Presence Of Active Inflammation Research Articles

P065 The evolution of inflammatory bowel disease can be monitored through multi-omics characterization of gut tissues

Abstract Background The aim of the study is to dissect the mechanisms associated with the evolution of Inflammatory Bowel Disease (IBD), including Crohn’s Disease (CD) and Ulcerative Colitis (UC) in both pediatric and adult patients, along with the severity of the disease and the risk to develop malignancy. Methods A multiomics approach, including miRNA (N=700), gene expression (N=800 genes) (nCounter platform; Nanostring) and methylation (Infinium Methylation Epic Bead Chip kit, Illumina), was utilized to characterize the gut tissue biopsies from pediatric (N=20) and adult (N=18) IBD patients. Moreover, a cohort of patients with gut malignancies with history of IBD were also enrolled in the study. Additionally, the role of Natural Killer Group 2D ligands (NKG2DLs) along with different stages of IBD (remission, mild, moderate and severe) were investigated. Results Differential miRNA and gene signatures were found by the comparison of tissues from pediatric and adult patients with different stages of the disease. N=83 miRs were significantly differentially detected between pediatric and adult patients (P<0.05). miR-630, miR-493-3p and miR-370-3p were found over-expressed in adult vs. pediatric gut tissues. These miRs are involved in epithelial-to-mesenchymal transition (EMT) through the WNT/β-catenin pathway. These miRNAs can also regulate cell proliferation, cell adhesion and migration and cancer development. Interestingly, miR-20a and miR-34a, which are known modulators of NKG2DLs expression were upregulated in tissues from severe vs. mild disease. The gene expression analysis highlighted, among multiple differentially detected pathways in tissues with different grades of IBD, genes, such as SMAD4, EGR1, CHUCK and JAG1, associated with inflammation, stemness, immune regulation, cell proliferation and migration. Through qPCR analyses, the higher expression of the NKG2DLs MICB was detected in tissues from left or right sides, respectively for both pediatric and adult patients while similar observation occurred for MICA only in adult patients. Soluble NKG2DLs were also detected in the plasma of IBD patients, with in some cases differences (P<0.05) in patients vs. healthy donors. sULBP3 correlated with the presence of active inflammation in adult IBD tissues. Confocal imaging of IBD tissues showed upregulation of stemness-associated markers (e.g., LGR5) and NKG2DLs (ULBP-1 and ULBP-3) in adult vs. pediatric patients. Conclusion The ongoing integration of data from multi-omics and the expression of immune-related molecules can lead to the identification of candidate molecular mechanisms associated with the evolution of IBD.

Pathophysiology of cartilage damage in knee osteoarthritis and regenerative approaches toward recovery

Abstract Osteoarthritis (OA) is a prevalent chronic ailment that significantly contributes to disability in the elderly population. Despite its widespread impact, recent years have witnessed remarkable strides in its treatment. This condition affects the entire joint, posing a significant challenge in regenerating articular cartilage, particularly in the presence of active inflammation. The contemporary approach to OA treatment encompasses a spectrum of therapeutic options, ranging from cell and gene therapies to innovative tissue engineering techniques. This review seeks to offer a comprehensive insight into the current landscape of regenerative strategies, delving into their respective advantages and drawbacks while addressing the inherent challenges and potential opportunities they present. By scrutinizing the existing methodologies, the aim is to guide future research endeavors toward targeted areas that hold promise for propelling advancements in the field of OA treatment. As the scientific community continues to explore novel avenues, the holistic understanding presented in this review sets the stage for a more nuanced and informed approach to managing this prevalent and debilitating condition.

Diagnosis and Treatment of Cardiac Sarcoidosis.

About 5% of sarcoidosis patients develop clinically manifest cardiac features. Cardiac sarcoidosis (CS) typically presents with conduction abnormalities, ventricular arrhythmias and heart failure. Its diagnosis is challenging and requires a substantial degree of clinical suspicion as well as expertise in advanced cardiac imaging. Adverse events, particularly malignant arrhythmias and development of heart failure, are common among CS patients. A timely diagnosis is paramount to ameliorating outcomes for these patients. Despite weak evidence, immunosuppression (primarily with corticosteroids) is generally recommended in the presence of active inflammation in the myocardium. The burden of malignant arrhythmias remains important regardless of treatment, thus leading to the recommended use of an implantable cardioverter defibrillator in most patients with clinically manifest CS.

54 FACTORS ASSOCIATED WITH TIME TO CLINICAL REMISSION IN PEDIATRIC LUMINAL CROHN'S DISEASE, A RETROSPECTIVE COHORT STUDY

Abstract Background The natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature. Objectives The aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission. Design/Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission. Results 654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (adjusted beta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission. Conclusion In children with newly diagnosed CD, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission. Figure 1 : Kaplan-Meier curve representing time to clinical remission in patients 13 years old and older by sex. Figure 2 : Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered.

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial

A188 FACTORS ASSOCIATED WITH CLINICAL REMISSION IN PEDIATRIC LUMINAL CROHN’S DISEASE: A RETROSPECTIVE COHORT STUDY

BackgroundThe natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature.AimsThe aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission.MethodsPatients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission.Results654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (ajusted bêta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission.ConclusionsTime to clinical remission did not improve during the decade and was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission. Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered.Funding AgenciesNoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine

The value of SPARCC sacroiliac MRI scoring in axial psoriatic arthritis and its association with other disease parameters.

This study aimed to assess patients with axial psoriatic arthritis (AxPsA) using the Canadian Spondyloarthritis Research Consortium (SPARCC) sacroiliac joint (SIJ) scores and to seek correlations between magnetic resonance imaging (MRI) scores and disease characteristics. Forty PsA patients (32 females, mean age 46.4years) who had been documented to have active or structural lesions on SIJ MRI were retrospectively evaluated. Disease duration, medications, and disease activity, including Disease Activity in Psoriatic Arthritis (DAPSA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) were recorded. On sacroiliac MRI scans, the SPARCC scores of sacroiliac joint inflammation (SIS) and sacroiliac joint structural damage (SSS) were evaluated. The mean disease duration was 51.4±70.4months. MRI showed active inflammation in 30 patients (75%) and at least 1 structural lesion in 32 patients (92.5%). The most prevalent structural lesion was erosion (82.5%), followed by fat metaplasia (65%), backfill (12.5%), and ankylosis (2.5%). Only fat metaplasia scores were significantly higher in men than in women (P=.007). Of clinical and laboratory parameters, only C-reactive protein (CRP) was significantly higher in the presence of active inflammation (P=.01). The SIS score was significantly correlated with disease duration (r=-.35) and CRP levels (r=.42,). The SSS score was inversely correlated with BASDAI (r=-.37), ASDAS-CRP (r=-.39), and ASDAS - erythrocyte sedimentation rate (r=-.32). The overall SPARCC scores did not differ between patients in DAPSA remission and non-remission and between those in MDA and non-MDA. Although radiologic involvement is generally not severe in AxPsA, MRI still provides additional information about inflammatory activity and structural lesions. CRP may be helpful in monitoring the radiologic disease activity in AxPsA.

P141 Factors Associated with Time to Clinical Remission in Pediatric Luminal Crohn’s disease: a Retrospective Cohort Study

Abstract Background The natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature. The aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission. Methods Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission. Results 654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (ajusted bêta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission. Figure 1: Kaplan-Meier curve representing time to clinical remission in patients 13 years old and older by sex. Figure 2: Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered. Conclusion Time to clinical remission did not improve during the decade and was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission.

Factors associated with time to clinical remission in pediatric luminal Crohn's disease: A retrospective cohort study.

Background and AimData on factors influencing time to remission in pediatric Crohn's disease (CD) are very limited in the literature. The aim of this retrospective cohort study was to describe the trends of time to clinical remission over the past decade and to identify factors associated with time to clinical remission in children with luminal CD.MethodsPatients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients' medical records. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological, and therapeutic factors on time to clinical remission.ResultsA total of 654 patients were included in the study. There was no change in the time to clinical remission over the decade. Female sex in adolescents (adjusted bêta regression coefficient [aβ] = 31.8 days, P = 0.02), upper digestive tract involvement (aβ = 46.4 days, P = 0.04) perianal disease (aβ = 32.2 days, P = 0.04), presence of active inflammation on biopsies at diagnosis (aβ = 46.7 days, P = 0.01) and oral 5‐aminosalicylates (5‐ASA) exposure (aβ = 56.6 days, P = 0.002) were associated with longer time to clinical remission. Antibiotic exposure (aβ = −29.3 days, P = 0.04), increased eosinophils (aβ = −29.6 days, P = 0.008) and combination of exclusive enteral nutrition with tumor‐necrosis‐factor‐alpha (TNF‐alpha) inhibitors as induction therapy (aβ = −36.8 days, P = 0.04) were associated with shorter time to clinical remission.ConclusionIn children with newly diagnosed Crohn's disease, time to clinical remission did not shorten during the decade. It was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF‐alpha inhibitors was associated with faster clinical remission.

Kawasaki disease presenting with hoarseness: A multinational study of the REKAMLATINA network.

Recently, hoarseness affecting the supraglottic structure has been reported in Kawasaki disease (KD). The objective of this study was to characterize the frequency of hoarseness in acute KD patients in Latin America. We used prospective data from the multinational Red de Enfermedad de Kawasaki en America Latina (REKAMLATINA) network. A total of 865 patients from 20 countries were enrolled during the 3 year study period. Data on hoarseness were available in 858 (99.2%) patients. The clinical and laboratory characteristics between hoarse and non-hoarse KD were compared. Hoarseness was documented in 100 (11.6%) patients. Hoarse patients were younger than those with KD without hoarseness (median age 18 vs 26months; P=0.002) and presented with lower hemoglobin (10.7g/dL vs 11.3g/dL; P=0.040) and hematocrit levels (32% vs 33%, P=0.048). Hoarseness was found to be prevalent as a presenting sign of acute KD in younger children. Anemia may indicate the presence of active inflammation.

How common is active inflammation in progressive multiple sclerosis?

In patients with progressive multiple sclerosis, the presence of active inflammation is associated with improved efficacy of anti-inflammatory therapies. However, the frequency of active inflammation in this patient population is unknown, and is the subject of a new study.

Increased Intracranial Hemorrhage Amid Elevated Inflammatory Markers in Those With COVID-19 Supported With Extracorporeal Membrane Oxygenation.

COVID-19-related coagulopathy is a known complication of SARS-CoV-2 infection and can lead to intracranial hemorrhage (ICH), one of the most feared complications of extracorporeal membrane oxygenation (ECMO). We sought to evaluate the incidence and etiology of ICH in patients with COVID-19 requiring ECMO. Patients at two academic medical centers with COVID-19 who required venovenous-ECMO support for acute respiratory distress syndrome (ARDS) were evaluated retrospectively. During the study period, 33 patients required ECMO support; 16 (48.5%) were discharged alive, 13 died (39.4%), and 4 (12.1%) had ongoing care. Eleven patients had ICH (33.3%). All ICH events occurred in patients who received intravenous anticoagulation. The ICH group had higher C-reactive protein (P = 0.04), procalcitonin levels (P = 0.02), and IL-6 levels (P = 0.05), lower blood pH before and after ECMO (P < 0.01), and higher activated partial thromboplastin times throughout the hospital stay (P < 0.0001). ICH-free survival was lower in COVID-19 patients than in patients on ECMO for ARDS caused by other viruses (49% vs. 79%, P = 0.02). In conclusion, patients with COVID-19 can be successfully bridged to recovery using ECMO but may suffer higher rates of ICH compared to those with other viral respiratory infections.

Effect of Crohn's Disease on Villous Length and CYP3A4 Expression in the Pediatric Small Intestine.

Changes in absorptive capacity and first‐pass metabolism in the small intestine affect oral drug bioavailability. Characterization of such changes as a consequence of inflammation is important for developing physiologically‐based pharmacokinetic (PBPK) models for inflammatory bowel disease. We sought to elucidate the impact of small intestinal Crohn’s disease (CD) on villous length and CYP3A4 expression in children. Freshly frozen duodenal and terminal ileum (TI) biopsies from 107 children (1–19 years) with and without CD were evaluated for active inflammation. Villous length and CYP3A4 mRNA/protein expression were compared among regions of active and inactive inflammation in CD and controls. A twofold reduction in villous length was observed in inflamed duodena and ilia of children with CD, but in the absence of regional inflammation, villi in CD were comparable in length to controls. Expression of CYP3A4 mRNA correlated significantly with villous length in the TI (P = 0.0003), with a trend observed in the duodenum that did not reach statistical significance. In the presence of active inflammation, a significant decrease in CYP3A protein expression was confirmed in the duodenum, where protein expression also correlated significantly with villous length across diagnoses (P < 0.0001). Our findings suggest that previous observations of decreased CYP3A4 expression and function in inflamed intestine may not be due solely to downregulation by inflammatory cytokines, but also to villous blunting and subsequent loss of surface area for protein expression. This information is relevant for PBPK model development and could aid with dose adjustment decisions for oral CYP3A4 substrates administered during CD flare (e.g., budesonide).

The Role of Portoenterostomy with Aggressive Hilar Dissection in Biliary Tract Tumors: Report of Case Series and Review of the Literature

Hepaticojejunostomy is a challenging and complex procedure to be done with confidence in conditions that contain a large number of segmental bile ducts. Portoenterostomy can be defined as the joining of multiple bile ducts into a single cavity using segmenter bile duct ends, stents, and surrounding connective tissues. During surgery, in cases with advanced stage biliary tract tumors that cannot be performed hepatectomy, after aggressive dissections to provide a negative surgical margin, a large number of segmental bile ducts can be revealed and needs to ensure the continuity of bile flow. Here, our clinical series of portoenterostomy (PE) in which we applied in patients who had aggressive hilar dissection and resection for hilar cholangiocarcinomas and biliary tract tumors were discussed. The study included 15 patients who underwent PE for biliary tract tumors and hilar cholangiocarcinomas between 2015 and 2019. Six of the patients had a tumor-negative surgical margin, with a mean follow-up of 14.4 months (range 2 to 28 months). Nine of the patients had a tumor-positive surgical margin, with a mean follow-up of 7.7 months (range 2 to 17 months). Portoenterostomy instead of hepaticojejunostomy in small and multiple biliary radicles and bile duct cancers has been successfully performed in 15 patients of bile duct cancer and Klatskin tumor. In the presence of active inflammation, fibrosis, major bile duct trauma, and thin bile duct radicles, this method, which is described in detail, provides an excellent salvage surgical procedure with less morbidity.

Inflammation without pain: Immune-derived opioids hold the key.

Visceral pain is commonly associated with acute or remitting inflammatory bowel disease (IBD). In marked contrast, chronic IBD is often painless, even in the presence of active inflammation. This suggests that inflammation in itself is insufficient to sustain altered nociceptive signaling and raises the possibility that there is an endogenous analgesic system in effect in chronic disease. A new study by Basso et al. published in this issue of Neurogastroenterology & Motility provides additional support for an immune-mediated mechanism that suppresses visceral hypersensitivity. The authors examined visceral pain in the IL-10-piroxicam model of chronic colitis, which differs from other experimental IBD models in that it involves immune suppression. During active inflammation, responses by these mice to graded increases in colorectal distension were equivalent to healthy controls, consistent with normal afferent signaling. However, treatment with a peripherally restricted opioid receptor antagonist resulted in marked visceral hypersensitivity to the same stimuli. This effect was attributed to the production of endogenous opioids by colitogenic CD4+ T cells present in the mucosa. This mini-review provides a brief overview of analgesia by immune-derived opioids under inflammatory conditions and highlights how the work of Basso et al. contributes to this area of research. Potential pharmacological approachesto harness or mimic this systemare provided. These strategiesmay prove to be an effective means through which targeted and sustained relief of IBD pain may be achieved.

Potential role of brain biomarkers in primary knee osteoarthritis patients using magnetic resonance spectroscopy

BackgroundPain in osteoarthritis (OA) primarily results from tissue damage but its' intensity does not essentially parallel the extent of joint destruction or presence of active inflammation, thus suggesting the likely involvement of a central component. The mid-anterior cingulate cortex (mACC) has an important role in pain perception, intensity and progression. In OA, low mACC γ-aminobutyric acid (GABA) was associated with high pain suggesting a role of prefrontal disinhibition. Aim of the work: To investigate the role of mACC (GABA) levels in chronic knee OA (KOA) pain and determine if magnetic resonance spectroscopy (MRS) brain neurotransmitters can serve as potential biomarkers. Patients and methods: Forty-five patients with primary KOA (M/F:33/12; age:57 ± 6 years) along with 15 matched controls were recruited. Pain was assessed using Visual Analogue Scale (VAS), Pain Catastrophizing Scale (PCS) and Western Ontario McMaster Osteoarthritis (WOMAC) questionnaire. mACC (GABA) was assessed and brain MRS neurotransmitters analysed including glutamate (Glx); N-acetylaspartate (NAA), total choline (tCho) and myo-inositol. Results: MRS analysis demonstrated no metabolite differences between controls and KOA patients in GABA, Glx, NAA and tCho. Myo-inositol:Glx ratio was significantly higher in patients (1.47 ± 0.37 vs 1.1 ± 0.29; p < 0.001). mACC (GABA) negatively correlated with VAS (r = −0.86, p < 0001), PCS (r = −0.94, p < 0001) and WOMAC (r = −0.96, p < 0001) in KOA patients. Myo-inositol:Glx significantly correlated with the age (r = 0.31, p < 0.038), disease duration (r = 0.61, p < 0.0001), VAS (r = 0.4, p < 0.02), PCS (r = 0.48, p < 0.001) and WOMAC (r = 0.53, p < 0.0001). Conclusions: This work confirms the importance of mACC in central sensitization of pain and highlights a promising role of the inflammatory neurotransmitter GABA and myo-inositol:Glx ratio as mechanistic biomarkers of chronic KOA pain.

655 Tumor Necrosis Factor Antagonists Are Superior to Ustekinumab and Vedolizumab for the Prevention of Postoperative Recurrence in Adult Crohn's Disease

INTRODUCTION: Relapse of Crohn's disease (CD) is common after surgical resection. Prior data have demonstrated that postoperative tumor necrosis factor antagonists (anti-TNF) may reduce recurrence, although little is known about the efficacy of other biologic therapies. The aim of this study was to compare biologics for preventing postoperative objective recurrence in adult CD patients. METHODS: We performed a retrospective chart review of CD patients who underwent intestinal resection from 2012 to 2018. Demographics, IBD history, pre- and postoperative course were obtained from the electronic medical record. The primary outcome was postoperative recurrence during follow up, defined as a composite of endoscopic (Rutgeerts grade &gt; i2), biochemical (increase in CRP &gt;5 mg/dL), or radiographic (presence of active inflammation) disease recurrence stratified by postoperative biologic exposure, including anti-TNF, vedolizumab (VDZ), ustekinumab (UST), and no therapy. Student's t-test, Pearson's chi-squared, logistic and Cox regression analyses were used to detect differences in the composite and components of the outcome among these groups. RESULTS: 123 patients were included. CD recurrence occurred in 36.6% of patients (13.0% biochemically, 24.4% endoscopically, 16.3% radiographically) at a median of 6.9 months (IQR 3.3-14.1) from surgery (Table 1). The number of patients in the anti-TNF, VDZ, UST, and no therapy groups were 57 (46.7%), 6 (4.9%), 13 (10.7%), and 46 (37.7%), respectively. Biologic therapy was initiated after ileostomy reversal within 3 months for 55 patients (72.4%), between 3-6 months for 11 patients (14.5%), and between 6-12 months for 10 patients (13.2%). Adjusting for prior resection and anti-TNF exposure, any biologic initiation within 6 months of surgery was superior to initiation after 6 months for preventing postoperative endoscopic recurrence (OR 0.24, 0.06-0.92), but not for the composite outcome. There were statistically significant differences among biologics for recurrence (Figure 1). Adjusting for prior resection and anti-TNF exposure, less patients relapsed under anti-TNF exposure compared to UST (HR 3.46, 1.45-8.23) for the composite outcome, and compared to UST (HR 3.95, 1.43-10.9) and VDZ (HR 4.42, 1.02-19.1) for endoscopic recurrence (Figure 2). CONCLUSION: Among CD patients, initiation of biologics within 6 months and anti-TNF agents were superior in preventing postoperative recurrence compared to other management strategies.

High prevalence of IBD-associated genetic variants in patients (pts) with immune checkpoint inhibitor (ICI) enteritis/colitis.

2582 Background: Colitis is a frequent toxicity of ICI therapy but there is paucity of data on risk factors. Specific serological markers and genetic polymorphisms have been associated with inflammatory bowel disease (IBD) (ulcerative colitis, Crohn’s disease). However, the prevalence of these markers in pts with ICI colitis is unknown. We performed a pilot study to determine the prevalence of IBD-associated genetic and serologic biomarkers in pts with ICI colitis. Methods: Cancer pts with histologically confirmed ICI enteritis/colitis and no history of IBD underwent commercial IBD panel testing. The panel included 4 genetic markers ( ATG16L1, NXK2–3, ECM1, STAT3), 8 serological markers (anti-A4-Fla2, anti-A4-FlaX, anti-CBir1, anti-OmpC, ASCAIgA, ASCA-IgG, pANCA, ANCA), and 5 inflammatory markers (vascular endothelial growth factor [VEGF], intracellular adhesion molecule 1[ICAM-1], vascular cell adhesion molecule 1 [VCAM-1], C-reactive protein, serum amyloid A [SAA]). Clinical testing on serum samples was performed by Prometheus Laboratories (San Diego, CA). Results: Of 15 cancer pts with biopsy confirmed ICI colitis, 10 (67%) were homozygous for 1 or more of 4 genetic markers. The remaining 5 pts were all heterozygous for two or more of the genetic markers. One or more serologic markers associated with IBD were elevated in 7/15 (47%) pts. Serum reactivity was noted for ASCA-IgA (1/15, 7%), ASCA-IgG (1/15, 7%), anti-OmpC (3/15, 20%), anti-CBR IgG (2/15, 13%), anti-A4-FlaX (1/15, 7%), and ANCA (2/15, 13%). One or more inflammatory markers were elevated in 13/15 (88%) pts. Elevations in VEGF, VCAM-1, ICAM-1, and SAA were noted in 2 (13%), 8 (53%), 8 (53%), and 11 (73%) pts, respectively. Only 6 (40%) pts had elevations in CRP levels despite the presence of active inflammation on biopsy. The IBD panel was reported as being consistent with Crohn’s disease in 2 pts, ulcerative colitis in 1 pt and inconclusive for type but consistent with IBD in 1 pt. Conclusions: In this pilot study, all patients with ICI colitis, were either homozygous or heterozygous for two or more high risk IBD alleles. If validated, such testing may prospectively identify pts at risk for developing ICI colitis.

Multimodalities Imaging of Immunoglobulin 4-related Cardiovascular Disorders.

Immunoglobulin 4 (IgG4)-related systemic disease (IgG4-RSD) is a systemic inflammato-ry disease characterized by elevation of serum IgG4. IgG4-RSD can affect any organ in the body, and the list of organs associated with this condition is growing steadily. IgG4-related cardiovascular dis-ease affects the coronary arteries, heart valves, myocardium, pericardium, aorta, pulmonary and pe-ripheral vessels. Echocardiography is the most commonly used non-invasive imaging method. Com-puted tomography angiography (CTA) can assess aortitis, periarteritis and coronary aneurysms. Cor-onary CTA is fast, offers high spatial resolution and a wide coverage field of view. Cardiac magnetic resonance imaging (CMR) offers a comprehensive evaluation of the cardiovascular system including cardiac function, extent of myocardial fibrosis, characterise cardiac masses with different pulse se-quences and guide to further treatment. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) can provide important information about the extent of disease, the presence of active inflammation and the optimum biopsy site. In general, the role of diagnostic imag-ing includes establishing the diagnosis, detecting complications, guiding biopsy and documenting re-sponse to therapy.

Higher Propofol Dosing Rates Needed for Colonoscopy in Inflammatory Bowel Disease Patients Compared to Non-Inflammatory Bowel Disease Patients

Introduction: Patients with inflammatory bowel disease (IBD) undergo frequent endoscopic procedures. Higher pain tolerance, chronic pain medication use, and presence of active inflammation may suggest higher dosing needs to sedate IBD patients. Differences in anesthesia requirements in IBD patients compared to non-IBD patients during endoscopy have not been well studied. Thus, we conducted a retrospective study comparing anesthesia requirements in IBD vs. non-IBD patients undergoing elective outpatient colonoscopy. Methods: Patients 18 years or older undergoing elective outpatient colonoscopies using total intravenous anesthesia (TIVA) from one anesthesiologist for both IBD and non-IBD were included in the study. Patients were excluded if they were pregnant, received concurrent upper endoscopy, received additional sedation medications, or sedated by another anesthesiologist. Age, weight, ASA score, relevant comorbidities and medications were recorded. The primary outcome was the difference in the groups of amount of propofol used per kilogram per minute of procedure time (mg/kg/min). Procedure time was defined as the moment the scope was inserted to the moment it was withdrawn from the patient. The estimated sample size for the primary outcome was 196 total patients based on a mean difference of 0.02mg/kg/min propofol use. Results: A total of 200 consecutive colonoscopies that met inclusion criteria were analyzed, 100 in the IBD group, and 100 in the non-IBD group. Baseline characteristics were similar except for age 43.8 ± 3.4 years in IBD group v 58.9 ± 2.6 years in non-IBD group (Table 1). No differences between the groups in regards to psychological comorbidities, narcotics, and benzodiazepine use were noted. Baseline characteristics of the IBD group are shown in Table 2. Propofol use was significantly greater in the IBD group 0.365 ± 0.030 mg/kg/min when compared to the non-IBD group 0.261 ± 0.021 mg/kg/min (p < 0.005). (Table 3) Conclusion: Propofol use in mg/kg/min of procedure time was significantly higher in outpatient, elective colonoscopies for IBD patients when compared to non-IBD patients. Reasons for this discrepancy may have included younger age, and possibly higher inflammatory burden. This study's results are useful for both anesthesia providers and gastroenterologists in that IBD patients may require higher doses of propofol for sedation than non IBD patients.648_A Figure 1. Baseline Characteristics between IBD and non-IBD groups648_B Figure 2. Characteristics of IBD Group648_C Figure 3. Comparison of Propofol Use Between IBD and non-IBD groups