Introduction

The primary treatment goals of gastroesophageal reflux disease (GERD) include resolving symptoms, preventing complications and symptom relapses, and healing erosive oesophagitis.^{1, 2} Heartburn and regurgitation are frequent and typical symptoms of GERD. Vonoprazan, a potassium-competitive acid blocker, is approved in China for the treatment of reflux oesophagitis.^{3, 4} However, there is a paucity of real-world data assessing the relief of typical daily symptoms achieved with vonoprazan in adult Chinese patients.

Aims & Methods

VIEW (NCT04501627) was a multicentre, single-arm, prospective, observational, real-world study conducted in China. Patients received 20 mg vonoprazan, orally, once daily for 4 weeks (8 weeks for insufficient healing). This post hoc subgroup analysis conducted in enrolled patients with GERD assessed changes in symptom scores for all-day or night-time heartburn and/or regurgitation during the first 14 days of treatment. A mixed-effects model for repeated measures assessed statistical differences in symptom scores from baseline for each day; least-squares mean (LSM) and its 95% confidence interval are reported (negative values indicate improvement).

Results

Among the 2214 patients included in the effectiveness analysis population of the GERD group, 86.7% were aged <65 years[A.G.1] and 60.8% were male. The LSM change in symptom scores from baseline demonstrated a significant improvement from day 1 of treatment in all-day heartburn and/or regurgitation, daytime heartburn or regurgitation, and night‑time heartburn or regurgitation (Table). Significant improvement continued to be observed on day 14 and throughout all previous days of treatment.

Conclusion

Vonoprazan provided rapid (from day 1), significant and durable symptom relief in patients with GERD.

Table: Improvement in symptom scores^a from baseline to day 14 of vonoprazan treatment (effectiveness analysis population; MMRM analysis)

References

1. Antunes C, Aleem A and Curtis SA. StatPearls. Treasure Island (FL), 2023.
2. Heidelbaugh JJ, Nostrant TT, Kim C, et al. Am Fam Physician 2003; 68: 1311-1318.
3. Xiao Y, Lu Y, Yang H, et al. Am J Gastroenterol 2023; 118: S345-S345.
4. Oshima T and Miwa H. J Neurogastroenterol Motil 2018; 24: 334-344.

Disclosure

This study was funded by Takeda (China) International Trading Co. Ltd. Yinglian Xiao, Dekui Zhang and Jianyong Chen have no conflicts of interest. Kailun Liang and Li Xie are Takeda employees and hold Takeda stock options. Minhu Chen received speaker honoraria from Takeda China, AstraZeneca China, Xian Janssen and Eisai China.

Introduction

Acetaminophen (APAP) overdose is a primary cause of drug-induced liver injury (DILI). Although the inflammatory microenvironment plays a critical role in APAP-induced liver injury (AILI), its cellular interaction network and molecular regulatory mechanisms remain incompletely elucidated. Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is known to regulate monocyte differentiation, but its functional role in the AILI inflammatory microenvironment remains unclear. This study aims to investigate the regulatory effects of myeloid KLF4 deletion on the AILI microenvironment.

Aims & Methods

By integrating multidimensional omics analysis and a myeloid-specific Klf4 knockout mouse model, we dynamically dissected microenvironmental remodeling during AILI progression. Liver samples were collected for RNA sequencing, combined with single-cell transcriptomics, flow cytometry, and molecular interaction validation to clarify the KLF4-dependent cellular subpopulation interaction network. In vivo liver imaging, histology, biochemical assays, and molecular experiments were performed to validate KLF4-dependent intercellular interactions. Primary hepatocytes and hepatocyte cell lines were used for in vitro verification.

Results

Myeloid-specific KLF4 deletion led to an increase in CXCL2⁺CXCL3⁺CD24⁺ monocytes, which activated the NF-κB signaling pathway to secrete CXCL2/CXCL3 chemokines. These chemokines bound to the CXCR2 receptor on neutrophils, driving neutrophil infiltration and neutrophil extracellular traps (NETs) formation, while amplifying the TNF-α signaling pathway. Concurrently, myeloid KLF4 knockout induced enrichment of CXCL1⁺IL17RA⁺ endothelial cells. Neutrophil-derived NETs promoted endothelial phenotypic switching toward pro-inflammatory polarization, while endothelial-derived CXCL1 further recruited neutrophils, establishing a "monocyte-neutrophil-endothelial" cellular subpopulation interaction that perpetuated microenvironmental inflammation.

Conclusion

This study reveals the molecular mechanism by which KLF4 drives inflammatory cascades in the AILI microenvironment through regulation of the myeloid-endothelial interaction network. We propose therapeutic strategies targeting NETs formation or the CXCL2/CXCL3-CXCR2 axis, providing novel targets for precise intervention in AILI.

Introduction

Prophylactic wound closure after Endoscopic Submucosal Dissection (ESD) is suggested in high-risk patients to reduce delayed AEs (e.g. bleeding). The closure of large wounds can be challenging with standard endoscopic devices (e.g. endoclips) and dedicated devices are needed. Endoscopic Hand-Suturing (EHS) can be a therapeutic option to close extensive gastrointestinal defects. The current study presents the EHS experience from two Italian centers, aiming to assess the feasibility and clinical effectiveness of the EHS technique.

Aims & Methods

Data from two high-volume endoscopic Italian centers were retrospectively collected. Patients with an ESD wound closed using the SutuArt (Olympus Medical Systems, Tokyo, Japan) device were enrolled in the study (Figure1). Demographics, technical data, success rate, suturing speed, and AEs were recorded

Results

Between June 2023 and August 2024 10 patients were enrolled in the study, demographics in Table 1. All patients were at high-risk for delayed bleeding after gastric or colorectal ESD (figure2). The mean lesion size was 34mm (range 15-45). In all cases SutuArt (Olympus Medical Systems, Tokyo, Japan) needle holder with V-LOC 180, size 3-0 threads (Medtronic) were used. All procedures were performed by two expert endoscopists. ESD-wound closure was successfully achieved in 90% of cases. The mean suturing time was 42 min (range: 25–65 min, SD=23.3 min) meanwhile the mean ESD time was 86 minutes (range: 15–185min, SD=38min). Suturing significantly increased the total procedure time (120min Vs 86min, p<0.001). In one case, the wound closure failed due to suture breakage, resulting in needle entrapment within the mesorectum, with the impossibility of retrieving it. No other AEs were reported.

Conclusion

ESD-defects closure with EHS is feasible and safe with promising outcomes. However, this technique is significantly time-consuming. Probably extended training may be required for endoscopists performing suturing, and further studies are needed to assess the real-life applicability and the cost-effectiveness of this technique.