Acute Crohn Research Articles

Targeting Inflammation and Oxidative Stress to Improve Outcomes in a TNBS Murine Crohn's Colitis Model.

Inflammation and oxidative stress are implicated in the pathogenesis of Crohn's disease. Cerium oxide nanoparticle (CNP) conjugated to microRNA 146a (miR146a) (CNP-miR146a) is a novel compound with anti-inflammatory and antioxidative properties. We hypothesized that local administration of CNP-miR146a would improve colitis in a 2,4,6-Trinitrobenzenesulfonic acid (TNBS) mouse model for Crohn's disease by decreasing colonic inflammation. Balb/c mice were instilled with TNBS enemas to induce colitis. Two days later, the mice received cellulose gel enema, cellulose gel with CNP-miR146a enema, or no treatment. Control mice received initial enemas of 50% ethanol and PBS enemas on day two. The mice were monitored daily for weight loss and clinical disease activity. The mice were euthanized on days two or five to evaluate their miR146a expression, inflammation on histology, and colonic IL-6 and TNF gene expressions and protein concentrations. CNP-miR146a enema successfully increased colonic miR146a expression at 12 h following delivery. At the end of five days from TNBS instillation, the mice treated with CNP-miR146a demonstrated reduced weight loss, improved inflammation scores on histology, and reduced gene expressions and protein concentrations of IL-6 and TNF. The local delivery of CNP-miR146a in a TNBS mouse model of acute Crohn's colitis dramatically decreased inflammatory signaling, resulting in improved clinical disease.

Safety and Efficacy of Inpatient Infliximab Rescue Therapy for Acute Crohn's Disease Flares.

Describe the safety, complications, and need for urgent surgery in patients requiring inpatient rescue infliximab for acute Crohn's disease (CD) flare. Infliximab is increasingly used for patients hospitalized with acute severe ulcerative colitis as rescue therapy; however, optimal management for patients hospitalized for CD flares remains unclear. A single-institution retrospective study of patients aged 18+ admitted from 2008 to 2020 with acute Crohn's flare requiring induction of rescue infliximab therapy. Outcomes included postoperative and medication-related complications and need for urgent surgery. 52 patients were included in analysis; 8% required surgery on index admission, and 19% required surgery within 90 days of infliximab. Postoperative complications included 1 anastomotic leak, 3 superficial wound infections, 3 prolonged ileus, and 1 urinary infection. There were no adverse reactions to infliximab infusion, and medical complication rates were low. Patients with penetrating disease were more likely to undergo surgery within 90 days of infliximab (43% vs 8%; P = .01). Mean LOS was longer for patients undergoing surgery within 90 days of therapy compared to those who did not (13.4 vs 8.3days, P = .04). Inpatient rescue infliximab is safe for treating acute Crohn's disease flare in addition to standard steroid therapy. The majority of patients hospitalized with Crohn's flare requiring rescue infliximab avoided surgery with low postoperative and medication-related complications. More research is needed to clarify the optimal rescue infliximab therapy dosage.

Shared and Distinct Gut Microbiota in Spondyloarthritis, Acute Anterior Uveitis, and Crohn's Disease.

Spondyloarthritis (SpA) is a group of immune-mediated diseases highly concomitant with nonmusculoskeletal inflammatory disorders, such as acute anterior uveitis (AAU) and Crohn's disease (CD). The gut microbiome represents a promising avenue to elucidate shared and distinct underlying pathophysiology. We performed 16S ribosomal RNA sequencing on stool samples of 277 patients (72 CD, 103 AAU, and 102 SpA) included in the German Spondyloarthritis Inception Cohort and 62 back pain controls without any inflammatory disorder. Discriminatory statistical methods were used to disentangle microbial disease signals from one another and a wide range of potential confounders. Patients were naive to or had not received treatment with biological disease-modifying antirheumatic drugs (DMARDs) for >3 months before enrollment, providing a better approximation of a true baseline disease signal. We identified a shared, immune-mediated disease signal represented by low abundances of Lachnospiraceae taxa relative to controls, most notably Fusicatenibacter, which was most abundant in controls receiving nonsteroidal antiinflammatory drug monotherapy and implied to partially mediate higher serum C-reactive protein. Patients with SpA showed an enrichment of Collinsella, whereas human leukocyte antigen (HLA)-B27+ individuals displayed enriched Faecalibacterium. CD patients had higher abundances of a Ruminococcus taxon, and previous conventional/synthetic DMARD therapy was associated with increased Akkermansia. Our work supports the existence of a common gut dysbiosis in SpA and related inflammatory pathologies. We reveal shared and disease-specific microbial associations and suggest potential mediators of disease activity. Validation studies are needed to clarify the role of Fusicatenibacter in gut-joint inflammation, and metagenomic resolution is needed to understand the relationship between Faecalibacterium commensals and HLA-B27.

Trends in gastrointestinal disease hospitalizations and outcomes during the first year of the coronavirus pandemic.

The impact of the coronavirus on hospitalizations for gastrointestinal (GI) disease, particularly at a population level is understudied. To investigate trends in hospitalizations, inpatient endoscopy resource utilization, and outcomes during the first year of the coronavirus pandemic and subsequent lockdowns. Using the California State Inpatient Database for 2018-2020, we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality (all-cause & viral pneumonia-specific) for common inpatient GI diagnoses including acute pancreatitis, diverticulitis, cholelithiasis, non-infectious gastroenteritis, upper and lower GI bleeding (LGIB), Clostridium difficile, viral gastroenteritis, inflammatory bowel disease, and acute cholangitis. Disease-specific hospitalizations decreased for all included conditions except nonvariceal upper GI bleeding (NVUGIB), LGIB, and ulcerative colitis (UC) (ptrend < 0.0001). All-cause inpatient mortality was higher in 2020 vs 2019, for acute pancreatitis (P = 0.029), diverticulitis (P = 0.04), NVUGIB (P = 0.003), and Crohn's disease (P = 0.004). In 2020, hospitalization rates were lowest in April, November, and December. There was no significant corresponding increase in inpatient mortality except in UC (ptrend = 0.048). Viral pneumonia and viral pneumonia complicated by respiratory failure increased (P < 0.001) among GI hospitalizations. Endoscopy utilization within 24 h of admission was unchanged for GI emergencies except NVUGIB (P < 0.001). Our findings suggest that hospitalization rates for common GI conditions significantly declined in California during the COVID pandemic, particularly in April, November and December 2020. All-cause mortality was significantly higher among acute pancreatitis, diverticulitis, NVUGIB, and Crohn's disease hospitalizations. Emergency endoscopy rates were mostly comparable between 2020 and 2019.

A review on the role of miR-671 in human disorders.

miR-671 is encoded by a gene on 7q36.1 and contributes to the pathogenesis of a variety of disorders, including diverse types of cancers, atherosclerosis, ischemic stroke, liver fibrosis, osteoarthritis, Parkinson's disease, rheumatoid arthritis, acute myocardial infarction and Crohn's disease. In the context of cancer, different studies have revealed opposite roles for this miRNA. In brief, it has been shown to be down-regulated in pancreatic ductal carcinoma, ovarian cancer, gastric cancer, osteosarcoma, esophageal squamous cell carcinoma and myelodysplastic syndromes. Yet, miR-671 has been up-regulated in glioma, colorectal cancer, prostate cancer and hepatocellular carcinoma. Studies in breast, lung and renal cell carcinoma have reported inconsistent results. The current review aims at summarization of the role of miR-671 in these disorders focusing on its target mRNA in each context and dysregulated signaling pathways. We also provide a summary of the role of this miRNA as a prognostic factor in malignancies.

S894 Inpatient Outcomes and Healthcare Utilization in Obese vs Non-Obese Patients Hospitalized with an Acute Crohn’s Disease Flare—A Nationwide Cohort Study

Introduction: Crohn’s Disease (CD) remains a leading cause of patient morbidity and in severe cases, mortality. Given the rise in prevalence of obesity in the United States, the goal of this study is to illustrate the impact of obesity on hospitalized patients admitted for acute flares of Crohn’s Disease (CD). Our primary outcome was odds of inpatient mortality. Secondary outcomes included length of hospitalization (LOS), total hospital charge (THC), and complications including sepsis, upper and lower GI bleed (UGIB)(LGIB), and acute kidney injury (AKI). Methods: The National Inpatient Sample (NIS 2016-2018) was sourced for hospitalization data from adult patients admitted for a CD flare. The queried pool of patients was stratified into obese (BMI ≥ 30), and non-obese cohorts using International Classification of Diseases, Tenth Revision (ICD-10) codes. After performing descriptive analysis on the involved cohorts, linear and multivariate regression was used to evaluate study outcomes. STATA 14 was used for data analysis. Results: Of 232,650 admissions for CD flare, 20,100 (8.64%) had comorbid obesity. Compared to non-obese-CD patients, obese-CD patients were significantly older (45.8 vs 43.7 years, p < 0.0001), were more often female (65.9% vs 52.7%, p < 0.0001), and had greater African American representation (17.3% vs 15.4%, p < 0.0001) compared to non-obese patients. Obese-CD patients had more comorbid disease as measured by a Charlson Comorbidity Index score ≥3 (9.80% vs 5.16, p < 0.0001), and had more patients belonging to the poorest quartile of family income (29.0% vs 26.3%, p< 0.0001). No difference in adjusted odds of inpatient mortality was noted between the two groups. Obese-CD had higher rates of AKI (OR 1.17, p = 0.011), and had significantly increased LOS (5.04 vs 4.78 days, p = 0.006). There were no differences in total hospital cost, LGIB, or shock. Conclusion: Obesity did not significantly increase inpatient mortality. However Obese-CD patients had increased odds of AKI and increased LOS relative to CD patients without obesity. Additional studies are needed to further investigate the effects of obesity in CD, and to help reduce the economic burden obesity places on the healthcare system.

Содержание CD4+-клеток с экспрессией эктонуклеотидаз CD39/CD73 у детей с воспалительными заболеваниями кишечника

The regulation of TNF inhibitor therapy-associated immune responses in inflammatory bowel diseases (IBD) in children remains an urgent problem. The study aimed at analyzing the expression of CD39/CD73 endonucleotidases by different subsets of peripheral blood T cells in children with IBD including Crohn's disease (n = 34) and ulcerative colitis (n = 33) having received TNF inhibitors in comparison with conditionally healthy children (n = 45). Lymphocyte subsets including regulatory T cells (Treg, CD4+CD127lowCD25high), activated T cells (Tact, CD4+CD25+CD127high) and Th17 cells (CD4+CD161+CD3+) were studied by flow cytometry. The results are presented as medians (Me) and quartiles (Q25–Q75). In children with IBD the highest and the lowest relative counts of CD39+ cells were found in Treg and Tact subsets — 31% (15–38) and 4% (1–7), respectively. The highest relative counts of CD73+ cells were found in Tact — 13% (8–21). The CD39 and CD73 expression ratio in patients with IBD, and in the control group as well, depended on particular subset. CD39 expression in Treg, Tact and Th17 of patients with IBD was not age-dependent. Patients with acute Crohn's disease revealed decreased expression of CD39 in Treg compared with the control group (12% (9–23) vs 35% (28–39), respectively; р = 10–6). Patients with Crohn's disease in remission revealed increased expression of CD39 in Treg compared with the acute of the disease (31% (27–40) vs 12% (9–23); р = 9.4 × 10–5). Patients with Crohn's disease in remission revealed no significant differences with the control group apart from reduced expression of CD73 by Treg in Crohn's disease. The results indicate significant association of CD39 and CD73 expression levels in particular subsets of CD4+ cells with the phase of the disease (acute vs remission) and, accordingly, with the anti-TNF regimen efficacy.

The use of, and outcomes for, inflammatory bowel disease services during the Covid-19 pandemic: a nationwide observational study.

BackgroundInflammatory bowel disease (IBD) services have been particularly affected by the Covid‐19 pandemic. Delays in referral to secondary care and access to investigations and surgery have been exacerbated.AimsTo investigate the use of and outcomes for emergency IBD care during the Covid‐19 pandemic.MethodsNationwide observational study using administrative data for England (2015‐2020) comparing cohorts admitted from 1 January 2015, to 31 January 2020 (pre‐pandemic) and from 1 February 2020, to 31 January 2021 (pandemic). Autoregressive integrated moving average forecast models were run to estimate the counterfactual IBD admissions and procedures for February 2020 to January 2021.ResultsLarge decreases in attendances to hospital for emergency treatment were observed for both acute ulcerative colitis (UC, 16.4%) and acute Crohn’s disease (CD, 8.7%). The prevalence of concomitant Covid‐19 during the same episode was low [391/16 494 (2.4%) and 349/15 613 (2.2%), respectively]. No significant difference in 30‐day mortality was observed. A shorter median length of stay by 1 day for acute IBD admissions was observed (P < 0.0001). A higher rate of emergency readmission within 28 days for acute UC was observed (14.1% vs 13.4%, P = 0.012). All IBD procedures and investigations showed decreases in volume from February 2020 to January 2021 compared with counterfactual estimates. The largest absolute deficit was in endoscopy (17 544 fewer procedures, 35.2% reduction).ConclusionThere is likely a significant burden of untreated IBD in the community. Patients with IBD may experience clinical harm or protracted decreases in quality of life if care is not prioritised.

Does exclusive enteral nutrition reduce the rate of stoma formation in patients requiring ileocolic resection for Crohn's disease? A single center experience.

Nutrition has a role in achieving and maintaining remission in Crohn's disease. The aim of this study was to determine the impact of a strategy of steroid-avoidance and Exclusive Enteral Nutrition (EEN) for 6 weeks (with a minimum of 4 weeks) in adult patients presenting with acute small bowel Crohn's disease followed by an interval ileocolic resection 4-6 weeks later. Retrospective review of prospectively collected data. Patients were administered exclusive enteral nutrition (EEN) for at least 4 weeks prior to surgery. 24 EEN patients included. Median age of 45 (range 23-73). 17/24 patients tolerated Modulen for at least 4 weeks, 5 were switched to Ensures and 2 a liquid diet. 6 patients underwent surgery earlier than planned. Prior to surgery, there was no change in the mean BMI, albumin increased from a mean of 36g/L (range 25-43) to 40g/L (range 30-48). CRP levels decreased by a mean of 35.8mg/L overall. 19 (79%) of operations were performed laparoscopically. 6 of the cases were re-do operations. All but 3 patients avoided a stoma at the time of the original operation. There were 5 post-operative complications: 1 anastomotic leak in a patient with a BMI of 42, 3 cases of paralytic ileus and 2 wound infections. Median length of stay was 7 days (range 3-76 days). Only 2 patients were readmitted within the 30-day post-operative period. The pre-operative use of EEN appears to avoid unnecessary stoma formation with acceptable clinical outcomes.

POS0410 BIOMARKERS REFLECTING DISTURBED GUT BARRIER DIFFER IN PATIENTS WITH SPONDYLOARTHRITIS, CROHN’S DISEASE AND ACUTE ANTERIOR UVEITIS

Background:Spondyloarthritides (SpA) are characterized by frequent extra-musculoskeletal manifestations (EMM) among them acute anterior uveitis (AAU) and Crohn’s disease (CD). Vice versa, about 50% of AAU and 20% of CD patients have concomitant SpA. SpA patients show gut dysbiosis together with frequent subclinical gut inflammation. Biomarkers reflecting disturbed gut barrier (intestinal-fatty acid binding protein (iFABP), lipopolysaccharide binding protein (LBP) and zonulin) were previously found to be elevated in patients with radiographic axial SpA (r-axSpA) (1).Objectives:To evaluate whether biomarkers reflecting leaky gut are altered in patients with AAU, CD and SpA compared to healthy controls and whether they differ between patients with EMM with and without concomitant SpA.Methods:A total of 100 patients from the German Spondyloarthritis Inception Cohort (GESPIC) were included – among them 20 patients with r-axSpA without EMM, 40 patients with CD and 40 patients with non-infectious AAU – out of which 19 and 20 patients, respectively, had concomitant SpA (11/8 and 20/0 axial/peripheral SpA, respectively). The GESPIC patients were compared to 20 age- and sex-matched healthy donors (HD). The following five serum biomarkers were analyzed with ELISA: calprotectin, iFABP, LBP, soluble CD14 (sCD14) and zonulin.Results:Patient characteristics are shown in Table 1. Serum levels of calprotectin, LBP, sCD14 and zonulin differed significantly between patients with r-axSpA, AAU and CD with and without concomitant SpA and HD (Figure 1). When comparing patients with EMM with and without underlying SpA, calprotectin serum levels were significantly elevated in CD patients with SpA (8.6µg/ml (SD 5.5µg/ml)) compared to CD patients without SpA (5.7µg/ml (SD 4.1µg/ml); Mann-Whitney U Test, p=0.031). Serum levels of the analyzed biomarkers did not differ between AAU patients with and without axSpA. Spearman rank correlation revealed a significant association between CRP and calprotectin (correlation coefficient r=0.230; p=0.012), LBP (r=0.596; p&lt;0.0001), sCD14 (r=0.428; p&lt;0.0001) and zonulin (r=0.221; p=0.016), respectively. Furthermore, LBP and zonulin serum levels correlated positively (r=0.208; p=0.023); as well as LBP and sCD14 levels (r=0.418; p&lt;0.0001).Table 1.Patient characteristics. Mean values (standard deviation) or absolute numbers are shown.CD + SpACDr-axSpAAAU + axSpAAAUHDN192120202020Age39.1 (11.3)38.7 (14.4)38.4 (10.3)39.6 (12.0)39.2 (12.5)38.6 (12.9)Male (%)9 (47%)9 (43%)9 (45%)9 (45%)9 (45%)9 (45%)HLA-B27 positive (%)5 (26%)3 (14%)17 (85%)17 (85%)13 (65%)2 (10%)CRP in mg/l14.3 (25.6)18.0 (41.8)9.1 (11.3)6.7 (9.9)2.3 (3.4)0.6 (0.7)ASDAS2.8 (1.1)3.2 (0.6)2.2 (1.0)BASDAI4.1 (2.2)5.4 (1.2)3.2 (2.4)Figure 1.Biomarkers reflecting disturbed gut barrier show distinct signatures in patients with acute anterior uveitis, Crohn’s disease and axial Spondyloarthritis. Kruskal Wallis Test; p values shown. Dunn-Bonferroni Post-Hoc analyses, significant pairwise differences are marked; * p&lt;0.05; **p&lt;0.01; ***p&lt;0.0001Conclusion:We found substantial differences in biomarkers reflecting disturbed gut barrier between with SpA, CD, AAU and healthy controls. The presence of SpA was associated with higher calprotectin serum levels in CD as compared to CD without SpA.

Steroids in inflammatory bowel disease: a clinical review

Corticosteroids are effective at inducing remission in inflammatory bowel disease (IBD). Acute severe ulcerative colitis and Crohn's disease are managed with intravenous steroids. In mild-to-moderate disease, corticosteroids can be given orally or topically. Long-term use should be limited to prevent commonly associated adverse effects. Corticosteroids should not be used to maintain remission. Blood pressure, body mass index and blood glucose monitoring are crucial while on steroids. Acid suppression along with calcium and vitamin D supplementation should be co-prescribed to all patients on long-term corticosteroids. Bridging these patients to a steroid-sparing agent early prevents steroid-refractory and steroid-dependent disease. GP education, IBD helplines, IBD clinics, multidisciplinary team meetings and regular auditing should be encouraged to prevent corticosteroid overprescribing.

Steroids in inflammatory bowel disease: a clinical review

Corticosteroids are effective at inducing remission in inflammatory bowel disease (IBD). Acute severe ulcerative colitis and Crohn's disease are managed with intravenous steroids. In mild-to-moderate disease, corticosteroids can be given orally or topically. Long-term use should be limited to prevent commonly associated adverse effects. Corticosteroids should not be used to maintain remission. Blood pressure, body mass index and blood glucose monitoring are crucial while on steroids. Acid suppression along with calcium and vitamin D supplementation should be co-prescribed to all patients on long-term corticosteroids. Bridging these patients to a steroid-sparing agent early prevents steroid-refractory and steroid-dependent disease. GP education, IBD helplines, IBD clinics, multidisciplinary team meetings and regular auditing should be encouraged to prevent corticosteroid overprescribing.

Pioderma gangrenoso em paciente portadora de doença de Crohn responsivo a terapia biológica com infliximabe: relato de caso no Amazonas

Esse artigo buscou relatar um caso de pioderma gangrenoso responsivo a terapia de resgate com infliximabe. Paciente do sexo feminino, 42 anos, portadora de Doença de Crohn em uso de Mesalazina. Evoluiu com artralgia em grandes articulações, quando foi prescrita Azatioprina e desde então apresentou sinais flogísticos em tecidos moles de ambos os antebraços e diarreia mucossanguinolenta. Necessitou de internação hospitalar, onde realizou inicialmente antibioticoterapia e posteriormente corticoterapia via endovenosa, sem melhora do quadro clínico. No final da segunda semana de tratamento, as lesões cutâneas tornaram-se bem características de pioderma gangrenoso e ainda apresentava diarreia. Foi iniciada terapia biológica com infliximabe, obtendo-se o desaparecimento do quadro articular, regularização do hábito intestinal e a cicatrização das úlceras cutâneas, logo após a primeira infusão. A terapia de resgate com infliximabe foi eficaz para a rápida resposta clínica de paciente com surto agudo de Doença de Crohn e cicatrização de pioderma gangrenoso.

IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators.

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils.

Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.

Enteral nutrition bibliometry from 2010 to 2019.

This study aimed to describe and analyze the research outputs on enteral nutrition, which is the administration of food through the gastrointestinal tract for nutrition maintenance. We searched the Web of Science Core Collection database for original publications on enteral nutrition research from 2010 to 2019. HistCite and VOSviewer software were used for analysis and visualization of the publication outputs, journals, institutions, keywords, cocitations, and collaborations among authors in different countries or regions. A total of 963 relevant articles were included. The number of publications in 2010 and 2019 were 68 and 139, respectively. Nutrition in Clinical Practice and the Journal of Parenteral and Enteral Nutrition had the highest number of publications and cocitations (76, 7.89%; 2058), respectively. The United States and China were the top contributors, accounting for 24.1% and 22.3% of the total articles, respectively. Andrew S. Day and Stephen A. McClave were core researchers in this field. Primary authors collaborated closely. Enteral nutrition, parenteral nutrition, and support were the three most common keywords. The top 10 cocited references concerned administering early enteral nutrition therapy in acutely ill patients and patients with acute Crohn's disease. Crohn's disease, acute pancreatitis, upper gastrointestinal malignancy, and other surgical diseases were among the research hotspots. Our findings can help researchers identify notable research trends and clinically relevant articles. New catheterization technologies are a future research direction.

3158 Sacral Osteomyelitis Secondary to Crohn's Disease

INTRODUCTION: Increased ostomy output and abdominal pain can be concerning symptoms for patients with underlying gastrointestinal pathology such as Inflammatory Bowel Disease (IBD). While the acute etiology is often directly related to said underlying condition, alternative causes should remain on the differential diagnosis. The following is a case of sacral osteomyelitis as a result of direct extension from the gastrointestinal tract. CASE DESCRIPTION/METHODS: A 43 year old male with Crohn's disease complicated by recurrent fistula/abscess status post multiple colectomies with ileostomy and blind colostomy presented from a rehabilitation facility due to increased non-bloody watery ileostomy output and abdominal pain. He also presented with chronic rectal ulcers that appeared stable with scant purulent drainage. Vital signs were notable for hypotension and tachycardia that responded to fluids and empiric vancomycin and imipenem. Labs were notable for significantly elevated inflammatory markers, negative stool infectious panel, negative clostridium difficile, negative lactoferrin, white blood cell count of 23.9, and negative blood/urine cultures. Ileoscopy revealed colonization of the ileum and no source of high ostomy output was identified. Ileal biopsy revealed acute Crohn's enteritis. MRI pelvis fistula protocol revealed S5 osteomyelitis which was confirmed clinically by visualization in the OR. However, bone biopsy was negative in the setting of empiric antibiotic therapy. Patient was treated with approximately six weeks of vancomycin and ceftriaxone. He then followed up with Infectious Disease and had resolution of the infection and significant improvement in rectal ulcer drainage. DISCUSSION: Determination of the source of infection in patients with IBD can be challenging due to the inflammatory nature of the disease. Patients often present with systemic symptoms and non-specific complaints that could be mistakenly attributed to the underlying chronic disease. In any patient with fistulizing Crohn's presenting with sepsis, clinicians should have a high level of suspicion for osteomyelitis, especially in chronically debilitated patients with non-healing wounds. If routine infectious evaluation is unrevealing, clinicians should consider musculoskeletal infections due to direct extension from organic intra-abdominal processes. A broad differential diagnosis should be maintained for these Crohn's patients as multiple organ systems may be affected both directly and indirectly.

Right-sided diverticulitis.

Right‐sided diverticulitis is uncommon in Western populations with few to zero reports on endoscopic correlations. Although ultrasound or imaging studies typically detect advanced forms to be differentiated from acute appendicitis and/or Crohn’s disease, in more subtle presentations with an indication of urgent ileocolonoscopy, endoscopy may reliably establish an unequivocal diagnosis.

Enabling clinical trials in an academic GMP setting through use of closed, semi-automated manufacturing of allogeneic amniotic epithelial cells

Background & Aim One of the major considerations with regards to the design, usage and ultimately, viability of academic GMP facilities for clinical trials is cost effectiveness. This is particularly the case when clinical trials are supported by scant research funds. In the case of the Monash Health Translation Precinct's Cell Therapy Platform, the Biospherix Xvivo isolator was determined to be a cost-effective method to rapidly create a Class A environment within a Class D room to support manual, open processing. This approach was sufficient for the needs of a small Phase 1, single low dose study where allogeneic amniotic epithelial cells (hAEC) were isolated, cryopreserved and formulated extremely premature babies with chronic lung disease (n=6). For that trial, only 5 placentas were processed. Since the successful completion of this first-in-human trial, the Monash Health Translation Precinct has seen an explosion of hAEC clinical trials including dose-escalation studies in acute stroke, liver cirrhosis, and Crohn's disease. The projected demand on our academic GMP facility is estimated at over 250 processes per year for hAEC isolation alone. Given the labour-intensive nature of hAEC isolation (approx. 4 hours per isolation), and competing demands on the isolator at our academic GMP facility, there is a clear need to move towards closed, automated processing. Methods, Results & Conclusion Accordingly, we applied the use of the RoteaTM (Scinogy Pty Ltd), a benchtop counterflow centrifugal device and single-use kit, to the post-trypsinisation steps of the process. Once separated from the underlying chorion, the amniotic membrane is trimmed into 4 × 4cm pieces and exposed to 0.25% Trypsin-EDTA for 1 hour at 37°C. This is then quenched with 2% (v/v) human serum albumin in saline. The subsequent steps involving red blood cell removal and repeated washing steps (∼ 90 mins in the isolator), were replaced by the use of the RoteaTM (∼10 mins). Furthermore, the RoteaTM steps could be performed outside of the isolator, in a Class D environment with no significant loss in total live cells recovered. This is critical, as it allows staff to clean the isolator and prepare for the entry of incoming material, thus allowing for a level of scalability and flexibility in our current academic GMP manufacturing workflow that could never previously be achieved. Comparing isolation processes alone, this semi-automation will approximately triple the efficiency of our facility due to its enclosed, single-use system.

Predictors in inflammatory bowel disease: Looking into the magic ball: Session one summary.

A diagnosis of inflammatory bowel disease (IBD) has a significant impact on a patient and their family that cannot be understated. The incidence of IBD is increasing worldwide and particularly in the Asia–Pacific region due to a variety of known and unknown factors.1 One of the difficult questions facing a clinician when considering a patient with a new diagnosis of Crohn's disease or ulcerative colitis is their prognosis. This is frequently one of the first questions from a patient. The answer to this question impacts both the patient's expectations of their disease and clinical decision-making. The clinician and patient must balance the need for early aggressive medical management, to avoid disease-related complications, with the risk of over treating patients who would otherwise have a mild disease course, potentially exposing them to an increased risk of treatment-related side effects or complications. Therefore, predicting the course of disease early is of clear importance to the field. From longitudinal experience with newly diagnosed patients, we know that disease course can be quite variable, both for ulcerative colitis and Crohn's disease.2-4 Some patients have a largely quiescent disease course requiring minimal interventions, while others have an aggressive course that can culminate in the need for surgery, hospitalization, and the development of disabling disease. For patients with more significant disease, clinical trials and real-world data support the use of earlier aggressive therapy, for example, with combination immunomodulator and biologic therapy, to prevent disease progression and complications such as need for surgery or disabling disease.5, 6 However, identifying which patients are likely to develop progressive disease, and therefore benefit from aggressive medical therapy, remains a clinical challenge. There has been significant improvement in our understanding of both genetic and environmental factors driving the development of IBD with insights into the pathogenesis of the disease.7, 8 In this session, Miles Parkes discusses the utility of genetic markers and transcriptional profiles of blood lymphocytes, examined with respect to their predictive capacity. There is clear potential for these methods to improve our risk stratification and identify patients who require aggressive therapy. Ashwin Ananthakrishnan reviewed the current data on clinical risk factors and assessed their utility. Clinical predictors including disease location for Crohn's disease, inflammatory burden, and need for steroids remain significant predictors of disease course. Finally, Peter De Cruz examined the utility of predictors of disease behavior in the context of risk assessment in specific clinical scenarios including acute severe colitis and postoperative Crohn's disease, two scenarios where the consequences of incorrect risk assessment can be significant. Overall, the speakers in this session emphasized the utility of using clinical predictors for risk assessment in the IBD setting and demonstrated the promising ongoing research into using genetic and other biomarkers for more precise prediction in the near future. JB has received honorariums and consulting fees from Takeda and Janssen-Cilag.