[Orale Manifestationen bei Morbus Crohn].

Patienten, welche an chronisch entzündlichen Darmerkrankungen leiden, weisen häufig eine orale Manifestation auf. Da in der Schweiz eine von 500 Personen an Morbus Crohn erkrankt, wird der niedergelassene Zahnarzt in seiner Laufbahn höchst wahrscheinlich mit betroffenen Personen in Kontakt kommen. Das Ziel der vorliegenden Arbeit ist es, anhand zweier klinischer Fallbeispiele die möglichen oralen Erscheinungsformen aufzuzeigen und Empfehlungen zur Vor- und Nachsorge in der Zahnarztpraxis abzugeben.

Clinical and health care utilization variables can predict 90-day hospital re-admission in adults with Crohn's disease for point of care risk evaluation.

BACKGROUND: Hospital re-admission for persons with Crohn's disease (CD) is a significant contributor to morbidity and healthcare costs. We derived prediction models of risk of 90-day re-hospitalization among persons with CD that could be applied at hospital discharge to target outpatient interventions mitigating this risk. METHODS: We performed a retrospective study in persons with CD admitted between 2009 and 2016 for an acute CD-related indication. Demographic, clinical, and health services predictor variables were ascertained through chart review and linkage to administrative health databases. We derived and internally validated a multivariable logistic regression model of 90-day CD-related re-hospitalization. We selected the optimal probability cut-point to maximize Youden's index. RESULTS: There were 524 CD hospitalizations and 57 (10.9%) CD re-hospitalizations within 90 days of discharge. Our final model included hospitalization within the prior year (adjusted odds ratio [aOR] 3.27, 95% confidence interval [CI] 1.76-6.08), gastroenterologist consultation within the prior year (aOR 0.185, 95% CI 0.0950-0.360), intra-abdominal surgery during index hospitalization (aOR 0.216, 95% CI 0.0500-0.934), and new diagnosis of CD during index hospitalization (aOR 0.327, 95% CI 0.0950-1.13). The model demonstrated good discrimination (optimism-corrected c-statistic value 0.726) and excellent calibration (Hosmer-Lemeshow goodness-of-fit p-value 0.990). The optimal model probability cut point allowed for a sensitivity of 71.9% and specificity of 70.9% for identifying 90-day re-hospitalization, at a false positivity rate of 29.1% and false negativity rate of 28.1%. CONCLUSIONS: Demographic, clinical, and health services variables can help discriminate persons with CD at risk of early re-hospitalization, which could permit targeted post-discharge intervention.

Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease: protocol for the Nordic inception cohort study (NORDTREAT).

INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death. METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits. ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences. CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.

Fecal proteolytic profiling of pediatric inflammatory bowel disease: A pilot study.

Colonoscopy is the gold standard for diagnosing inflammatory bowel disease (IBD). However, this invasive procedure has a high burden for pediatric patients. Previous research has shown elevated fecal amino acid concentrations in children with IBD versus controls. We hypothesized that this finding could result from increased proteolytic activity. Therefore, the aim of this study was to investigate whether fecal protease-based profiling was able to discriminate between IBD and controls. Protease activity was measured in fecal samples from patients with IBD (Crohn's disease (CD) n = 19; ulcerative colitis (UC) n = 19) and non-IBD controls (n = 19) using a fluorescence resonance energy transfer (FRET)-peptide library. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of each FRET-peptide substrate. Screening the FRET-peptide library revealed an increased total proteolytic activity (TPA), as well as degradation of specific FRET-peptides specifically in fecal samples from IBD patients. Based on level of significance (p < .001) and ROC curve analysis (AUC > 0.85), the fluorogenic substrates W-W, A-A, a-a, F-h, and H-y showed diagnostic potential for CD. The substrates W-W, a-a, T-t, G-v, and H-y showed diagnostic potential for UC based on significance (p < .001) and ROC analysis (AUC > 0.90). None of the FRET-peptide substrates used was able to differentiate between protease activity in fecal samples from CD versus UC. This study showed an increased fecal proteolytic activity in children with newly diagnosed, treatment-naïve, IBD. This could lead to the development of novel, noninvasive biomarkers for screening and diagnostic purposes.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Capsule endoscopy and panendoscopy: A journey to the future of gastrointestinal endoscopy.

In 2000, the small bowel capsule revolutionized the management of patients with small bowel disorders. Currently, the technological development achieved by the new models of double-headed endoscopic capsules, as miniaturized devices to evaluate the small bowel and colon [pan-intestinal capsule endoscopy (PCE)], makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders. This technology is expected to identify which patients will require conventional invasive endoscopic procedures (colonoscopy or balloon-assisted enteroscopy), based on the lesions detected by the capsule, i.e., those with an indication for biopsies or endoscopic treatment. The use of PCE in patients with inflammatory bowel diseases, namely Crohn's disease, as well as in patients with iron deficiency anaemia and/or overt gastrointestinal (GI) bleeding, after a non-diagnostic upper endoscopy (esophagogastroduodenoscopy), enables an effective, safe and comfortable way to identify patients with relevant lesions, who should undergo subsequent invasive endoscopic procedures. The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract, is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract, from mouth-to-anus, meeting the expectations of the early developers of capsule endoscopy.

Multicenter registry of pediatric inflammatory bowel disease from a developing country.

BACKGROUND: Despite the rising incidence of pediatric inflammatory bowel disease (PIBD) globally, multicenter collaborative studies of PIBD children among developing countries remain sparse. We therefore aimed to define the initial presentation and short-term outcomes of Thai children with PIBD from a multicenter registry. METHODS: Four teaching hospitals participated in this study. A diagnosis of PIBD requires gastrointestinal endoscopy and histopathology in children aged < 19 years. Besides demographics, we collected clinical information and treatment with the data at 1-year follow up. RESULTS: We included 35 Crohn's disease (CD), one IBD-unclassified, and 36 ulcerative colitis (UC) children (total n = 72 with 60.6% males). The mean age at diagnosis was 7.9 years (SD 4.1) with 38% being very early onset IBD (VEO-IBD). When compared with UC, the CD children were more likely to exhibit fever (42.3 vs. 13.9%), weight loss/failure to thrive (68.6 vs. 33.3%), and hypoalbuminemia (62.9 vs. 36.1%) but less likely to have bloody stools (51.4 vs. 91.7%) (all P < 0.05). No significant differences in demographics, clinical data and medications used with regards to VEO-IBD status. At 1 year after diagnosis (n = 62), 30.7% failed to enter clinical remission and 43.7% remained on systemic corticosteroids. Diarrhea (OR 9.32) and weight issues (OR 4.92) at presentation were independent predictors of failure to enter clinical remission; and females (OR 3.08) and CD (vs. UC) (OR 3.03) were predictors of corticosteroids use at 1-year follow-up. CONCLUSIONS: A high proportion of VEOIBD is noted, and CD was more likely to present with significant inflammatory burden. Diarrhea and weight issues at presentation were independent predictors of failure to enter clinical remission; and females and CD (vs. UC) were predictors of corticosteroids use at 1-year follow-up.

[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.

Mobile monitoring system detects the disease activity pattern and shows the association with clinical outcomes in patients with newly diagnosed Crohn's disease.

We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD.

Absolute monocyte counts could predict disease activity and secondary loss of response of patients with Crohn's disease treated with anti-TNF-α drug.

BACKGROUND: Assessing Crohn's disease (CD) activity is critical for monitoring disease progression. In CD, monocytes could release TNF-α. Thus, it is extremely important to study its role in the disease activity and loss of response to anti-TNF-α biologics. METHODS: In this study, we collected CD patients treated with biologics from January 2017 to May 2022. Indicators associated with disease activity were evaluated by Spearman correlation analysis and Mann-Whitney U test. Specifically, logistic analyses were used to explore the predictors of primary nonresponse (PNR) and secondary loss of response (SLOR) within 1 year of anti-TNF-α agents. In addition, a nomogram was developed for therapeutic effect prediction. RESULTS: 283 patients with CD were identified. Disease activity group, defined as CDAI equal to or greater than 150, had significant elevated absolute monocyte counts than disease remission group based on CDAI score (p = 0.019, Z = -2.354). Logistic analyses showed that absolute monocyte counts could be an independent predictor of 1-year SLOR of anti-TNF-α agents in CD patients (p = 0.013). A nomogram established based on gender, absolute monocyte counts, and hemoglobin could predict SLOR within 1 year of anti-TNF-α agents reliably. CONCLUSION: The results of this study support the utility of absolute monocyte counts detecting disease activity and anti-TNF-α therapy effect in patients with CD.

Recurrent Crohn's disease.

Although surgical management of the ileocolic segment in pediatric Crohn's disease is not curative, the main goal of therapy is to allow for growth, adequate nutrition, and age-appropriate development. Recurrent disease at the site of anastomosis presents as a major morbidity. Several factors have been implicated in the development of surgical recurrence though data in the literature is scarce. This review explores the epidemiology of recurrent ileocolic disease following primary surgery, indications for surgical intervention, and techniques reported in the literature. Pediatric data is scarce, and therefore, much of it is extrapolated from adult literature.

Perianal disease: Updates and controversies in closing the gaps.

Perianal complications are common and morbid in children with Crohn's disease. In this review, we describe the epidemiology, the presentation and diagnosis, evaluation and management. We focus on updates such as the increasing frequency of biologic medications and MRI for evaluation. We also highlight controversies on the timing and approaches to surgical techniques. Finally, perianal disease requires the coordination of multidisciplinary care with nursing, radiology, gastroenterology, and surgery to optimize outcomes - both medical and patient-centered.

Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

Cutaneous Crohn disease presenting as "knife-edged" ulcers: a case report.

BACKGROUND: CCD presents as non-caseating granulomas within the skin at a site distant from the GI tract. CCD is a debilitating extraintestinal sequela of CD that can sometimes precede its GI manifestations. In the absence of GI symptoms, the histopathologic and clinical features of CCD can present as a variety of inflammatory skin conditions that can range from ruptured follicle-associated granulomas to cutaneous ulcerations. While a variety of therapeutic options for patients with CCD and concurrent luminal CD have been described in the literature, there is no standard treatment algorithm for the management of refractory CCD with limited or covert GI involvement. CASE REPORT: The authors discuss the case of a 33-year-old female who presented to the wound care clinic with multiple "knife-edged" cutaneous ulcerations involving the intertriginous spaces, found to be consistent with CCD. Her original cutaneous symptoms and diagnosis manifested with minimal GI involvement and responded to IVIG treatment. CONCLUSIONS: This case supports the inclusion of CCD in the differential diagnosis in patients with knife-edged granulomatous skin lesions in intertriginous locations. This clinical condition may present in the setting of no or limited GI symptoms. The management of CCD and a proposed treatment algorithm are also presented.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

BACKGROUND/AIMS: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. METHODS: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). RESULTS: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. CONCLUSION: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.