Introduction

A major difficulty in treating Crohn’s disease (CD) lies in the unreliable association between clinical symptoms and underlying inflammation, hindering effective monitoring. Intestinal ultrasound (IUS) has emerged as a valuable, non-invasive, and well tolerated tool for assessing inflammatory activity in CD. The "Selecting Therapeutic Targets in Inflammatory Bowel Disease" (STRIDE-II) guidelines recognize the transformative impact of IUS in inflammation assessment but hesitate to endorse transmural healing as a primary treatment target due to current limitations of available therapies in achieving this outcome. However, limited data exist on the applicability of IUS in patients with newly diagnosed CD who might not have developed irreversible fibrotic alterations.

Aims & Methods

The primary aim of this study was to characterize the sonographic features of CD at diagnosis and throughout the initial year post-diagnosis. Additionally, we sought to assess the predictive capability of IUS herein.
We conducted a prospective, population-based cohort study involving newly diagnosed patients with CD. Patients were systematically monitored using IUS in tandem with symptomatic, biochemical, and endoscopic evaluations throughout the first year following diagnosis. Transmural remission (TR) was defined as BWT ≤ 3 mm without colour Doppler signal, and symptomatic remission as Harvey-Bradshaw Index ≤ 4.

Results

During the study period (May 2021 – May 2023), 201 patients with adult-onset CD were included. No significant associations were observed between sonographic characteristics of inflammation and diagnostic delay.
At three months post-diagnosis, TR was achieved in 38% of patients, with a higher proportion observed in those with colonic disease (L1: 33%, L2: 52%, L3: 27%; p= 0.05). TR at three months was significantly associated with symptomatic remission at subsequent follow-ups during the first year (3 months: 87% vs. 51%, p < 0.001; 6 months: 87% vs. 61%, p = 0.004; 9 months: 76% vs. 49%, p = 0.012; 12 months: 87% vs. 64%, p = 0.013), as well as a reduced risk of treatment escalation (20% vs. 65%, p < 0.0001) during this period.
By 12-month, 41% of patients achieved TR, with no significant association observed with disease location. In a multivariable analysis adjusted for age, sex, smoking, disease location, and baseline sonographic inflammation, a higher body mass index (BMI) significantly decreased the likelihood of achieving transmural remission (overweight: Odds ratio (OR) = 0.13, 95% confidence interval (CI): 0.02–0.93; obesity: OR = 0.06, 95% CI: 0.01–0.64).
Among the 126 patients with ileal or ileocolonic disease, 16 (13%) underwent ileocecal resection (ICR) within the first year. In an analysis of receiver operating characteristic area under the curve (ROC AUC), which included endoscopic, symptomatic, sonographic, and biochemical findings, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in the terminal ileum at diagnosis emerged as the most accurate predictor of ICR during this period: IBUS-SAS 63 (AUC = 0.92, sensitivity = 100%, specificity = 73%).

Conclusion

The findings of this study highlight TR as an attainable goal for newly diagnosed CD patients with a positive impact on the disease course. Moreover, the negative influence of high BMI on the likelihood of achieving TR underscores the necessity for further investigation into the impact of weight on the disease course of IBD. The study also reveals that sonographic inflammation in the terminal ileum at diagnosis is the most accurate predictor of the need of ICR within the first year.

Introduction

The relationship between disruptions in the intestinal microbiome, psychological well-being, and modern lifestyle factors in individuals with prevalent non-communicable diseases, such as atherosclerosis, has been partially elucidated but remains inadequately investigated. This raises the inquiry into the feasibility of diagnosing, preventing, and treating atherosclerosis through the measurement and adjustment of disease markers associated with intestinal microbiome, psychological state, and lifestyle indicators.

Aims & Methods

This study aims to broaden the spectrum of these markers to a degree adequate for establishing models to diagnose atherosclerosis within the alternative categories of "no atherosclerosis," "asymptomatic atherosclerosis," and "symptomatic atherosclerosis," as well as by the level of associated health risks (non-significant, significant, and high). Our cohort study data were employed to fulfill this goal.

Results

We identified microbial markers from 955 gut microbiome species and other markers from 52 indicators of psychological state and lifestyle among participants. Marker properties were assessed based on their ability to distinguish between "no atherosclerosis," "asymptomatic atherosclerosis," and "symptomatic atherosclerosis" groups, as well as "not significant risk," "significant risk," and "high risk" groups. We measured their correlation with each participant's group membership using the p-level parameter to prioritize markers, resulting in a rating for each. Eleven microbial species (including Oxalobacter aliiformigenes, Lactobacillus acidophilus, and Bifidobacterium longum) and six other indicators (including "feeling of slowness" and "duration of physical activity") showed the highest scores. Cluster-type models based on these markers accurately predict group membership, with predictive accuracies ranging from 93.7% to 97.1%. This study provides novel insights into atherosclerosis-associated markers, laying a foundation for future research in this field.

Conclusion

The inclusion of microbial, psychological state, and lifestyle indicators has significantly enhanced the existing markers for atherosclerosis. These new markers have facilitated the development of models that, for the first time, enable the diagnosis of atherosclerosis within the categories of "no atherosclerosis," "asymptomatic atherosclerosis," and "symptomatic atherosclerosis," as well as by the associated health risks (non-significant, significant, and high). In addition to microbial markers, these models also incorporate an individual's psychological state and lifestyle indicators.

References

1. Meleshko T. V., Pallah O. V., Rukavchuk R. O., Yusko L. S., & Boyko N. V. (2020). Edible Fruits Extracts Affect Intestinal Microbiota Isolated from Patients with Noncommunicable Diseases Associated With Chronic Inflammation. Biotechnologia Acta, 13 (5), 87-100.
2. Toth, S., Boyko, N., & Sihotsky, V. (2021). Hypothesis of “stroke-stop” formula: a tool for risk index determination in development of acute cerebrovascular disease in asymptomatic individuals with carotid stenosis.
3. Bubnov, R. V., Spivak, M. Y., Lazarenko, L. M., Bomba, A., & Boyko, N. V. (2015). Probiotics and immunity: provisional role for personalized diets and disease prevention. EPMA Journal, 6, 1-11.
4. Kopolovets, I., Berek, P., Stefanic, P., Lotnyk, D., Mucha, R., Hertelyova, Z., ... & Sihotsky, V. (2020). Relevance of Lp-PLA2 blood concentration for morphological structure of atherosclerotic plaque: a shift from reactive to predictive, preventive and personalized medicine to predict stroke in patients with asymptomatic internal carotid artery stenosis.

Introduction

Currently, there is no approved medication for the treatment of Metabolic Associated Fatty Liver Disease (MASLD). However, numerous clinical trials have examined the effect of antihyperglycemic agents on MASLD in type 2 diabetic (T2D) patients, given the close association between T2D and this hepatopathy, both of which are closely linked to insulin resistance. Our aim is to evaluate and compare the therapeutic effects of different hypoglycemic agents in patients with MASLD and T2D.

Aims & Methods

This is a prospective cross-sectional study involving 200 T2D patients over a 6-month period. The presence of hepatic steatosis was confirmed by abdominal ultrasound and/or a Fatty Liver Index (FLI) score greater than 60 in 122 patients. Hepatic fibrosis was assessed using FibroScan in all patients with MASLD. Two comparative studies were conducted to identify the therapeutic effects of hypoglycemic medications on hepatic steatosis and significant fibrosis, defined by a LSM value ≥ 8 kPa.

Results

Patients were predominantly female (73.2%) with a median age of 59.76 ± 10 years. The duration of T2D, although longer in cases of steatosis, was not statistically significant. Glycemic control, assessed by fasting blood glucose and HbA1c levels, was less optimal in patients with MASLD, with an average HbA1c level of 8.98%, compared to patients without hepatic steatosis, who had an average HbA1c level of 8.74% (p=0.002). A similar trend was observed with fasting blood glucose levels (81.96% vs 73.07%), but it did not reach statistical significance.

Degenerative complications, regardless of their type, were comparable between the two groups.

The prescription of biguanides was associated with a reduced risk of hepatic steatosis (p=0.05), while insulin use was frequently observed in patients with steatosis, with a statistically significant correlation for long-acting human insulin and rapid-acting analogs (33.61% vs 19.23% in the absence of steatosis, p=0.02) and (4.92% vs 0% in the absence of steatosis, p=0.05) respectively. No other therapeutic modality, including different classes of oral antidiabetic agents, was correlated with the risk of steatosis.

The prescription of sulfonylureas and rapid-acting insulin analogs was associated with a higher risk of significant hepatic fibrosis, with p-values of 0.05 and 0.008 respectively. In contrast, the use of long-acting human insulin was less frequent in patients with significant fibrosis, with a statistical correlation of 0.03. No other treatment modality, including various types of oral antidiabetic agents, was associated with the risk of fibrosis.

Conclusion

The use of biguanides appears to reduce the risk of hepatic steatosis, while insulin therapy, particularly rapid-acting analogs, is associated with an increased risk of hepatic steatosis and fibrosis. These observations emphasize the importance of an individualized therapeutic approach to optimize the management of MASLD in type 2 diabetic patients. Further studies are needed to validate these associations

References

Tang W, Xu Q, Hong T, Tong G, Feng W, Shen S, et al. Comparative efficacy of anti‐diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis of randomized and non‐randomized studies. Diabetes Metabolism Res. févr 2016;32(2):200‑16.

Yan J, Yao B, Kuang H, Yang X, Huang Q, Hong T, et al. Liraglutide, Sitagliptin, and Insulin Glargine Added to Metformin: The Effect on Body Weight and Intrahepatic Lipid in Patients With Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease. Hepatology. juin 2019;69(6):2414‑26.