Inflammatory Intestinal Diseases最新文献

Introduction: Lymphocytic esophagitis (LyE) represents a chronic inflammatory disease of the esophagus with low response rates to topical steroids. Thus, novel treatment options such as swallowed topical tacrolimus, particularly for refractory cases, are urgently needed.

Methods: We retrospectively analyzed patients with LyE enrolled in the Swiss eosinophilic esophagitis database that received treatment with a swallowed tacrolimus syrup (1 mg bid). We compared clinical (visual analogue scale [VAS] 0-10), endoscopic (VAS, Endoscopic Reference Score [EREFS]), and histological (peak lymphocyte count) disease activity before versus after treatment.

Results: Out of 17 LyE patients, we identified a total of 7 patients undergoing tacrolimus treatment (4 males, median age 71.3 years, IQR: 61.3-76.5, median diagnostic delay of 51.0 months, IQR: 24.5-62.0). Six patients had been previously treated with PPI, five with topical and/or systemic steroids. All patients were treated with topical tacrolimus corresponding to 1 mg bid (for a median of 13 weeks, IQR: 11-15). All patients had clinically, and histologically active disease at baseline. Topical tacrolimus treatment resulted in histological remission (<30 lymphocytes/hpf) in 3/7 patients (42.9%), while 4/7 patients achieved symptomatic remission (VAS for dysphagia ≤2, 57.1%). Overall, clinical (VAS 5 vs. 2, p = 0.0625) and endoscopic activity (VAS 5 vs. 2, p = 0.0625, and EREFS 3 vs. 2, p = 0.125) decreased. Measurement of tacrolimus trough levels in 4/7 patients (range 2.1-3.9 μg/L) revealed some degree of systemic absorption. Mild adverse events to the tacrolimus treatment were seen in 2 patients (esophageal candidiasis, hyposensitivity around lips). No impact on kidney function was observed during the treatment period.

Conclusion: Topical tacrolimus appears to be a potential treatment option for severe LyE, particularly after failure of PPI and/or topical steroids. Further studies are needed, in particular regarding the optimal galenic formulation to avoid systemic absorption.

Background: Eosinophilic esophagitis (EoE) has been described as a chronic allergen/immune-mediated disease characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the mucosa.

Summary: Over the past decades, EoE has been increasingly recognized in various geographical areas with a high socioeconomic development (mostly industrialized countries) and has evolved from an unknown to a clinically distinct disease with increasing prevalence and incidence. An average age at diagnosis between 30 and 50 years and a male predominance have been consistently observed. In both children and adults, EoE is clearly associated with allergies, predominantly food - but also aeroallergens. Most EoE patients present with a personal allergic background such as asthma, rhino-conjunctivitis, and oral allergy syndrome.

Key message: Knowledge of epidemiological characteristics is crucial for identifying risk factors and understanding of the pathogenic mechanisms.

Introduction: Autonomic imbalance has been reported to correlate with clinical remission in patients with ulcerative colitis (UC). This study evaluated heart rate variability (HRV), a potential digital biomarker, in patients with active UC using a smartwatch that is easy to handle.

Methods: Patients with active UC were recruited for this prospective study. The patients' HRV was measured via the Fitbit Inspire2^™ linked via Bluetooth to their smartphone. HRV during nighttime sleep was obtained from continuous data. Patients were required to input the Simple Clinical Colitis Activity Index (SCCAI) score once daily by the application on their smartphones for 3 months.

Results: Nine patients with UC were included. In clinically active disease, SCCAI scores showed a weak inverse relationship with parasympathetic activity, differences of successive R-R pulse intervals (RMSSD) (r = -0.44, p < 0.0001), high frequency (HF) (r = -0.42, p < 0.0001), and total autonomic nervous activity, low frequency (LF) (r = -0.43, p < 0.0001). Receiver operating characteristic analysis indicated that the RMSSD, HF, and LF were significantly higher in patients with active UC. Meanwhile, LF showed the most correlation with severity for bowel urgency scores.

Conclusion: Longitudinal nighttime HRV recorded using a smartwatch is associated with disease activity in patients with active UC. In particular, RMSSD and HF, which are indices of the parasympathetic nervous system, have been suggested as potential digital biomarkers for UC.

Introduction: The number of patients with inflammatory bowel disease (IBD) in Japan has continued to increase, leading to diverse and complex patient backgrounds. Despite these challenges, the education of IBD nurse specialists has not kept pace with the evolving circumstances. Therefore, our research aimed to develop and validate an educational program for the training of IBD nurse specialists.

Methods: We designed an educational program targeting nurses involved with IBD care. The program included e-learning on the assessment of IBD activity and self-care support, as well as face-to-face group discussions. The understanding and practice of disease activity assessment and self-care support were evaluated before and after the e-learning sessions and face-to-face training. Face-to-face training satisfaction was assessed using the Course Interest Survey (CIS) scale and summarized through descriptive statistics.

Results: Overall, data from 19 participants were analyzed. Scores for understanding and practice of disease activity assessment and self-care support increased across all training processes. Moreover, the items that significantly increased before and after e-learning were "inflammation" (p = 0.012), "IBD recognition" (p = 0.026), and "treatment" (p = 0.013) in terms of understanding and "inflammation" (p = 0.036) in terms of practice. The items that increased significantly from e-learning to face-to-face training were "inflammation" (p = 0.042), "subject symptoms" (p = 0.018), and "treatment" (p = 0.017) in terms of understanding. No significant differences in mean scores for understanding and practice were observed between the two groups. According to the CIS scale, the "attention" and "relevance" factors indicate that the training design was highly interesting and relevant. However, the "confidence" factor received a slightly lower average score than did the other factors.

Conclusion: The educational program showed promising implications for the development of IBD nurse specialists. However, further consideration is needed to devise training content that fosters confidence in clinical practice.

Background: Since the first description of eosinophilic esophagitis (EoE) as clinicopathologic syndrome three decades ago, considerable progress has been made to standardize and validate instruments to assess symptom severity, quality of life, endoscopic, and histologic activity for the purpose of randomized controlled trials (RCTs) and observational studies. Standardized assessment of EoE activity is crucial to be able to compare the results of therapeutic interventions and bring much needed therapies to patients. This review focuses on outcome assessment of disease activity in adults with EoE.

Summary: The choice of endpoints/instruments to be used depends on the setting, which might be either an RCT, an observational study, or clinical practice. In RCTs, the choice of endpoints further depends on requirements from regional regulatory authorities. Primary endpoints chosen in RCTs typically focused on symptoms and esophageal peak eosinophil counts, although that likely will change, as therapies with new mechanism of action are explored. Validated symptom-based PRO instruments used in RCTs include the Daily Symptom Questionnaire (DSQ), the EoE activity index (EEsAI) PRO instrument, and numeric rating scales for dysphagia and pain. Histologic activity in RCT is assessed using the EoE histologic scoring system (EoEHSS) that takes into account the severity and extent of eight distinct histologic features. Endoscopic activity is assessed using the EREFS (Exudates, Rings, Edema, Furrows, Stricture) grading system. For observational studies, activity assessment is based on EEsAI PRO, epithelial peak eosinophil counts, and EREFS. In daily clinical practice, EoE activity is based on assessment of symptoms using a visual analog scale (VAS, from 0-10), peak eosinophil count, and EREFS. Several other instruments including the I-SEE, dysphagia-free days over a defined period, the dysphagia stress test, and impedance planimetry (EndoFLIP), to assess EoE severity in clinical practice are currently under evaluation.

Key messages: EoE activity assessment based on symptom-based PRO, histology, and endoscopy has become increasingly complex and varies depending on the setting. While more stringent endpoints and daily recall PRO instruments are being used in RCTs, new instruments aimed at broader disease activity assessment and weekly recall PRO instruments are being used in observational studies and daily clinical practice.

Introduction: Perioperative optimization of Crohn's disease (CD) patients is mandatory in order to ensure favorable outcomes and limit perioperative morbidity such as anastomosis-related complications. The use of perioperative tacrolimus may offer beneficial inflammatory control and improve postoperative outcome. However, it also may exhibit unwanted effects of immunosuppression on infectious complications and wound healing.

Methods: This is a single-center, retrospective study of CD patients undergoing intestinal resection between 2009 and 2018. Characteristics of CD patients receiving infusional perioperative tacrolimus or not were systematically evaluated and exploratively compared. To investigate the impact of tacrolimus and other predictors on postoperative infectious complications, simple regression with a threshold of p < 0.05 was used. Significant predictors of the simple regression analysis, as well as tacrolimus, were then included into multiple logistic regression.

Results: This analysis included 30 patients (34.88%) having received tacrolimus perioperatively and 56 patients (65.12%) that were not treated with tacrolimus. In median, 1 mg/day of tacrolimus was given intravenously for 11 days. Adverse events occurred in 3 patients (10%). The most common adverse events were headache and paresthesia. Tacrolimus showed no significant correlation to postoperative infectious complications. Furthermore, multiple regression analysis found no significant effect of tacrolimus on postoperative infectious complications when controlling for previously identified confounders.

Conclusion: Administration of tacrolimus showed no negative impact on postoperative infectious complications in the study cohort, indicating safety of perioperative tacrolimus therapy. By describing in detail our study population of patients receiving perioperative tacrolimus, we provide data guiding future prospective studies.

Background: In patients with eosinophilic esophagitis (EoE), the correlation between symptoms of esophageal dysfunction and endoscopic and histologic disease activity is generally poor and probably related to multiple causes such as esophageal remodeling processes that might go undetected using endoscopy and histology as well as esophageal hypervigilance and symptom-specific anxiety. Hence, there is a need for a holistic management of patients that goes beyond the control of eosinophilia and symptoms.

Summary and key messages: Physiological esophageal testing using high-resolution manometry, functional lumen imaging probe, pH-impedance, wireless pH monitoring, and mucosal impedance may unveil the effects of chronic transmural fibro-inflammatory changes of the esophageal wall as well as esophageal hypervigilance, thereby assisting to phenotype patients, predict therapeutic response to therapy, and identify motility disorders that may need a specific targeted therapy to ameliorate patients' outcomes. This article discusses the role of functional esophageal examinations in the diagnosis and management of EoE.

Introduction: Carotegrast methyl (CGM) is an oral, small-molecule α4-integrin antagonist, which became clinically available in Japan in May 2022. CGM is approved for remission induction treatment for moderately active ulcerative colitis (UC) with an inadequate response or intolerance to 5-aminosalicylates.

Methods: We performed a single-center, retrospective, observational study of Japanese patients with moderately active UC to assess the real-world effectiveness and safety of CGM as remission induction treatment.

Results: Of 14 patients, 71% (10/14) were women, and the median (range) age was 47 (20-68) years. Disease types were proctitis in 7% (1/14), left-sided colitis in 50% (7/14), and total colitis in 43% (6/14). With a median (range) treatment duration of 8 (2-26) weeks, the rate of endoscopic improvement (Mayo endoscopic subscore [MES] of 0 or 1) was 64% (9/14), and the rate of endoscopic remission (MES of 0) was 57% (8/14). After treatment with CGM, the median (range) MES decreased significantly from 3.0 (2-3) to 0.0 (0-3) (p = 0.008), the Mayo score decreased significantly from 7.0 (5-9) to 0.0 (0-9) (p = 0.006), and the clinical activity index decreased significantly from 6.0 (1-11) to 0.0 (0-9) (p = 0.015). Stool and diarrhea frequencies decreased significantly after initiating CGM, and the percentage of patients with bloody stool and abdominal pain tended to decrease. The cumulative relapse-free rate at week 26 among 9 patients who achieved endoscopic improvement with CGM was 77.8% (95% confidence interval, 36.5%-93.9%). No adverse drug reactions, including progressive multifocal leukoencephalopathy, were reported during the study period.

Conclusion: This single-center, retrospective, observational study of 14 Japanese patients with UC showed that CGM was safe and effective as a remission induction treatment for moderately active UC with an inadequate response to 5-aminosalicylates in real-world settings.

Introduction: Patients with inflammatory bowel disease (IBD) are increasingly using online platforms to communicate with other patients and healthcare professionals seeking disease-related information and support. Free-text posts on these platforms could provide insights into patients' everyday lives, which could help improve patient care. In this proof-of-concept (POC) study, we applied text mining to extract patient needs from free-text posts on a community forum in Japan, holistically visualized the patients' perceptions and their connections, and explored the patient characteristic-dependent trends in the use of words.

Methods: Free-text posts written between May 11, 2020 and May 31, 2022 on the community forum were retrieved and subjected to text mining analysis. Trends in the use of words were extracted from the posts for correspondence and co-occurrence network analyses using KH Coder open-source text mining software.

Results: Seventy-four posts were analyzed. Using text mining methods, we successfully extracted and visualized a variety of patient concerns and their connections. The correspondence and co-occurrence analyses revealed patient segment-dependent trends in the use of words. For example, patients with a disease duration of ≤5 years were more likely to use words related to emotions or their desire to change or quit their job, such as "anxiety" and "resignation." Patients with a disease duration of >10 years were more likely to use words showing that they are finding ways to live with or accept their disease, and are getting used to the lifestyle, but some patients continued to experience worsening disease.

Conclusions: We found that free-text posts on an IBD community forum can be a useful source of information to capture the wide variety of thoughts of patients. Text mining procedures can help visualize the relative importance of the topics identified from free-text posts. Our findings of this POC study will be useful for generating new hypotheses to better understand and address the needs of patients with IBD.

Introduction: There is a close relationship between the relapse of inflammatory bowel disease (IBD) and lifestyle factors, including concomitant medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, smoking status, and alcohol consumption. However, solid evidence is limited regarding the risk factors at diagnosis and initial disease course. This study aimed to explore the impact of concomitant prescriptions and lifestyle factors in patients with newly diagnosed IBD using a large-scale real-world database.

Methods: This is a retrospective inception cohort study using the insurance claims database. Newly diagnosed patients with UC and CD were enrolled between January 2005 and May 2020. Concomitant prescriptions and lifestyle factors were assessed for new biologics use, surgery, and hospitalization during the first year.

Results: In total, 6,743 patients with UC and 1,000 patients with CD were enrolled. Proton pump inhibitors, antithrombotics, antibiotics, and NSAIDs were identified as associated factors for both biologics use and hospitalization in UC patients (all p < 0.01), and antithrombotics were identified as associated factors for both biologics use and hospitalization in CD patients (all p < 0.01) in multivariable analyses. Interestingly, smoking was protective against hospitalization in UC patients (p < 0.01) but not in CD patients (p = 0.997), analyzed by univariate analysis. Alcohol consumption was protective against hospitalization outcomes in UC patients (p = 0.02) but not in CD patients (p = 0.27), analyzed by univariate analysis.

Conclusion: Immediate attention should be paid to concomitant medications at diagnosis because they may have impact on the initial course of IBD.