Introduction

Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics.

Aims & Methods

The aim of our study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. A retrospective, multicentre study was performed in 7 IBD Units, including all patients with refractory UC who received combined plus GMA and TOFA. The number of GMA sessions, its frequency, filtered blood volume and length of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding TOFA intensification, need for new immunomodulators/biologics and colectomy were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results

Twelve patients with UC were included (median 46 years [IQR, 37-58]; 67% female; 67% E3; 75% non-smokers). Patients were receiving TOFA 10 mg bid (75%), 5 mg bid (16%), or 15 mg bid (8%), with 33% receiving steroids at baseline. All patients had prior exposure to anti-TNF agents, 42% to vedolizumab and 8% ustekinumab. Median baseline Mayo score was 7 (IQR, 5-7), median CRP of 11 mg/L (IQR, 5-32) and faecal calprotectin 800 mg/kg (IQ, 715-2,094). GMA was started mostly after PNR (73%), and the median number of GMA sessions was 11 (IQR, 3-20) and 50% received maintenance GMA. Partial Mayo score significantly decreased 1 month after the last GMA session (p=0.027). Four patients (36%) were switched to a new therapy and no patient required colectomy during follow-up. All patients under steroids at baseline were able to stop them. No patient reported adverse events related to the combination therapy.

Conclusion

Combination of GMA with TOFA can be an effective and safe therapy in selected cases of UC after PNR or LOR to this drug.

Introduction

Patients with acute-on-chronic liver failure (ACLF) have traditionally been considered with a tendecy for bleeding however, they frequently display a paradoxical prothrombotic state. ACLF is characterized systemic inflammation and an increased risk of both bleeding and thrombosis. Bleeding arises from decreased pro-coagulation factors and platelet sequestration due to portal hypertension, while thrombosis is exacerbated by endothelial dysfunction and elevated heparinoids, thrombomodulin, or von Willebrand factor.

Aims & Methods

The aim of this study was to evaluate platelet aggregation pattern in patients with ACLF compared to acute decompensated (AD) liver cirrhosis.
The study took place in between the 1^st of July 2024- 31^st of January 2025 and we prospectively included cirrhotic patients, divided in two groups: ACLF group and AD group. The exclusion criteria were people with compensated liver cirrhosis, antiaggregant or anticoagulant treatment and patients with hepatocellular carcinoma or other malignancies. We investigated platelet aggregability in whole blood, by using multiplate aggregometry. For analysis, platelet aggregometry was performed induced by: adenosine diphosphate (ADP), arachidonic acid (ASPI), prostaglandin E2 (PGE2) and thrombin receptor-activated peptide (TRAP-6) as agonist were determined. TRAP‑6 is a peptide that stimulates protease-activated receptor 1 (PAR1) on platelet membrane.

Results

In this study we included 52 patients – 25 patients with ACLF and 27 patients with AD. There were no differences regarding demographic parameters and liver disease etiology between the two study groups. Compared to AD group, patients with ACLF showed an enhanced maximal platelet aggregation with TRAP-6 (AUC 85±12 U vs 45±10 U, p<0.0001). In contrast, we did not detect any differences in platelet aggregation between the two groups after ADP, ASPI or PGE2 activations. We observe that PAR-1 stimulation induces the highest aggregation curve and area under the curve in patients with ACLF and AD, but ACLF patients show the strongest response, highlighting that the degree of liver decompensation influences aggregation results. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

Conclusion

Our results indirectly indicate that platelet reactivity is higher in patients with ACLF likely due to enhanced PAR-1 receptor activity. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

References

1. EASL Clinical Practice Guidelines on acute on liver failure; J. Hepatol. 2023
2. Napolitano et al. European Journal of Internal Medicine 2017
3. Tripodi et al. Hepatology 2006
4. Lisman et al. Hepatology 2006
5. Nassar et al. BIOMEDICINES 2023
6. Rogalski et al. Scandinavian Journal of Gastroenterology 2019
7. Zanetto et al. Liver International 2022
8. Vecerzan et al. Cureus 2024
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Introduction

Acute variceal bleeding (AVB) is a common and life-threatening complication of cirrhosis and portal hypertension. Despite advances in therapeutic strategies, the 6-week mortality rate remains high, ranging from 10% to 20%. Current clinical guidelines recommend standard treatment for cirrhotic patients with AVB, including vasoactive agents, prophylactic antibiotics, and endoscopic intervention. However, real-world clinical practices are often influenced by physician awareness, institutional resources, and patient preferences. In late 2019, West China Hospital of Sichuan University established a multidisciplinary rapid-response pathway for the emergency management of high-risk upper gastrointestinal bleeding (UGIB). This initiative aimed to improve the treatment protocol, integrate endoscopic and interventional resources, and finally improve the outcomes.

Aims & Methods

The present study evaluates the impact of this rapid-response pathway on clinical outcomes in cirrhotic patients with AVB. This retrospective study included consecutive patients admitted for acute UGIB to West China Hospital between January 2016 and November 2022. Inclusion criteria were: (1) cirrhosis; and (2) presentation with hematemesis and/or melena within five days before admission. Exclusion criteria included: (1) non-variceal bleeding or an unconfirmed bleeding source on endoscopy; and (2) less than six weeks of follow-up. Patients were categorized into two groups based on the timing of rapid-response pathway implementation: Group A (2016–2019, pre-implementation) and Group B (2020–2022, post-implementation). Primary outcomes were 6-week mortality and 5-day treatment failure. Propensity score matching (PSM) was applied to adjust for baseline confounders: a 1:1 PSM was used to compare Group A and B.

Results

A total of 1,529 cirrhotic patients with AVB were included. Following 1:1 PSM, Groups A and B comprised 654 patients each. The most common etiology of cirrhosis is chronic hepatitis B virus infection. No significant intergroup differences were observed in Child-Pugh score, MELD score, MELD-Na score, prevalence of PVT, HCC, infection, ascites, or hepatic encephalopathy (all P > 0.05). Group B had a higher rate of prophylactic antibiotics, early endoscopic or interventional treatment use, and less balloon tamponade and intubation. Group B demonstrated significantly lower 6-week mortality compared to Group A [52 (8.0%) vs. 88 (13.5%), P = 0.001]. Multivariate Cox regression identified Child-Pugh score (HR = 1.203), MELD-Na score (HR = 1.040), PVT (HR = 1.733), HCC (HR = 2.398), and 5-day treatment failure (HR = 4.385) as independent risk factors for 6-week mortality. Similarly, Group B exhibited a significantly reduced 5-day treatment failure rate [64 (9.8%) vs. 137 (20.9%), P < 0.001]. While no significant differences in overall 6-week mortality or 5-day treatment failure were observed between the PVT and non-PVT groups, patients with coPVT had significantly higher 6-week mortality compared to non-PVT patients (HR = 4.81).

Conclusion

The implementation of a multidisciplinary rapid-response pathway significantly improved early intervention, endoscopy utilization, and TIPS procedures in cirrhotic patients with AVB. These changes were associated with marked reductions in both 6-week mortality and 5-day treatment failure. Key independent predictors of 6-week mortality included Child-Pugh score, MELD-Na score, HCC, PVT, and 5-day treatment failure.

Introduction

Volatile organic compounds (VOC) in stool samples may reflect functional activity of gut microbiome. Previous studies showed that gut flora may influence transient relaxations of lower esophageal sphincter through short-chain fatty acids production and thus - participate in pathogenesis of gastroesophageal reflux disease (GERD). However, the role of VOC in pathogenesis of GERD is poorly studied yet.

Aims & Methods

The aim of this study (FGMF-2025-0003) was to perform correlation analysis between concentrations of VOC in stool samples and GERD-Q score.
We enrolled willing to participate patients referred to perform multichannel 24-h pH-impedance recording (Ohmega, Laborie). According to the Lyon 2.0 criteria patients were allocated to the GERD or the control group. GERD-Q questionnaire was filled in by the participants on the same day as stool samples were collected. Thermo TSQ 8000 triple quadrupole mass-spectrometer (GC/MS) was used for the measurement of VOCs in stool samples were analyzed with. Correlation analysis (Spearman rank R) was performed between values of 80 VOCs in stool samples and the results of GERD-Q questionnaire.

Results

Data of 76 patients were eligible: 42 with GERD and 34 - of the control group. Participants in the GERD group were older (54.7±12.2 y.o. vs 46±14.9 y.o., P<0.05) and their BMI was greater (30.9±5.2 vs 27.2±6.5 kg/m², P<0.05). GERD-Q score was logically greater in GERD group (11.0±2.5 vs 5.2±1.2, p<0.01). Correlation analysis revealed significant correlations between GERD-Q score and concentrations of 2-methylbutyric acid (Spearman R =-0.31), caproic acid (0.34) and enantiic acid (0.396) in stool samples.

Conclusion

GERD-Q score positively correlates with concentrations of Caproic acid (0.34) and Enantiic acid (0.396) in stool samples and negatively – with 2-Methylbutyric acid. The data of this pilot study may serve as a basis for further research on the role of functional activity of gut microbiome in pathogenesis of GERD.

Introduction

The increasing accessibility of upper gastrointestinal endoscopy has led to a rise in its prescription. However, its overuse and inappropriate indications result in environmental and economic costs, potential iatrogenesis, and a paradoxical reduction in access. This study aims to assess the indications for elective diagnostic upper gastrointestinal endoscopy (UGE) requested in the hospital setting.

Aims & Methods

A retrospective analysis was conducted on elective diagnostic UGE requests from both outpatient and inpatient settings. The appropriateness of the requests was classified according to the recommendations of the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy.

Results

A total of 314 requests were analyzed over a three-month period: 90.8% (n=285) from outpatient consultations and 7.6% (n=24) from inpatient settings. A previous UGE had been performed in 53.8% (n=169) of patients, with an average interval of 27.13 ± 2.12 months between requests. Overall, 59.6% (n=187) of the requests were deemed appropriate, with the most frequent indications being the need for biopsies (15%, n=28), gastrointestinal bleeding or anemia (14.4%, n=27), and post-endoscopic intervention surveillance (10.7%, n=20).
Clinical information indicated the presence of alarm symptoms in 27.7% (n=87) cases, the most frequent being gastrointestinal bleeding or anemia (33.3%, n=29), age >50 years with new-onset symptoms or suspected structural disease (21.8%, n=19), and progressive dysphagia (17.2%, n=15). Conversely, 40.4% (n=127) of requests were considered inappropriate, mainly due to non-compliance with guidelines and surveillance intervals. The most common inappropriate indications included symptoms attributed to disorders of the gut-brain axis (20.5%, n=26), surveillance of atrophic gastritis, fundic gland polyps, hyperplastic polyps, and gastric intestinal metaplasia (11.8%, n=15), as well as post-gastric surgery surveillance for benign conditions in asymptomatic patients (8.7%, n=11). Additionally, 39 (28.3%) UGEs were requested for gastric cancer screening.

Conclusion

This study identified a significant proportion of UGE requests lacking appropriate and timely indications. These findings emphasize the need for well-defined criteria to ensure the rational and optimized use of this resource.