Advancements in Targeted Therapies for the Management of Crohn's Disease: A Comprehensive Review.

Crohn's disease (CD) is a complex clinical condition characterized by persistent gastrointestinal inflammation that leads to episodes of flare-ups and subsequent healing. The treatment options for this disease are heterogeneous as its impact on different patients is also different. This study aims to evaluate the effectiveness of recently approved drugs that specifically target certain pathways within cells that are involved in CD pathogenesis. These medicines include biologics like anti-TNF agents, interleukin inhibitors, and small molecule inhibitors; they work by altering the modulation of immune responses and reducing inflammation. These drugs seem promising in terms of inducing remission in moderate to severe CD among various patient populations. Conversely, it is possible to examine how well these drugs perform using gene expression and molecular markers. By understanding these results along with other ongoing trials, personalized medicine can be used more frequently by doctors who will adopt a strategy for an individual patient, maximizing benefits while minimizing adverse effects. There are still some issues that need to be worked out like the high cost associated with these drugs or immunogenicity risk and infectious complications too. In conclusion, there has been a remarkable improvement in CD management over the past decade with customized drugs leading toward a precision medical era. Further understanding of molecular mechanisms implicated in CD pathogenesis and new therapeutic approaches could potentially improve treatment outcomes among affected individuals. This research is crucial in understanding how CD therapeutics are changing, thus facilitating selection by doctors on the most appropriate methods for individualized patient care.

Gastrointestinal Basidiobolomycosis: A Case Series.

Gastrointestinal basidiobolomycosis (GIB) is a rare fungal infection caused by Basidiobolus ranarum, a saprophytic fungus that belongs to the class of Basidiobolomycetes. It mainly infects immunocompetent individuals and is mainly found in arid tropical and subtropical regions, including Southwestern America, Saudi Arabia, Africa, and Asia. Not surprisingly, a great number of human infections have been reported from these warm, humid climate regions that are felicitous for the growth of this fungus, especially from the southern region of Saudi Arabia and Arizona in the United States of America. GIB is easily misdiagnosed as malignancy, inflammatory bowel disease, diverticulitis, lymphoma, and chronic intestinal infections due to its rarity. In this case series, we summarize the clinical features, imaging, histopathological features, and treatment of patients diagnosed with GIB in our institution.

Crohn's disease is associated with higher rates of implant-related complications following primary total knee arthroplasty.

INTRODUCTION: In Western countries, there has been a rise in the prevalence of Crohn's Disease (CD) and primary total knee arthroplasty (TKA). This study delves deeper into the effects of CD on TKA patients by examining (1) the length of in-hospital stay (LOS); (2) the rates of readmission; (3) complications related to implants; and (4) the costs associated with care. METHODS: A retrospective analysis using the PearlDiver database was conducted, encompassing the time frame between January 1st, 2005 and March 31st, 2014, focusing on patients who underwent TKA and were either diagnosed with CD or not. Patients with CD were paired with control subjects at a 1:5 ratio based on age, gender, and medical comorbidities. The analysis comprised a total of 96,229 patients (CD = 16,039; non-CD = 80,190). RESULTS: Patients with CD had a notably longer hospital stay (3 v. 2 days, p < 0.0001) and faced significantly higher rates of 90-day readmissions and complications (19.80% v. 14.91%, OR: 1.40, p < 0.0001; 6.88% v. 4.88%, OR: 1.43, p < 0.0001 respectively). Additionally, CD patients incurred greater expenses on the surgery day ($18,365.98 v. $16,192.00) and within 90 days post-surgery ($21,337.46 v. $19,101.42). CONCLUSION: This study demonstrates longer in-hospital LOS, higher rates of readmissions, implant-related complications, and costs of care among CD patients following primary TKA.

Biofilm's Impact on Inflammatory Bowel Diseases.

The colon has a large surface area covered with a thick mucus coating. Colon's biomass consists of about 1,012 colony-forming units per gram of feces and 500-1,000 distinct bacterial species. The term inflammatory bowel disease (IBD) indicates the collection of intestinal illnesses in which the digestive system (esophagus, large intestine, mouth, stomach, and small intestine) experiences persistent inflammation. IBD development is influenced by environmental (infections, stress, and nutrition) and genetic factors. The microbes present in gut microbiota help maintain intestinal homeostasis and support immune and epithelial cell growth, differentiation, as well as proliferation. It has been discovered that a variety of variables and microorganisms are crucial for the development of biofilms and mucosal colonization during IBD. An extracellular matrix formed by bacteria supports biofilm production in our digestive system and harms the host's immunological response. Irritable bowel syndrome (IBS) and IBD considerably affect human socioeconomic well-being and the standard of living. IBD is a serious public health issue, affecting millions of people across the globe. The gut microbiome may significantly influence IBS pathogenesis, even though few diagnostic and treatment options are available. As a result, current research focuses more on disrupting biofilm in IBD patients and stresses primarily on drugs that help improve the quality of life for human well-being. We evaluate studies on IBD and bacterial biofilm to add fresh insights into the existing state of knowledge of biofilm formation in IBD, incidence of IBD patients, molecular level of investigations, bacteria that are involved in the formation of biofilm, and present and down the line regimens and probiotics. Planning advanced ways to control and eradicate bacteria in biofilms should be the primary goal to add fresh insights into generating innovative diagnostic and alternative therapy options for IBD.

Predictors of pouch failure: A tertiary care inflammatory bowel disease centre experience.

AIM: Rates of pouch failure after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) range from 5% to 18%. There is little consistency across studies regarding the factors associated with failure, and most include patients who underwent IPAA in the pre-biologic era. Our aim was to analyse a cohort of patients who underwent IPAA in the biologic era at a large-volume inflammatory bowel disease institution to better determine preoperative, perioperative and postoperative factors associated with pouch failure. METHODS: A retrospective cohort analysis was performed with data from an institutional review board approved prospective database with ulcerative colitis or unclassified inflammatory bowel disease patients who underwent total proctocolectomy with IPAA at Mount Sinai Hospital between 2008 and 2017. Preoperative, perioperative and postoperative data were collected and univariate and multivariate analyses were performed to identify factors associated with increased risk of pouch failure. RESULTS: Out of 664 patients included in the study, pouch failure occurred in 41 (6.2%) patients, a median of 23.3 months after final surgical stage. Of these, 17 (41.4%) underwent pouch excision and 24 (58.5%) had diverting ileostomies. The most common indications for pouch failure were Crohn's disease like pouch inflammation (CDLPI) (n = 17, 41.5%), chronic pouchitis (n = 6, 14.6%), chronic cuffitis (n = 5, 12.2%) and anastomotic stricture (n = 4, 9.8%). On multivariate analysis, pre-colectomy biologic use (hazard ratio [HR] 2.25, 95% CI 1.09-4.67), CDLPI (HR 3.18, 95% CI 1.49-6.76) and pouch revision (HR 2.59, 95% CI 1.26-5.32) were significantly associated with pouch failure. CONCLUSIONS: Pouch failure was significantly associated with CDLPI, preoperative biologic use and pouch revision; however, reassuringly it was not associated with postoperative complications.

The Utility of Faecal Calprotectin, Lactoferrin and Other Faecal Biomarkers in Discriminating Endoscopic Activity in Crohn's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn's disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD. METHODS: We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria. RESULTS: The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing. CONCLUSION: FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.

Conventional versus ultra-low dose computed tomogram in Crohn's disease: Do morphomics correlate with clinical data?

BACKGROUND: Cross-sectional study to assess the body composition of patients with Crohn's disease (CD) on standard (SDCT) and low dose CT (LDCT) protocols for the abdomen and pelvis (CTAP). We aimed to assess if a low dose CT protocol reconstructed with model-based iterative reconstruction (IR) could evaluate body morphometric data comparable to standard dose examination. METHODS: The CTAP images of 49 patients who underwent a low dose CT scan (20% of standard dose) and a second at standard dose minus 20% were assessed retrospectively. Images were collected from the PACS system, deidentified and analysed using a web-based semi-automated threshold-based segmentation tool (CoreSlicer), capable of identifying tissue type based on differences in attenuation co-efficient. The cross-sectional area (CSA) and Hounsfield units (HU) of each tissue was recorded. RESULTS: Muscle and fat CSA is well preserved on comparing these derived metrics from low dose and standard dose CT scans of abdomen and pelvic in CD ((LDCT:SDCT mean CSA (cm2); Psoas muscle - 29.00:28.67, total lumbar muscle - 127.45:125.55, visceral fat- 110.44:114.16, subcutaneous fat - 250.88:255.05)). A fixed difference exists when assessing the attenuation of muscle, with higher attenuation on the low dose protocol (LDCT:SDCT mean attenuation (HU); Psoas muscle - 61.67:52.25, total lumbar muscle - 49.29:41.20). CONCLUSION: We found comparable CSA across all tissues (muscle and fat) on both protocols with a strong positive correlation. A marginally lower muscle attenuation suggestive of less dense muscle was highlighted on SDCT. This study augments previous studies suggesting that comparable and reliable morphomic data may be generated from low dose and standard dose CT images. IMPLICATIONS FOR PRACTICE: Threshold-based segmental tools can be used to quantify body morphomics on standard and low dose computed tomogram protocols.

Current management of bowel failure due to Crohn's disease in Spain: Results of a GETECCU survey. / Manejo actual del fracaso intestinal por enfermedad de Crohn en nuestro medio: resultados de una encuesta GETECCU.

INTRODUCTION: Intestinal failure is a rare pathology which requires knowledge and highly specialized multidisciplinary management. Crohn's disease (CD) being one of the most frequent causes in adults. MATERIAL AND METHODS: Survey format study carried out within the GETECCU group, included closed format questions about the diagnosis, management and current knowledge of intestinal failure in CD. RESULTS: Forty-nine doctors participated, belonging to different Spanish centers (19 cities). It was considered that a patient suffered from intestinal failure, in 67.3% (33/49 surveyed) when there was a disorder malabsorptive associated regardless of the intestinal length resected, with surgeries resective ileal repeated (40.8%, 20/49), the most frequent cause. It highlights frequent ignorance about the pathology (24.5%) did not know if there were patients in their center and also 40% did not know the pharmacological treatment. A total of 228 patients were registered for follow-up due to intestinal failure of any aetiology, 89 patients (39.5%) were identified with CD. Regarding the therapeutic management of patients with CD and intestinal failure (72.5%) were receiving total parenteral nutrition (NTP) and 24 patients (27%) with teduglutide. Regarding the response to the drug: 37.5% had no response to teduglutide, 37.5% partial response (reduce NTP) and 25% good response (withdrawal of home NTP). In questions related to knowledge about intestinal failure, it was considered limited (53.1%) or very limited (12.2%) by the surveyed. CONCLUSION: It is necessary to carry out a combined management of intestinal failure and CD in the context of a multidisciplinary approach.

The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease.

Landmark genome-wide association studies (GWAS) identified that mutations in autophagy genes correlated with inflammatory bowel disease (IBD), a heterogenous disease characterised by prolonged inflammation of the gastrointestinal tract, that can reduce a person's quality of life. Autophagy, the delivery of intracellular components to the lysosome for degradation, is a critical cellular housekeeping process that removes damaged proteins and turns over organelles, recycling their amino acids and other constituents to supply cells with energy and necessary building blocks. This occurs under both basal and challenging conditions such as nutrient deprivation. An understanding of the relationship between autophagy, intestinal health and IBD aetiology has improved over time, with autophagy having a verified role in the intestinal epithelium and immune cells. Here, we discuss research that has led to an understanding that autophagy genes, including ATG16L, ATG5, ATG7, IRGM, and Class III PI3K complex members, contribute to innate immune defence in intestinal epithelial cells (IECs) via selective autophagy of bacteria (xenophagy), how autophagy contributes to the regulation of the intestinal barrier via cell junctional proteins, and the critical role of autophagy genes in intestinal epithelial secretory subpopulations, namely Paneth and goblet cells. We also discuss how intestinal stem cells can utilise autophagy. Importantly, mouse studies have provided evidence that autophagy deregulation has serious physiological consequences including IEC death and intestinal inflammation. Thus, autophagy is now established as a key regulator of intestinal homeostasis. Further research into how its cytoprotective mechanisms can prevent intestinal inflammation may provide insights into the effective management of IBD.

Revisão sistemática e meta-análise das tendências de frequência e reclassificação da doença inflamatória pediátrica intestinal - não classificadas / Systematic review and meta - analysis of the frequency and re-classification trends of pediatric inflammatory bowel disease - unclassified

ABSTRACT Background: The term inflammatory bowel disease-unclassified (IBDU) is used when an individual has chronic colitis but cannot be sub-typed into ulcerative colitis (UC) or Crohn's disease (CD) on the basis of the clinical, endoscopic, imaging and histopathological features. On follow-up a proportion of patients with IBDU are re-classified as CD or UC. There has been considerable variability in the frequency and reclassification rates of pediatric IBDU in published literature. Methods: PubMed and Scopus and were searched for publications related to Pediatric Inflammatory Bowel Disease (PIBD) published between Jan,2014 and July,2021. Two reviewers independently searched and selected studies reporting the frequency of IBDU and/or their re-classification. The pooled prevalence was expressed as proportion and 95%CI. Meta-analysis was performed using the inverse variance heterogeneity model. Results: A total of 2750 studies were identified through a systematic search of which 27 studies were included in this systematic review. The overall pooled frequency of IBDU (n=16064) was found to be 7.1% (95%CI 5.8-8.5%). There was no variation in IBDU frequency by geographical location. Seven studies (n=5880) were included in the IBDU re-classification analysis. Overall, 50% (95%CI 41-60%) children with IBDU were re-classified on follow-up. Amongst these 32.7% (95% 21-44%) were re-classified to UC and 17% (95%CI 12-22%) were re-classified to CD. Conclusion: IBDU comprises 7.1% of PIBD at initial diagnosis. Half of these children are re-classified into UC or CD on follow-up with a higher likelihood of re-classification to UC as compared to CD.

RESUMO Contexto: O termo doença inflamatória intestinal não classificada (DIINC) é usado quando um indivíduo tem colite crônica, mas não pode ser sub tipificado em colite ulcerativa (UC) ou doença de Crohn (DC) com base nas características clínicas, endoscópicas, de imagem e histopatológicas. No acompanhamento, uma proporção de pacientes com DIINC são reclassificadas como DC ou UC. Houve considerável variabilidade nas taxas de frequência e reclassificação de DIINC pediátrico na literatura publicada. Métodos: Foram procuradas publicações no PubMed e Scopus relacionadas à doença inflamatória pediátrica intestinal publicadas entre janeiro de 2014 e julho de 2021. Dois revisores pesquisaram e selecionaram estudos independentemente relatando a frequência da DIINC e/ou sua reclassificação. A prevalência agrupada foi expressa em proporção e para IC95%. A meta-análise foi realizada utilizando o modelo de heterogeneidade de variância inversa. Resultados: Foram identificados 2.750 estudos por meio de uma busca sistemática, dos quais 27 estudos foram incluídos nesta revisão sistemática. A frequência total agrupada da DIINC (n=16064) foi de 7,1% (IC95% 5,8-8,5%). Não houve variação na frequência da DIINC por localização geográfica. Sete estudos (n=5880) foram incluídos na análise de reclassificação da DIINC. No geral, 50% (IC95% 41-60%) foram reclassificadas no seguimento. Entre esses 32,7% (95% 21-44%) foram reclassificados para UC e 17% (IC95%12-22%) foram reclassificados para DC. Conclusão: DIINC compreende 7,1% da doença inflamatória pediátrica intestinal no diagnóstico inicial. Metade dessas crianças são reclassificados em UC ou DC no seguimento com maior probabilidade de reclassificação para UC em comparação com o DC.

Blau syndrome NOD2 mutations result in loss of NOD2 cross-regulatory function.

The studies described here provide an analysis of the pathogenesis of Blau syndrome and thereby the function of NOD2 as seen through the lens of its dysfunction resulting from Blau-associated NOD2 mutations in its nucleotide-binding domain (NBD). As such, this analysis also sheds light on the role of NOD2 risk polymorphisms in the LRR domain occurring in Crohn's disease. The main finding was that Blau NOD2 mutations precipitate a loss of canonical NOD2 signaling via RIPK2 and that this loss has two consequences: first, it results in defective NOD2 ligand (MDP)-mediated NF-κB activation and second, it disrupts NOD2-mediated cross-regulation whereby NOD2 downregulates concomitant innate (TLR) responses. Strong evidence is also presented favoring the view that NOD2-mediated cross-regulation is under mechanistic control by IRF4 and that failure to up-regulate this factor because of faulty NOD2 signaling is the proximal cause of defective cross-regulation and the latter's effect on Blau syndrome inflammation. Overall, these studies highlight the role of NOD2 as a regulatory factor and thus provide additional insight into its function in inflammatory disease. Mutations in the nucleotide binding domain of the CARD15 (NOD2) gene underlie the granulomatous inflammation characterizing Blau syndrome (BS). In studies probing the mechanism of this inflammation we show here that NOD2 plasmids expressing various Blau mutations in HEK293 cells result in reduced NOD2 activation of RIPK2 and correspondingly reduced NOD2 activation of NF-κB. These in vitro studies of NOD2 signaling were accompanied by in vivo studies showing that BS-NOD2 also exhibit defects in cross-regulation of innate responses underlying inflammation. Thus, whereas over-expressed intact NOD2 suppresses TNBS-colitis, over-expressed BS-NOD2 does not; in addition, whereas administration of NOD2 ligand (muramyl dipeptide, MDP) suppresses DSS-colitis in Wild Type (WT) mice it fails to do so in homozygous or heterozygous mice bearing a NOD2 Blau mutation. Similarly, mice bearing a Blau mutation exhibit enhanced anti-collagen antibody-induced arthritis. The basis of such cross-regulatory failure was revealed in studies showing that MDP-stimulated cells bearing BS-NOD2 exhibit a reduced capacity to signal via RIPK2 as well as a reduced capacity to up-regulate IRF4, a factor shown previously to mediate NOD2 suppression of NF-κB activation. Indeed, TLR-stimulated cells bearing a Blau mutation exhibited enhanced in vitro cytokine responses that are quieted by lentivirus transduction of IRF4. In addition, enhanced anti-collagen-induced joint inflammation in mice bearing a Blau mutation was accompanied by reduced IRF4 expression in inflamed joint tissue and IRF4 expression was reduced in MDP-stimulated cells from BS patients. Thus, inflammation characterizing Blau syndrome are caused, at least in part, by faulty canonical signaling and reduce IRF4-mediated cross-regulation.

Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease.

Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fibrogenesis, considers potential cross-talk between Wnt and transforming growth factor ß1 (TGFß) signalling pathways, and assesses the therapeutic potential of small-molecule Wnt inhibitors. ß-catenin expression was explored by immunohistochemistry (IHC) in formalin-fixed paraffin embedded (FFPE) tissue from patient-matched nonstrictured (NSCD) and strictured (SCD) intestine (n=6 pairs). Functional interactions between Wnt activation, TGFß signalling, and type I collagen (Collagen-I) expression were explored in CCD-18Co cells and primary CD myofibroblast cultures established from surgical resection specimens (n=16) using small-molecule Wnt inhibitors and molecular techniques, including siRNA-mediated gene knockdown, immunofluorescence (IF), Wnt gene expression arrays, and western blotting. Fibrotic SCD tissue was marked by an increase in ß-catenin-positive cells. In vitro, activation of Wnt-ß-catenin signalling increased Collagen-I expression in CCD-18Co cells. Conversely, ICG-001, an inhibitor of ß-catenin signalling, reduced Collagen-I expression in cell lines and primary CD myofibroblasts. TGFß increased ß-catenin protein levels but did not activate canonical Wnt signalling. Rather, TGFß up-regulated WNT5B, a noncanonical Wnt ligand, and the Wnt receptor FZD8, which contributed directly to the up-regulation of Collagen-I through a ß-catenin-independent mechanism. Treatment of CCD-18Co fibroblasts and patient-derived myofibroblasts with the FZD8 inhibitor 3235-0367 reduced extracellular matrix (ECM) expression. Our data highlight small-molecule Wnt inhibitors of both canonical and noncanonical Wnt signalling, as potential antifibrotic drugs to treat SCD intestinal fibrosis. They also highlight the importance of the cross-talk between Wnt and TGFß signalling pathways in CD intestinal fibrosis.

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the use of abdominal ultrasound in inflammatory bowel disease. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el empleo de la ecografía abdominal en la enfermedad inflamatoria intestinal.

Ultrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units.

Stage at Diagnosis and Survival of Colorectal Cancer With or Without Underlying Inflammatory Bowel Disease: A Population-based Study.

BACKGROUND: Inflammatory bowel disease [IBD] is a risk factor for colorectal cancer [CRC]. The aim of this study is to determine whether stage at diagnosis and survival differ between sporadic, ulcerative colitis [UC]- and Crohn's disease [CD]-related CRC. METHODS: The English National Cancer Registry [NCIN], Hospital Episode Statistics [HES] and Office for National Statistics [ONS] datasets between 2000 and 2010 were linked, providing data on comorbidities, stage and date of death. A logistic regression model determined whether IBD was associated with an early [I/II] or late [III/IV] cancer. Cox regression analysis was used to examine survival differences between sporadic, UC- and CD-related cancers. RESULTS: A total of 234 009 patients with CRC were included, of whom 985 [0.4%] and 1922 [0.8%] had CD and UC, respectively. UC, but not CD, was associated with an earlier stage compared with sporadic cancers (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.79 to 0.98, p = 0.02). CD had a significantly worse survival compared with sporadic patients for stage II [HR = 1.71, CI 1.26 to 2.31 p <0.005] and III [1.53, CI 1.20 to 1.96, p <0.005] cancer. UC patients were associated with worse survival compared with the sporadic group for both stage III [1.38, CI 1.17 to 1.63, p <0.0005] and IV [1.13, CI 1.01 to 1.28, p = 0.04] cancer. After excluding sporadic patients, UC was associated with improved survival compared with CD [0.62, CI 0.43 to 0.90, p = 0.01] for stage II cancer. CONCLUSIONS: Patients with IBD are diagnosed at an earlier stage but tend to have a worse survival compared with sporadic cases of CRC, in particular for nodal disease [stage III].Specifically, patients with CD-related CRC appear to fare worst in terms of survival compared with both the sporadic and UC groups.

An unusual case of diffuse large B-cell lymphoma complicating a Crohn's disease.

Clinicians should keep in mind that Crohn's disease may be complicated by neoplasia such as adenocarcinomas or lymphomas, especially if the disease duration is long and the patient is under immunosuppressive therapy.

Case report: Tension pneumoperitoneum after diagnostic colonoscopy in an 11 y/o boy with Crohns disease.

INTRODUCTION: Endoscopy is an established diagnostic and therapeutic tool in paediatric gastroenterology and a save method with rare complications. PRESENTATION OF CASE: We present the case of an 11-year-old Caucasian boy with a long history of inflammatory bowel disease. Three years prior an ileostomy was created and is still in position. After diagnostic panendoscopy (colonoscopy, gastroscopy, endoscopy of small intestine via ileostomy) the patient showed progressive abdominal distension and pain. After diagnosis of tension pneumoperitoneum by radiological proof of massive intraabdominal air and altered vital signs, we initiated emergency laparotomy. Surgical intervention ruled out a free gastrointestinal perforation as well as peritonitis. There was a gaseous insufflation of the mesenteric tissue of the sigmoid and upper rectum most likely according to microperforations to the mesentery. Due to the pre-existing ileostomy, we took no further surgical action. The abdomen was lavaged and drains inserted. Upon further conservative treatment with intravenous antibiotics, the patient showed quick recovery and was discharged on postoperative day 6. DISCUSSION: With an incidence of 0.01%, perforation after diagnostic colonoscopy in children is very uncommon. The zone most frequently affected is the sigmoid colon due to direct penetration or indirect force due to flexure, or insufflation. Even without macroscopic perforation, the development of a tension pneumoperitoneum seems to be possible. CONCLUSION: Even though Colonoscopy in children is a safe tool, the treating physician must never underestimate the risks of such an intervention. Especially chronically altered intestine as in long-time persisting chronic inflammatory bowel disease demand special care and intensive observation of the patient after intervention.

Inflammatory colitis associated with Teriflunomide.

Teriflunomide is an oral disease modifying therapy for relapsing-remitting multiple sclerosis (RRMS). Gastrointestinal (GI) side effects occurred in 15-17.9% of patients in the clinical trials and usually were mild and self-limiting. Few cases of inflammatory colitis related to teriflunomide and leflunomide, a prodrug which converts to teriflunomide and is used in the treatment of rheumatoid arthritis, have been reported but no clinical data is available except for a single case of lymphocytic colitis. We here report a 49-year-old man with RRMS who developed severe diarrhea and weight loss six months after starting teriflunomide and eventually was found to have multiple ulcers and inflammatory changes consistent with Crohn's disease. After stopping teriflunomide and chelation therapy, he was started on immunotherapy for Crohn's given the highly inflammatory degree of GI symptoms and histology findings.

A 12-month pilot study outcomes of vagus nerve stimulation in Crohn's disease.

BACKGROUND: The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. METHODS: Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up. KEY RESULTS: After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorß1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated. CONCLUSION & INFERENCES: Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.

Predicting Post-operative Complications in Crohn's Disease: an Appraisal of Clinical Scoring Systems and the NSQIP Surgical Risk Calculator.

BACKGROUND: Surgery is common in patients with Crohn's disease and can contribute significantly to patient morbidity. The National Surgical Quality Improvement Program surgical risk calculator (NSQIP-SRC) that is currently utilized to predict surgical risk does not take Crohn's disease into account and, as a result, seems to underestimate risk in this patient population. This study aimed to evaluate the accuracy of the NSQIP-SRC in Crohn's disease patients and to evaluate the utility of disease severity scores in predicting surgical risk. METHODS: Between 2011 and 2017, there were 176 surgical cases involving Crohn's disease patients. Demographic data and 30-day surgical outcomes were collected. Disease severity scores including Harvey Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn's Disease (SES-CD), and NSQIP-SRC risk percentages were calculated. RESULTS: Patients in remission based on HBI had a complication rate of 8.57% (n = 3), while those with mild or moderate-severe disease had rates of 33.33% (n = 11) and 38.46% (n = 20) respectively (p = 0.0045). In multivariable analysis, those with mild (OR; 8.37, 95% CI; 1.64, 42.78; p = 0.011) or moderate-severe (OR; 11.69, 95% CI; 2.42, 56.46; p = 0.002) disease had increased odds of complication compared to remission. Complication rate was not associated with NSQIP-SRC percent risk of any complication. CONCLUSION: NSQIP-SRC does not accurately predict risk in patients with CD undergoing surgery. Higher disease activity based on HBI is associated with increased odds of complication and may prove to be more predictive of surgical complication in the Crohn's patient population.