Acute Crohn's Disease Research Articles

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.

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.

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.

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.

Infliximab as Rescue Therapy for Hospitalized Patients With Crohn's Disease Failing Intravenous Corticosteroids.

Infliximab (IFX) has been shown to be effective rescue therapy for hospitalized ulcerative colitis patients failing intravenous (IV) corticosteroids (CS). There is little evidence, however, describing its use in similar hospitalized Crohn's Disease (CD) patients. To determine if IFX is an effective rescue therapy for IV CS resistant CD patients. A retrospective study of inpatients with CD who received IFX as rescue therapy at 2 tertiary care hospitals from January 1, 2006, to December 31, 2016. Records were reviewed for demographics, disease activity, preadmission and inpatient treatment, surgical rates, and 30- and 90-day readmission rates. Measures and Outcomes: Efficacy of IFX as rescue therapy was defined by discharge without surgery and readmission rates. Only patients failing IV CS before IFX were included in the final analysis. Forty patients received IFX, of which 17 had failed IV CS. Four patients were receiving outpatient IFX therapy, but still received IV CS during hospitalization before IFX. The mean duration of IV CS therapy before IFX was 6.9 days. Of the 15 patients (88%) who responded to rescue IFX, the median hospital stay following IFX was 3 days (range 3-18 days). Readmission rates were 29% and 47% at 30 and 90 days respectively, without further surgeries noted. In our series of hospitalized CD patients failing IV CS, those treated with IFX had low rates of urgent surgery and a generally rapid response to treatment, supporting IFX as an effective rescue therapy. By only including those with prior failure of IV CS, we have likely excluded patients for whom IFX was given in the hospital for reasons other than severe disease. Our results suggest that individuals with severe acute CD flare can be treated with early introduction of IFX, avoiding prolonged CS use, and hospitalization.

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.

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.

Survey on practice patterns in imaging utilization in patients with Crohn's disease

PurposeTo perform a survey-based assessment of imaging practice preferences in Crohn's disease (CD). MethodsAn internet-based questionnaire was sent to physicians involved in CD care. The questionnaire addressed the experience, practice patterns, choice of modality, and recent trends in imaging utilization. ResultsThe response rate was 7.57% (122/1598) with 43.8% of respondents involved in care of CD for ≥10 years. CT was mostly preferred by ED physicians, internists and primary care physicians, while MRI by gastroenterologists and pediatricians. Practitioners from non-teaching facilities had higher preference for CT (CT:42% andMR:27%), compared to teaching/academic hospitals (MR:45% and CT: 40%) (p = 0.06). MR was preferred by pediatric practitioners compared to physicians serving older age group of patients (>16 yrs) (p = 0.01). CT was preferred by physicians taking care of <50 patients/year (CT:37, MR:27, No preference = 19) and MR preferred by physicians serving ≥50 patients/year (CT:12, MR:21, No preference:3)(p = 0.02). CT/CT enterography was the most widely used exam (93.3%) and preferred modality for evaluation of acute CD exacerbation (87.7%), followed by assessment for new symptoms (73.7%) and extra-intestinal manifestations (61.3%). MR/MR enterography (58%) was more preferred for asymptomatic CD patients for disease surveillance.Nearly 80% of respondents reported a change in imaging preferences, 46.5% respondents indicating growing preference for MRI while 33.3% reported increasing preference for CT. 29.6% physicians reported a patient preference for MRI over CT (13%) with the most common factor for choice of MRI being fear of harmful effects of radiation (60.2%). ConclusionPhysician practices reported continued preference for CT in evaluation of patients with CD, particularly for evaluation of acute exacerbation, new symptoms or extra-intestinal manifestations. Physician providers with large practice volume, younger patient population and GI sub-specialty expertise report growing MRI utilization.

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.

Crohnʼs Disease Presenting With Superior Mesenteric Vein Thrombosis and Pyogenic Liver Abscess

INTRODUCTION: Pyogenic liver abscess (PLA) and superior mesenteric vein (SMV) thrombosis are infrequent complications of Crohn's disease (CD). A combination of the two is even rarer. Our review of literature revealed only two other such cases. This case not only demonstrates a concurrent presence of two rare manifestations of Crohn's disease, but also the challenges associated with management. CASE DESCRIPTION: We present the case of a 30 year old male diagnosed with Crohn's disease 8 years ago managed with Azathioprine therapy. He initially presented with severe left lower quadrant abdominal pain for 4 weeks. CT scan of the abdomen revealed segmental thickening in the small bowel wall, indicating a flare up. He was prescribed a course of oral prednisone for four weeks. His pain initially improved, but recurred two weeks later, now in the right upper quadrant and epigastrium along with nausea, vomiting and diarrhea. Upon presentation, he was febrile at 38.4 celsius. Laboratory workup showed a WBC count of 13.4, ESR 69, CRP 23.2, AST 45, ALT 34, total bilirubin 1.1, lipase 84. A repeat CT scan now showed new SMV thrombosis and a 5.4 x 4.1cm abscess in the right hepatic lobe. Steroids were discontinued and the patient was treated with IV fluids, heparin drip, piperacillin-tazobactam and percutaneous hepatic drain placement. The purulent fluid grew Streptococcus intermedius and Staphylococcus aureus on culture. A colonoscopy was also done showing severe active ileitis and colitis. At this point, the decision was made to commence immunosuppressive therapy with Adalimumab, as the flare up needed to be addressed. The patient was switched to oral Augmentin for a total 4 weeks of antibiotics and was discharged on Rivaroxaban for 6 months, after his clinical status improved.Figure: CT scan of abdomen with IV contrast with an abscess in the right hepatic lobe measuring 5.4 x 4.1cm.Figure: CT of the abdomen demonstrating complete occlusion of the superior mesenteric vein by a thrombosis.DISCUSSION: PLA and SMV thrombosis are uncommon manifestations of CD. SMV thrombosis has been reported as low as 1.3% and 1.7% of CD patients whereas PLA has been seen in 5.45 per 10,000 person years. This case poses a dilemma on how a patient with PLA in the setting of an acute CD flare up should be treated. It also brings to light the lack of adequate evidence on choice and duration of anticoagulation therapy for splanchnic vein thromboses, as the current guidelines rely mainly on expert opinion. The current standard of care is warfarin for 6 months with a target INR of 2.0 - 3.0. Novel oral anticoagulants have not been studied sufficiently and are prescribed on a case to case basis.

Infliximab as Rescue Therapy for Hospitalized Patients With Crohnʼs Disease Failing Intravenous Corticosteroids

Introduction: Infliximab (IFX) has been shown to be effective rescue therapy for ulcerative colitis in hospitalized patients failing intravenous (IV) corticosteroids (CS). However there is little evidence describing its use in similar hospitalized Crohn's Disease (CD) patients. Our aim was to determine if IFX is effective rescue therapy for corticosteroid (CS) resistant CD in hospitalized patients. Methods: All in-patients with CD who received IFX as rescue therapy at Northshore University and Long Island Jewish hospitals from 2007 to 2016 were selected. Records were reviewed for demographics, Montreal classification of CD, pre-admission and inpatient treatment, surgical rates, and 30 and 90-day readmission rates. Only patients failing IV CS prior to IFX were included in the final analysis.Table: Table. Patient DemographicsTable: Table. Dosage of intravenous corticosteroid and infliximab administered during hospitalizationResults: A total of 40 patients received IFX, of which 17 had failed IV CS. Patient demographics are listed in table 1. Mean hospital stay was 9.8 days (range 4 to 30). At admission, 55% were taking oral CS (n=9). Four patients were on outpatient IFX therapy, but still received IV CS during hospitalization prior to IFX. Doses of IV CS and IFX are listed in table 2. The mean duration of IV CS therapy before IFX was 6.9 days (range 4 to 18). Two patients failed IFX and required surgery including a colectomy for pan-colitis with spontaneous perforation, and an ileocolectomy for terminal ileal stricture. Neither patient had received IFX as an outpatient. Of the 15 patients who responded to rescue IFX, the median duration of hospital stay following IFX was 3 days (range 3 to 18 days). Re-admission rates were 29% and 47% at 30 and 90 days respectively, without further surgeries noted. Conclusion: In our series severe CD patients failing IV CS treated with IFX had low rates of urgent surgery and a generally rapid response to treatment, supporting IFX as an effective rescue therapy. By only including those with prior failure of IV CS, we have likely excluded patients for whom IFX was given in the hospital for reasons other than severe disease. Our results suggest that even individuals with severe acute CD flare can be treated with early introduction of IFX, avoiding prolonged CS use and hospitalization. With more biologic therapies becoming available, further trials are needed to assess the efficacy of IFX and newer agents to correctly position rescue therapies for severe CD.

No difference in postoperative outcome after acute surgery whether the patients presented for first time or are known with Crohn's disease

PurposesAcute operations (within 48 h) or urgent (within 2–7 days) carry the risk of unfavorable outcome as the patient is not optimized, the operation is performed by trainees and the disease is severe necessitating acute/urgent intervention. However, Crohn's disease (CD) patients who present as acute disease may have more favorable outcome because they did not receive medications, surgery is performed early and the disease is promptly controlled. AimTo investigate whether CD patients presented first time have more favorable outcome compared to those who are known with CD. MethodRetrospective multi-center study. Rate of complications, duration of hospitalization and rate of re-admission were used as a measure of postoperative outcome. Univariate and multi-variate analyses were used. ResultsSixty-one patients in whom acute CD was first presentation (group 1) did not have more favorable outcome compared to 167 patients known to have CD (group 2) and presented acute. Mean duration of hospitalization was 8.7 days in group 1 compared to 9.4 days in group 2. Complications occurred in 12/61 patients (19.7%) in group 1 compared to 39/167 patients (23.4%) in group 2: odds ratio 1 .113, CI [0.611–2.024]. No difference in intra-abdominal septic complications rate was found between the two groups: odds ratio 0.932, CI [0.369–2.355]. Re-admission was seen in six patients (9.8%) in group 1 vs. 23 (13.8%) in Group 2: odds ratio 1.464, CI [0.566–3.788]. ConclusionPatients undergoing acute surgery for the first CD presentation did not have more favorable outcome compared to those undergoing acute intestinal resection for known CD.

Crohnʼs Disease Is Associated with Increased Morbidity and Resource Utilization in Patients Hospitalized with Acute Pancreatitis: Results of a Nationwide Analysis

Introduction: Crohn's disease (CD) is associated with pancreatitis due to drug toxicity, duodenal disease, biliary involvement or autoimmune disease. To date, the impact of CD on mortality and other outcomes among patients with Acute Pancreatitis (AP) has not been investigated. Therefore, the aim of this study is to explore the impact of past or current CD on mortality, morbidity and resource utilization among patients hospitalized for AP. Methods: This was a retrospective cohort study using the 2013 National Inpatient Sample, the largest publically available inpatient database in the United States. All patients with an ICD-9 CM code for a principal diagnosis of AP were included. There were no exclusion criteria. The primary outcome was in-hospital mortality. Secondary outcomes were morbidity measured by intensive care unit (ICU) admission, shock and multi-organ failure; resource utilization measured by abdominal CT scan, abdominal ultrasound (US), total parenteral nutrition (TPN) use, length of hospital stay (LOS) and total hospitalization charges. Patients were classified as having CD or not having CD using ICD-9 CM codes. Using multivariate regression analysis, odds ratios and means were adjusted for age, sex, race, median income in the patient's zip code, Charlson Comorbidity Index, hospital region, urban location, size and teaching status. Results: 274,775 patients with AP were included in the study, 2,255 (0.8%) of whom had CD. Mean age was 51 years and 47% were female. The overall in-hospital mortality rate was 0.8% (0.2% in patients with CD). Table 1 shows all adjusted odds ratios, adjusted means and p-values. On multivariate analysis, patients with CD had similar in-hospital mortality rates compared to patients without CD (OR:0.43, 95%CI:0.06-3.12, p=0.41). Looking at morbidity, patients with CD displayed higher odds of shock, malnutrition and TPN use. Resource utilization did not differ between groups. Patients with CD had significantly longer hospital lengths of stay but not total hospitalization charges when compared to patients without CD.Table 1: Adjusted odds ratios, means and p-values for the evaluated parameters in patients with acute pancreatitis and CD compared to patients with no CD.Conclusion: CD is not associated with increased mortality in patients hospitalized with AP. Importantly, CD is associated with increased morbidity reflected by higher odds of shock and malnutrition. Furthermore, CD in patients with AP is associated with longer LOS when compared to patients without CD.

Successful Treatment of Both Acute Leukemia and Active Crohn's Disease After Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-Intensity Conditioning With Fludarabine and Busulfan: A Case Report

BackgroundA 32-year-old man diagnosed with acute myelomonocytic leukemia (M4) concurrently had active Crohn's disease (CD) that was refractory to azathioprine and anti-tumor necrosis factor. Case ReportHe underwent an allogeneic bone marrow transplantation from a one HLA-DR allele-mismatched unrelated donor to achieve the first complete remission of leukemia. The conditioning regimen consisted of fludarabine (180 mg/m2) and busulfan (8.0 mg/kg) without T-cell depletion. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and mycophenolate mofetil. Cefotaxime was prescribed for a secondary bacterial infection in a perianal abscess before the start of conditioning chemotherapy. Although low-grade diarrhea persisted, there were no signs of either acute GVHD or CD in the mucosal biopsy specimens on day 24. Complete remission of leukemia and near remission of CD were sustained for 20 months after transplantation without any immunosuppressive drug. ConclusionsAllogeneic heamtopoietic stem cell transplantation with reduced-intensity conditioning is a possible therapeutic option for patients with severe and/or refractory CD.