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

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

International guidelines recommend performing emergency gastroscopy within 12 hours for variceal (V) bleeding and within 24 hours for non-variceal (NV) bleeding in cases of upper gastrointestinal bleeding (UGIB).

Aims & Methods

This study aimed to analyze the time elapsed between emergency department admission and time of endoscopy, referred to as "door-to-endoscopy time" (DET), and to identify factors influencing DET across different UGIB subgroups. We conducted a retrospective cohort analysis of patients who underwent emergency gastroscopy for UGIB between January 1, 2022, and December 31, 2023, at the Department of Emergency Medicine at Semmelweis University. Data were collected on clinical parameters and 30-day mortality. NV patients were categorized into high-risk (HNV) and low- risk (LNV) groups based on endoscopic findings (Forrest classification). Welch’s t-test was used for comparing mean DET among the subgroups, whereas for hemoglobin linear regression was applied. The significance level was set at 0.05 for all analyses.

Results

Among 654 patients, we identified 126 V and 528 NV UGIB cases, with the latter comprising 99 HNV and 429 LNV cases. Rebleeding occurred in 5.4% of patients (V: 12.7%, HNV: 10.1%, LNV: 2.1%), and 30-day mortality was 19.7% in the cohort (V: 24.8%, HNV: 22.6%, LNV: 17.6%). The mean DET was 7.28 hours (SD=±6.04), with subgroup averages as follows: V: 5.87±3.77 hours, HNV: 6.33±4.04 hours, and LNV: 7.92±6.83 hours, with significant differences between LNV-HNV (p=0.003) and LNV-V (p<0.0001) groups; no significant difference was observed between HNV-V (p=0.37). In the entire cohort, shorter DET was significantly associated with tachycardia (6.61 vs. 7.73 hours, 95% confidence interval (CI) -1.99 to -0.25, p=0.01), hematemesis (5.82 vs. 8.09 hours, 95% CI -3.11 to -1.43, p<0.0001), syncope (6.25 vs. 7.57 hours; 95% CI -2.30 to -0.33, p=0.009), and lower hemoglobin levels (1 g/L decrease in hemoglobin reduced DET by an average of 1 minute, p=0.029). DET was not associated with 30-day mortality (p=0.501), vasopressor use (p=0.857), shock index (p=0.091), coffee-ground emesis (p=0.192), hematochezia (p=0.564), intubation (p=0.566), rebleeding rate (p=0.462), or melena (p=0.961). In the V group, DET was significantly shorter in case of hematemesis (5.20 vs. 7.25 hours, 95% CI -3.61 to -0.49, p=0.011) and tachycardia (5.19 vs. 6.64 hours, 95% CI -2.84 to -0.08, p=0.039); whereas in HNV patients with coffee-ground emesis, DET was significantly reduced (4.94 vs. 6.58 hours, 95% CI -3.08 to -0.20, p=0.026); in LNV patients, DET was shorter in patients with hematemesis (6.42 vs. 8.38 hours, 95% CI -3.20 to -0.71, p=0.002) and syncope (6.56 vs. 8.25 hours, 95% CI -3.10 to -0.29, p=0.019).

Conclusion

In our retrospective cohort study, DET significantly differed between LNV-V and LNV-HNV subgroups. Shorter DET correlated with tachycardia, hematemesis, syncope, and lower hemoglobin levels. DET showed no association with 30-day mortality or rebleeding rate.

Introduction

The current universal standard of care in primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), although its clinical benefit in PBC has never been reported in absolute measures.

Aims & Methods

This cohort aimed to assess the prevalence of incomplete response to UDCA and determine non-response predictors.
Patients with PBC as main diagnosis were included from the hospital's centralized electronic medical records system, over a 10-year period. Overlap syndromes (PBC-Auto-Immune Hepatitis) were also included. Main endpoints included incomplete response to UDCA treatment according to Paris I, Paris II criteria, and Globe score.

Results

A total of 50 patients were included in this study. The mean age at diagnosis was 52.74 years (24-73 years) and 92% females. Only one patient was asymptomatic at onset and 82% had positive anti‐mitochondrial antibodies. All patients were treated with ursodeoxycholic acid (UDCA). Corticosteroids and immunosuppressive therapies were associated in 26% of cases. Incomplete response to UDCA was observed in 28% and 34% of patients according to Paris I and II criteria, respectively. Non-response predictors were poor therapeutic adherence, Overlap syndrome and hepatocellular carcinoma in 14%, 6% and 4% respectively. Five patients were lost to follow-up and five cases died from cirrhosis ’complications. The median ΔGLOBE score was 0.42 (IQR: -1.58 to 3.92). The 5, 10 and 15 years liver transplantation-free survival (median) was: +10%, +7.38% and +5% respectively. Liver transplantation (LT) was considered in one patient with excellent outcomes at last follow-up.

Conclusion

A considerable proportion of patients showed incomplete response to UDCA treatment according to Paris II criteria. Early identification of patients at risk of incomplete response could improve patient management and overall disease prognosis.

References

- Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis. DOI: 10.1016/j.dld.2022.12.010
- Pretreatment prediction of response to ursodeoxycholic acid in primary biliary cholangitis: development and validation of the UDCA Response Score. doi: 10.1016/S2468-1253(18)30163-8. Epub 2018 Jul 13.

Introduction

Metabolic dysfunction-associated steatotic liver disease (MASLD) has a global prevalence of 30%, with 10-30% progressing to advanced liver fibrosis in 5 years. It is essential to assess advanced liver fibrosis – a predictor of liver-related outcomes. FIB-4 is a good screening test, but its low specificity leads to unnecessary referrals to hospital, especially in individuals over 65 years and with type 2 diabetes (T2D). To address these limitations, machine-learning techniques are developing scores like FIB-6 (validated for Hepatitis B and C).

Aims & Methods

We aimed to assess the performance of FIB-6 score in screening for advanced fibrosis in a Portuguese cohort of MASLD patients.
A retrospective-cohort study was conducted with MASLD patients who had undergone liver vibration-controlled transient elastography (VCTE) between January-October 2024. inclusion criteria: adult patients (age >18years) diagnosed with MASLD; undergone liver VCTE; complete biochemical and hematological data. Exclusion criteria: coexistence of other liver diseases; decompensated cirrhosis; hepatocellular carcinoma; hematological/bone‑related diseases. We used liver stiffness measurement by VCTE as a reference standard for liver fibrosis. Fibrosis was staged on a 0–4 scale: F0, F1 and F2, patients without advanced fibrosis; F3 and F4, patients with advanced fibrosis/cirrhosis.
Non invasive tests (FIB-6, FIB‑4, APRI, NFS) were calculated using blood results available within the month of the VCTE. Statistical analysis was performed using R version 4.2.3. AUC-ROC curve analysis with cutoff points were calculated using the Youden index.

Results

115 MASLD patients (58 males (50.43%),57 females (49.57%), median age of 62years) where included. 41 (35.65%) had diabetes mellitus type 2 (T2D) (10 of those insulin-treated), 74 (64.35%) arterial hypertension, 76 (66.09%) dyslipidemia and with a median body mass index of 29.9mg/Kg/m². Regarding hepatic fibrosis, 79 patients had F0-2 and 17 patients had F3-4.
In the general sample, AUC-ROC curve analysis showed an AUC 0.771 (CI 95% :0.662, 0.88) for FIB-4, AUC 0.788 (CI 95% :0.686, 0.889) for APRI, AUC 0.709 (CI 95% :0.595, 0.823) for NFS and AUC 0.695 (CI 95% :0.571, 0.819) for FIB-6.
A subanalysis of the sample over 65 years old revealed AUC 0.807 (CI 95% : 0.665, 0.949) for FIB4; AUC 0.788 (CI 95% : 0.686, 0.889) for APRI; AUC 0.788 (CI 95% : 0.65, 0.926) for NFS; AUC 0.663 (CI 95% : 0.475, 0.852) for FIB-6. A subanalysis of the sample of T2D patients revealed AUC 0.747 (CI 95% :0.584, 0.911) for FIB4; AUC 0.811 (CI 95% :0.676, 0.946) for APRI; and AUC 0.765 (CI 95% : 0.612, 0.918) for FIB6.
Using the optimal cut‑offs of FIB6 (cutoff= 1.8992) for the diagnosis of F3+F4 indicated a reliable performance of FIB‑6 score (sensitivity was 70%, specificity was 52.6%).
The cutoff values of FIB-6 for the general sample was 2.4420 (sensitivity 53%, specificity 87%); for the subset of patients over 65 years was 2.7668 (sensitivity 40%, specificity 96%); for the subset of T2D patients was 2.2230 (sensitivity 55%, specificity 90%).

Conclusion

FIB-6 demonstrated good performance in screening advanced fibrosis in MASLD patients, when compared to those of FIB‑4, APRI, and NFS, surpassing FIB-4, particularly in individuals with T2D. This study is the first to evaluate the applicability of FIB-6 in a Portuguese MASLD cohort. Although the findings warrant validation in larger and more diverse populations, they suggest that FIB-6 may be more efficient to evaluate liver fibrosis in MASLD and offer a more efficient tool to identify patients that need specialized care.

References

Anushiravani A, et al. 2023.
Alswat K, et al. 2024.
Shiha G, et al. 2022
Tacke, Frank et al. 2023
Boursier, Jerome et al. 2022
Papatheodoridi, Margarita et al. 2021
Hannes Hagström et al. 2024.
Rinella, Mary E. et al.2023

Introduction

Most inflammatory bowel disease (IBD) randomised controlled trials (RCTs) only permit tapering of corticosteroids after initiating the maintenance period, either as adaptive or forced tapering, resulting in different corticosteroid exposure among participants.¹ These practices result in inappropriately, prolonged, and excessive exposure to corticosteroids that is not consistent with optimal clinical care and may inflate placebo response rates.^2-7

Aims & Methods

We aimed to provide comprehensive standardised recommendations on key aspects of corticosteroid use in RCTs for adults with moderately-to-severely active IBD, through a multi-phase, international expert consensus. The consensus was informed by a systematic review of MEDLINE, EMBASE, and the Cochrane CENTRAL Register of Controlled Trials which determined the corticosteroid management rules used in placebo-controlled trials of advanced therapies in IBD. Expert consensus recommendations for all aspects of corticosteroid management in RCTs were then developed using a modified Delphi process with two rounds of survey questions and a ratification meeting. For the surveys, corticosteroid management practices were divided into several domains describing the key stages of an IBD RCT and were directly reflected in clinical trial protocols: corticosteroid management during screening, induction, and maintenance; and corticosteroid-related endpoints.

Results

The international Delphi panel consisted of 45 IBD RCT experts. The recommendations propose management of corticosteroid intake during screening, induction, and maintenance phases of pharmacologic RCTs in IBD, and define corticosteroid-related endpoints. The need for minimising corticosteroid exposure through expedited tapering and shorter fixed-dosing periods that more closely reflect routine clinical care was emphasised, and recommendations for standardised definitions of corticosteroid-free remission were provided (Table). The panellists recommended a 2-week stable dosing period before screening, and favoured beginning dosage tapering at ≤2 weeks of induction. Panellists supported a unified tapering protocol of 5 mg prednisone equivalents/week, and voted that enteric- and colonic-release corticosteroids do not require tapering. A point of consensus was that both the beginning of tapering and its rate should be mandated by the trial protocol, rather than the investigators’ discretion. Consensus was not reached on the duration of corticosteroid withdrawal prior to the final study visit for defining corticosteroid-free remission. During the ratification meeting, the panellists highlighted the need for meticulous documentation of corticosteroid use during RCTs to avoid underreporting.

Conclusion

This set of internationally guided recommendations will serve to improve optimisation of RCT design and facilitate appropriate, acceptable, and standardised corticosteroid handling practices in RCTs, as well as maximise comparability between trials and minimise steroid-related harm to trial participants.

References

¹George et al. Inflamm Bowel Dis. 2020;26:515-523. DOI:10.1093/ibd/izz193
²Candy et al. Gut. 1995;37:674-678. DOI:10.1136/gut.37.5.674
³D’Haens et al. N Engl J Med. 2023;388:2444-2455. DOI:10.1056/NEJMoa2207940
⁴D’Haens et al. Lancet. 2022;399:2015-2030. DOI:10.1016/S0140-6736(22)00467-6
⁵Feagan et al. Lancet. 2021;397:2372-2384. DOI:10.1016/S0140-6736(21)00666-8
⁶Danese et al. Lancet. 2022;399:2113-2128. DOI:10.1016/S0140-6736(22)00581-5
⁷Almradi et al. J Crohns Colitis. 2022;16:717-736. DOI:10.1093/ecco-jcc/jjab194

Disclosure

JH has received consulting fees from Alimentiv Inc.
SKV has received consulting fees from Alimentiv Inc.
VS, ZR, and VA report no disclosures.
RA, MA, CNB, PB, RVB, BLC, JFC, FDA, AD, MD, RG, PF, SBH, ALH, MK, TK, PL, EL, FM, NN, RWL, TR, MR, WR, SS, AHS, RCU, CJW, TY, DTR, and PD report no disclosures related to Alimentiv Inc.
RP reports being a consultant and on the Advisory Board for Alimentiv Inc.
BES reports consulting fees from Alimentiv Inc.
LPB reports consulting for Alimentiv Inc.
SD reports consultancy fees from Alimentiv Inc.
GRDH reports advisor fees from Alimentiv Inc.
BB reports advisor/speaker fees from Alimentiv Inc.
JP has received consultancy fees/honorarium from Alimentiv Inc., and has served on a data safety monitoring board for Alimentiv Inc.
ST reports receiving consulting fees from Alimentiv Inc.
LJC and MH are employees of Alimentiv Inc.
WJS is a consultant for Alimentiv Inc.
BGF is the Senior Scientific Officer of Alimentiv Inc.
VJ has received consulting/advisory board fees from Alimentiv Inc.
CM has received consulting fees from Alimentiv Inc.