Appendectomy at age <20 years for appendicitis or mesenteric lymphadenitis has been associated with a lower risk of Ulcerative Colitis (UC), but this association has not been detected when appendectomy is performed at an older age or for non-specific abdominal pain. Similar findings have been reported upon combining data from Swedish and Danish registers. However, in a Danish cohort study of familial units, individuals who had first-degree relatives with appendicitis, but no personal history of appendicitis, at age <20 years also had a lower risk of UC. This risk was even lower in those with a family history of UC.
Interventional studies on elective appendectomy for UC therapy are underway. The impact of appendiceal inflammation on UC outcomes, including cancer, are not well understood.
The overall aim of this study is to understand the role of the appendix (appendicitis and appendectomy) in IBD risk and IBD outcomes.
Dietary interventions have been shown to ameliorate symptoms in patients with mild or moderate IBD. Nevertheless, these therapies are only effective for a subset of patients, raising the need for novel dietary intervention strategies that aim to prevent IBD development. Glycosylation is a major post-translational mechanism characterised by the addition of carbohydrate structures, called glycans, to essentially all cells. We have revealed that mucosal T cells from Ulcerative Colitis patients exhibit alterations in mucosal glycosylation, which positively correlate with T cell hyperactivity and disease severity. We have also demonstrated that mice deficient in branched N-glycosylation display increased susceptibility to severe colitis. Supplementation of these mice with glycans resulted in disease control via inhibition of Th1/Th17 immune responses.
In this research we aim to explore whether dietary supplementation with glycans promotes a superior function for nutraceutical intervention to promote IBD prevention, characterising the effect of mucosal glycosylation reprogramming in shaping the intestinal environment.
Invariant natural killer T (iNKT) cells are unconventional T lymphocytes that play a critical role in mucosal immunity. Although iNKT cells sense the microbiota of IBD patients, promoting pro-inflammatory responses, their rapid responsiveness to the intestinal microenvironment can be harnessed to promote immunoregulatory rather than pro-inflammatory responses. OCELOT’s central hypothesis is that iNKT cells are the primary immune cells that sense microbiota-derived metabolic signals promoting the resolution of inflammation. In particular, OCELOT argues that microbiota-derived lactate can tightly control iNKT cell function, promoting mucosal tolerance while preventing T cell-mediated inflammation and tissue injury.
In Crohn’s Disease (CD), the treat-to-target strategy has become the standard of care [1, 2]. This clinical concept consists in escalating/optimising the treatment (e.g. dose, frequency, type of drugs) until a state of remission (target) is achieved. Overall, treatment targets evolve towards a deeper level of remission and it is in this context that endoscopic remission has become a primary objective. However, endoscopy remains invasive and costly, is not well accepted by patients and does not allow tight control of disease activity. Thus, attention is turning to non-invasive biomarkers that can replace endoscopy. Our group recently made progress in monitoring disease activity with blood proteins. More precisely, we found distinct biological profiles to be associated with the risk of short-term and mid/long-term relapse in CD patients who stop infliximab [3–5]. By measuring 161 blood proteins, we captured a more complete picture of the disease activity than is achieved with classic inflammatory markers. Clearly, looking beyond inflammation is necessary in order to monitor disease activity more effectively. Based on our previous work, we aim to develop biomarker signatures as an alternative to endoscopy.
Combination treatment with partial enteral nutrition and biologics as induction therapy for adults with active ileocolonic Crohn’s Disease: a pilot study
There is strong interest in investigating combination therapies for active Crohn’s Disease (CD) to improve response to biologics and to mitigate secondary loss of response, without increasing the risk of drug-associated side effects. Exclusive enteral nutrition is an established treatment for active CD, but tolerance is poor. In partial enteral nutrition (PEN) only part of the habitual diet is replaced by the proprietary formula, allowing patients to eat some normal food. PEN at high volume (>50% energy requirements) can prolong remission compared to unrestricted diet. Therefore, the aim of the present study is to compare clinical remission/response rates to standard treatment with adalimumab (ADA) between a group of CD patients on unrestricted diet and another group on 50% PEN. Secondary aims are to explore how these two treatments change the gut microbiome composition and its diet-related function.
Sexual dysfunction (SD) rates are higher in the Inflammatory Bowel Disease (IBD) patient population compared with the general population. Overall among IBD patients, low sexual desire and greater difficulty in achieving orgasms are the most frequently reported sexual problems. In addition, women report worse body image and lower sexual desire. Being diagnosed with major depression, undergoing surgery or suffering IBD symptoms are the usual triggers.
Despite the importance of sexual well-being, there is a lack of research focusing on sexual desire in IBD patients. This study aims to assess the prevalence of sexual dysfunction and to analyse sexual desire from a dual viewpoint: a dyadic and a solitary perspective. The intention is to describe sexual function and its possible correlations with the presence of anxiety and depression, disease activity and quality of life.
Recognizing the prevalence of sexual dysfunction in IBD patients can improve clinical practice and optimize resource planning for sexual healthcare. Early diagnosis and primary prevention can help address sexuality-related concerns in this population.
Krisztina Gecse is a consultant gastroenterologist at the Amsterdam University Medical Centre. She is well known to ECCO as a past Chair of ClinCom and is now at the forefront of the international push towards bowel ultrasound as President Elect of the International Bowel Ultrasound Group. I met with her to hear about her journey from Hungary to Amsterdam and how bowel ultrasound might just be your future….
Crohn’s Disease (CD) is a chronic condition resulting in continuous or episodic inflammation that manifests endoscopically with mucosal ulcerations, strictures, bleeding and/or fistulae. Clinical response and clinical remission have been identified as immediate and medium-term treatment targets, respectively. Endoscopic remission (ER) has been recognised as a long-term treatment target, one specifically associated with improved disease outcomes and reduced bowel damage and colectomy rates [1]. Recommendations from the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD) were recently updated. In this update, it was suggested that changes in therapy should be considered in patients who do not achieve ER [2].
In current clinical practice, endoscopy remains the gold standard for assessing mucosal healing [3]. Serial endoscopic examinations are therefore typically performed in cases of IBD, beginning at diagnosis and thereafter following changes in treatment, to document disease activity and extent and assess therapeutic response.
To measure and quantify mucosal inflammation objectively, different endoscopic indices have been implemented in clinical practice and clinical trials. Among these, the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and the Crohn’s Disease Endoscopic Index of Severity (CDEIS) have been the most used metrics in clinical trials [1].
Compared to the CDEIS and other indices, the SES-CD offers the advantages of both simplicity and ease of use. Furthermore, the SES-CD has proven responsive to changes in disease activity, with good intra- and inter-observer agreement [4]. The SES-CD contains four parameters, each of which receives a uniform score between 0 and 3 in all disease locations. The SES-CD therefore assumes no differential weighting of each individual parameter according to its importance in predicting ER while on active therapy. In essence, the SES-CD score lacks prognostic potential.
In a prior study, it was observed that each of the SES-CD parameters has its own prognostic value in predicting treatment response and ER; further, this value is non-linear among disease locations [5].
Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the Immunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study
Anti-TNF monoclonal antibodies play an important role in the management of immune-mediated inflammatory diseases, including Inflammatory Bowel Disease [1]. However, anti-TNF failure is common [2]. Loss of response is usually associated with the development of anti-drug antibodies and low anti-TNF drug levels.
The aim of this study was to evaluate the relationship between immunogenicity to a patient’s first anti-TNF therapy and immunogenicity and drug persistence to the second anti-TNF therapy, irrespective of drug sequence.
I hope you are all well and into the winter workflow. Many of us were representing IBD at the UEGW earlier in October, and many will have taken advantage of the excellent postgraduate course. Here in the ECCO Community we are excited soon to be launching The IBD Communication Toolbox. This is a series of podcasts where you can hear how IBD experts deal with questions that are commonly asked by patients. Firstly, the questions and topics addressed in the Communication Toolbox were selected in collaboration with patient representatives, ensuring that these are topics with high relevance for the IBD patients you meet in your practice.
