions. Neurocartography introduces two scalable summarization techniques: (1) neuron clustering groups neurons based on the semantic similarity of the concepts detected by neurons (e.g., neurons detecting "dog faces" of different breeds are grouped); and (2) neuron embedding encodes the associations between related concepts based on how often they co-occur (e.g., neurons detecting "dog face" and "dog tail" are placed closer in the embedding space). Key to our scalable techniques is the ability to efficiently compute all neuron pairs' relationships, in time linear to the number of neurons instead of quadratic time. Neurocartography scales to large data, such as the ImageNet dataset with 1.2M images. The system's tightly coordinated views integrate the scalable techniques to visualize the concepts and their relationships, projecting the concept associations to a 2D space in Neuron Projection View, and summarizing neuron clusters and their relationships in Graph View. Through a large-scale human evaluation, we demonstrate that our technique discovers neuron groups that represent coherent, human-meaningful concepts. And through usage scenarios, we describe how our approaches enable interesting and surprising discoveries, such as concept cascades of related and isolated concepts. The Neurocartography visualization runs in modern browsers and is open-sourced.

Aggressive Cholesterol Pericarditis With Minimal Effusion Masquerading as Treatment-Refractory Autoimmune Disease.

A middle-aged woman with rheumatoid arthritis presented with treatment-refractory pericarditis. Symptoms persisted despite escalation of immunosuppression, and she had recurrent admissions for heart failure. Imaging revealed minimal pericardial effusion and a thickened pericardium. Invasive hemodynamics confirmed constrictive physiology, and a pericardiectomy was required. Pathology testing confirmed cholesterol pericarditis, a rare condition of inflammatory cholesterol deposits within the pericardium. Previous reports describe moderate-to-large volumes of gold-coloured pericardial fluid. This case illustrates that cholesterol pericarditis can present with minimal pericardial effusion and rapidly progress to pericardial constriction.

Une femme d'âge moyen atteinte d'arthrite rhumatoïde a présenté une péricardite réfractaire. Les symptômes ont persisté en dépit de l'escalade de l'immunodépression. Elle a été admise de façon répétitive en raison d'insuffisance cardiaque. L'imagerie a révélé un épanchement péricardique minimal et un péricarde épaissi. L'exploration hémodynamique invasive a permis de confirmer la physiologie constrictive. Une péricardectomie a été nécessaire. L'examen pathologique a permis de confirmer la péricardite cholestérolique, une affection inflammatoire rare due aux dépôts de cholestérol dans le péricarde. Les observations précédentes décrivent des volumes modérés à élevés de liquide péricardique doré. Ce cas illustre que la péricardite cholestérolique peut se traduire par un épanchement péricardique minimal et progresser rapidement vers la péricardite constrictive.

CNN Explainer: Learning Convolutional Neural Networks with Interactive Visualization.

Deep learning's great success motivates many practitioners and students to learn about this exciting technology. However, it is often challenging for beginners to take their first step due to the complexity of understanding and applying deep learning. We present CNN Explainer, an interactive visualization tool designed for non-experts to learn and examine convolutional neural networks (CNNs), a foundational deep learning model architecture. Our tool addresses key challenges that novices face while learning about CNNs, which we identify from interviews with instructors and a survey with past students. CNN Explainer tightly integrates a model overview that summarizes a CNN's structure, and on-demand, dynamic visual explanation views that help users understand the underlying components of CNNs. Through smooth transitions across levels of abstraction, our tool enables users to inspect the interplay between low-level mathematical operations and high-level model structures. A qualitative user study shows that CNN Explainer helps users more easily understand the inner workings of CNNs, and is engaging and enjoyable to use. We also derive design lessons from our study. Developed using modern web technologies, CNN Explainer runs locally in users' web browsers without the need for installation or specialized hardware, broadening the public's education access to modern deep learning techniques.

Recombinant expression of aryl hydrocarbon receptor for quantitative ligand-binding analysis.

Recombinant expression of the aryl hydrocarbon receptor (AhR) yields small amounts of ligand-binding-competent AhR. Therefore, Spodoptera frugiperda (Sf9) cells and baculovirus have been evaluated for high-level and functional expression of AhR. Rat and human AhR were expressed as soluble protein in significant amounts. Expression of ligand-binding-competent AhR was sensitive to the protein concentration of Sf9 extract, and coexpression of the chaperone p23 failed to affect the yield of functional ligand-binding AhR. The expression system yielded high levels of functional protein, with the ligand-binding capacity (Bmax) typically 20-fold higher than that obtained with rat liver cytosol. Quantitative estimates of the ligand-binding affinity of human and rat AhR were obtained; the Kd for recombinant rat AhR was indistinguishable from that of native rat AhR, thereby validating the expression system as a faithful model for native AhR. The human AhR bound TCDD with significantly lower affinity than the rat AhR. These findings demonstrate high-level expression of ligand-binding-competent AhR, and sufficient AhR for quantitative analysis of ligand binding.

Nonverbal synchrony in virtual reality.

How might nonverbal synchrony naturally evolve in a social virtual reality environment? And how can avatar embodiment affect how participants coordinate nonverbally with each other? In the following pre-registered between-subjects experiment, we tracked the movements of pairs of users during a collaborative or competitive task in immersive virtual reality. Each conversational partner controlled either a customized avatar body or an abstract cube that responded to their movements. We compared the movements of the actual user pairs between the two conditions, and to an artificial "pseudosynchrony" dataset composed of the movements of randomly combined participant pairs who did not actually interact. We found stronger positive and negative correlations between real pairs compared to pseudosynchronous pairs, providing evidence for naturally occurring nonverbal synchrony between pairs in virtual reality. We discuss this in the context of the relationships between avatar appearance, task success, social closeness and social presence.

The genetic association study of TP53 polymorphisms in Saudi obese patients.

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.

The potential protective influence of flaxseed oil against renal toxicity induced by thioacetamide in rats.

The present study was aimed to evaluate the influence of flaxseed oil on renal toxicity induced by thioacetamide in male rats. The animals were distributed into four groups. Rats of the first group were served as control. Rats of the second group were exposed to thioacetamide. Rats of the third group were treated with flaxseed oil and thioacetamide. Rats of the fourth group were treated with flaxseed oil. Significant increases of blood creatinine and uric acid were observed in TAA-treated rats after three weeks. In thioacetamide group, the levels of serum creatinine, blood urea nitrogen and uric acid were significantly elevated after six weeks. Histopathologically, the renal sections from thioacetamide-treated rats showed severe alterations in the structure of renal corpuscles including a degeneration of glomeruli and Bowman's capsules. Administration of flaxseed oil protects the observed biochemical and histopathological alterations induced by thioacetamide exposure. Hence, the results of this study suggest that flaxseed oil protects against thioacetamide-induced renal injury and the protective influence of flaxseed oil may be attributed to its antioxidant role.

Negative impact of severity of pain on mood, social life and general activity in Parkinson's disease.

OBJECTIVE: Pain is an important non-motor symptom of Parkinson's disease (PD); however, it remains understudied. The purpose of previous studies on the relationship between PD and pain, has been to explore the cause, origin and types of pain. This case control study is designed for clinicians and rehabilitation specialists to effectively identify pain from the patient's point of view. Pain present in PD patients correlates with significant disruption to their daily lives, which was seen by analysing characteristics, frequency, severity and interference of pain. METHOD: A total of 100 PD patients and 100 control healthy individuals, consisting of 66 males and 34 females were evaluated during routine clinical assessment followed by a neurological exam. The Brief Pain Inventory (BPI) was used to measure chronic pain in terms of pain severity, pain interference and pain frequency between the two groups. RESULTS: It was determined that PD patients had significantly higher pain severity scores compared to controls (p < 0.05). PD patients with depressive symptoms had significantly higher pain severity and pain interference scores than controls without depressive symptoms. PD patients reported greater scores on Global BPI pain interference and all components of the pain interference subscale. DISCUSSION: PD and depression seem to be correlated with higher perceived pain, severity and interference. These findings have not been reported by other case control studies, and warrant further causal research into pain, depression and PD.

Rectal roflumilast improves trinitrobenzenesulfonic acid-induced chronic colitis in rats

Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.