In Search of Newer Targets for Inflammatory Bowel Disease: A Systems and a Network Medicine Approach

After a new look at the history of the Marchioness del Valles conspiracy as part of the tensions that queen Margaret and her ladies caused at the Court of Philip III, the essay stresses the doubts, questions poned and interest that these circumstances aroused in the Spanish political and popular media in the early 17th century. Special attention is given to the information media which prepared and passed on these facts: rumours and oral narrations, announcements, historical and literary texts, relations of ambassadors, all in the framework of a budding public opinion structure.

Does Consuming the Recommend Daily Level of Fiber Prevent Crohn's Disease?

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

AGA Medical Position Statement on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease

STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD

Beyond Gene Discovery in Inflammatory Bowel Disease: The Emerging Role of Epigenetics

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Antineutrophil cytoplasmic antibodies and anti-Saccharomyces cerevisiae antibody: clinical tools or clues for research?

Genetics and Environmental Interactions Shape the Intestinal Microbiome to Promote Inflammatory Bowel Disease Versus Mucosal Homeostasis

The aim of this study was to review all histopathologic sections from surgical specimens with inflammatory bowel disease and colorectal carcinoma filed at this hospital between 1951 and 1996. A total of 40 surgical (n = 39) or autopsy (n = 1) colon or colorectal specimens were reviewed. Internationally accepted histologic criteria were strictly applied to differentiate Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). Of the 40 specimens with inflammatory bowel disease and carcinoma, 22 (55 percent) had CD, 16 (40 percent) had UC, and the remaining 2 (5 percent) had IC. Males accounted for 72.7 percent or 16 of the 22 patients with colorectal carcinoma in CD and for 68.7 percent or 11 of the 16 patients with carcinoma in UC. Both patients with IC and carcinoma were males. The median age of patients at diagnosis was as follows: CD, 20 (range, 7-68) years; UC, 23 (range, 5-21) years. In IC, the age was 61 and 81 years, respectively. The median disease duration (before detection of colorectal cancer) was as follows: CD, 18.5 (range, 1-45) years; UC, 19 (range, 6-38) years. For cases with IC, it was 13 and 19 years, respectively. Median age of patients at cancer diagnosis was as follows: CD, 48 (range, 21-78) years; UC, 49 (range, 21-81) years. Ages at cancer diagnosis in IC were 68 and 81 years. Colorectal carcinoma tend to develop among relatively young patients with CD and UC. Mucinous adenocarcinomas accounted for approximately one-third of the carcinomas affecting CD. Thirty percent of old specimens (before the end of 1982) had in fact carcinoma complicating CD and not UC (the latter being the diagnosis appearing in old pathologic reports). During a time lapse of 38 years (i.e., between 1951 and 1989), only 11 cases of colorectal CD with carcinoma (i.e., 0.2 cases/year) were found, but as many as 11 during the past 6.5 years (i.e., 1.7 cases/year) have been diagnosed. Only 42.3 percent (11/26) of cases with colorectal inflammatory bowel disease and carcinoma operated on between 1951 and the end of 1989 had Crohn's colitis but as many as 78.6 percent (11/14) of those operated on between 1990 and May 1996 had Crohn's colitis. Review of the literature indicated that 64.8 percent or 191 of the 295 cases of colorectal carcinomas in CD so far reported occurred in the past 6.5 years. It would seem as if the risk of colorectal carcinoma in Crohn's colitis has increased in later years. 1) Reports on cancer frequency in UC based on old histopathologic records should be subjected to critical histologic re-evaluation; 2) carcinoma in Crohn's colitis has increased at this hospital, particularly since 1990; 3) the surveillance program strategy used in patients with long-standing UC at this hospital should also embrace patients with Crohn's colitis.

Background/Objectives: Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). The availability of an increasing number of new molecules approved for IBD treatment has increased our ability and aspirations to change the trajectory of the disease. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) II consensus (2018) is the current suggested strategy for IBD management, which recommends a treat-to-target approach. The primary objective of this study is to describe the clinical history of IBD in the post-STRIDE II era and to quantify the burden of IBD in terms of hospitalisation rate. The secondary objective is to estimate the 6-year risk of intestinal resection among IBD patients. Methods: A population-based time series analysis was conducted on administrative data; retrospective data from January 2011 to December 2021 were collected for the Local Health Authority "Roma 1" population (∼1.5 million residents). Hospitalisation and surgical events were prospectively recorded for patients newly diagnosed between January 2018 and February 2022 (n = 556), with follow-up throughout May 2024. A Kaplan-Mayer survivor analysis was performed to estimate the cumulative surgery risk. Results: In 2021, the IBD prevalence was 218.3 cases/100,000 people (77.2 CD, 141.1 UC). The incidence trend slowly increased during the last decade, up to 5.3 (CD) and 9.4 (UC) cases/100,000 ppl/year. The yearly hospitalisation rate remained stable, near 16.5%. The 6-year cumulative risk of surgery was 36% for CD and 20% for UC. Conclusions: The incidence of IBD has increased in the last few decades, with substantial stability in regard to the incidence of surgery and hospitalisations. Thus, the current IBD management approach has only had a small effect on changing the natural history of the disease.

: The objective of the present study was to quantify the national pediatric inpatient inflammatory bowel disease (IBD) burden in terms of the number of IBD-related hospitalizations, the number of days spent in the hospital, and hospitalization costs. : Hospitalizations for children and adolescents 20 years and younger with a primary diagnosis of either Crohn disease (CD) or ulcerative colitis (UC) were selected from the 2006 Kids' Inpatient Database (KID). Length of the hospital stay in days (LOS) and charges for the hospitalization were found directly in the Kids' Inpatient Database, and cost was calculated using the hospital's cost-to-charge ratio. Predictor variables included patient characteristics, such as age and severity of illness, and hospital characteristics. Ordinary-least-squares regressions were developed and estimated to explain hospitalization costs. : In 2006, there were 10,777 IBD-related hospitalizations. The total and mean costs for CD were $66.3 million and $10,176 (95% confidence interval [CI] $9647-$10,705), and for UC were $48.6 million and $11,836 (95% CI $10,760-$12,912). For CD, 0- to 5-year-old patients had the highest mean LOS (8.10, 95% CI 5.53-10.67, days) and mean cost ($13,894, 95% CI $9053-$18,735), whereas, for UC, 11- to 15-year-old patients had the highest mean LOS (7.49, 95% CI 6.88-8.10, 95% CI 5.53-10.67, days) and mean cost ($13,407, 95% CI $11,704-$15,110). : For a pediatric disease with a rather low prevalence rate, the estimated annual inpatient pediatric burden of IBD is a sizeable $152.4 million (2010 US$) and 64,985 days spent in the hospital. As medications and outpatient treatments improve for the treatment of IBD, there is an opportunity for significant reduction in inpatient burden.

Future Therapeutic Approaches for Inflammatory Bowel Diseases

The inflammatory bowel diseases Crohn's disease and ulcerative colitis are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. To identify genetic factors that might contribute to these disorders, we performed a genome-wide association study. We found a highly significant association between Crohn's disease and the IL23R gene on chromosome 1p31, which encodes a subunit of the receptor for the proinflammatory cytokine interleukin-23. An uncommon coding variant (rs11209026, c.1142G>A, p.Arg381Gln) confers strong protection against Crohn's disease, and additional noncoding IL23R variants are independently associated. Replication studies confirmed IL23R associations in independent cohorts of patients with Crohn's disease or ulcerative colitis. These results and previous studies on the proinflammatory role of IL-23 prioritize this signaling pathway as a therapeutic target in inflammatory bowel disease.