Introduction

The incidence of caustic ingestion has remained stable in recent years due to its difficult prevention and limited changes in its management.

Aims & Methods

Aims:
1. To explore changes in the epidemiological and clinical characteristics of caustic ingestion over the last decades
2. To identify epidemiological risk factors of adverse outcomes.
Methods: We present data from an observational study that prospectively collected caustic ingestions in our centre since 1995 and included all adult patients whose acute episode was evaluated in the emergency department. Epidemiological data and variables related to the type of ingestion, prognostic risk factors and the adverse outcomes, defined as the need for admission to the intensive care unit, emergency surgery, patient death and oesophageal or gastric stricture development, were analysed; the results were compared for the periods 1995-2009 and 2010-2024.

Results

A total of 582 episodes of caustic ingestion were included, 305 during the first period and 277 during the second.
Epidemiological characteristics and type of ingestion were overall similar in both periods, as were the clinical, analytical, endoscopic and radiologic indicators of severity.
Adverse outcomes were also similar in the two time periods, both in the short term (comparable frequency of intensive care unit admission, need for surgery and death) and in the long term (stricture development).
The main risk groups for severe ingestions were patients older than 45 years (OR 4.3; 95%CI: 2.3-7.9) and psychiatric comorbidity (OR 5.2; 95%CI: 3.0-9.1), especially depressive syndrome (OR 7.2; 95%CI: 4.2-12.4).
Recurrent ingestions were more frequent in men (OR 1.9; 95%CI: 1.0-3.5) and psychiatric illness (OR 7.6; 95%CI: 3.5-16.5), mainly personality disorder (OR 11.0; 95%CI: 5.5-21.9).

	1995-2009	2010-2024	p value
Women	164 (53,8)	133 (48,0)	0,192
Age	44 (30)	50 (30)	0,193
Voluntary intake	154 (50,5)	121 (44,0)	0,139
pH of caustic Strong acid Weak acid Weak alkali Strong alkali	50 (16,9) 17 (5,8) 215 (72,9) 13 (4,4)	40 (14,7) 25 (9,2) 200 (73,3) 8 (2,9)	0,318
Psychiatric illness Depression Bipolar disorder Personality disorder Psychotic disorder Alcohol/toxic substances consumption	155 (50,8) 112 (36,7) 5 (1,6) 28 (9,2) 16 (5,2) 23 (7,5)	119 (43,0) 75 (27,1) 11 (4,0) 20 (7,2) 13 (4,7) 26 (9,4)	0,007 0,016 0,143 0,479 0,908 0,515
Intensive care unit admission	40 (13,1)	29 (10,5)	0,391
Emergency surgery	8 (2,6)	10 (3,6)	0,655
Death	15 (4,9)	19 (6,9)	0,412
Stricture formation	11 (5,1)	8 (3,7)	0,624

Conclusion

No relevant changes were identified in the epidemiological and clinical characteristics of caustic ingestions over the last decades, nor in their evolution. The most vulnerable groups to prioritise prevention measures would be patients with psychiatric cormobility.

Introduction

Pain, discomfort, and bloating can occur during and after colonoscopy, secondary to bowel distention. Insufflation is the major reason for bowel distention after a colonoscopy. Room air (RA) has slower re-absorption through the intestinal mucosa than carbon dioxide (CO2). Theoretically, with a faster resorption speed, abdominal pain, discomfort, and bloating are expected to be less with CO2 use. Nevertheless, in some clinical studies, CO2 was not found to be superior to RA in terms of post-procedure pain sensation.

Aims & Methods

The aim of this study was to compare abdominal pain sensation and bloating after colonoscopy using RA versus CO2 insufflation. A prospective randomized controlled study conducted on patients performing diagnostic colonoscopy. Enrolled patients were randomized to RA (group 1) versus CO2 insufflation (group 2). All patients were sedated with midazolam (2.5-5 mg) and all colonoscopies were performed by a single endoscopist. Abdominal pain sensation and bloating after the procedure as the primary outcome measure was assessed by a 10-point visual analogue scale (VAS), numerical rating scales from 0 (no pain) to 10 points (maximal pain). The participants were asked about abdominal pain and bloating at 15, 60, and 180 minutes and 24 hours post-procedural.

Results

From July 2021 to August 2022, a total of 64 patients were enrolled. There was 31 males and 33 females. Their mean age was 48.27±16 years. There was a statistically significant increase in abdominal bloating in group 1 (59.4%) compared to group 2 (18.7%), (P=0.018). Also, there was a statistically significant increase in abdominal pain sensation in group 1 compared to group 2 at 60 min (43.8% vs 21.9%) (P=0.011), 180 min (28.1% vs 9.4%) (P=0.017), respectively. None of the studied patients developed pain after 24 hours and there was no statistically significant difference between the studied groups regarding cecal intubation time and total examination time. No adverse events were noted in both groups.

Conclusion

CO2 insufflation is associated with significantly less bloating and less abdominal pain after diagnostic colonoscopy compared to RA insufflation.

Introduction

The impact of achieving endoscopic remission in ulcerative proctitis (UP) is unclear. The preferred long-term treatment goal in ulcerative colitis (UC) is achieving both the symptomatic resolution and endoscopic remission (ER),¹ which has been associated with reduced risk of complications, including colectomy.^2,3 UP is an anatomically limited form of UC, involving only the rectum. Unlike in extensive or left-sided UC, UP has not been associated with elevated colorectal cancer risk. Therefore, the achievement of endoscopic healing as compared to clinical remission in UP represents an uncertain therapeutic target.⁴

Aims & Methods

This study assessed the impact of achieving EH on subsequent outcomes in UP patients. This was a single-center retrospective cohort study including patients aged ≥ 18 with a confirmed diagnosis of UP based on clinical and endoscopic criteria. Included patients had at least two endoscopies and active endoscopic disease (Mayo endoscopy score [(MES) of 1, 2, or 3]) at the first (baseline) endoscopy. EH was defined as an MES of 0 or 1 at the second (follow-up) procedure. A minimum time of 1 month between scopes was required for inclusion. Descriptive statistics were used for baseline characteristics. The relationship of EH to IBD-related outcomes was assessed using univariate analysis (Pearson's Chi-squared test; Fisher's exact test; Welch Two Sample t-test) and we identified those independently associated with EH using multivariable logistic regression analysis (odds ratio with 95% confidence interval).

Results

Among 200 UP patients with baseline endoscopic activity, 109 patients (54.5%) achieved EH at follow-up. The median time from baseline to follow-up was 15 months (IQR: 6, 31). EH at follow-up was significantly associated with fewer IBD-related ED visits (healing: 8.3%, no healing: 21%) or hospitalizations (5.5% vs 18%) and fewer GI visits (mean: 8 [SD: 9], vs 17 [22]) after the second scope. Patients with EH were less likely to have iron deficiency anemia (IDA; 23% vs 41%), iron infusion (10% vs 25%), C. difficile infection (0.9% vs 6.6%), or to initiate a new biologic after relapse (15% vs 33%). Patients with EH also had a greater time to clinical relapse (650 days [730] vs 270 days [416]). In multivariable analysis, patients with mucosal healing had 68% lower odds of an IBD-related ED visit (OR: 0.32, 95% CI: 0.13, 0.73), 74% lower odds of IBD-related hospitalization (0.26 [0.09, 0.67]), and 64% lower odds of biologic initiation after relapse (0.36 [0.13, 0.95]) compared to patients with no mucosal healing, adjusting for the index MES score.

Conclusion

UP patients with endoscopic healing had less IBD-related healthcare utilization (ED visits, hospitalizations, GI visits), fewer IBD-related complications (IDA, iron infusion, C. difficile infection), and were less likely to escalate to biologics after relapse. Our findings suggest that using a treatment target of endoscopic healing is desirable in UP and shed light on its potential utility in preventing disease-related complications and improving long-term outcomes.

References

1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Off J Am Coll Gastroenterol ACG. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233
2. Colombel JF, Rutgeerts P, Reinisch W, et al. Early Mucosal Healing With Infliximab Is Associated With Improved Long-term Clinical Outcomes in Ulcerative Colitis. Gastroenterology. 2011;141(4):1194-1201. doi:10.1053/j.gastro.2011.06.054
3. Impact of mucosal healing on long‐term outcomes in ulcerative colitis treated with infliximab: a multicenter experience - Laharie - 2013 - Alimentary Pharmacology & Therapeutics - Wiley Online Library. Accessed September 24, 2022. https://onlinelibrary.wiley.com/doi/full/10.1111/apt.12289
4. Zhou Q, Shen ZF, Wu B sheng, et al. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract. 2019;2019:1-11. doi:10.1155/2019/5363261

Disclosure

E.L., A.A.: no conflicts of interest to disclose
R.B.: Consulting/Speaker: Janssen, Abbvie, Bristol Myers Squibb, Prometheus Laboratories, Pfizer, Takeda
R.L.: Consulting/Speaking Fees: Pfizer, Enzymetrics, Ancilia Biosciences. Grant Support: National Institute of Health (NIH)
E.S.: Consulting/Speaking Fees: AbbVie, Crohn’s and Colitis Foundation of America (CCFA), Entera Health, Evidera, GI Health Foundation, Janssen, Protagonist Therapeutics, Seres Health, Takeda Pharmaceuticals, Bristol Myers Squibb. Grant Support: Abbott (AbbVie), AstraZeneca, CCFA, Janssen Research & Development, Johns Hopkins University, National Institute of Diabetes and Digestive and Kidney (NIDDK), National Institute of Health (NIH), New York Crohn’s Foundation, Pfizer, UCB, UCSF–CCFA Clinical Research Alliance, Genentech, Seres Therapeutics, Celgen. R.B.: Consulting: Prometheus
D.L.: Consulting/Speaking Fees: Abbvie, Boehringer Ingelheim, Eli Lilly, Fresenius Kabi, Janssen, Palatin, Pfizer, Prometheus Biosciences, Takeda; Grants: Abbvie, Janssen, Takeda

Introduction

This report presents the results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study (VP-VLY-686-3301) assessing the efficacy of tradipitant in relieving symptoms of gastroparesis. Tradipitant, a novel NK-1 receptor antagonist, previously demonstrated efficacy in diabetic and idiopathic gastroparesis in reducing gastroparesis symptoms in a phase 2 study (VP-VLY-686-2301).

Aims & Methods

N=201 idiopathic and diabetic gastroparesis patients with delayed gastric emptying, moderate to severe nausea, and at least 1 vomiting episode were included in the ITT (Intent-to-Treat) population. Subjects were randomized to receive 85 mg tradipitant twice a day (n=102) or placebo (n=99) for 12 weeks. Nausea was assessed daily using the 5-point Gastroparesis Core Symptom Daily Diary (GCSDD). Overall gastroparesis symptom improvement was evaluated using the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales. Sensitivity analyses were also performed to control for confounders that may have masked the true treatment effect size.

Results

At the primary endpoint of change in nausea from baseline as measured by the GCSDD at week 12, both tradipitant and placebo showed significant and similar reductions from baseline at 1.55 and 1.49 respectively. Comparison between treatment arms did not reach statistical significance in this measure. However, in the PGI-C scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (74% v. 58%, p=0.019) and at week 12 (78% v. 66%, p=0.065). Similarly, in the OPB scale, more tradipitant treated patients demonstrated response as compared to placebo both at week 2 (81% v. 62%, p=0.0003) and week 12 (86% v. 71%, p=0.011).
Sensitivity analysis adjusting for rescue medication use further confirmed the ITT findings in both the PGI-C and OPB analysis at both week 2 and week 12.

Conclusion

Significant but similar improvements from baseline for tradipitant and placebo may have masked the true treatment effect size at the primary endpoint of the study of change in nausea severity as measured by daily diary at week 12 leading to no statistically significant difference between treatments. Despite this large placebo effect, tradipitant was shown to be significantly better than placebo in global measures of patient improvement including the Patient Global Impression of Change (PGI-C) and the Overall Patient Benefit (OPB) scales.

Disclosure

Study was sponsored by Vanda Pharmaceuticals, Inc. Authors are employees of Vanda Pharmaceuticals, Inc.