Outcomes and Incidence of PF-ILD According to Different Definitions in a Real-World Setting

Background: Almost one-third of fibrosing ILD (fILDs) have a clinical disease behavior similar to IPF, demonstrating a progressive phenotype (PF-ILD). However, there are no globally accepted criteria on the definition of a progressive phenotype in non-IPF fILD yet. Four different definitions have been used; however, no internationally accepted definition currently exists.Research Question: To compare the clinical and functional characteristics of progressive fILD according to the currently available definitions.Study design and methods: Cases of fILD were identified retrospectively from the database of the tertiary referral center for ILD in Heidelberg. Lung function, clinical signs of progression, and radiological changes were evaluated. Patients with fILD were considered to have progression according to each of the four available definitions: Cottin (CO), RELIEF (RE), INBUILD (IN), and UILD study. Lung function changes, expressed as mean absolute decline of FVC%, were reported every 3 months following diagnosis and analyzed in the context of each definition. Survival was also analyzed.Results: A total of 566 patients with non-IPF fILD were included in the analysis. Applying CO-, RE-, IN-, and UILD-definitions, 232 (41%), 183 (32%), 274 (48%), and 174 (31%) patients were defined as PF-ILD, respectively. RE- and UILD-criteria were the most stringent, with only 32 and 31% patients defined as progressive, while IN- was the most broad, with almost 50% of patients defined as progressive. CO- definition was in-between, classifying 41% as progressive. PF ILD patients with a UILD definition had worse prognosis.Interpretation: Depending on the definition used, the existing criteria identify different groups of patients with progressive fILD, and this may have important prognostic and therapeutic implications.

Long-term Disease Behavior and Surgical Intervention Analysis in Hospitalized Patients with Crohn's Disease in China: A Retrospective Cohort Study

Background There is lack of real-world data for disease behavior and surgery of Crohn’s disease (CD) from large-scale Chinese cohorts. Methods Hospitalized patients diagnosed with CD in our center were consecutively included from January 2000 to December 2018. Disease behavior progression was defined as the initial classification of B1 to the progression to B2 or B3. Clinical characteristics including demographics, disease classification and activity, medical therapy, development of cancers, and death were collected. Results Overall, 504 patients were included. Two hundred and thirty one (45.8%) patients were initially classified as B1; 30 (13.0%), 71 (30.7%), and 95 (41.1%) of them had disease progression at the 1-year follow-up, 5-year follow-up, and overall, respectively. Patients without location transition before behavior transition were less likely to experience behavior progression. However, patients without previous exposure to a corticosteroid, immunomodulator, or biological agent had a greater chance of experiencing behavior progression. When the long-term prognosis was evaluated, 211 (41.9%) patients underwent at least one CD-related surgery; 108 (21.4%) and 120 (23.8%) of these patients underwent surgery before and after their diagnosis, respectively. An initial classification as B1, no behavior transition, no surgery prior to diagnosis, and previous corticosteroid exposure during follow-up were associated with a lower risk of undergoing surgery. Conclusions This study depicts the clinical features and factors associated with behavior progression and surgery among hospitalized CD patients in a Chinese center. Behavior progression is associated with a higher probability of CD-related surgery, and strengthened therapies are necessary for them in the early phase.

Defects in MMR Genes as a Seminal Example of Personalized Medicine: From Diagnosis to Therapy

Microsatellite instability (MSI) is the landmark feature of DNA mismatch repair deficiency, which can be found in 15–20% of all colorectal cancers (CRC). This specific set of tumors has been initially perceived as a niche for geneticists or gastroenterologists focused on inherited predispositions. However, over the years, MSI has established itself as a key biomarker for the diagnosis, then extending to forecasting the disease behavior and prognostication, including the prediction of responsiveness to immunotherapy and eventually to kinase inhibitors, and possibly even to specific biological drugs. Thanks to the contribution of the characterization of MSI tumors, researchers have first acknowledged that a strong lymphocytic reaction is associated with a good prognosis. This understanding supported the prognostic implications in terms of the low metastatic potential of MSI-CRC and has led to modifications in the indications for adjuvant treatment. Furthermore, with the emergence of immunotherapy, this strong biomarker of responsiveness has exemplified the capability of re-activating an effective immune control by removing the brakes of immune evasion. Lately, a subset of MSI-CRC emerged as the ideal target for kinase inhibitors. This therapeutic scenario implies a paradox in which appropriate treatments for advanced disease are effective in a set of tumors that seldom evolve towards metastases.

Analyses of Changing Disease Patterns and Factors Related to Disease Outcomes in Patients with Crohn’s Disease after 7 Years of Follow-up: A Single-center Retrospective Study

Background: The clinical spectrum and disease course of Crohn’s disease (CD) are heterogeneous and difficult to predict based on initial presentation. Aim: To analyze the long-term disease course and factors leading to poor prognosis of the disease.Methods: In total, 112 patients with CD who were initially diagnosed or treated at our institution were included. We analyzed their clinical data, disease characteristics according to Montreal classification, endoscopic and computed tomography (CT) examinations at initial visit, and 2-year, 5-year, and last follow-ups. We categorized the long-term disease course into four categories: remission, stable, chronic refractory, and chronic relapsing. Significant factors associated with a poorer prognosis were analyzed.Results: The median follow-up period was 107 (range, 61-139) months. Complicated disease behavior increased slightly (20.5% to 26.2%). Chronic refractory (19.6%) and relapsing (16.1%) courses were defined as unfavorable disease course. Two-year disease characteristics were significant factors for unfavorable disease course, and the combination of 2-year perianal disease and 2-year moderate-to-severe CT activity could predict unfavorable disease course with the highest accuracy (0.722, area under the curve 0.768, p<.0001). Conclusions: One-third of our CD patients showed an unfavorable disease course (35.7%) and 2-year disease characteristics were significant factors for an unfavorable disease course.

Computed tomography-based multiple body composition parameters predict outcomes in Crohn’s disease

Background The efficacy of computed tomography-based multiple body composition parameters in assessing disease behavior and prognosis has not been comprehensively evaluated in Crohn’s disease. This study aimed to assess the association of body composition parameters with disease behavior and outcomes in Crohn’s disease and to compare the efficacies of indexes derived from body and lumbar spinal heights in body composition analysis. Results One hundred twenty-two patients with confirmed Crohn’s disease diagnoses and abdominal computed tomography scans were retrospectively included in this study. Skeletal muscle, visceral, and subcutaneous fat indexes were calculated by dividing each type of tissue area by height2 and lumbar spinal height2. Parameters reflecting the distribution of adiposity were also assessed. Principal component analysis was used to deal with parameters with multicollinearity. Patients were grouped according to their disease behavior (inflammatory vs. structuring/penetrating) and outcomes. Adverse outcome included need for intestinal surgery or anti-TNF therapy. Predictors of disease course from multiple parameters were evaluated using multivariate analysis. Indexes derived from body and lumbar spinal heights were strongly correlated (r, 0.934–0.995; p < 0.001). Low skeletal muscle-related parameters were significantly associated with complicated disease behavior in multivariate analysis (p = 0.048). Complicated disease behavior (p < 0.001) and adipose tissue parameters-related first principal component (p = 0.029) were independent biomarkers for predicting adverse outcomes. Conclusions Skeletal muscle and adipose tissue principle component were associated with complicated Crohn’s disease behavior and adverse outcome, respectively. Indexes derived from body and lumbar spinal heights have similar efficacies in body composition analysis.

Progressive Fibrosing Interstitial Lung Diseases: A Current Perspective

Interstitial lung diseases (ILDs) are a large and diverse group of rare and chronic respiratory disorders, with idiopathic pulmonary fibrosis (IPF) being the most common and best-studied member. Increasing interest in fibrosis as a therapeutic target and the appreciation that fibrotic mechanisms may be a treatable target of IPF prompted the development and subsequent approval of the antifibrotics, pirfenidone and nintedanib. The management of ILDs has changed considerably following an understanding that IPF and some ILDs share similar disease behavior of progressive fibrosis, termed “progressive fibrosing phenotype”. Indeed, antifibrotic treatment has shown to be beneficial in ILDs characterized by the progressive fibrosing phenotype. This narrative review summarizes current knowledge in the field of progressive fibrosing ILDs. Here, we discuss the clinical characteristics and pathogenesis of lung fibrosis and highlight relevant literature concerning the mechanisms underlying progressive fibrosing ILDs. We also summarize current diagnostic approaches and the available treatments of progressive fibrosing ILDs and address the optimization of treating progressive fibrosing ILDs with antifibrotics in clinical practice.

5-Aminosalicylic Acid Prevents Disease Behavior Progression and Intestinal Resection in Colonic and Ileocolonic Crohn’s Disease Patients: A Retrospective Study

Background and Aims. The efficacy of 5-aminosalicylic acid (5-ASA) in the long-term outcome of Crohn’s disease (CD) patients was uncertain. This study aimed to evaluate the efficacy of the 5-ASA in preventing disease behavior progression and intestinal resection in CD patients. Methods. CD patients were prospectively enrolled from January 2008 to September 2019 in Xijing Hospital. Disease behavior progression was defined as the development of stricturing (B2) or penetrating disease (B3) in patients with nonstricturing/nonpenetrating disease (B1) at diagnosis. Cox regression analyses were used to investigate the associations between disease location progression, disease behavior progression, and intestinal resection and multiple covariates. Results. In total, 122 CD patients were followed up for 4.3 years. At the time of diagnosis, disease location was ileal in 19.7% (24/122), colonic in 41.0% (50/122), and ileocolonic in 39.3% (48/122). A total of 87 (71.3%) patients had B1 at diagnosis. The disease behavior progression and intestinal resection rates were 42.5% (37/87) and 29.5% (36/122). The use of 5-ASA reduced the risk of disease behavior progression (HR 0.30, 95% CI 0.14–0.61, P = 0.001) and intestinal resection (HR 0.33, 95% CI 0.17–0.90, P = 0.027) in colonic and ileocolonic CD patients. Patients who presented with ileal disease at diagnosis did not have the same protective effects when taking 5-ASA ( P > 0.05). Conclusions. The use of 5-ASA could improve the long-term outcome of CD patients with colon involvement. The result emphasized the importance of early use of 5-ASA in the daily management of colonic involved CD.

Profiling non-coding RNA levels with clinical classifiers in pediatric Crohn’s disease

Background Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) > 2 and FDR < 0.05 after multiple test corrections. Results In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up. Conclusions We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.