Inflammation assessment and therapeutic monitoring based on highly sensitive and multi-level electrochemical detection of PGE2.

Prostaglandin E2 (PGE2), an eicosane, regulates the physiological activity of inflammatory cells and represents a potential therapeutic target for facilitating tissue repair in vivo. In our work, an electrochemical immunosensor employing Ketjen black-Au nanoparticles (KB-Au) and poly tannic acid nanospheres conjugated with anti-PGE2 polyclonal antibody (PTAN-Ab) was designed to ultra-sensitively analyze PGE2 levels secreted by living cells and tissues. Antibody assembly strategies were explored to achieve signal amplification. Moreover, we studied the therapy effects of docosahexaenoic acid (DHA), arachidonic acid (AA), hyaluronic acid (HA), and small molecule 15-hydroxyprostaglandin dehydrogenase inhibitor (SW033291) on inflammation and evaluated the protective functions of HA and SW033291 in a murine model subjected to colitis induced by dextran sulfate sodium (DSS) using the developed sensor. The sensor exhibited a linear range of 10-5-106 fg/mL and a detection limit (LOD) of 10-5 fg/mL. Fetal bovine serum (FBS) samples were used to achieve high recovery of target analytes. This study not only presents an effective strategy for ultra-sensitively monitoring PGE2 but also provides valuable insights into assessing the degree of inflammation and the therapeutic effect of related drugs. Research on human health monitoring and regenerative medicine could greatly benefit from the findings.

Prevalence of Enteric Infections in Patients on Immune Checkpoint Inhibitors and Impact on Management and Outcomes.

BACKGROUND: Stool pathogen testing is recommended as part of the initial evaluation for patients with new-onset diarrhea on immune checkpoint inhibitors (ICIs), yet its significance has not been well-studied. We aimed to determine the impact of multiplex gastrointestinal (GI) pathogen PCR testing on the clinical course and use of immunosuppressive therapy in patients who develop diarrhea on ICIs. METHODS: This retrospective cohort included individuals who underwent GI pathogen panel PCR for diarrhea on ICIs at Memorial Sloan Kettering between 7/2015 and 7/2021. The primary outcome was use of immunosuppressive therapy for suspected immunotherapy-related enterocolitis (irEC). Secondary outcomes included diarrhea severity and endoscopic and histologic disease patterns. RESULTS: Among 521 ICI-treated patients tested for GI pathogens, 61 (11.7%) had a positive PCR. Compared to patients without detectable infections, patients with infections had more frequent grades 3-4 diarrhea (37.7% vs. 19.6%, P < .01) and colitis (39.3% vs. 14.7%, P < .01). However, patients with infections did not have higher rates of persistent or recurrent diarrhea and were less likely to receive steroids (P < .01) and second-line immunosuppressive agents (P = .03). In 105 patients with lower endoscopy, similar trends were observed and no differences in endoscopic severity or histologic patterns were noted between groups. CONCLUSIONS: GI infections in ICI-treated patients presenting with diarrhea are linked to more severe but self-limited clinical presentations and may be optimally treated with observation and supportive care alone. Routine and timely stool pathogen testing may help avert unnecessary empiric immunosuppression for suspected irEC, which has been linked to blunted antitumor responses and numerous adverse effects.

Transrectal Absorber Guide Raster-Scanning Optoacoustic Mesoscopy for Label-Free In Vivo Assessment of Colitis.

Optoacoustic imaging (OAI) enables microscale imaging of endogenous chromophores such as hemoglobin at significantly higher penetration depths compared to other optical imaging technologies. Raster-scanning optoacoustic mesoscopy (RSOM) has recently been shown to identify superficial microvascular changes associated with human skin pathologies. In animal models, the imaging depth afforded by RSOM can enable entirely new capabilities for noninvasive imaging of vascular structures in the gastrointestinal tract, but exact localization of intra-abdominal organs is still elusive. Herein the development and application of a novel transrectal absorber guide for RSOM (TAG-RSOM) is presented to enable accurate transabdominal localization and assessment of colonic vascular networks in vivo. The potential of TAG-RSOM is demonstrated through application during mild and severe acute colitis in mice. TAG-RSOM enables visualization of transmural vascular networks, with changes in colon wall thickness, blood volume, and OAI signal intensities corresponding to colitis-associated inflammatory changes. These findings suggest TAG-RSOM can provide a novel monitoring tool in preclinical IBD models, refining animal procedures and underlines the capabilities of such technologies to address inflammatory bowel diseases in humans.

Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System.

Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.

Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. METHODS: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. RESULTS: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. CONCLUSION: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

Immunotherapy-induced Colitis: A Comprehensive Review of Epidemiology, Clinical Presentation, Diagnostic Workup, and Management Plan.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a variety of malignancies including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers among others. Since their introduction, there has been significant improvement in survival and prognosis in patients with advanced malignancies. Unfortunately, improved outcomes have come at a price of significant immune-related adverse events, with those of the gastrointestinal tract being the most common. Gastrointestinal immune-related adverse events frequently present as diarrhea and colitis, the severity of which can range from mild diarrhea to fulminant colitis with intestinal perforation. Currently, management of ICI-induced colitis is primarily guided by retrospective studies and expert opinion. A significant number of ICI-induced colitis responds to high-dose corticosteroids; however, some patients require further therapy with biologics. There is limited information on the factors which may predispose patients to ICI-induced colitis. Future research elucidating these risk factors along with development of a scoring system could allow for risk-stratification of patients before initiation of ICI therapy. Such a system may help clinicians and patients keep a high index of suspicion regarding ICI-induced colitis and could hopefully reduce the incidence of severe cases. Similarly, future studies should investigate protective factors against ICI-induced colitis, which could potentially allow more patients to safely benefit from ICI therapy.

[Assessment of histologic activity in colitis]. / Otsenka gistologicheskoi aktivnosti kolitov.

The histological activity of the bowel inflammation is an extremely important morphological criterion that is encountered in the diagnosis of colitis. However, the determining of its degree is subjective and still does not have a generally accepted principle of gradation. The article describes the most common scale-schemes for assessing the severity of colitis, that include the degree of microscopic changes. The results of the analysis of the of histological activity degree on the material of colonobioptates in colitis of various etiologies (467 patients) are presented. It has been shown that the Geboes scale of ulcerative colitis can be used to assess histological activity in all forms of colitis. The histological features of inflammation should be reflected in the pathological diagnosis and are essential for clinical decision making. This index allows for a comparative analysis of clinical, endoscopic and morphological parameters and better control of the patient's condition during the treatment.

Recommendations for standardizing biopsy acquisition and histological assessment of immune checkpoint inhibitor-associated colitis.

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority.

Assessment of Murine Colon Inflammation Using Intraluminal Fluorescence Lifetime Imaging.

Inflammatory bowel disease (IBD) is typically diagnosed by exclusion years after its onset. Current diagnostic methods are indirect, destructive, or target overt disease. Screening strategies that can detect low-grade inflammation in the colon would improve patient prognosis and alleviate associated healthcare costs. Here, we test the feasibility of fluorescence lifetime imaging (FLIm) to detect inflammation from thick tissue in a non-destructive and label-free approach based on tissue autofluorescence. A pulse sampling FLIm instrument with 355 nm excitation was coupled to a rotating side-viewing endoscopic probe for high speed (10 mm/s) intraluminal imaging of the entire mucosal surface (50-80 mm) of freshly excised mice colons. Current results demonstrate that tissue autofluorescence lifetime was sensitive to the colon anatomy and the colonocyte layer. Moreover, mice under DSS-induced colitis and 5-ASA treatments showed changes in lifetime values that were qualitatively related to inflammatory markers consistent with alterations in epithelial bioenergetics (switch between ß-oxidation and aerobic glycolysis) and physical structure (colon length). This study demonstrates the ability of intraluminal FLIm to image mucosal lifetime changes in response to inflammatory treatments and supports the development of FLIm as an in vivo imaging technique for monitoring the onset, progression, and treatment of inflammatory diseases.

Artificial Intelligence for Disease Assessment in Inflammatory Bowel Disease: How Will it Change Our Practice?

Artificial intelligence (AI) has arrived and it will directly impact how we assess, monitor, and manage inflammatory bowel disease (IBD). Advances in the machine learning methodologies that power AI have produced astounding results for replicating expert judgment and predicting clinical outcomes, particularly in the analysis of imaging. This review will cover general concepts for AI in IBD, with descriptions of common machine learning methods, including decision trees and neural networks. Applications of AI in IBD will cover recent achievements in endoscopic image interpretation and scoring, new capabilities for cross-sectional image analysis, natural language processing for automated understanding of clinical text, and progress in AI-powered clinical decision support tools. In addition to detailing current evidence supporting the capabilities of AI for replicating expert clinical judgment, speculative commentary on how AI may advance concepts of disease activity assessment, care pathways, and pathophysiologic mechanisms of IBD will be addressed.

Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier.

With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.

Magnetic resonance colonography assessment of acute trinitrobenzene sulfonic acid colitis in pre-pubertal rats.

Pre-pubertal murine models of acute colitis are lacking. Magnetic resonance colonography (MRC) is a promising minimally invasive tool to assess colitis. We aimed to: 1/ Adapt a model of acute experimental colitis to pre-pubertal rats and determine whether MRC characteristics correlate with histological inflammation. 2/ Test this model by administering a diet supplemented in transforming growth factor ß2 to reverse inflammation. Twenty-four rats were randomized at weaning to one of 3 groups: Trinitrobenzene Sulfonic Acid (TNBS) group (n = 8) fed a standard diet, that received an intra-rectal 60 mg/kg dose of TNBS-ethanol; Control group (n = 8) fed standard diet, that received a dose of intra-rectal PBS; TNBS+MODULEN group (n = 8) that received a dose of TNBS and were exclusively fed MODULEN-IBD® after induction of colitis. One week after induction of colitis, rats were assessed by MRC, colon histopathology and inflammation markers (Interleukin 1ß, Tumor necrosis factor α, Nitric Oxide Synthase 2 and Cyclooxygenase 2). TNBS induced typical features of acute colitis on histopathology and MRC (increased colon wall thickness, increased colon intensity on T2-weighted images, target sign, ulcers). Treatment with MODULEN-IBD® did not reduce signs of colitis on MRC. Inflammatory marker expression did not differ among study groups.

Research-Based Product Innovation to Address Critical Unmet Needs of Patients with Inflammatory Bowel Diseases.

Despite progress in recent decades, patients with inflammatory bowel diseases face many critical unmet needs, demonstrating the limitations of available treatment options. Addressing these unmet needs will require interventions targeting multiple aspects of inflammatory bowel disease pathology, including disease drivers that are not targeted by available therapies. The vast majority of late-stage investigational therapies also focus primarily on a narrow range of fundamental mechanisms. Thus, there is a pressing need to advance to clinical stage differentiated investigational therapies directly targeting a broader range of key mechanistic drivers of inflammatory bowel diseases. In addition, innovations are critically needed to enable treatments to be tailored to the specific underlying abnormal biological pathways of patients; interventions with improved safety profiles; biomarkers to develop prognostic, predictive, and monitoring tests; novel devices for nonpharmacological approaches such as minimally invasive monitoring; and digital health technologies. To address these needs, the Crohn's & Colitis Foundation launched IBD Ventures, a venture philanthropy-funding mechanism, and IBD Innovate®, an innovative, product-focused scientific conference. This special IBD Innovate® supplement is a collection of articles reflecting the diverse and exciting research and development that is currently ongoing in the inflammatory bowel disease field to deliver innovative and differentiated products addressing critical unmet needs of patients. Here, we highlight the pipeline of new product opportunities currently advancing at the preclinical and early clinical development stages. We categorize and describe novel and differentiated potential product opportunities based on their potential to address the following critical unmet patient needs: (1) biomarkers for prognosis of disease course and prediction/monitoring of treatment response; (2) restoration of eubiosis; (3) restoration of barrier function and mucosal healing; (4) more effective and safer anti-inflammatories; (5) neuromodulatory and behavioral therapies; (6) management of disease complications; and (7) targeted drug delivery.

We highlight the pipeline of investigational therapies, diagnostics, and devices with potential to address pressing unmet needs of patients with inflammatory bowel diseases, including biomarkers for prognosis and treatment response, restoration of eubiosis and mucosal healing, neuromodulation, and improved control of inflammation and disease complications.

Immunomodulatory assessment of Portulaca oleracea L. extract in a mouse model of colitis.

Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.

An Observational Analysis of a Novel Digital Rectoscope.

BACKGROUND: This is an analysis of the first 50 in-human uses of a novel digital rigid sigmoidoscope. The technology provides digital image capture, telemedicine capabilities, improved ergonomics, and the ability to biopsy under pneumorectum while maintaining the low cost of conventional rigid sigmoidoscopy. The primary outcome was adverse events, and the secondary outcome was diagnostic view. PRELIMINARY RESULTS: Fifty patients underwent outpatient (n = 25) and surgical rectal assessment (n = 25), with a mean age of 60 years. This included 31 men and 19 women with 12 different clinical use indications. No adverse events were reported, and no defects were reported with the instrumentation. Satisfactory diagnoses were obtained in 48 (96%) of 50 uses, images were captured in 48 (96%) of 50 uses, and biopsies were successfully taken in 13 uses (26%). No adverse events were recorded. Independent reviewers of recorded videos agreed on the quality and diagnostic value of the images with a κ of 0.225 (95% CI, 0.144-0.305) when assessing whether the target pathology was adequately visualized. IMPACT OF INNOVATION: The improved views afforded by digital rectoscopy facilitated a satisfactory clinical diagnosis in 96% of uses. The device was successfully deployed in the operating room and outpatients irrespective of bowel preparation method, where it has the potential to replace flexible sigmoidoscopy for specific use cases. The technology provides a high-quality image and video that can be securely recorded for documentation and medicolegal purposes with agreement between blinded users despite a lack of standardized training and heterogenous pathology. We perceive significant impact of this technology for the assessment of colorectal anastomoses, the office management of colitis, "watch and wait," and for diagnostic support in rectal cancer diagnosis. The technology has significant potential to facilitate proctoring and training, and it now requires prospective trials to validate its diagnostic accuracy against more costly flexible sigmoidoscopy systems.

Codesign and implementation of an equity-promoting national health literacy programme for people living with inflammatory bowel disease (IBD): a protocol for the application of the Optimising Health Literacy and Access (Ophelia) process.

INTRODUCTION: Non-government organisations (NGOs) often represent people who are underserved or experiencing vulnerability. Crohn's & Colitis Australia (CCA) is aware that many Australians with inflammatory bowel disease (IBD) are not reached by current communication and engagement activities. The aim of the CCA IBD project is to implement the Optimising Health Literacy and Access (Ophelia) process over 3 years to collaboratively codesign ways to improve delivery of information, services and resources for people with IBD and their carers. METHODS AND ANALYSIS: Health literacy and other data for phase 1 will be collected using the Health Literacy Questionnaire, eHealth Literacy Questionnaire, IBD-related questions and qualitative interviews with people with IBD and their carers to ascertain their lived experience. Quantitative data will be analysed using descriptive statistics and cluster analysis. Identified clusters will be combined with qualitative data to develop vignettes (narratives of people's experiences of living with IBD) for stakeholder workshops to generate ideas for useful, accessible and sustainable solutions for identified health literacy needs. Selection and testing of health literacy actions happens in phase 2 and implementation and evaluation in phase 3 (2021-2023). Outcomes of this project include giving voice to people living with IBD, their carers and frontline healthcare practitioners. Genuine codesign informs the development and implementation of what is needed and wanted to improve access to and availability and quality of information and resources that support people to manage their health. There is potential for other NGOs to use the CCA Ophelia model in other health contexts to improve engagement with and understanding of the needs of the people they serve and to reduce health inequalities and improve health outcomes. ETHICS AND DISSEMINATION: Ethics approval for Ophelia phase 1 has been obtained from the Human Research Ethics Committee of Swinburne University of Technology (Ref: 20202968-4652) and by the South West Sydney Local Health District Research and Ethics Office for the purposes of questionnaire recruitment at Liverpool Hospital (Ref: 20202968-4652). Dissemination of the study findings will be the national codesign process and ownership development across the CCA community and through the genuine engagement of clinicians and relevant managers across Australia. The model and process will be directly distributed to international IBD associations and to other NGOs. It will also be disseminated through publication in a peer-reviewed journal, conference presentations and public reports on the CCA and Swinburne University of Technology website.

Assessment of the impact of age and of blood-derived inflammatory markers in horses with colitis.

OBJECTIVES: To determine the impact of age on survival in horses with colitis and to elucidate whether a lower type-1/type-2 cytokine ratio or an exaggerated inflammatory state contribute to reduced survival in aged horses. DESIGN: Part 1: Retrospective cohort analysis. Part 2: Analytic observational study. ANIMALS: Part 1: One hundred twenty-four adult horses with colitis. Part 2: Twenty-nine adult horses with new diarrhea onset while hospitalized. MEASUREMENTS AND MAIN RESULTS: Part 1: Patient signalment, select clinicopathological data, diagnoses, treatment, hospitalization length, and invoice were compared between survivors (n = 101) and nonsurvivors (n = 23). Only age and plasma transfusion retained statistical significance in the final multivariate outcome model, with 8.5 times lower odds of survival in transfused horses (95% confidence interval [CI], 2.6-27.2%). Additionally, the likelihood of nonsurvival increased by 11.8% (95% CI, 4-20.2%) for every year the horse aged (P = 0.002). Similarly, geriatric horses (≥20 years) were 15.2 times more likely to die than young-adults (2-12 years, P = 0.03), independent of financial investment, documented comorbidities, and duration of hospitalization. Part 2: Select cytokine analyses were performed on serum collected from hospitalized horses within 1 hour of diarrhea onset (T0) and 6 hours later. At T0, all recorded clinicopathological variables were comparable between geriatric and young-adult horses, suggesting a similar degree of systemic illness. The median concentration of type-2 cytokines interleukin-4 and interleukin-10, and type-1 cytokine interferon-γ did not differ between age groups. Inflammatory cytokines interleukin-6 and tumor necrosis factor-α were significantly higher in geriatric compared to young-adult horses at both sampling time points. CONCLUSIONS: Outcome of colitis was less favorable in aging horses and patients receiving a plasma transfusion. Although an exaggerated inflammatory state, based on increased interleukin-6 and tumor necrosis factor-α concentrations, in geriatric horses may contribute to reduced survival, a lower type-1/type-2 cytokines ratio was not identified in our geriatric population.