Introduction

The consumption of sugar-sweetened beverages is correlated with the development of obesity and type 2 diabetes mellitus which have become major health problems in our century. Consequently, the World Health Organization has proposed sugar reduction as a preventive and therapeutic strategy [1]. The use of artificial low-caloric sweeteners (e.g., sucralose) as sugar alternatives remains controversial due to the mismatch between their sweet taste (rewarding oral effect) and energy content (lack of post-oral satiating effects). Erythritol, a non-caloric bulk sweetener, might be a promising alternative due to its similar sweetness to sucrose and its ability to release gastrointestinal (GI) satiation hormones without affecting glucose or insulin concentrations.
Acquired preference for sweet-flavored beverages could be based on oral (flavor-flavor learning FFL, e.g., sweet taste) and post-oral associations (flavor-nutrient learning FNL, e.g., calories, hormones) [2]. In human studies, evidence is weak whether liking of a novel flavor increases most when it’s paired with sucrose (FFL + FNL_{calories+hormones}) than with an artificial sweetener (only FFL). Furthermore, the rewarding properties of erythritol remain to be determined.

Aims & Methods

The aim of this study was to assess the effect of the non-caloric sweetener erythritol (FFL + FNL_hormones) on the reward responses (liking and wanting), GI hormone release and glycemic control compared to sucrose and sucralose.
In this randomized, double-blind crossover study, 20 participants (10 women, 10 men; mean ± SD; age: 25.8 ± 7.5 years, BMI: 22.3 ± 1.8 kg/m²) rated explicit liking and wanting of three novel and neutral flavored beverages before and after three conditioning visits where the beverages were paired with either erythritol, sucrose or sucralose. Doses of erythritol and sucralose were individually matched to the perceived sweetness of a 10% sucrose solution. After conditioning, participants had to perform a computerized forced choice task to measure implicit wanting. Blood samples were collected to analyze GI hormones (glucagon-like peptide 1 GLP-1, cholecystokinin CCK) and glycemic control (glucose, insulin).

Results

All 20 participants completed the test visits. The results show that: i) explicit liking increased significantly after the conditioning (all p < 0.01) with no differences between the sweeteners (all p_Tukey > 0.4); ii) explicit wanting increased significantly after the conditioning (p = 0.07 for erythritol, p < 0.01 for sucrose and sucralose) with no differences between the sweeteners (all p_Tukey > 0.8); iii) implicit wanting did not differ between the sweeteners (all p_Tukey > 0.5); iv) conditioning with the sweeteners had no effect on GI satiation hormone release and glycemic control.

Conclusion

Erythritol led to similar ratings in explicit liking and wanting compared with sucrose and sucralose. Conditioning with all three sweeteners increased the reward responses. Since erythritol appears to be as rewarding as sucrose and sucralose, this sweetener can be seen as potential sugar alternative. These effects may not to be associated with FNL.

References

1. World Health Organization (WHO). Guideline: Sugars intake for adults and children. 2015.
2. Yeomans, M., et al., Differential hedonic, sensory and behavioral changes associated with flavor-nutrient and flavor-flavor learning. Physiology & behavior, 2008. 93: p. 798-806.

Clinical Case Summary

A 29 year old women was diagnosed with Crohn’s disease with ileocolonic involvement and a penetrating behaviour (Montreal classification A2L3B3). After the pre imunosupression workup we proposed the patient to start Infliximab (IFX) with a dosage of 5 mg/kg.
During the first infusion the patient referred sudden visual impairment. There were no visible inflamation of the sclera, conjunctiva or peri orbital area. The patient reported no pain and there were no signs of ophthalmoparesis. We stopped the infusion immediately and asked for an urgent observation by Ophtalmology. Although the fundoscopic examination didn’t detect any abnormalities, there was a significant decrease in the visual acuity of the left eye.
The patient regained full visual acuity the day after the event. We decided to switch the biologic therapy to Ustekinumab. The patient was reevaluated in the outpatient clinic two weeks after discharge, she maintained full visual acuity and showed significant improvement of her symptoms.
IFX is a generally well tolerated drug, participating in the therapeutic approach of a wide variety of autoimmune conditions. Despite its favorable safety profile, IFX is associated with rare paradoxical adverse events that correspond to the development or exacerbation of an inflammatory condition during IFX therapy. Ocular adverse events represent part of this group of complications known as paradoxical adverse events. In the literature we can find reports of: uveitis, optic neuritis, endophthalmitis and orbital apex syndrome.
We report a case of a paradoxical adverse event manifested as a transitory sudden asymmetric loss of visual acuity.
From our research, this is the first report in the literature of transitory visual loss due to IFX. We intend to publish this case to further amplify the medical knowledge regarding the therapy with this drug and better inform both patients and physicians regarding the potential advserse events of IFX.

Introduction

Fecal Microbiota Transplantation (FMT) delivered through capsules is an effective therapy against recurrent Clostrdioides difficile infections (rCDI). Studies suggests that the viral part (mainly represented by bacteriophages) of donor stool plays an important role in FMT treatment effect[1]. Through filtration steps the viral fraction of donor stool can be separated from the bacterial part to produce material that can be capsulized and delivered as fecal virome transplantation (FVT) through capsules[2].
The goal of this study was to compare the effect of FVT capsules against FMT capsules as treatment of rCDI in a randomized controlled pilot trial.

Aims & Methods

In the VISION study treatment with FVT capsules was compared to the standard treatment of FMT capsules in 40 patients with first or second recurrence of C. difficile infection.
Participants were randomized 1:1 to receive either one dose of FMT or FVT capsule treatment preceded by approximately 10 days of Vancomycin 125 mg x 4 daily or Fidaxomycin 200 mg x 2 daily. The same four fecal donors were used to produce FMT and FVT material. The primary endpoint was clinical resolution defined as resolution of diarrhea with ≤ 3 daily bowel movements or persistent diarrhea with a negative C. difficile test result, eight weeks following treatment. Patients receiving antibiotics as treatment of other infections were treated with concurrent Vancomycin and were defined as treatment failures in the Intention-to-treat analysis but were excluded from the per-protocol analysis.

Results

Forty patients were randomized and received FMT or FVT capsule treatment with no significant difference between groups in baseline characteristics (Table 1). The primary outcome was achieved by 70 % (14/20) in the FVT group and 75% (15/20) in the FMT group with no significant difference between groups (p = 1). Three patients were omitted from the per-protocol analysis. Here the primary outcome was achieved by 73.7 % (14/19) in the FVT group and 83.3 % (15/18) in the FMT group with no significant difference between groups (p = 0.69).

Table 1. Baseline characteristics

Conclusion

FVT capsules were effective as treatment of rCDI and were non-inferior to FMT capsules. Larger trials are needed to further explore the efficacy of FVT capsules as treatment of rCDI.

References

[1] Liu Q, Xu Z, Dai M, Su Q, Leung Chan FK, Ng SC. Faecal microbiota transplantations and the role of bacteriophages. Clinical Microbiology and Infection 2023;29:689–94. https://doi.org/10.1016/j.cmi.2022.11.012.
[2] Rasmussen TS, Mao X, Forster S, Larsen SB, Von Münchow A, Tranæs KD, et al. Overcoming donor variability and risks associated with fecal microbiota transplants through bacteriophage-mediated treatments. Microbiome 2024;12:119. https://doi.org/10.1186/s40168-024-01820-1.

Disclosure

Frederik Cold declares support for attending meeting and/or travel from AbbVie and Orion Pharma, Andreas Munk Petersen declares support for attending meeting and/or travel from AbbVie, grants or contracts from Chr. Hansen A/S part of Novonesis and consulting fee from Genfit, Hengameh Chloe Mirsepasi-Lauridsen, Torben Sølbeck Rasmussen, Lars Hestbjerg Hansen, Sofie Ingdam Halkjær, Dennis Sandris Nielsen and Morten Helms declares no conflicts of interest.

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.

Introduction

Antiplatelets and anticoagulants significantly increase the risk of upper gastrointestinal bleeding by impairing normal clotting mechanisms. Patients on dual or combined therapy often present with more severe bleeds and poorer endoscopic control. This leads to higher rates of rebleeding, complications, and mortality compared to those not on these therapies.

Aims & Methods

To evaluate the risk and outcomes of non-variceal upper gastrointestinal bleeding (UGIB) in patients on single antiplatelet therapy, dual antiplatelet therapy, and combined antiplatelet-anticoagulant therapy, and to assess associated morbidity, mortality, and rebleeding rates.
A prospective study was conducted involving 150 patients (90 males, 60 females) aged 40–60 years, presenting with upper GI bleeding between 1st January 2023 till 1st January 2025. Patients had co-morbid conditions including hypertension, diabetes mellitus, coronary artery disease, or prior cerebrovascular events, and were on their respective medications for at least 3 months. Patients using NSAIDs, having liver disease, or known bleeding disorders were excluded. Clinical presentations included melena, hematemesis, or both. All patients underwent upper GI endoscopy, with Forrest classification used to characterize ulcers. Laboratory investigations included CBC, LFTs, renal function, PT, and APTT. Bleeding profiles and endoscopic outcomes were analyzed across three medication groups: single antiplatelet (n=60), dual antiplatelet (n=50), and combined antiplatelet-anticoagulant therapy (n=40).

Results

UGIB was reported in 6 (10%) of the single antiplatelet group, 16 (32%) of the dual antiplatelet group, and 14 (35%) of the combined therapy group. Endoscopic findings predominantly revealed Forrest class IIA ulcers. Patients on dual or combined therapy had poorer endoscopic hemostasis. Four patients experienced rebleeding refractory to standard endoscopic measures, requiring angioembolization. One mortality was recorded in the dual antiplatelet group due to massive bleeding and shock.

Conclusion

Dual antiplatelet and combined antiplatelet-anticoagulant therapies significantly increase the risk and severity of non-variceal UGIB, with higher rates of poor endoscopic hemostasis, rebleeding, and mortality. These findings underscore the importance of risk stratification and prophylactic strategies in patients requiring long-term antithrombotic therapy.

References

1. Hao, W., Liu, A., Zhu, H. et al. Risk factors and management of gastrointestinal bleeding in patients with or without antiplatelet and anticoagulation therapy: a multicenter real-world prospective study. BMC Gastroenterol 24, 155 (2024). https://doi.org/10.1186/s12876-024-03238-3
2. Risk of Gastrointestinal Bleeding Increases With Combinations of Antithrombotic Agents and Patient Age Abraham, Neena S. et al. Clinical Gastroenterology and Hepatology, Volume 18, Issue 2, 337 - 346.e19