RE-CELLULARIZATION VIA ELECTROPORATION THERAPY (RECET) COMBINED WITH GLP-1RA TO REPLACE INSULIN THERAPY IN PATIENTS WITH TYPE 2 DIABETES 6 MONTHS RESULTS OF THE EMINENT STUDY

Background & Aim:
Non-variceal upper gastrointestinal bleeding (NVUGIB) accounts for a significant number of patient visits to emergency rooms and remains a major cause of mortality and morbidity worldwide. The re-bleeding rates of NVUGIB after endoscopic treatment within 72 hours have been reported to be up to 25%. re-UI-EWD is a newly developed novel endoscopic hemostatic powder UI-EWD(UI-EWD) that forms an adhesive hydropolymer when sprayed on the surface of the gastrointestinal tract. The aim of this study was to evaluate efficacy of UI-EWD on decreasing the re-bleeding rate after standard endoscopic treatment (SET) of acute NVUGIB.
Methods:
This prospective, multicenter, randomized controlled trial was conducted from December 2018 to November 2021. Consecutive patients with acute NVUGIB from high-risk lesions (Forrest classification Ia, Ib, and IIa) who achieved immediate hemostasis through SET were randomized in a 1:1 ratio to UI-EWD powder (P) with SET group (SET+P, test) vs SET only group (SET, control). Primary outcomes were defined as re-bleeding rate within 72 hours following treatment and secondary outcomes were re-bleeding rate within 30 days following treatment, as well as safety of UI-EWD.
Results:
A total of 348 patients were randomized into the test (n=175) vs control (n=173) groups. Baseline characteristics were not statistically different between groups. The classification of lesion type (test vs control: Forrest Ia and Ib, 115(66.8%) vs 113(67.3%), p=0.831), Glasgow-Blatchford bleeding score (test vs control: 10.7 vs 10.4, p=0.589) was not statistically different between groups. Re-bleeding rate within 3 days was statistically significantly lower in the test group than in the control group (2.9% (n=5) vs 11.3% (n=19), p=0.005). The 30-day cumulative re-bleeding rate was also lower in the test group than in the control group [7.0% (n=12) vs 18.5% (n=31), p=0.003] There was no reported UI-EWD related adverse events such as perforation, bowel obstruction, or gas embolization during the study period.
Conclusion:
This study demonstrates that UI-EWD application following SET significantly reduced 3-day and 30-day re-bleeding rates in patients treated for NVUGIB without any adverse reactions.

Introduction

The utilization of PuraStat® (3D Matrix Europe SAS, Caluire-et-Cuire, France), a viscous transparent gel which utilizes self-assembling peptide (SAP) technology, as a hemostatic agent has been reported in cardiac and sinus surgery. Recently, several studies have evaluated its use in acute gastrointestinal bleeding (GIB). To appraise the published literature further, we conducted a systematic review & meta-analysis of the efficacy and safety of PuraStat® in upper and lower GIB.

Methods

A systematic search of several databases was performed through November 2022 to identify studies assessing the utilization of endoscopically delivered PuraStat® as a primary or salvage hemostatic agent for upper and lower GIB. Endpoints assessed included technical success, defined as complete coverage of the lesion by the gel, initial hemostasis, defined as visual confirmation of bleeding cessation following application, and cumulative 7-day and 30-day rebleeding rates. Pooled proportions of outcomes assessed were calculated using the random-effects model. Heterogeneity was assessed using I² statistics. All p-values <0.05 were considered statistically significant.

Results

A total of 7 studies with 404 patients (256 males and 148 females) were included in the final analysis. The mean/median age ranged from 66.9 to 76 years. A variety of lesions and etiologies of high-risk (oozing/spurting) GIB including peptic ulcer disease (PUD), vascular lesions e.g., angiectasias, mucosal lesions e.g., Mallory-Weiss, refractory radiation proctitis as well as post-resection bleeding [endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD)], among others, were included. The overall pooled rate of technical success was 100% [95% Confidence Interval (CI) 0-100; I² 0%]. The pooled rate of initial hemostasis as primary and salvage therapy was 92.98% (95% CI 87.5-96.17; I² 32%) and 86.12% (95% CI 70.55-94.15; I² 81%), respectively. The quantity of PuraStat® needed to achieve hemostasis ranged from 1-6 mL and the average application time was 2 minutes (from 2 studies).

The pooled proportions of cumulative, 7-day, and 30-day rebleeding rates were 11.39% (95%CI 4.78-24.79; I² 84%), 10.56% (95%CI 1.53-47.29; I² 88%), 10.46% (95%CI 5.97-17.67; I² 54%), respectively. No adverse events were noted after PuraStat® application.

Conclusion

Our study demonstrates that application of PuraStat® to bleeding culprit gastrointestinal lesions is safe, technically feasible and is highly effective in achieving hemostasis as primary as well as salvage therapy. Furthermore, it can be applied quickly and significantly reduces the risk of delayed bleeding. Further studies are warranted to validate our findings.

Introduction
Exogenous insulin is the final treatment for controlling hyperglycemia in patients with type 2 diabetes (T2D) but contributes to weight gain and deterioration of metabolic health. Earlier studies have shown that duodenal mucosal ablation and regeneration (DMR) results in better glycemic control by improving insulin resistance, the root cause of T2D and metabolic syndrome. Pulsed Electric Field technology induces electroporation of the cell membrane by intermittent electric fields, causing apoptosis of affected cells. Re-Cellularization via Electroporation Therapy (ReCET™), is a novel endoscopic procedure that uses electroporation to elicit cell apoptosis and renewal while preserving tissue structure. In this study we aimed to eliminate insulin treatment in T2D patients with a single ReCET procedure combined with a GLP-1 receptor agonist (GLP-1RA). Safety, feasibility, and efficacy of the procedure were assessed.

Methods
Single arm, single center, first in human study in 14 T2D patients, between 28-75 years old, body mass index (BMI) 24-40 kg/m², with a glycosylated hemoglobin (HbA1c) ≤ 8.0%, basal insulin dose <1U/kg/day, C-peptide ≥ 0.2 nmol/l. All patients underwent the endoscopic ReCET procedure under deep sedation, followed by a 2 week post-procedural isocaloric liquid diet. Thereafter semaglutide (GLP-1RA) was started and titrated up to 1 mg/week. Primary feasibility endpoints (procedure time [time from catheter-in to catheter-out], technical success rate, % of patients tolerating GLP-1RA) and safety endpoints ((S)AEs, hypoglycemic events) were assessed. Primary efficacy endpoint was the number of subjects off insulin at 6 months with HbA1c ≤ 7.5%. Baseline and 6 months follow-up glycemic and metabolic data and treatment satisfactory scores were collected and assessed with Wilcoxon paired signed-rank test.

Results
All 14 patients underwent the ReCET procedure and completed 6 months follow-up. ReCET showed a technical success rate of 100% with a median axial treatment length of 12 centimeter (Table 1). Procedure time was 58 (IQR 49–79) minutes. The maximum dosage semaglutide was tolerated by 13 (93%) patients. No device related SAEs were observed. One patient experienced a hypoglycemic event without need for third party assistance. At 6 months, 12 (86%) patients were off insulin, yet showed a significant improvement in glycemic control (HbA1c, fasting plasma glucose, time in range of glucose values) and metabolic parameters with improvement of treatment satisfaction (Table 2).

Conclusion
These results suggest that the ReCET procedure is safe and feasible. ReCET in combination with semaglutide is a promising new therapeutic option that may effectively eliminate insulin therapy in selected T2D patients, while improving glycemic control and overall metabolic health.